Fourth International Meeting on Pharmacy & Pharmaceutical Sciences

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2 Fourth International Meeting on Pharmacy & Pharmaceutical Sciences 8- September 04, İstanbul ABSTRACT BOOK

3 Press: Gezegen Basım San. ve Tic. Ltd.şti. 00. Yıl Mah. Matbaacılar Sit.. Cad. No: 0/A Bağcılar/ İSTANBUL Copyright 04 Marmara University Faculty of Pharmacy. All Rights reserved st Edition, 500 September, 04

4 Dear Participants, With all my respect, I welcome you to the 4th International Meeting on Pharmacy & Pharmaceutical Sciences (IMPPS-4) which will take place between 8th September 04. I would like to thank you so much on behalf of our faculty for honoring us with your grace. We are very glad to be hosting this event in our historical building representing the history of our faculty that goes back half a century in Istanbul, which is a Metropolitan city, with historical and cultural richness beginning with about 330 AD and coming up to day. As Marmara University Faculty of Pharmacy we have realized the first three of the series of the International Pharmaceutical Congresses in 994, 998 and 00. Today we gathered here for the fourth time for exchanging research, sharing ideas and networking. The broad content of the congress offers opportunity for discussion of the recent developments in pharmaceutical sciences with international experts from all disciplines of pharmaceutical sciences as well as sharing the experience with pharmacy professionals. I sincerely thank you to Istanbul Ecza Koop for the publication of the congress abstract book and to all my friends who contributed to the organization of the congress; Flap Tour Company s valuable team; our sponsors who support us and to my colleagues from Turkey and from abroad for participating in the congress. I wish all an efficient and successful congress, and a pleasant time in Istanbul. Prof. Dr. Gülden Zehra OMURTAG President of Congress -3-

5 Honorary President of the meeting M. Emin Arat, Prof. Dr. Rector of Marmara University COMMITTEES President Gulden Z. Omurtag Prof. Dr. Secretary Mesut Sancar, Assoc. Prof. Dr. Treasurer H. Kubra Elcioglu, Assoc. Prof. Dr. Organizing Committee Feyza Arıcıoglu, Prof. Dr. Sinem Gokturk, Prof. Dr. Guniz Kucukguzel, Prof. Dr. Betul Okuyan, Assist. Prof. Dr. Ali Demir Sezer, Assoc. Prof. Dr. Semra Sardas, Prof. Dr. Esra Tatar, Assist. Prof. Dr. Timucin Ugurlu, Assoc. Prof. Dr. Fikriye Uras, Prof. Dr. Scientific Committee A.Seza Bastug Adile Cevikbas Afife Mat Ahmet Araman Akgul Yesilada Azize Sener Barry P. Rosen Bedia Kaymakcıoglu Bernd Kaina Betul Dortunc Buket Alpertunga Ebrahim F. Razzazi Fikret Vehbi İzzettin George J. Christ Social Committee Ahmet Dogan Ayfer Beceren Bahar Goker Ceren Sahin Emine Alarcin Filiz Arıoz-Ozdemir Gizem Bulut Necla Kulabas Rabia Oba Local Sub-Committee Ahmet Ozer Sehirli Ali Sen Aslı Demirci Aylin Sancar Aysen Cucu Beyza Betül Koçak Burcak Gurbuz Caglar Demirbag Deniz Cıkla-Yılmaz Derya Ozsavcı Dilek Bilgic Alkaya Goksel Sener Gulactı Topcu Guler Yalcın Gulgun Tınaz Hulya Akgun Ilkay Kucukguzel Imer Okar Jawed Fareed Julide Akbuga Kadir Turan Levent Kabasakal Leyla Bitis Mert Ulgen Seher Karslı-Ceppioglu Sevgi Karakus Sevda Suzgec-Selcuk Suna Ozbas-Turan Sule Apikoglu-Rabus Turgut Taskın Yusuf Kemal Demir Yesim Canturk-Talman Elif Calıskan-Salihi Erkan Rayaman Esra Dalkılıc Fatma Ozaydın Gokcen Yasayan Gulbin Erdogan Halil Aksoy Ismail Senkardes Nese Erdinc Nuray Yuktas Oya Kerimoglu Morando Soffritti Myron A. Mehlman Mursit Pekin Osman Ziya Sayhan Sarfraz Ahmad Sena F. Sezen Sidney J. Stohs Seref Demirayak Sermin Tetik Turkan Yurdun Umran Soyoglu-Gurer Yıldız Ozsoy William W. Au Ozlem Bingol-Ozakpınar Pelin Suzgun-Cıkla Pervin Rayaman Serap Ayaz-Seyhan Serap Karaderi Sevcan Gül Akgün Sevil Aydın Sevinc Sahbaz Tugce Yesil Turgut Şekerler

6 SCIENTIFIC PROGRAM -5-

7 THURSDAY, SYMPOSIUM ON BIOSIMILARS OPENING SEMAZEN CEREMONY Chairman: Semra ŞARDAŞ COFFEE BREAK Medicinal plants and microorganisms in drug development Professor Doctor Her Royal Highness Princess Chulabhorn (Chulabhorn Research Institute THAILAND) Chairman: Betul DORTUNC Role of Nanotechnology in Drug Delivery Hayat ONYUKSEL Safety considerations when designing oral solid dosage forms Ali Rajabi SIAHBOOMI 8.00 WELCOME RECEPTION Bulent HalvaSi Trio FRIDAY, HALL A Biosimilars Chairman: Ferhat FARŞİ Biopharmaceuticals: status, trends and future Gary WALSH Production of Biopharmaceuticals from Transgenic Animals Sema BIRLER Biosimilars, To be or not to be Haleh HAMEDIFAR COFFEE BREAK - POSTER VIEWING Psycotherapy Chairman: Feyza ARICIOGLU Pharmacoenhancement of endocannabinoid signalling: new avenues of anxiety therapy? Carsten WOTJAK Where do we stand in the era of psychotherapy? Feyza ARICIOGLU Synthetic Cannabinoids: The New Tsunami That Hits The Nation İlhan YARGIC LUNCH, POSTER VIEWING EXHIBITION Recent Advances in Pharmacotherapy I Chairman: Turay YARDIMCI -6-

8 The role played by the HLA complex in adverse drug reactions Mehmet Tevfik DORAK Growth Arrest Specific-6 (Gas6)/Axl Pathway: Potential new strategy for drug development Fikriye URAS COFFEE BREAK - POSTER VIEWING Drug Safety and Personalized Medicine Chairman: Ahmet AYDIN Disease Caused by Benzene Myron MEHLMAN New Translation Models to Link OMICS to Health Innovation: Micro-grants for Big Data Vural OZDEMIR HALL B Phytotherapy Chairman: Leyla BITIS Phytotherapy in Turkey and the plants of Turkey as source of herbal medicinal products Filiz MERICLI Disclosure of the activity mechanism of a Turkish folk remedy to combat rheumatic complaints Erdem YESILADA Potential anti-alzheimer Agents from Lamiaceae Family Plants Gulactı TOPCU COFFEE BREAK - POSTER VIEWING Drug Design I Chairman: Ilkay KUCUKGUZEL New cyclin dependent kinase inhibitors. Elucidation of their molecular mechanism of action. Hervé GALONS Recent developments in enantioseparation of chiral drugs Bezhan CHANKVETADZE LUNCH, POSTER VIEWING EXHIBITION Pharmaceutical Analysis Chairman: Sinem GOKTURK Application of mass spectrometry based proteomics for production and characterization of biopharmaceuti cals E. RAZZAZI-FAZELI Cuprac Methods Of Antıoxidant Capacity/Activity Measurement Applicable To Food, Pharmaceuticals And Biological Fluids Resat APAK New Trends in Analytical Chemistry Guler YALCIN COFFEE BREAK - POSTER VIEWING Oxidative Stress and Antioxidants Chairman: Eren CİVELEK ÖZÇAĞLI Drug-Induced Oxidative Stress and Toxicity Sibel OZDEN -7-

9 ROS Diagnostics and Biomarkers A. Suha YALCIN HALL C Oral Presentations Chairman: Esra TATAR GPCR-interacting proteins and their individual functional roles Livia BASILE Pros and Cons of Pilus: A target for antivirulence therapeutics and an unlikely player in the fight against cancer Ender VOLKAN Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase Gizem CAKIR Synthesis, characterization, phosphate buffer stability, and antiproliferative effects of a novel modified male ic anhydride containing Copolymer/Anticancer Drug conjugates Gulderen KARAKUS COFFEE BREAK - POSTER VIEWING Oral Presentation Chairman: Emine ALARCIN Preparatıon And In Vıtro- In Vıvo Evaluatıon Of Transdermal Formulatıons Of Betahıstıne Sevinc SAHBAZ Characterization studies of well-defined block co-polymer assemblies Gokcen YASAYAN Degradative Activities of Antibiotic-resistant Staphylococcus saprophyticus, Bacillus pumilus, Gracilibacillus dipsosauri and Idiomarina loihiensis Pınar CAGLAYAN Effect of Using Antibacterial Agent, Direct and Alternating Electric Currents to Kill Bacteria in Hide Curing and Pre-Soaking Liquors Meral BIRBIR LUNCH, POSTER VIEWING EXHIBITION Pharmacoeconomics and Pharmacoepidemiology Chairman: Levent KABASAKAL Evidence Based Medicine: Critical appraisal of epidemiological studies Pınar AY Health Economics in Turkey Deniz GURANLIOGLU -8-

10 COFFEE BREAK - POSTER VIEWING Cosmetics Chairman: Oya KERIMOGLU Challenging Materials for Cosmetic Use Yasemin YAZAN SATURDAY, HALL A Ethnobotany Chairman: Sevda SUZGEC SELCUK Quality control of herbal medicine Rudolf BAUER A summary and comparison of folk medicinal plant uses in Catalonia Joan Valles XIRAU A review on ethnobotany in Turkey Kerim ALPINAR An ethnobotanical study in Marmara Islands (Balıkesir-Turkey Gizem BULUT COFFEE BREAK - POSTER VIEWING Recent Advances in Pharmacotherapy III Chairman: Fikriye URAS Mechanism of INPP4B tumor suppression Irina AGOULNIK Use of mechanism-based evidence for the development of therapy for human cancers William W. AU Ticks, Crimean-Congo Haemoragic Fever and pharmacological prospects Aysen GARGILI LUNCH, POSTER VIEWING EXHIBITION Clinical Pharmacy and Pharmaceutical Care Chairman: Fikret Vehbi IZZETTIN Pharmacists and pharmaceutical care Foppe van MIL Clinical Pharmacist Counseling in Cardio- Metabolic Diseases Sule APIKOGLU RABUS Medication Related Problems in Geriatric Patients: The Role of Pharmacist Betul OKUYAN COFFEE BREAK - POSTER VIEWING -9-

11 Drug Design II Chairman: İlkay KUCUKGUZEL D Analysis of the Binding Site Images for Predicting Binding Affinities in Drug Design Erdem BUYUKBINGOL Better understanding of the monoamine oxidases associated I binding site : Combining molecular modelling and enzymology Salvatore GUCCIONE 0.00 GALA DINNER HALL B Recent Advances in Pharmacotherapy II Chairman: Kubra ELCIOGLU Recent Advances in Pharmacotherapy Gul BAKTIR New treatment strategies in peripheral neuropathies Sena SEZEN COFFEE BREAK - POSTER VIEWING Drug Development Chairman: Bedia KAYMAKCIOGLU Jamming bacterial communication ( Quorum Sensing ): A new approach to the control of bacterial infections Gulgun TINAZ Interference with bacterial cell-to-cell communication - a novel strategy to combat infections Rolf W. HARTMANN Chaperone-Usher Pilus Assembly Mechanisms and Antivirulence Therapeutics Ender VOLKAN LUNCH, POSTER VIEWING EXHIBITION Industrial Pharmacy Chairman: Julide AKBUGA Biotechnological Industry in Turkey and The Biosimilars As The New Driving Force Cem KOCAK New Trends in Quality of Pharmaceuticals Buket AKSU Innovative Developments In Turkish Pharmaceutical Industry Seyfullah DAGISTANLI COFFEE BREAK - POSTER VIEWING Industrial Pharmacy Chairman: Oya Kerimoğlu Evaluation of Hexagonal Boron Nitride as a new tablet lubricant Timucin UGURLU -0-

12 Product Development, Clinical Trials; From Laboratory to Pharmacy Asligul KENDİRCİ HALL C Social and Administrative Pharmacy Chairman: Sule APIKOGLU RABUS Pharmacy Management: Today and Tomorrow Nazlı SENCAN COFFEE BREAK - POSTER VIEWING Pharmaceutical Waste and Environment Chairman: Seher CEPPİOĞLU Drug content of waters. Is it important for human health? Ahmet AYDIN LUNCH, POSTER VIEWING EXHIBITION Stem Cell Chairman: Gulgun TINAZ Stem cells in Medical Training Tunc AKKOC WORKSHOP by BAB Microscope and Image Analysis Systems Comet Assay Solution with Mathematical Modeling Babacan UGUZ & OGulcan Berk UGUZ COFFEE BREAK - POSTER VIEWING Oral Presentation Chairman: Betül OKUYAN & Ozlem BINGOL OZAKPINAR Life Span Effect Dıffernt Infusions of Verbascum Trıchostylum on Caenorhabdıtıs Elegans Exposed to Chronic Heat Stress Hasan KILICGUN Effect of taurine on chemotherapy induced nausea and vomiting in acute lymphoblastic leukemia. Mina ISLAMBULCHILAR Investigation of histone lysine trimethylation or acetylation in sporadic breast tumors and matched normal tissues Seher KARSLI-CEPPIOGLU Cytokine Levels and Platelet Functions in Preeclampsia Fikriye URAS Plasma Growth Arrrest Specific (GAS6) levels in B-cell chronic lymphocytic leukemia patients Dilvin GUNEY The Role of GAS6/TAM Signalling in Differentiation of Mesenchymal Stem Cells Nese ERIZ The Plasma Levels of GAS6 in Recurrent Pregnancy Losses Fikriye URAS --

13 SUNDAY, HALL A Recent Advances in Pharmacotherapy IV Chairman: Sermin TETIK Hypercoagulability in Ovarian Cancer: Laboratory and Clinical Perspectives Sarfraz AHMAD Gene silencing molecules and using in therapy Emine SALVA Chemotherapy resistance: Cancer genetics on behalf of clinical therapy Betul KARADEMIR COFFEE BREAK - POSTER VIEWING Drug Delivery Chairman: Ahmet ARAMAN & Timuçin UĞURLU Nanocarriers as vaccine and gene delivery Oya ALPAR Nanoscale drug delivery systems and the blood-brain barrier Yılmaz CAPAN Poly( Lactic-co-Glycolic Acid) Based Drug Delivery Devices For Tissue Engineering and Regenerative Medicine Oya KERIMOGLU LUNCH, POSTER VIEWING EXHIBITION Pharmacy Education Chairman: Mesut SANCAR - Gul BAKTIR Major Changes in Clinical Pharmacy Education and Practice Sid STOHS Professional Practice and Competency Standarts in Pharmacy Levent USTUNES Importance of Clinical Rounds in Pharmacy Education and Practice Fikret Vehbi IZZETTIN Patient Centered Pharmacy Education: Do we really need it or not? Akgul YESILADA COFFEE BREAK - POSTER VIEWING CLOSING & AWARDS CEREMONY HALL B Pharmacy Practices Chairman: Betul OKUYAN Role of Community Pharmacies in Promoting Rational Use of Drugs In Developing Countries-A Way Forward Azhar HUSSAIN Role of Dietary Supplements in Disease Prevention and Management Sid STOHS --

14 COFFEE BREAK - POSTER VIEWING Food and Drug Chairman: Gulden Z. OMURTAG The carcinogenic risks of artificial sweeteners: the cases of aspartame and sucralose Morando SOFFRITTI Prebiotics and probiotics Dilek HEPERKAN Risk factors and assessment of bacterial pathogens in food Irem Omurtag KORKMAZ LUNCH, POSTER VIEWING EXHIBITION Recent Advances in Pharmacotherapy V Chairman: Gül ÖZHAN & Ayfer BECEREN Drug transporters: Circadian rhythms and therapeutic implications Alper OKYAR Blast injury induced functional and structural changes in brain Nihal TUMER Leptin Resistance: Perdisposing Factor in Obesity Philip J. SCARPACE COFFEE BREAK - POSTER VIEWING HALL C Therapeutic Drug Monitoring & ADME Chairman: Guler YALCIN Metabolites. Friends or Enemies? for Drug Development Mert ULGEN Twenty-four Years of Experience in Therapeutic Drug Monitoring: Past,Present, and Future Goncagul HAKLAR Ensuring Bioanalytical Principles on BA/BE studies Seda UNSALAN COFFEE BREAK - POSTER VIEWING Oral Presentation Chairman: Erkan RAYAMAN & & Pervin RAYAMAN Health Professional Students Knowledge on Pharmacovigilance (PV) Meri KOLUACIK Clinical Pharmacotherapy Education by Problem Based Learning in Clinical Pharmacy Courses Sule APIKOGLU-RABUS -3-

15 An example of a workshop about the use of creative drama in pharmacy education for development of communication skills of pharmacy students Filiz Arıoz OZDEMIR, Goknil Pelin COSKUN LUNCH, POSTER VIEWING EXHIBITION Oral Presentation Chairman: Gizem BULUT & Hulya AKGUN Sustainable Collection and Characterization of Colchicum L. Species in the Flora of Turkey for Etnobotanical Purposes Ahu ALTINKUT UNCUOGLU The investigation of antidiabetic and in vivo antioxidant capacity of fruits, barks and leaves of Cornus mas L. Aylin SEPICI DINCEL Validated Methods in Bioalalysis Somaieh SOLTANI Sequential injection technique as a tool for sample pre-treatment in pharmaceutical analysis Ivana ŠRÁMKOVÁ Determination and Pharmacokinetics of Olanzapine in Human Plasma by LC/MS Method Mehmet Emrah YAMAN COFFEE BREAK - POSTER VIEWING CLOSING & AWARDS CEREMONY -4-

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18 PLENARY LECTURES -7-

19 PL MEDICINAL PLANTS AND MICROORGANISMS IN DRUG DEVELOPMENT PROFESSOR DOCTOR HER ROYAL HIGHNESS PRINCESS CHULABHORN CHULABHORN RESEARCH INSTITUTE AND CHULABHORN GRADUATE INSTITUTE Natural products constitute a significant repertoire of chemicals, many of which have been used as drugs and they may be used as indispensable tools in biomedical research. Many local folk medıcınes contain natural products of plant origin, which remain a largely untapped reservoir of natural compounds with novel chemical structures and biological activities. One common objective of practicing research in the field of natural products is to study plants and other bioresources including microorganism and marine organisms for chemicals that may serve as lead compounds for further development into new drugs for various diseases. We have recently investigated some Thai medicinal plants as well as some microorganisms, particularly fungi for new bioactive natural products. The identification of these compounds by various spectroscopic techniques will be presented. In some special cases, the unique chemistry as well as the biosynthesis and biological activities exhibited by some of these compounds will be presented. PL ROLE OF NANOTECHNOLOGY IN DRUG DELIVERY HAYAT ONYUKSEL UNIVERSITY OF ILLINOIS AT CHICAGO, COLLEGE OF PHARMACY, DEPARTMENT OF BIOPHARMACEUTICAL SCIENCES, US Local delivery of drugs to target tissues after systemic (mostly intravenous) application is relatively new approach to achieve higher drug efficacy with low toxicity. Drug targeting can be achieved by multiple mechanisms and one of them is the passive targeting using nanotechnology. This type of targeting involves drug carriers or drug particles that are big enough (> 0nm) not to escape out of the normal vasculature (with pores <4nm) and not subject to renal clearance (pores <0nm), but can easily extravasate at diseased sites with leaky vasculatures (pores <00nm), such as cancer or inflamed tissues. Nanotechnology based targeted drug delivery significantly changes the biodistribution, pharmacokinetics, and pharmacodynamics of the drug compared to the conventional delivery of the free drug, resulting with high efficacy and hardly any drug toxicity to healthy tissues. Therefore, nanotechnology may play an important role in the future drug therapy of some diseases making cure a realistic possibility. PL 3 BIOPHARMACEUTICALS, STATUS, TRENDS AND FUTURE GARY WALSH CHAIR, INDUSTRIAL BIOTECHNOLOGY, CES DEPT AND MSSI, UNIVERSITY OF LIMERICK, IRELAND To date 46 biopharmaceuticals containing 66 distinct active biopharmaceutical ingredients have been approved in the EU and/or the US, generating sales of US $40 billion in 03. Since January 00, 54 such biopharmaceutical products have been approved in the US and/or EU. Highlights include the approval of the first glycoengineered monoclonal antibody (mab), the first biosimilar mab, as well as the first gene therapy-based product. Ongoing technical trends include the increasing relative importance of mabs, and mammalian cell-based expression systems, and the European biosimilar market is finally taking hold. Approvals over the next several years will continue to be dominated by mab-based products, by products synthesized using conventional expression systems and administered via conventional parenteral delivery. -8-

20 PL 4 PRODUCTION OF BIOPHARMACEUTICALS FROM TRANSGENIC ANIMALS SEMA BIRLER ISTANBUL UNIVERSITY, FACULTY OF VETERINARY MEDICINE, DEPARTMENT OF REPRODUCTION AND ARTIFICIAL INSEMINATION Biopharmaceuticals are important products synthesized only from living biological sources rather than other pharmaceuticals synthesized chemically. Despite of some restrictions or hazards, there are several sources to obtain biopharmaceuticals from living organisms, humans or animals. After the development of recombinant DNA technologies there are new sources to produce biopharmaceuticals such as bacterial and mammalian cell culture, transgenic plants and transgenic animals. Transgenic animals offer an inexpensive and easy way for the production of biopharmaceuticals. Especially after the approval of the products obtained from transgenic animals by European medıcınes Agency (EMA), generation of transgenic animals which produce pharmaceutically important proteins in their milk has received increased interest. The first product approved by EMA in 006 is Atryn, human antithrombin, produced in transgenic goats milk by the company GTC Biotherapeutics. The second product Rhucin, human C esterase inhibitor, manufactured from rabbits milk by the company Pharming was approved in 009. Although methods still reqire improvement, recent advances in transgenic technology can allow reliable and efficient production of transgenic animals. There are different methods for generating transgenic animals. Injection of gene consruct into the pronucleus of an early embryo is the best method for the production of transgenic mice. Somatic cell cloning by using transfected somatic cells is another method, particularly used for the production of transgenic livestock animals. Viral vectors are important tools for the efficiency of transgenic production. Hyperactive plasmids are also promising in the respects of efficiency and reliability. In Turkey, the first transgenic rabbits and lamb were generated in Istanbul UNIVERSITY in 03 by using hyperactive plasmids in collaboration with Hawaii unıversıty. PL 5 BIOSIMILARS, TO BE OR NOT TO BE HALEH HAMEDIFAR CINNAGEN CO. TEHRAN IRAN Patent Cliff of blockbuster brands in biopharmaceutical market by early 000 brought a new approach for manufacturing theirs generics which later named as biosimilars. The world market for biopharmaceuticals is now about >$90 billion; growing at ~5% annually. The biopharmaceutical market now constitutes 5%, approaching 0%, of the World s total pharmaceutical market, which is now essentially at $ trillion/year. While biosimilars are finally starting to substantially penetrate the market, it is crucial to know how to survive in this complicated environment and how to take more share from this attractive market. Biosimilars due to their lower price and same quality are attractive enough for payers and policy makers to be seriously considered. During last decade several biosimilar products came to the market, but their market share were quite different in each case. Based on quality, nature of the market, and type of disease the approach and the success rate become different. Biosimilar role in health care budget becomes more and more significant and payers all over the world find them a promising way to skip crisis due to new expensive medicines come to the market day by day. However the way, time, and manner for entering to the market is the key factor to have a portion of this complicated biopharmaceutical market. -9-

21 PL 6 DISCLOSURE OF THE ACTIVITY MECHANISM OF A TURKISH FOLK REMEDY TO COMBAT RHEUMATIC COMPLAINTS ERDEM YESILADA YEDITEPE UNIVERSITY FACULTY OF PHARMACY The leaves of Sambucus ebulus L. (Adoxaceae) (SE) have been used in Turkish folk medıcıne against a battery of diseases from peptic ulcer to hyperglycaemia and to rheumatic complaints. The methanolic and aqueous extracts of SE showed potent in vivo anti-inflammatory activity against carrageenan-induced hind paw edema as well as adjuvant-induced chronic arthritis models (). Chlorogenic acid was isolated as one of the active metabolite from methanol extract. Hexane subextract produced statistically significant inhibition on edema induced by carrageenan comparable to diclofenac. The methanol extract also exerted significant inhibitory activity against IL-α and IL-β, while hexane subextract showed the highest inhibitory activity on TNFα (). Ursolic acid from the diethyl ether subextract of ethanol extract of the leaves was the active principle against TNFα-induced expression of VCAM- and ICAM- on the surface of HUVECs as monitoring tool (3). Recently through in vitro activity-guided isolation processing several nuclear factor kappa-b inhibitory constituents have been isolated. Their chemical structures were identified; a mixture of two flavonoids [] (quercetin-3-o-β-d-glucopyranoside and quercetin-3-o-β-d-galactopyranoside), two flavonoids (isorhamnetin-3-o-β-d-glucopyranoside [] and isorhamnetin-3-o-β-rutinoside [3]) and two iridoids (Sambulin A [4] and Sambulin B [5]). Among these [] inhibited NO, inos, TNFα, while [3] inhibited PGE/COX while both exerted their effects through p38/iκbα. Iridoids [3, 4] suppressed inos/cox levels, NO/PGE and TNFα, as well as JNK and IκBα phosphorylations. Additionally [5] inhibited IL-6 and [4] also inhibited p38 phosphorylation. Consequently, in vitro/in vivo experimental data have provided molecular and mechanistic evidences supporting the traditional use of this remedy.. Yeşilada E. Antiinflammatory Activity of the Aerial Parts of Sambucus ebulus; Isolation of an Antiinflammatory Principle. Doğa Turkish Journal of Pharmacy 99; : -3.. Yeşilada E, Üstün O, Sezik E, et al.. Inhibitory Effects of Turkish Folk Remedies on Inflammatory Cytokines; Interleukin-α, Interleukin-β, and Tumor Necrosis Factor α. Journal of Ethnopharmacology 997; 58: Schwaiger S, Zeller I, Pölzelbauer P, et al. Identification and pharmacological characterization of the anti-inflammatory principal of the leaves of dwarf elder (Sambucus ebulus L.). J. Ethnopharmacol. 00; 33: PL 7 RECENT DEVELOPMENTS IN ENANTIOSEPARATION OF CHIRAL DRUGS BEZHAN CHANKVETADZE INSTITUTE OF PHYSICAL AND ANALYTICAL CHEMISTRY, SCHOOL OF EXACT AND NATURAL SCIENCE, TBILISISTATE UNİVERSITY, CHAVCHAVADZE AVE, GEORGIA The first part of this presentation shortly summarizes recent developments in liquid phase enantioseparation techniques such as high-performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), nano-liquid chromatography (nano- LC), capillary electrochromatography (CEC) and capillary electrophoresis (CE). In HPLC, novel chiral selectors, mobile phases, mobile phase additives and inert carriers, as well as some unusual effects and approaches for a better understanding of the chiral recognition mechanisms are summarized. In the SFC part of the presentation, the emphasis will be made on uncommon additives of the mobile phases and chemometric-based efforts for classification of the available stationary phases as well as getting some information about the chiral recognition mechanisms. The nano-lc and CEC parts of the presentation will discuss the application of novel materials (chiral molecular frameworks) and inert carriers (core-shell silica) while the CE part focuses on chiral recognition mechanisms with cyclodextrin-type chiral selectors in aqueous and non-aqueous CE. The second part of the presentation will highlight the efforts of our group with regard to separations of enantiomers in the liquid phase with the highest possible coverage of analytes, separation selectivity, plate numbers and shortest analysis time. In order to achieve this goal, the systematic optimization of the composition of polysaccharide-based chiral selectors, the structures of the studied analytes (chiral sulphoxides), composition of the mobile phases, mobile phase additives and separation temperature have been performed. In a parallel project, the particle size of the silica, its morphology (porosity and pore size), the nature of the chiral selector and its content in the chiral stationary phase were optimized in order to reach the highest possible column performance. Chiral analytes studied involved chiral drugs such as dihydropyridine and arylpropionic acid derivatives, b-blockers, imidazole derivatives and sulphoxides. -0-

22 PL 8 SYNTHETIC CANNABINOIDS: THE NEW TSUNAMI THAT HITS THE NATION İLHAN YARGIÇ İSTANBUL UNIVERSITY ISTANBUL MEDICAL FACULTY PSYCHIATRY DEPARTMENT Natural cannabis (Δ9-THC, tetrahidrokanabinol) is derived from the plant called Cannabis Sativa. Acute effects of cannabis include euphoria, relaxation, subjective slowing in time perception, dizziness, analgesia, difficulties in memory and problem solving, ataxia, tachycardia, systolic hypertension, postural hypotension, increased apatite, anxiety, paranoid thoughts and depression. Cannabis can cause dependence and withdrawal. DSM-5 lists withdrawal symptoms as: anger, irritability or feelings of aggression; depressed mood; feelings of restlessness; loss of appetite; insomnia; feelings of anxiety or nervousness; physical symptoms of withdrawal, such as headache, stomach pains, increased sweating, fever, chills or shakiness. Cannabis is also known to have some therapeutic effects such as antiemetic in cancer patients, spasmolytic in multiple sclerosis (MS), appetizer in AIDS, anti-inflammatory in rheumatoid arthritis, antidiarrheic in Chrone s disease and also useful in neuropathic pain, glaucoma and movement disorders. Cannabis acts on cannabinoid receptors (CB and CB). Main endogen cannabinoids are anandamide and arachidonilglyserol. Marijuana contains approximately 60 cannabinoids. Δ9-tetrahydrocannabinol which is the most effective one activates mesolimbic dopaminergic system so that it affects reward and reinforcement mechanism.today there are a few medications containing cannabinoids used for medical purposes: Dronabinol (Marinol ), Nabilone (Cesamet ), Nabiximols (Sativex ) and medical marijuana. Nabiximols (Sativex oral spray) was approved for decreasing stress, muscle rigidity and pain in MS. It can be used in moderate to severe cases that are refractory to other spasmolytic medications. Good results have also been reported with neuropathic pain, overactive bladder, cancer pain and Tourette syndrome. Medical uses of cannabis have led investigators to search for synthetic cannabinoids (SC). These compounds which were initially used for analgesia have THC like effects. They were not marketed as medicine due to their psychoactive properties, however, their abuse spread rapidly. These compounds are marketed on the street with names such as Spice, K, Genie in Europe and USA. In Turkey they have street names such as Bonzai, Jamaica and Jamaican Gold. Their chemical structure is quite different than THC. They are designated with chemical formulas like JWH-08, JWH-073, HU-0, CP-47, CP-497, JWH-08 and a new one is added every day. They were officially registered as illegal substances on in Turkey. Their cannabinoid receptor (CBR) affinity and activity is higher than those of THC. They have a larger effect size and more frequent and more severe adverse effects compared to THC (). Their effect starts more rapidly but lasts shorter. There is risk of intoxication depending on amount and degree of purity. Their adverse effects which are not seen or less frequently seen with natural THC include convulsions, anxiety, aggressiveness, muscle rigidity and confusion. Their abuse has been popular rapidly due to their easy access and being undetectable in routine urine screens. SC s have been reported to cause dependence and physiological withdrawal (). Poison Control Center data in USA report agitation, confusion, hallucination, hypertension, myocardial ischemia, heart attack linked to the use of SC. Toxic effects usually resolve in 3-4 hours (3). There are many case reports of convulsions due to SC. They are generalized tonic clonic (GTC), usually multiple and don t leave sequel (4). Emergency department physicians should suspect from SC abuse in young males who apply with first time GTC seizure (5). In cases of new and sudden onset psychosis who are on urine drug screen follow-up or in cases who demonstrate signs of cannabis abuse but give negative urine test, SC abuse should be suspected (6). SC have also been reported to cause some other serious medical adverse effects like acute kidney failure, acute loss of vision and Wernike Syndrome. Although in the international literature intoxication of synthetic cannabinoids has been reported to resolve without sequel, our country has been shocked by the increasing number of Bonzai related deaths recently. Until now, exact mechanism of causality underlying these cases has not been resolved. References:. Brents LK, Reichard EE, Zimmerman SM, Moran JH, Fantegrossi WE, Prather PL. Phase I hydroxylated metabolites of the K synthetic cannabinoid JWH-08 retain in vitro and in vivo cannabinoid receptor affinity and activity. PLoS One. 0; 6(7):e97.. Castellanos D, Thornton G. Synthetic cannabinoid use: recognition and management. J Psychiatr Pract. 0;8(): Wells DL, Ott CA. The new marijuana. Ann Pharmacother. 0; 45(3): Tofighi B, Lee JD. Internet highs--seizures after consumption of synthetic cannabinoids purchased online. J Addict Med. 0; 6(3): de Havenon A, Chin B, Thomas KC, Afra P. The secret spice : an undetectable toxic cause of seizure. Neurohospitalist. 0; (4): Cohen J, Morrison S, Greenberg J, Saidinejad M. Clinical presentation of intoxication due to synthetic cannabinoids. Pediatrics. 0; 9(4):e

23 PL 9 PHARMACOENHANCEMENT OF ENDOCANNABINOID SIGNALING: NEW AVENUES OF ANXIETY THERAPY CARSTEN T. WOTJAK MAX PLANCK INSTITUTE OF PSYCHIATRY, DEPARTMENT OF STRESS NEUROBIOLOGY AND NEUROGENETICS, RESEARCH GROUP NEURONAL PLASTICITY KRAEPELINSTR MUNICH, GERMANY Anxiety disorders such as specific and social phobias, panic disorder and posttraumatic stress disorder belong to the most frequent psychiatric disorders in our societies. They bear enormous personal and economic burdens. With benzodiazepines, we have a class of drugs in our hands which successfully ameliorates anxiety symptoms. However, benzodiazepines cannot be applied in combination with exposure-based therapies due to state dependency and amnesic effects. This illustrates the interest of preclinical and clinical research in developing novel therapeutic interventions. The endocannabinoid system of the brain represents one of the new promising targets. This system is comprised by a distinct set of synthesizing and degrading enzyme, uptake mechanisms and selective binding sites. Remarkably, endocannabinoids are synthesized and released on demand in postsynaptic nerve terminals. As retrograde messengers, they travel to primarily presynaptically localized receptors. Receptor binding leads to reduced (in case of cannabinoid receptor type, CB) or enhanced (in case transient receptor potential vanilloid receptors, TRPV) of neurotransmitter signaling. The complexity of the endocannabinoid system is further increased by the existence of different endocannabinoids (e.g. anandamide or -AG). Preclinical studies illustrate the potential of enhanced endocannabinoid signaling (e.g. by blocking re-uptake or degradation) in reducing fear expression and facilitating safety learning. The efficacy of this intervention critically depends on the players targeted (i.e. anandamide vs. -AG, CB vs. TRPV). Preclinical studies hold the promise of future application in anxiety patients. PL0 WHERE DO WE STAND IN THE ERA OF PSYCHOTHERAPY? FEYZA ARICIOGLU MARMARA UNIVERSITY, SCHOOL OF PHARMACY, DEPARTMENT OF PHARMACOLOGY AND PSYCHOPHARMACOLOGY RESEARCH UNİT, HAYDARPASA, ISTANBUL, TURKEY Rapidly accumulating evidence suggests that the glutamatergic system plays an important role in the neuropathology and treatment of major depressive disorder, bipolar disorder (BD) and schizophrenia. Recently it has been shown that ketamine has a rapid and long lasting antidepressant activity after a single dose, which acts on the human brain by blocking the N-methyl-Daspartate (NMDAR) receptors. In studies with rats, basic researchers demonstrated that ketamine rapidly activates the so called mammalian target of rapamycin (mtor) pathway, one of many such pathways that perform signal transduction in neurons. This new approach may be a revolutionary break-through in the treatment of depression and it might lead to novel therapeutic targets for antidepressant drug development. BD is one of the common psychiatric diseases that leads to certain corrupted certain brain abilities. Today a growing body of evidence has directed much attention to the hyperactivation of glycogen synthase kinase-3 (GSK-3) in several psychiatric disorders including BD. GSK-3 is widely expressed in many tissues with the highest levels in the brain and the importance of regulatory mechanisms on GSK-3 is highlighted through the aspect of Akt-GSK-3 engagement by possibly bringing novel aspects to the treatment of BD. The involvement of GSK-3 in BD is also supported by the fact that GSK-3 is also regulated by neuromodulators such as brain-derived neurotrophic factor (BDNF), a well-known neurotrophin that regulates differentiation, survival and development of neurons and synaptic plasticity. When binding to TrkB, BDNF is responsible for activating the PI3K/ AKT pathway and consecutively phosphorylating GSK-3 finally resulting in its inhibition. In fact, targeting Toll like receptors as initiator molecular mechanisms of cytokine-mediated inflammatory responses, namely Nod-like receptor protein 3 (NLRP3) inflammasome, is now holding huge promise. GSK-3 has been shown to play a regulatory role in immune responses through cytokine production namely as TNF-α and IL-6. NLRP3 inflammasome, a multiprotein complex that is formed by the activation of NLRP3 and is responsible for initiating IL-β and IL-8-mediated inflammatory responses, has become an important topic which may add novel aspects to the cytokine hypothesis of depression. High plasma levels of pro-inflammatory cytokines such as IL-β, IL-6 and TNF-α have been reported by several clinical studies in patients with depression. In addition, plasma levels of these pro-inflammatory cytokines are shown to be decreased with antidepressant therapies. Thus, great effort has been made to discover novel therapeutic implications targeting immune mechanisms that would replace currently available drugs. --

24 PL THE ROLE PLAYED BY THE HLA COMPLEX IN ADVERSE DRUG REACTIONS MEHMET TEVFIK DORAK HEALTH SCIENCES LIVERPOOL HOPE UNIVERSITY, UK The human leukocyte antigen (HLA) complex located in chromosome 6p.3 is the most gene dense region in the human genome. HLA genes encode cell proteins whose main function is presentation of peptide antigens. HLA molecules are the most polymorphic proteins and show a very high number of disease associations mainly with autoimmune and infectious diseases. Most polymorphisms concentrate in antigen-binding clefts. Over the past decade, HLA molecules are also recognised as being modulators of hypersensitivity against drugs. Of these, HLA- B*57:0 (abacavir) and B*5:0 (carbamazepin) associations are best studied. Variuos HLA mediated adverse drug reactions for allopurinol, aspirin, D-penicillamine, fluoxacilline, levamisole, phenytoin, sulfonamides and other drugs are recognised. Such adverse reactions are mediated by different classes of HLA molecules (A,B,C,DR) and more than one mechanism may be involved. Potential mechanisms involving haptens, super antigens and pharmacologic interference with immune receptors have been ruled out. Recent molecular studies identified the mechanism for adverse reaction to abacavir as alteration in HLA-B*57:0 peptide binding motif by occupying sites within the cleft leading to presentation of novel peptides to T-cells causing polyclonal activation similar to what happens in HLA - mismatched transplantation. Besides providing clinical testing opportunities for drug safety, these developments may also provide insight into immunopathogenesis of disorders also mediated by HLA molecules. PL GROWTH ARREST SPECİFİC-6 (GAS6)/AXL PATHWAY: POTENTİAL NEW STRATEGY FOR DRUG DEVELOPMENT FIKRIYE URAS MARMARA UNIVERSITY, TURKEY Growth arrest-specific 6 protein, GAS6, is expressed in several kinds of cells and tissues, such as hematopoietic cells, endothelial and vascular smooth muscle cells, and brain tissue. It is evident that GAS6 is related to certain physiological and physiopathological conditions including cell migration, adhesion, and cell growth and survival, but its precise physiological role has not yet been clarified. GAS6 has been implicated in inflammation, autoimmune, vascular and kidney diseases. It is the ligand for Tyro 3, Axl and Mer (TAM receptors) of the tyrosine kinase family. GAS6/TAM pathway controls various cellular functions, including macrophage clearance of apoptotic cells and natural killer cell differentiation. GAS6 is overexpressed in various cancers including glioblastoma, lung, gastric, breast, colon, and ovarian cancer. Whereas increased GAS6/Axl interaction indicated a poor prognosis in patients with glioblastoma and ovarian carcinoma, low tumor Axl mrna levels was independently correlated with improved survival in patients with renal cell carcinoma, demonstrating the complexity of the system. There is also evidence in some cancer types that GAS6 may have a role in resistance to chemotherapy. The GAS6/Axl pathway may provide a focus for new strategies for treatment of certain types of cancer. Treatment of AXL-transfected U937 acute myeloid leukaemia cells with recombinant GAS6 resulted in resistance to some drugs such as doxorubicin, VP6, and cisplatin. The cancer-restricted action of GAS6, together with its passivity on stroma cells and its therapeutic inhibition may help target cancer-related inflammation. -3-

25 PL 3 PHYTOTHERAPY IN TURKEY AND THE PLANTS OF TURKEY AS SOURCE OF HERBAL MEDICINAL PRODUCTS FILIZ MERICLI DEPARMENT OF PHARMACOGNOSY, FACULTY NORTHERN CYPRUS OF PHARMACY, NEAR EAST UNIVERSITY, NICOSIA, TURKISH REPUBLIC OF Turkey is the point of the encounter of 3 different eco-systems and it is very rich in plant diversity. Flora of Turkey is represented with more than 0000 plants and about one-third of them are endemic. Besides a rich plant diversity, Turkey is also very rich in cultural varieties. The plant and cultural diversities in Turkey, provide very rich traditional treatments and folk medıcınes. Folk remedies and medicinal plants of Turkey are investigated by Turkish scientists working in Faculties of Pharmacy and nearby professions. More than 000 new compounds have been isolated from Turkish plants and published by the researchers from pharmacognosy departments in Turkey(). The biological activities of Turkish medicinal plants are also investigated by our colleagues. Today Phytotherapy applications in Turkey can be evaluated in groups. A. Traditional folk medicines: The usage of herbs with advices of people or media, such as TV and newspapers. Herbal materials are provided from markets called aktar. B. Rational Phytotherapy: According to the prescriptions of the physicians and/or pharmacists suggestions. The herbal products (medicinal teas and phytomedicines) are provided from pharmacies. Example: Hedera helix, Pelargonium sidoides (). As the results of our investigations, there are a lot of plants like Silybum marianum, Crataegus, Thymus,Origanum, species that can be used as sources of herbal medicinal products(3). References. Meriçli F, Meriçli AH, Seyhan GV et al. Willipelletierine, a New Diterpenoid Alkaloid from Consolida scleroclada. Pharmazie 00; 57, Meriçli F, Alp İ. Bronşit ve Öksürükte Doğal ve Etkin Çözüm Duvar Sarmaşığı Hedera helix. Fitomed 00,8, Topal G, Koç, Meriçli AH et al. Effects of Crataegus microphylla on Vascular Dysfunction in Streptozotocin-induced Diabetic Rats. Phythother. Res. 03; 7, PL 4 POTENTIAL ANTI-ALZHEIMER AGENTS FROM LAMIACEAE FAMILY PLANTS GULACTI TOPCU DEPARTMENT OF PHARMACOGNOSY & PHYTOCHEMİSTRY, FACULTY OF PHARMACY BEZMIÂLEM VAKİF UNIVERSITY, ISTANBUL, TURKEY Alzheimer s disease (AD) is one of the most common and progressive neurodegenerative disorders with dementia in the world. Current AD treatment is symptomatic and is mainly focused on the inhibition of cholinesterases. However, none of them provides a satisfactory treatment for AD, and studies are still going on to find new potential drugs from both synthetic chemicals and natural sources (). In this study, investigation of new cholinesterase inhibitors from Lamiaceae family plants were evaluated and a number of terpenoids and phenolics/flavonoids isolated will be presented as potential drugs in the treatment of AD. For this purpose, Lavandula, Leonurus, Melissa, Micromeria, Nepeta, Origanum, Rosmarinus, Salvia, Satureja, Scutellaria, Sideritis, Stachys and Thymus species from Lamiaceae family plants were investigated (). As terpenoids, triterpenoids, especially oleanane, ursane, and lupane triterpenoids, have high potential in the treatment of AD in the future (3). Diterpenes, especially phenolic ring-containing diterpenes, such as abietanes, were tested for anticholinesterase activity, and most abietanes have been found to be active against BChE rather than AChE (). Ferruginol and taxodione are fairly common abietanes isolated from a number of Salvia species () that exhibited high BChE inhibition activity and moderate AChE inhibition activity, indicating their dual inhibition properties. Some kaurane diterpenes of Sideritis species were also found to be active (4). As a conclusion, a number of Lamiaceae plants that have been investigated should be considered as anticholinesterase agents in the potential treatment of AD with dual inhibition on AChE and BChE, or selective inhibition against only one of them (-5). References. Murray AP, Faraoni MB, Castro MJ, Alza NP and Cavallaro V. Natural AChE Inhibitors from Plants and Their Contribution to Alzheimer s Disease Therapy. Curr Neuropharm 03; : Topcu G, Kusman T. Lamiaceae Family Plants as a Potential Anticholinesterase Source in the Treatment of Alzheimer s Disease, Bezmiâlem Science 04; : Culhaoglu B, Yapar G, Dirmenci T, Topcu G. Bioactive Constituents of Salvia chrysophylla Stapf. Nat Prod Res 03; 7: Ertas A, Ozturk M, Boga, M, Topcu G. Antioxidant and Anticholinesterase Activity Evaluation of ent-kaurane Diterpenoids from Sideritis arguta. J Nat Prod 009; 7: Ozturk M, Kolak U, Topcu G, Oksuz S, Choudhary MI. Antioxidant and Anticholinesterase Active Constituents from Micromeria cilicica by Radical-Scavenging Activity-Guided Fractionation. Food Chem 0; 6:

26 PL 5 APPLICATION OF MASS SPECTROMETRY BASED PROTEOMICS FOR PRODUCTION AND CHARACTERIZATION OF BIOPHARMACEUTICALS EBRAHIM RAZZAZI-FAZELI VETCORE FACILITY FOR RESEARCH / PROTEOMICS UNIT, VETERINARY MEDICINE UNIVERSITY VIENNA / AUSTRIA Proteomics has become one of the most growing discipline within the systems biology nowadays and plays an important role in characterization of biological processes. An essential part of modern proteomics is the biological mass spectrometry. There are exactly 00 years, when Joseph John Thomson has developed the first mass spectroscope in 93 for separation and analysis of isotopes. Now a day mass spectrometry has become the most ubiquitous tool in analytical chemistry and biochemistry. It has definitively revolutionized the field of biosciences with regard to protein analysis. Particularly, the biological mass spectrometry has been shown to be the method of choice for characterization and evaluation of therapeutic proteins. Mass spectrometry can provide detail information on not only amino acid sequence but also their alteration and post translational modifications. In recombinant protein technology the study of host cell proteome such as Chinese Hamster Ovary cells or Escherichia coli (E. coli) provide valuable information for optimizing the fermentation process. The achieved knowledge can help to enhance the product yield and reduce degradation or aggregates of recombinant proteins []. Another example is the use of proteomics in characterization of biological medicinal products such as therapeutic human polyclonal immunoglobulin concentrates []. In this paper an overview of different strategies used in proteomics and biological mass spectrometry for characterization of therapeutic immunoglobulin as well as recombinant proteins and their host cell proteome will be given and its potential will be discussed. References. K. Marisch et al. A comparative analysis of industrial Escherichia coli K- and B strains in high-glucose batch cultivations on process-, transcriptome- and proteome level (03), PLoS One Volume 8 / Issue 8. F. Lackner et al. Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (04) Electrophoresis 04, 35, 55 5 PL 6 CUPRAC METHODS OF ANTIOXIDANT CAPACITY/ACTIVITY MEASUREMENT APPLICABLE TO FOOD, PHARMACEUTICALS AND BIOLOGICAL FLUIDS RESAT APAK, KUBILAY GUCLU, MUSTAFA OZYUREK, S. ESIN CELIK, BURCU BEKTASOGLU, SEMA DEMIRCI CEKIC AND MUSTAFA BENER ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY, DIVISION OF ANALYTICAL CHEMISTRY, AVCILAR ISTANBUL Measuring the antioxidant activity/capacity levels of biological fluids and foods is carried out for the diagnosis and treatment of oxidative stress associated diseases in clinical biochemistry, for meaningful comparison of foods in regard to their antioxidant content, and for controlling variations within or between products. Some drugs owe their activity totally to their antioxidative activity, e.g., improvement of genetic stability in lymphocytes from Fanconi anemia patients originates from the combined effect of α-lipoic acid and N-acetylcysteine. Various antioxidant activity/capacity methods have been used to monitor and compare the antioxidant activity of food and drug. Complementary to existing methods in literature, novel approaches have recently been developed such as CUPRAC (CUPric Reducing Antioxidant Capacity) total antioxidant capacity (TAC) assay (introduced by our research group to world literature in 004), its modified ROS scavenging assays and other modifications (e.g., antioxidant sensor, post-column online HPLC technology). Antioxidants react with the CUPRAC reagent (cupric neocuproine) to produce the Cu(I)-neocuproine (Nc) chromophore measured spectrophotometrically []. The method was successfully applied in our laboratory to various food extracts (i.e., apricot, apple, hazelnut, herby cheese and vegetables) and human serum. Hydrophilic antioxidants in serum were measured in aqueous phase after precipitation of proteins, while lipophilics were determined in dichloromethane []. Main and modified CUPRAC assays have recently been compiled in a comprehensive review [3]. A salicylate probe was converted to its CUPRAC reactive hydroxylation products (dihydroxybenzoates) in a Fenton system, and the hydroxyl radical scavenging rate constants of the tested antioxidants were determined by competition kinetics. Lipophilic and hydrophilic antioxidants could be simultaneously assayed in acetone-water as their inclusion complexes with methyl-βcyclodextrin. Xanthine oxidase scavenging activity of polyphenolics was determined by urate measurement with CUPRAC. Cupric neocuproine reagent in urea buffer also responded to thiol-containing proteins in food. Hydrogen peroxide scavenging activity of polyphenolics was measured in the presence of Cu(II) catalyst with a modified CUPRAC method. A low-cost optical antioxidant sensor (CUPRAC sensor) was developed by immobilizing the Cu(II)-Nc reagent onto a perfluorosulfonate cationexchange polymer membrane (Nafion ). A novel on-line HPLC-CUPRAC method was developed for the selective determination of polyphenols in complex plant matrices. This type of pharmaceutical profiling may also be useful to identify, classify and compare the antioxidant-active ingredients of drugs. Another modified CUPRAC method for measuring the superoxide (SO) anion radical scavenging activity of plasma antioxidants (including thiols) utilized a tert-butylhydroquinone (TBHQ) probe with PMS-NADH non-enzymic SO generation system [4]. The current direction of CUPRAC methodology can be best described as a selfsufficient and integrated train of measurements providing a useful antioxidant and antiradical assay package in biochemistry and food chemistry comprising many assays, and the results are in accordance with those of independent reference methods, having distinct advantages over certain established methods. -5-

27 References [] R. Apak, K. Güçlü, M. Özyürek, S. E. Karademir, J. Agric. Food Chem., 004, 5, [] R. Apak, K. Güçlü, M. Özyürek, S. E. Karademir, M. Altun, Free Radical Res., 005, 39, 949 [3] M. Özyürek, K. Güçlü, R. Apak, Trends Anal. Chem., 0, 30, [4] B. Bekdeşer, M. Özyürek, K. Güçlü, R. Apak, Anal. Chem., 0, 83, PL 7 NEW TRENDS IN CHROMATOGRAPHY GULER YALCIN MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, HAYDARPASA CAMPUS, HAYDARPASA ISTANBUL The first thing the chemist must do is to isolate the substances he is interested in from the material and prepare them in a pure state. The next step is, if possible, to identify these substances and find out what they consist of and how they are built up from simple constituents. These words are from the Presentation Speech of Prof. Arne Tíselius in the Ceremony of A.J.P. Martin, R.L.M. Synge awarded with The Nobel Prize in 95, on chromatography. However, chromatography gained progress since 95, the needs are still remain the same. Separating, purifying, identifying, quantifying of the substances in the complex natural/artificial matrixes. Eventually find out how they are built up from simple constituents. On the other hand, there are some environmental issues that require attention to make the ecology friendly. Chromatographic separations needs to take some measures. These can be summarized in 0 points:. Improving resolution and selectivity;. Having cost effective analysis. 3. Shortening the analysis time. 4. Obtaining the reproducible and the repeatable results. 5. Lowering the detection limits. 6. Using the column packings resistant to heat and ph. 7. Using less organic solvent, 8. Alternatively to organic solvents, using pressurized hot water (PHW-LC) 9. Compatibility with some detectors, like NMR, Mass, flame ionization. 0. Increased confidence on analyte identification. New trends meets the above mentioned essential points in chromatography are being summarized in this study. The columns for increasing the resolution and selectivity and resistant the heat, ph are being produced: Nanostructured thin films for ultrathin layer chromatography (), diamond based adsorbents (), metal organic frameworks (3), monolithic columns (4). Along with the column technology, the instrument technology is getting improved. Ultra High Performance Liquid Chromatography (UHPLC), Ultra Thin Layer Chromatography (UTLC) (), Nanoflow Liquid Chromatography (5), Nano Chromatography, Termal Gradient Liquid Chromatography, Pressurized Hot Water Liquid Chromatography (PHW-LC) (6) are some of these newly designed instruments. The most interesting progress in chromatography is the minimization and contingently lowering the amount of detectable analyte. It probably would be helpful to find out that how substances are built up from simple constituents as Prof. Tiselius told us. References Ultrathin-layer chromatography on SiO, AlO3, TiO, and ZrOnanostructured thin films, Julia Wannenmacher, Steven R. Jim, Michael T. Taschuk, Michael J. Brett, GertrudE. Morlock, J. of Chromatogr. A, 38 (03) Diamond based adsorbents and their application in chromatography Review Anton A. Peristyya, Olga N. Fedyaninab, Brett Paulla, Pavel N. Nesterenkoa, J. of Chromatogr. A, 357 (04) Applications of metal-organic frameworks as stationary phases in chromatography, Yuebo Yu, Yuqian Ren, Wei Shen, Huimin Deng, Zhiqiang Gao, Trends in Analytical Chemistry, 50 (03) Monolithic columns in high-performance liquid chromatography, Guiochon G., J Chromatogr A. 007 Oct 9;68(-):0-68; discussion 00. Epub 007, Jun 3. 5 A direct nanoflow liquid chromatography-tandem mass spectrometry system for interaction proteomics. Natsume T, Yamauchi 6 Y, Nakayama H, Shinkawa T, Yanagida M, Takahashi N, Isobe T, Anal Chem. 00 Sep 5;74(8): Liquid chromatography at elevated temperatures with pure water as the mobile phase, Kari Hartonen, Marja-Liisa Riekkola, TrAC Trends in Analytical Chemistry, 0/008; 7():

28 PL 8 DRUG-INDUCED OXIDATIVE STRESS AND TOXICITY SIBEL OZDEN ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, ISTANBUL, TURKEY Reactive oxygen species (ROS), can be generated from a variety of sources both endogenous and exogenous. ROS at low or moderate concentration can play important physiological roles. However, excessive production of ROS can occur in response to such stressors as toxicant exposure, radiation damage, and disease resulting in oxidative stress. ROS are generated due to induction of various cytochrome P450 isoenzymes during detoxification of xenobiotics, lipid peroxidation and other intracellular processes and involved in regulation of numerous factors, such as transcription factors kappa B, NFkB and AP-, and PPARg (Kakehashi et al., 03). ROS have effects on key cellular components including DNA, protein and lipid macromolecules. Druginduced oxidative stress is implicated as a mechanism of toxicity in numerous tissues and organ systems. For example, cisplatin, an antineoplastic agent, has been shown to increase oxidative stress by increasing levels of superoxide anion, HO, and hydroxyl radical, resulting in nephrotoxicity. Acetaminophen caused hepatotoxicity due to the formation of reactive metabolites and depletion of glutathione (Deavall et al., 0). The aim of this review is to provide a comprehensive overview of the role of oxidative stress in drug induced-toxicity. Furthermore, this review also provides an overview of current in vitro and in vivo methods that measure oxidative stress biomarkers throughout the drug discovery process. References: -Deavall DG, Martin EA, Horner JM, Roberts R. J Toxicol. 0;0: Kakehashi A, Wei M, Fukushima S, Wanibuchi H. Cancers. 03;5(4):33-54 PL 9 ROS DIAGNOSTICS AND BIOMARKERS A. SUHA YALCIN DEPARTMENT OF MEDICAL BIOCHEMİSTRY, SCHOOL OF MEDICINE, MARMARA UNIVERSITY, MALTEPE-ISTANBUL, TURKEY Free radicals are involved in different pathological conditions including atherosclerosis, cardiac disease, cancer, cerebrovascular diseases, neurodegenerative diseases, diabetes, acute renal failure, emphysema, lung disease, bronchitis and alcoholic liver diseases almost all of which are age-dependent conditions. Free radicals and reactive oxygen species (ROS) are continuously formed during conversion of foods to energy using oxygen. These molecules can easily damage major components of the cell such as proteins, lipids and DNA. An antioxidant defense system exists in aerobic organisms in order to control free radical production and to prevent their harmful effects. However, in most cases the antioxidant defense system can not completely protect against damaging effects of free radicals. This results in a conditon that is called oxidative stress. In this presentation different methods used to assess the level of ROS and oxidative stress status will be discussed. Additionally, methods that measure oxidative stress related effects such as antioxidant capacity, lipid peroxidation, protein oxidation and DNA damage will be presented. PL 0 BIO-IMAGE-INFORMATICS: A NEW TOOL TO MONITOR CELL ORGANELLE DYNAMICS H. BIROL COTUK, A. DENIZ DURU MARMARA UNIVERSITY DEPARTMENT OF SPORT HEALTH SCIENCES With the advent of super-resolution imaging techniques such as PALM (photo-activation localization microscopy, STORM (stochastic optical reconstruction microscopy) and STED (stimulated emission depletion) it became possible to visualize cell structures beyond the optical diffraction limit. Together with advances in biological tissue labeling (e.g. enhanced green fluorescent proteins, EGFP), multi-color images which pinpoint to the location of individual proteins or sub-organelle structures in the several nanometer dimension can be collected digitally. By implementing the time domain during live cell imaging experiments, the dynamics of these complex biological images warrants specialized time series analysis based on various image data extraction and informatics techniques. Recent studies highlight the potential of this new approach, which can be termed bio-image-informatics, to produce new insights into cellular and sub-cellular processes. -7-

29 PL BETTER UNDERSTANDING OF THE MONOAMINE OXIDASES -ASSOCIATED I BINDING SITE COMBINING MOLECULAR MODELLING AND ENZYMOLOGY SALVATORE GUCCIONE DIPARTIMENTO DI SCIENZE DEL FARMACO -UNIVERSITA DEGLI STUDI DI CATANIA- VIALE A.DORIA 6 ED. CITTA UNIVERSITARIA, ITALY Since the demonstration of the existence of non-adrenoceptor imidazoline binding sites, numerous studies have focused on the functional role of imidazoline receptors in the central nervous system. The roles of imidazoline receptors, first identified by the non-selective agonist clonidine, are beginning to emerge as selective agonists and antagonists are designed and synthesised to enable investigation. Selective I- ligands are used as antihypertensive drugs; selective I- ligands which are only now being properly understood because the ligands lacked specificity induce hypothermia and have emerging roles in attenuation of withdrawal anxiety and pain; and I-3 ligands influence insulin secretion in the pancreas. Selective I- receptor ligands modulate monoamines in the brain, making it possible that they have potential for modulating behavior (and so use for anti-depressant, anti-anxiety, or in drug withdrawal) and for use in degenerative diseases, for example, in preventing amyloid beta-induced neuronal apoptosis. One protein known to bind imidazoline ligands is monoamine oxidase (MAO). High-affinity I binding sites were convincingly localized to MAO in 995 when expression of human MAO A and MAO B in yeast resulted in a gain of previously nonexistent I ligand binding with nanomolar affinity. The next step in medicinal chemistry is to investigate structure activity correlations using molecular dynamics and enzymology so that clear links between these studies and the pharmacology of these elusive sites can be determined. Docking and molecular dynamics were used to explore how -(-benzofuranyl)--imidazoline hydrochloride (-BFI) binds to MAO A and to explain why tranylcypromine increases tight binding to MAO B. PL EVIDENCE BASED MEDICINE; CRITICAL APPRAISAL OF EPIDEMIOLOGICAL STUDIES PINAR AY MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PUBLIC HEALTH, ISTANBUL / TURKEY Clinicians, public health practitioners and health-care policy makers come across to new queries during their practice every day. A clinician might be questioning the efficacy and a safety of a new treatment regimen and whether it has superiority to the conventional approach or not. A public health practitioner might be trying to understand the effectiveness of a school based obesity prevention program whereas a policy maker might be interested in the cost effectiveness of adapting such a program for the community. The decision making process is not easy since answers for such questions are not usually accessible through textbooks. This necessitates the practice of Evidence Based medicine for all health-care workers in their daily practice. David L. Sackett defines Evidence Based medicine as the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research. Today it is accepted that the use of Evidence Based medicine is not limited to clinical questions, but encompasses all issues related to health and health-care. The practice of Evidence Based medicine starts with formulating the well-built research question. The second step is searching the best available evidence relevant to the formulated question. Evidence refers to scientifically sound research and the main focus is the critical appraisal of the retrieved study. At this stage, the validity of the study and its applicability to practice are discussed. This involves three major questions; Are the results of the study valid? What are the results and are they important? and Will the results be applicable to my problem?. If the evidence is valid then it is integrated with the expertise and evaluated within the socio-cultural context e.g. the preferences and values of the patient or the community in making a decision. -8-

30 PL 3 HEALTH ECONOMICS IN TURKEY DENIZ GURANLIOGLU ASTRA ZENECA TURKEY Since 003, Turkey has been implementing its Health Transformation Program (HTP) with the goal of realizing universal health coverage. HTP emphasized the need for better quality information to make sound health system policies and administrative decisions. With 95% of the country s population now receiving of public health coverage for which the government has had to make a significant financial commitment. The problem is how to meet rising health spending of Turkey and how to most effectively use available limited resources for the benefit of the human health. Budgetary constraints have already led the government to implement cost-containment measures in the short-term in the pharmaceutical field. Health economics has become increasingly important throughout the world for long-term vertical and horizontal efficiency, as spending on health witnessed substantial increases. In the light of all of the preceding, it will be important to make adequate use of health economics at all the areas of healthcare for Turkey in the next years. PL 4 CHALLENGING MATERIALS for COSMETIC USE YASEMIN YAZAN ANADOLU UNIVERSITY, DEPARTMENT OF PHARMACEUTICAL AND COSMETIC TECHNOLOGY Scientific evidence about safety of natural/chemical cosmetic ingredients are reported in CIR (Cosmetic Ingredient Review), EEC Cosmetic Directives, FDA Monographs of sunscreens, antiperspirants and skin protectants treated as OTC, IFRA (International Fragrance Association) and the Journal of the American College of Toxicology. Safety of cosmetics are reviewed by technical experts in those organizations and are the only reliable results.cosmetic industry is generally guided and motivated by the consumers. Concerns of consumers are the principal challenges of the cosmetic industry. Scientific acceptability of complete safety but adequate efficacy related to cosmetics is not thoroughly understood by the consumers and therefore the cosmetic industry is under commercial pressure for some issues. Environmental Working Group (EWG) considering the user-friendly resources is among the organizations affecting the consumers. Several materials which are with limited use (eg alpha hydroxy acids, formaldehyde), fragrances and parabens challenging for the cosmetic industry will be discussed scientifically in this presentation. It can be concluded that there is little scientific evidence to leading short and long-term health risks under normal use conditions for cosmetic ingredients. More research is needed to better define any possible risks. PL 5 A SUMMARY AND COMPARISON OF FOLK MEDICINAL PLANT USES IN CATALONIA (IBERIAN PENINSULA) JOAN VALLÈS, AIRY GRAS, MONTSE PARADA, MONTSE RIGAT, GINESTA SERRASOLSES, TERESA GARNATJE LABORATORIDE BOTA NICA UNITAT ASSOCİADA CSIC, FACULTAT DE FARMA CIA, UNIVERSITAT DE BARCELONA, CATALONIA, SPAIN Catalonia occupies the north-eastern corner of the Iberian Peninsula, with an extension of ca. 30,000 km and ca. 7 million inhabitants. Extended from the Pyrenees to the Mediterranean Sea and the Iberian arid plains, with altitudes going from sea level to 3,44 m, this country holds a huge variety of landscapes, its vascular flora being constituted by approx.,500 taxa. The own language, Catalan (co-official with Spanish), is shared with other areas of the Spanish, French, Italian and Andorran states. Its location in a biodiversity hotspot and its cultural identity make this territory attractive for ethnobiological studies. From the end of 980ies, extensive ethnobotanical research is performed in this area, having led to numerous PhD theses and other academic works, from which a high number of books and scientific papers have derived (see and, and references therein for an idea). In the late years, the research team on ethnobotany of the UNIVERSITY of Barcelona and the Botanical Institute of Barcelona (www.etnobiofic.cat) is coordinating this research and is compiling the results in a database (to date internal for the group, with a perspective of becoming of public access), some of which are starting to become accessible in the Catalonia s Biodiversity Database (http://biodiver.bio.ub.es/biocat). From ethnobotanical interviews to more than 900 informants, data have been obtained of more than,000 vascular plant taxa with folk uses in the field of health, mostly medicinal and food ones, including those in the interface of both activities. In this communication we present a summary of the state-of-the-art of pharmaceutical ethnobotany in Catalonia, stressing the most used plants and the most addressed troubles, we analyse these data and compare them with those of other territories, and we depict the perspectives for further research in this field. References. Parada M, Carrió E, Bonet MA, Vallès J. Ethnobotany of the Alt Empordà region (Catalonia, Iberian Peninsula). Plants used in human traditional medicine. J Ethnopharmacol 009;4: Rigat M, Vallès J, Iglésias J, Garnatje T. Traditional and alternative natural therapeutic products used in the treatment of respiratory tract infectious diseases in the eastern Catalan Pyrenees (Iberian Peninsula). J Ethnopharmacol 03;48:4 4. *This abstract has been orally presented in the Fourth International Meeting on Pharmacy & Pharmaceutical Sciences, Istanbul, Turkey on 8- September

31 PL 6 A REVIEW ON ETHNOBOTANY IN TURKEY KERIM ALPINAR GIZEM BULUT KEMERBURGAZ UNIVERSITY, ISTANBUL, TURKEY MARMARA UNIVERSITY, ISTANBUL, TURKEY While the ethnobotanical research reveals some part of the cultural wealth, it is also possible to benefit from the conclusions thereof. For instance, researches comprising the plants used in folk medicine can be of help to health issues in respect of their results. Gathering the written information and recording the verbal transfer without them being lost enable us to comprehend the place of the plants in our life and to benefit from them in various fields in the future. Richness in the plant diversity of Turkey, which is a land for their settlement for thousands of years, has brought a big fund of knowledge about making use of the plants along. There is an increase in the number of publications regarding this knowledge. Believing in the requirement of assessing the information on the plants mentioned in the publications, part of which has the title of folk culture of a certain region, folk medicine, folk medicines, regional folklore, the identity tags; all serious publications comprising the use of plants are being worked up into a bibliography in order to give support to the researchers who will be using such knowledge in their further researches. In order to make the aforementioned researchers save time and help in providing resources, information on 00 publications is present in the bibliography which has been prepared by reviewing various references since 993. Furthermore, information about the attempts which were materialized as paper, data base and publication also exists in this paper. Based on approximately 00 researches existing in the references in the form of books, congress papers, and periodicals since 98 -when the Latin characters were accepted- until the first half of 04, the evaluation of Turkey with regard to these publications involving ethnobotany has been made. Meanwhile, we think that it is not possible to carry out a reliable evaluation unless these publications are gathered as an archive; however, the bibliography will serve the purpose, even if limited, as we could not find a study in which the publications on ethnobotany in our country are been presented collectively up to the present. PL 7 AN ETHNOBOTANICAL STUDY IN MARMARA ISLAND (BALIKESIR-TURKEY) GIZEM BULUT MARMARA UNIVERSITY Marmara ısland is situated on the Marmara Sea and it covers an area of 7 km and its higest point is 700 m. There is no previous ethnobotanical research on Marmara island. According to our ethnobotanical studies in 009 and 04, 50 vascular plant taxa are used in the island. The usage of the plants are as follows: traditional folk medicine (3 taxa), food ( taxa), fuel (6 taxa), toys (5 taxa), herbal tea (4 taxa), and others (3 taxa). The results are compared with those of other ethnobotanical researches perfomed in neghboring areas. PL 8 USE OF MECHANISM-BASED EVIDENCE FOR THE DEVELOPMENT OF THERAPY FOR HUMAN CANCERS WILLIAM W. AU MPH EDUCATION CENTER AND FACULTY OF PREVENTIVE MEDICINE, SHANTOU UNIVERSITY MEDICAL COLLEGE, SHANTOU, CHINA Improved therapeutic protocols can be developed based on better knowledge of mechanisms for causation of cancers. For cervical cancer, it is the second leading cause of cancer mortality among females in the world. Current therapeutic protocols require surgery, and radiation and chemotherapy which rendered most patients infertile. We have investigated the possibility of using gene therapy for treatment of cervical cancer. Specifically, we used a dominant-negative gene against estrogen and transfected it into cervical cancer cells in vitro, using adenovirus as the delivery agent. Upon transfection of the gene into two cancer cell lines, cells showed cell cycle arrest within hours and the arrest occurred at the G/S border. Other observed changes were: inhibition of cyclin D expression, blockage of human papilloma virus E6 and E7 gene expression, activation of caspase 3 and expression of apoptosis. Therefore, the transfected gene blocked estrogen activities leading to a cascade of events towards apoptosis. The observed mechanism needs to be validated in vivo and then in patients. If successful, the approach can be used as a new gene therapy protocol for cervical cancer. Breast cancer incidence and mortality have been increasing rapidly in China recently. We have investigated the involvement of risk factors and the mechanisms for the increase. From our survey of patients, we observed that both endogenous and externally introduced life-style factors were involved. The former involved cooking with lard instead of vegetable oil. The latter involved exposure to cigarette smoke and having sedated life style. Using our challenge assay, we observed that inherent and functional DNA repair deficiency was the broad-based and important risk factor. The repair deficiency was independent of the BRCA and mutations. In addition, the repair deficiency was significantly associated with poor prognosis: lymph node metastasis, negative expression of estrogen receptor, increased Ki-7 expression, having diabetes, and increased mortality. The mechanism can be used to develop improved therapeutic protocol for breast cancer, e.g. personalized therapy. -30-

32 PL 9 TICKS, CRIMEAN-CONGO HAEMORAGIC FEVER AND PHARMACOLOGICAL PROSPECTS AYSEN GARGILI MARMARA UNIVERSITY, FACULTY OF HEALTH SCIENCES, ISTANBUL, TURKEY Crimean-Congo hemorrhagic fever is a severe, often fatal zoonosis, caused by Crimean-Congo hemorrhagic fever virus (CCHFv; family Bunyaviridae, genus Nairovirus). Among the tick-borne viruses, CCHFv is the most important cause of severe and fatal human hemorrhagic disease, with mortality rates ranging from 5% to more than 70%. Disease is widely distributed in African continent, Russia, Southern European and Middle Eastern countries. Since it has first been diagnosed in 003, Crimean-Congo haemorrhagic fever (CCHF) is an endemic disease in Turkey. Number of annual cases and death rates were around 800 and 5% respectively, between 004 and 03. Farmers, people dealing with animal husbandry and health workers were determined as risk groups in epidemiologic studies. CCHF viruses are mainly transmitted by the bite of ticks of the genus Hyalomma. The virus has been repeatedly isolated and/ or detected in these ticks since 960, when the virus was first detected in arthropods. The virus has also been detected in species from other tick genera such as Rhipicephalus, Dermacentor, Ixodes and Ornithodororos. Nevertheless, it is unclear what vector status each has and what role each plays in the maintenance of the virus. The ecology and epidemiology of CCHFV is complex and largely depends on the tick vector species and the geographic area. CCHFV is maintained in a silent vertical and horizontal transmission cycle involving ticks as vectors and reservoirs, and a variety of small feral and large domestic mammals as vertebrate hosts. Small mammals, such as hares, hedgehogs, and rodents, and domestic ruminants, such as goats, sheep, and cattle serve as viral amplifying hosts. With the exception of ostriches in South Africa, Aves are not considered to be amplifying host for CCHFV. However, migrating birds serve as a source of blood meals for ticks, and therefore provide a mode of dispersal of uninfected and infected ticks, which contribute to the spread and subsequent emergence of foci. Also, long distance movement of livestock may contribute to the dispersal of CCHFV infected ticks. Current studies showed that Hyalomma marginatum is the main (if not only) vector in Turkey. Some studies have addressed the question of the distribution of ticks involved in the viral transmission in different regions of Turkey and pointed out the importance of sylvatic cycles of virus amplification under natural conditions. In the last years, clusters of cases of CCHF in Russia, Bulgaria, Albania and Greece have been also reported. However, the viral strain recorded in Greece (Europe strain) is different from other viral isolates in that region. Such an isolate was made from Rhipicephalus bursa ticks collected from goats in and near Thessaloniki in 975. Interestingly, this strain is the most divergent of all the CCHFv strains, including those isolated in the neighboring Balkan countries of Albania, Kosovo, and Bulgaria. Treatment regimes for CCHF infection are mainly supportive practices such as plasma and fresh platelet replacements. Only known etiologic treatment option, Ribavirin, was reported to be highly effective at early stage (first 3 days) of infection. Along with the vaccine studies there is a substantial need for the development of effective anti viral agents. Considering that the ticks are the major transmitting factor, control of the tick population is also important for the fight against the endemic infections. Although there are numerous acaricides commercially available for treatment of the tick infestations of domestic animals, most of them have residual effects. There is still a need for the development of anti-tick agents with long term efficacy but not residual in meat or milk. Another important issue is the protection of humans from tick-bites. For this aim, repellents seem to be practical for protection and studies are needed for the development of harmless and long-term effective substances. -3-

33 PL 30 PHARMACISTS AND PHARMACEUTICAL CARE J.W.FOPPE VAN MIL COMMUNITY PHARMACIST & PROFESSIONAL SECRETARY OF THE PHARMACEUTICAL CARE NETWORK EUROPE Pharmacy is part of healthcare, and pharmacists are health care professionals. Society has given pharmacists a mandate to care for the medicine-related aspects of the population. The profession is characterized by the fact that it links two areas of expertise: the provision of a medicine, the product, and care for the patient. The pharmacist brings these two areas together and classes it as his domain. Within this domain, the pharmacist makes his own independent assessments. This means that every pharmacist is a pharmaceutical care provider with a typical identity, knowledge and specific core values. This in turn demands an autonomous definition of the knowledge domain and, at the same time, establishing the core values. The basis for the knowledge domain of a pharmacist is () the medicine, () the human body, and (3) the human behavior. Core values of pharmacists are () Commitment to the patient s well-being, () Pharmaceutical expertise, (3) Social responsibility, (4) Reliability and care and (5) Professional autonomy. As a professional, pharmacists are independent, and maintain their own standards in their field of expertise. As health care professionals, pharmacists should do no harm. The practice of pharmacy can be divided in three levels: a basic level of production and distribution, a clinical level of issues relating to patients and pharmacotherapy in a broader sense, and a care level (pharmaceutical care) of the care for the individual patient. The newer elements of the tasks of pharmacists, such as counselling, medication reconciliation and review and therapeutic outcome monitoring are all part of pharmaceutical care. In most countries, pharmaceutical care is now the new paradigm for the work of the pharmacist, certainly in community but increasingly also in hospital. With the increasing industrialization of the preparation and compounding of medicines, the modern community and hospital pharmacists have more time to care for the individual patient, and thus to implement pharmaceutical care. In many studies it has now been proven that the implementation of pharmaceutical care improves patient outcomes, on clinical, humanistic and economic level. PL 3 CLINICAL PHARMACIST COUNSELING IN CARDIOMETABOLIC DISEASE SULE APIKOGLU-RABUŞ MARMARA UNIVERSITY FACULTY OF PHARMACY - CLINICAL PHARMACY DEPARTMENT, ISTANBUL TURKEY Cardiometabolic disease, also known as the metabolic syndrome consists of interrelated risk factors which may lead to atherosclerotic cardiovascular disease and type diabetes. The most frequently occurring risk factors include abdominal obesity, hypertension, hyperglycemia and dyslipidemia. Also, some patients may display characteristics of prothrombotic and proinflammatory states. Patients with metabolic syndrome are more likely to develop some other conditions, such as polycystic ovary syndrome, gallstones, asthma and sleep apnea. The main goal of the treatment is to mitigate or modify the risk factors in order to prevent or delay the development of cardiovascular disease. The primary treatment modality is the establishment and adoption of a healthy life-style. In circumstances where lifestyle changes are insufficient and for those at high risk of cardiovascular diseases, drug treatment may be required. All components of the cardiometabolic disease are needed to be treated to improve metabolic and cardiovascular consequences. Yet, this cannot be managed by a single drug. Patients would be prescribed one or more of the drug classes of cholesterol-lowering, antihypertensive, antidiabetic and antiaggregant drugs. Adherence is a growing problem with many drugs including the statins, antihypertensives and antidiabetics. Experts agree that successful intervention requires more comprehensive patient education, with interdisciplinary coordination among healthcare providers. Therefore, pharmacists have an essential role in the management of the cardiometabolic disease. They can assess patient risk communicating cardiometabolic disease risk factors, plan and suggest patient-specific interventions, and identify barriers to lifestyle modifications. They can help patients with adherence to health lifestyle and drug therapy as well as guide them through cardiometabolic disease self-care process. -3-

34 PL 3 MEDICATION RELATED PROBLEMS IN GERIATRIC PATIENTS: THE ROLE OF PHARMACIST BETUL OKUYAN CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY, FACULTY OF PHARMACY - TURKEY The identification of inappropriate medication usage in elderly patients; which would tend to predispose medication related problems resulting in adverse drug reaction, medication induced hospitalization and economic burden, presents significant challenges for pharmacists when considering polypharmacy frequency in geriatric patients. Pharmacists should evaluate risks and benefits of current medications by predicting possible medication related problems and defining individual requirements of elderly patients towards their medications in order to optimize patient safety and enhance the benefits of therapy. Pharmacists should comprehensively evaluate suitability of the present pharmacotherapy in geriatric patients with the means of well defined and commonly used tools for elderly patients such as Beers Criteria. The STOPP and START criteria which have been recently developed to identify potentially inappropriate medications and potential prescribing omissions respectively in elderly patients can be used. Medication reconciliation program could be performed in transmission between different health care settings and would give opportunities to pharmacists to provide accurate medication lists in geriatric patients. Individualization is an important component, which improves the overall quality of pharmaceutical care. During the pharmaceutical care process in geriatric patients, tailoring medication therapy to individual requires would optimize therapy outcomes and lower drug related problem. As a result of physiological changes related to age in the normal aging process, alterations in pharmacokinetics and pharmacodynamics should be also considered by pharmacists while using medications in geriatric patients. Patients with Alzheimer s disease and dementia are more likely to be non-adherence to their medications and also it is more difficult to evaluate patient reported health outcomes in these patients. Pharmacists should provide individualized patient education in geriatric patients especially ones with Alzheimer s disease. To minimize unintentional non-adherence to medications in geriatric patients, their physical ability especially manual dexterity and visual impairment and cognitive capacity should be assessed in order to determine the appropriate medication dosage forms and simplify dose regimen complexity. Some medications (eg. Alzheimer therapy) may cause undesirable effects which can impact on daily activities such as: falling down, constipation, urinary incontinence, and cognitive impairment. Exposure to anticholinergic effects and sedative agents in elderly patients should be also evaluated considering these medications are more likely to induce adverse outcomes especially on physical and cognitive functions. The lack of knowledge regarding medication would also cause drug related problems, thus pharmacists should periodically assess elderly patients knowledge and attitude towards their medications. A geriatric self-care plan should be generated by the pharmacist especially for common conditions such as constipation, urinary incontinence and insomnia. Pharmacist should consult about over counter medicines and dietary supplements, which are commonly used by geriatric patients, in order to provide geriatric patients tolerability and safety. PL 33 3D ANALYSIS OF THE BINDING SITE IMAGES FOR PREDICTING BINDING AFFINITIES IN DRUG DESIGN ALI OSMAN ATAC OZLEM ERDAS FERDA NUR ALPASLAN ERDEM BUYUKBINGOL - DEPARTMENT OF COMPUTER ENGINEERING, INSTITUTE OF NATURAL SCIENCES, MIDDLE EAST TECHNICAL UNIVERSITY, ANKARA, TURKEY - DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY, ANKARA, TURKEY Understanding the interaction between drug molecules and proteins is one of the main challenges in drug design. Several tools have been developed recently to decrease the complexity of the process. Artificial intelligence and machine learning methods have promising results in predicting the affinities. Recently, accurate estimations (CIFAP) have been performed by extracting the electrostatic potentials from images of the drug-protein binding sites which were generated by autodocking simulator (). In this study, a new algorithm, which is a modified version of CIFAP, has been implemented to predict binding affinities of Caspase3 inhibitors. Reference. Erdas O, Andac CA, Gurkan-Alp AS, Alpaslan FN, Buyukbingol E. Compressed images for affinity prediction (CIFAP): a study on predicting binding affinities for checkpoint kinase protein inhibitors. Journal of Chemometrics. 03;7(6):

35 PL 3 34 MEDICATION RECENT ADVANCES RELATED IN PHARMACOTHERAPY PROBLEMS IN GERIATRIC PATIENTS: THE ROLE OF PHARMACIST GUL BAKTIR YENI YUZYIL UNIVERSITY, HEAD OF PHARMACOLOGY DEPARTMENT The number of people living with severe chronic diseases is growing and as almost all chronic disorders develop gradually over a certain period of time, changes are often irreversible until a level is reached where it could be diagnosed and treated properly. For many acute and chronic disorders, current treatment outcomes are considered as being inadequate and severe chronic conditions such as cardiovascular disorders, diabetes and cancer are treated after onset of the disease, frequently at near end-stages. Predictive, preventive and personalized medicine (PPPM) is a new integrative concept in the healthcare system that provides prediction of individual predisposition to a disease before its onset, to take targeted preventive measures and offer personalised treatment principles tailored to the person. Identification of a person s risk of developing a particular medical condition, detection of the disease at a subclinical stage, when it is easier and less expensive to treat effectively, determination of how individual patients react differently to diseases and to their treatments, stratification of patients for the optimal therapy planning, prediction and reduction of adverse drug-drug or drug-disease interactions by more effective early assessment of individual drug responses and to improve pharmacotherapeutic outcomes in acute and chronic diseases are among targets as well as benefits of PPPM. This presentation includes examples of novel personalized therapies providing important new treatments for patients in various disease areas. PL 35 NEW TREATMENT STRATEGIES IN PERIPHERAL NEUROPATHIES SENA F. SEZEN, KARADENIZ TECHNICAL UNIVERSITY SCHOOL OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, TRABZON, TR JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE, BRADY UROLOGICAL INSTITUTE, BALTIMORE, MD, USA Peripheral neuropathy (PN) refers to damage of the peripheral somatic or autonomic nerves. Although a variety of factors and diseases cause PN, it commonly occurs due to traumatic injury, chemotherapy, and metabolic disorders. This presentation will discuss the pathophysiology and treatment approaches of PN with an emphasis on diabetes-induced autonomic neuropathy (DPN). DPN is a common complication of diabetes that leads to significant mortality and morbidity. It is associated with axonal damage, blunted neuroregenerative capacity, and the loss of nerve function that control the cardiovascular, gastrointestinal and urogenital systems. Hyperglycemia plays a major role in the development and progression of DPN but is also affected by insulin deficiency, hyperlipidemia and numerous biochemical mechanisms including increased oxidative/nitrosative stress, mitochondrial dysfunction and distrupted intracellular signalling pathways. Despite advances in understanding the etiology, DPN treatment remains a challange with current therapeutics still having suboptimal outcomes. Therefore, identifying novel therapeutic strategies remains a paramount and also an intense area of research. This presentation aimed to review the current literature about the etiology of DPN, summarize the new advancements in experimental therapeutics and briefly present new findings from our laboratory, which contribute toward understanding the mechanisms of DPN and development of potential new treatments. -34-

36 PL 36 JAMMING BACTERIAL COMMUNICATION ( QUORUMSENSING ): A NEWAPPROACH TO THE CONTROL OF BACTERIAL INFECTIONS GULGUN TINAZ DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Antibiotics, which act either by killing or inhibiting the growth of bacteria, are commonly used for the treatment of bacterial infections. The inappropriate and indiscriminate application of antibiotics in pharmacotherapy has led to the development of widespread bacterial resistance to these agents (). The harsh selection for resistant bacteria, coupled with the lack of investment in antibacterial research and development, has resulted in a steady decline in the efficacy of existing therapies. Today, a global concern has emerged that we are heading a post-antibiotic era with a reduced capability to fight bacteria and there is an urgent need for the discovery of novel antibacterial drug targets and treatment strategies. One such new target is quorum sensing (QS). QS is a cell-to-cell communication system employed by a variety of Gram (-) and Gram (+) bacteria to co-ordinate group behaviors as function of cell-density (). The discovery that many pathogenic bacteria employ QS to regulate their pathogenicity and virulence factor production makes the QS system an attractive target for antimicrobial therapy (3).The disruption of QS systems of pathogenic bacteria may offer an avenue of alternative therapy. Therefore, compounds with QS inhibitory activity hold great expectations for the treatment of infectious diseases in an era where availability of effective antibiotics is no longer guaranteed. Furthermore, such compounds could potentially be used in combination with conventional antibiotics to increase the efficiency of disease control and to extend the life span of current antimicrobials. Additionally, inhibition of bacterial QS, rather than bactericidal or bacteriostatic strategies, offers a promising way to overcome the bacterial resistance problem. It is assumed that targeting the pathogenesis instead of killing the organism will apply a gentler selective pressure for the development of bacterial resistance. References Livermore DM. The need for new antibiotics. Clin Microbiol Infect. 004; 0(Suppl 4):-9. Hentzer M, Givskov M. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest. 003;: Rasmussen TB, Givskov M. Quorum-sensing inhibitors as antipathogenic drugs.int J Med Microbiol.006; 96:49-6. PL 37 INTERFERENCE WITH BACTERIAL CELL-TO-CELL COMMUNICATION A NOVEL STRATEGY TO COMBAT INFECTIONS HARTMANN R. W., HELMHOLTZ-INSTITUTE FOR PHARMACEUTICAL RESEARCH SAARLAND (HIPS), CAMPUS C.3, SAARBRUCKEN, GERMANY PHARMACEUTICAL AND MEDICINAL CHEMISTRY, SAARLAND UNIVERSITY, CAMPUS C.3, SAARBRUCKEN, GERMANY The emergence and spread of bacteria resistant to current antibiotics are a serious and growing health problem worldwide. In pursuing our objective to develop new strategies to combat resistance in bacterial infections, we have focused our interest on the bacterial cell-to-cell communication. Among other infections, Pseudomonas aeruginosa causes severe pneumonia in patients suffering from cystic fibrosis. It is difficult to be eradicated, especially when present in biofilms. Biofilm formation and virulence factor production are regulated by intercellular signal molecules. A selective blockade of this so called quorum sensing system is a novel therapeutic strategy to limit pathogenicity and is considered to delay resistance development. Two proteins are targeted, PqsD, a key enzyme in the biosynthesis of the signal molecules PQS and HHQ and their receptor PqsR. Following different approaches, structure-based and ligand-based-4 via transition states analogs of the enzymatic reaction3-4, the first PqsD inhibitors described so far were obtained. The nitrophenylmethanols were able to permeate the gram-negative bacterial cell wall and inhibited signal molecule production and biofilm formation. Regarding PqsR, SPR biosensor experiments led to the discovery of highly efficient binders with low molecular weights including antagonists5. Site-directed mutagenesis combined with isothermal titration calorimetry led to insights into the binding mode. The first highly potent antagonists have been developed by structural modification of the natural ligand6. After an unexpected functional inversion of these antagonists in P. aeruginosa had been revealed, second generation PqsR antagonists were rationally developed and able to efficiently reduce virulence factor formation7. One of these antagonists showed a strong reduction of P. aeruginosa pathogenicity in vivo. References Sahner et al, J. Med.Chem. 03, Weidel et al, J. Med. Chem. 03, Storz et al, J. Am. Chem. Soc. 0, Storz et al, ACS Chem. Biol. 03, Zender et al, J. Med. Chem. 03, Lu et al, Chem. Biol. 0, Lu et al, Angewandte, 04, 53,

37 PL 38 CHAPERONE-USHER PILUS ASSEMBLY MECHANISMS AND ANTIVIRULENCE THERAPEUTICS ENDER VOLKAN SCOTT HULTGREN CYPRUS INTERNATIONAL UNIVERSITY WASHINGTON UNIVERSITY IN ST. LOUIS, SCHOOL OF MEDICINE Chaperone-usher pili are adhesive, filamentous, rigid, polymeric protein appendages assembled on surfaces of pathogenic bacteria. P- pili, assembled by uropathogenic Escherichia coli are virulence factors in urinary tract infections (UTIs). In Gramnegative bacteria, assembly of P-pili requires the crossing of subunits through the inner membrane, the periplasmic space (with the help of the chaperone PapD to fold correctly) and assembly into an ordered structure at the outer membrane. These appendages are required to bind host surfaces and establish infection; so their inhibition is a way to prevent infection. Antivirulence therapeutics named pilicides are bicyclic -pyridones designed to inhibit P-pilus biogenesis by binding the chaperone protein (PapD) in uropathogenic Escherichia coli. Using coomassie blue stained SDS-PAGE gels and Western blotting, our studies indicate that upon in vitro incubation of purified pilus subunits with certain pilicides at x or 00x molar excess concentrations, the polymerization of P-pilus subunits (PapE) that form the tip section of the pilus is disrupted. These pilicides likely induce non-productive aggregation of PapDE subunits as demonstrated by smears on Western blotting analysis. Electron microscopic examination of PapDE incubated plus or minus pilicide revealed that the non-productive PapE aggregates induced by pilicide were altered morphologically compared to PapE tip polymers. Some high molecular weight bands were consistent with a PapD dimer, suggesting that disruption of PapE polymerization may be via formation of unproductive PapD dimers. These findings indicate that studies on chaperone-usher pili can help improve our approaches of designing antivirulence therapeutics for treatment of infections, while steering clear from antimicrobial resistance. PL 39 NEW TRENDS IN QUALITY OF PHARMACEUTICALS N. BUKET AKSU CORPORATE RELATIONS DIRECTOR AT SANTA FARMA PHARMACEUTICALS, TURKEY Pharmaceutical product development knowledge is intensive, and the product development process is quite complex. Recently, the drug industry has experienced major developments in production information, quality management systems and risk management and has developed modern production tools that can assist in ensuring the production quality. Since decades, adoption of systematic approaches for developing products with robust quality, enhanced resource economics and improved process capability has yielded high fruition in several technology-driven industries. The pharma industry, however, was quite late in adopting the systematic approaches. Despite continuous innovations in the pharma industry for developing futuristic new drugs and drug products, there has been a repeated set back owing their poor quality and manufacturing standards. With the consequent growing concern and criticism, in this regard, the ICH instituted a series of quality guidances like Q8, Q9, Q0 and Q, all emphasizing the adoption of systematic principles of Quality by Design (QbD) and Process Analytical Techniques (PAT). ICH aims to produce a single set of technical requirements for the registration of drug products and hence the development process. Its objective is to improve efficiency of new drug development and registration process It is accomplished through the development and implementation of harmonized guidelines and standards. Thanks to ICH for leading us to the discussion regarding all the guidelines and Q8 (Pharmaceutical Development), Q9 (Quality Risk Management), Q0 (Quality System). The new guidelines help industry professionals and regulators improve efficiency and flexibility while maintaining high quality standards. ICH Q8 is related to design a quality product and manufacturing process and deliver consistent performance. It is collation of knowledge establishing the rationale for type of dosage form, formulation proposed is suitable for the intended use, proces and product understanding. ICH Q8 is an opportunity to present the knowledge gained through the aplication of scientific approaches to product and process development (scientific understanding). ICH Q8 guideline supports knowledge gained through the lifecycle of a product and using scientific approaches and quality risk management principles. Within the scope of ICH Q8, an important step in the QbD approach to the development of drug products requires a distinction between critical and non-critical product attributes and process parameters. ICH Q9 is a systematic process for the assesment, control, communation and review of risks to the quality of the drug product across the product lifecycle. A process which includes assessment, control, comunication and review of risk consisting of well defined steps which, when taken is sequence, support better decision making by contributing to a greater insight into risks and their impacts. ICH Q0 guideline describes a comprehensive approach to an effective pharmaceutical quality system based on ISO concepts, includes applicable current GMP regulations including GAMP (Good Automated Manufacturing Practices), and complements ICH Q8 and ICH Q9. If the principles described in the ICH Q8, Q9 and Q0 guidance documents are implemented together in a holistic manner, then an effective system that emphasizes a harmonized science and risk-based approach to product development and maintenance is in place. This provides an even greater (quality) assurance that the patient will receive product that meets the critical quality attributes (CQA) -36-

38 As QbD approach embarks upon science and risk-based understanding, it helps in developing quality products rather than building quality into the products, with minimal investment of time, money and resources, eventually leading to cost reduction and faster market access. Various guidelines like ICH Q8- Q, in this regard, are highly helpful for guiding the product development scientists. Quality risk management (QRM) and science-based knowledge management are the two key elements of QbD. QRM primarily focuses on the systematic and structured planning of reviews and inspections. QRM must be an integral element of the pharmaceutical quality system to meet the predefined quality of the drug products as per the regulators and consumers point of view. On the other hand, the science-based knowledge management system relies on decision making regarding review and inspections, and for accomplishing desired cgmp compliance to the manufacturer. It provides thorough and thought-through analysis of the concept by sharing of data and information to develop the products and processes understanding. Target Product Profile (TPP) describes the general objective of the product development program and provides information about the development works. TPP includes concepts that are required on the label of the pharmaceutical product. TPP is a patient and labeling based concept and can be considered as the user interface of the ready-made pharmaceutical product. Therefore, TPP is expected to be the same for a generic and the reference product. A generic product may use a different formulation or design for applying the TPP. Many features of TPP are restricting or determining works of formulation and process development researchers. Among them there are route of administration, form and amount of dosage, maximum and minimum doses, presentation of pharmaceutical product and target patient population. Quality Target Product Profile (QTPP) is a summary of product quality and relevant features and characteristics and thus aims to guarantee product efficacy and safety. QTPP constitutes the basis of product development and begins by design in the mind. QTPP is a sub-branch of the TPP published by the FDA and is focused on the chemistry, production and control phases of development. QTPP, defines quantitative targets for features of a pharmaceutical product (such as dissolution, potency, impurity and stability). Also, it includes specifications such as drug delivery dosage form, route of administration, packaging, appearance and diagnosis. Critical Quality Attributes (CQAs) are the physical, chemical, biological and microbiological characteristics that should be directly or indirectly controlled in order to meet the QTPP and ensure product quality. CQA is generally related to active substance and excipients, intermediate products and finished products. The performance of CQAs depends on the independent product and process variables called as material attributes and process parameters. Critical Process Parameters (CPPs) are process parameters with variability effective on critical quality feature(s), therefore they should be monitored and controlled in order to achieve required quality. The parameter expresses a characteristic of a system or process that is measurable or countable. These parameters are usually considered as features related to processes such as temperature, mixing speed, mixing time, type of stirrer, etc. Separating characteristics or parameters as critical or non-critical is an important result of the development process. Among the several process parameters, the non-critical and critical process parameters are classified which actually affect the product quality. If the real change in a parameter does not meet QTPP of the product, then that parameter is critical. Accordingly, whether a parameter is critical or not depends on the extent of the considered change. In the development of a design space, the important point in activity is proving or determining that uncategorized parameters left outside Design of Experiments (DoE) are really non-critical process parameters and that this is the reason for their non-interaction. Before starting to generate a design space, effort must be shown to reduce the number of unclassified process parameters. A screening DoE can be carried out on this, to exclude meaningful interactions among process parameters. Single variable ranges are appropriate for non-critical parameters and they can be added to the design space without any extra works, when there are no interactions among them. Selection of correct instruments for developing design space can depend on various factors such as complexity of the evaluated system, precision, relevant scientific information and company preference. There is no single tool or approach that is ideal for all cases. Very valuable information can be obtained from all of them, there are certain reasons to aid in determining which tool is to be used. Realizing the restricting features of today s pharmaceutical product development approaches, the FDA, together with the ICH has supported the concept of Quality by Design. Accordingly design space has started to gain an important place in the pharmaceutical industry. Design space is defined as multi-dimensional combinations and interactions of input material variables (i.e. material features) and process parameters with proven assured quality. Design space is specific to a single unit operation, multiple unit operation or a single manufacturing process and defines operational process parameters that are known to affect product quality. Design spaces can be considered as the link between CQAs and CPPs. Design space (DS) is a production space provided by the control of critical parameters that are determined by the formulation and manufacturing process. In addition, as stated in the ICH Q8 guidelines, working within this DS is not considered a change. Process Analytical Technology (PAT) is a system for designing, analyzing, and controlling manufacturing through timely measurements of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality. PAT brings a systems perspective to the design and control of manufacturing processes. Scientists from Development, Manufacturing, Quality and Engineering will be able to engage with regulators to turn Q8, Q9, and the imminent Q0 into a cross-functional and practical reality, helping to shape the future thinking of the industry. Regulators will be present to listen to audience views and to provide their perspective. As an example for QbD; in order to evaluate the QbD principles, Ramipril was used as a model drug and produced tablets were designed with the application of INForm v.4 ANN which is a program using neural networks. The Program covers not only neural networks with different backwards distributing algorithms, but also genetic algorithm, fuzzy logic, statistic methods and graphical visualization. The results of the tablets manufactured by direct compression containing respectively MgSt and SSF were evaluated by the program. The program provided the model properties for each tablet property. With reference to the data obtained, all required measurements and evaluations were performed and the CQAs (tablet hardness, dissolution in 30 minutes, assay, impurity C and impurity D) were determined upon risk control. -37-

39 The results of the tablets manufactured by direct compression containing respectively MgSt and SSF were evaluated by the program. The program provided the model properties for each tablet property. With reference to the data obtained, all required measurements and evaluations were performed and the critical quality attributes (tablet hardness, dissolution in 30 minutes, assay, impurity C and impurity D) were determined upon risk control. The objective of the study was to optimize ramipril tablet formulation manufacturing by direct compression method, that complying with predefined specifications, by using ANN program and QbD principles. Tablets prepared as optimized formulation analyzed and as a conclusion all the parameters defined as critical quality attributes were in the range of specification limits. This study showed that a huge amount of detailed data for QbD studies could be gained from ANN programs, that could not obtained with the routin R&D experiments QbD applications allows for understanding critical and non-critical parameters in developing design space, provides opportunity for focusing on important parameters in product quality in validation works. As the control range where product and process are not affected, are better understood than a range generated only empirically, a wider validation acceptance criteria is achieved. Product quality cannot be tested at the end of manufacturing process using QbD approach, but quality is designed at product design phase and quality is embedded in the product. Rather than controlling quality, quality assurance is ensured, which is more superior. Development and innovation are hindered because of processes and systems that are not changed. However, with the design space brought by QbD, flexibilities such as real time release have become a part of the process. Because of these changes, operability of the processes has been proven and reliance on the system has increased. Testing of quality in process begins as the process is halted and testing is removed. Controls have been carried out based on critical features in the process and changes made in relation to these have been managed and the process has been continuously advanced. As continuous process improvement has become possible, an approach implementation has come where process performance intended for process validation is continuously monitored, evaluated and adjusted. Most importantly, other than these, this new approach has allowed for acting and decision making with scientific and risk based information. PL 40 EVALUATION OF HEXAGONAL BORON NITRIDE (HBN) AS A NEW TABLET LUBRICANT TIMUCIN UGURLU MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ISTANBUL, TURKEY It is rare to find a solid oral dosage product consisting of drug alone. To produce a final product that is not only practical and convenient to handle but also facilitates patient compliance, the drug substance needs to be processed with other excipients. The drug fillers or excipients serve many purposes in the formulation. One class of functional excipients that is essential in the most tablet formulations is lubricants. Lubricants are pharmaceutical excipients that decrease friction at the interface between a tablet surface and the die wall during ejection and reduce wear on punches and dies, prevent sticking to punch faces, improve the fluidity and filling properties and manufacturing efficiency of solid preparations. However, since most of the lubricants have hydrophobic characters, they have deteriorating effects on tablet properties. The deteriorating effects are due to formation of a hydrophobic layer on particles of powder during mixing process. If the concentration of a lubricant is too high, or the mixing time is too long, the potential problem will be decrease in tablet hardness, inability to compress into tablets, increase in tablet disintegration time and a decrease in dissolution rate. To get rid of negative effects of lubricants an alternative lubricant was used in our study. The objective of our study was to investigate the lubrication properties of hexagonal boron nitride (HBN) as a new tablet lubricant and compare it with conventional lubricants such as magnesium stearate (MGST), stearic acid (STAC), and glyceryl behenate (COMP). Tablets were manufactured on an instrumented single-station tablet press to monitor lower punch ejection force (LPEF) containing varied lubricants in different ratio (0.5,, %). Tablet crushing strength, disintegration time and thickness were measured. Tensile strength of compacted tablets were measured by applying a diametrical load across the edge of tablets to determine mechanical strength. The deformation mechanism of tablets was studied during compression from the Heckel plots with or without lubricants. MGST was found to be the most effective lubricant based on LPEF lubrication concentration profile and LPEF of HBN was found very close to that of MGST. HBN was better than both STAC and COMP. A good lubrication was obtained at 0.5% for MGST and HBN. Where COMP and STAC showed 35% more LPEF compare to that of MGST. Even at the concentration of % COMP and STAC did not decrease LPEF as much as 0.5% of MGST and HBN. Like all conventional lubricants the higher the concentration of HBN the lower the mechanical properties of tablets because of its hydrophobic character. However, this deterioration was not as pronounced as MGST. HBN had no significant effect on tablet properties. Based on the Heckel plots, it was observed that after the addition of % lubricant granules showed less plastic deformation. As a result our studies showed HBN can be used as a new lubricant in tabletting technology -38-

40 PL 4 CLINICAL TRIALS; FROM LABORATORY TO PHARMACY ASLIGUL KENDIRCI MENA & TURKEY CLINICAL OPERATIONS HEAD ROCHE ISTANBUL, TURKEY A clinical trial is a research study conducted in human beings with the goal of answering specific questions about new therapies, vaccines or diagnostic procedures, or new ways of using known treatments. Clinical trials are used to determine whether new drugs, diagnostics or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that help people. After researchers test investigational new therapies or procedures in the laboratory and in animal studies, those with the most promising possibilities are moved into human clinical trials. Clinical trials are broken down into different phases. During a trial, more and more information is gained about the potential treatment, its risks and how well it may or may not work, along with aspects related to quality of life. Clinical trials are categorized as Phase I to IV trials. They are generally described as follows: Phase I (small number of participants, normally between 6-0 healthy volunteers, or very sick patients for whom treatment options are lacking) Phase I studies are designed to allow scientists and medical doctors to understand what effects an investigational compound has in human subjects. Phase II (once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups of patients, generally depending on the type of disease) Phase II studies are designed to begin to evaluate the safety and efficacy of an investigational medicine in patients, and often used to determine if different dosages of the treatment have different effects Phase III (carried out on large patient groups, 300 3,000 or more depending upon the disease being studied) Phase III studies are designed to confirm the safety and efficacy of an investigational medicine. Large numbers of patients are generally involved in order to adequately confirm benefit and safety. Phase IV (also known as Post-Marketing Surveillance Trials) Phase IV studies take place after the medicine has received regulatory approval (market authorization) and are designed to provide broader efficacy and safety information about the new medicine in large numbers of patients, subpopulations of patients, and to compare and/or combine it with other available treatments. Clinical trials are an integral part of the drug and diagnostics discovery and development process. Before a new medicine or diagnostic test can be made available, evidence of its safety and effectiveness must be provided by well-designed, wellcontrolled, and carefully monitored clinical studies in patients consenting to participate. To develop a product from laboratory to Pharmacy takes -5 years and costs about.3 Billion dollars. PL 4 DRUG AND PERSONAL CARE PRODUCT CONTENT OF WATER. IS IT IMPORTANT FOR HUMAN HEALTH? AHMET AYDIN YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF TOXICOLOGY The contamination of water resources with chemicals due to pharmaceuticals and personel care products attracts attention recently. US Environmental Protection Agency handled this case as Pharmaceuticals and Personal Care Products (PPCP) in water. All drugs prescribed for a special disease in human and VETERINARY purposes and cosmetic ingridients including the fragrances (musks) in toiletory products and the ultraviolet filters in sunscreens are covered by PPCP explanation. The contribution of these products to chemical burden of surface and underground water is due to excretion from the body as parent molecule or metabolite and bathing. Improper disposal of expired pharmaceuticals like draining into sewage is another threat for our water resources. Drug factories are another potential source for the contamination of water with pharmaceuticals. Available water treatment systems are not effective to eliminate PPCPs. Some ecological toxic effects are caused by PPCPs in water system, but human health risks are not known properly. Most pronounced health effects of PPCPs are antibiotic resistance and endocrin function impairment. Many other PPCPs have unknown consequences. Following drug classes have a great concern for their potential unwanted health effects exposure via water resources: Antimicrobials, estrogenic steroids, antidepressants, calcium-channel blockers, antiepileptic drugs, multi-drug transporters (efflux pumps), musk fragrances. Even if the level of these pharmaceuticals in drinking water is low, special attention for vulnerable individuals is taken account. Stem cells are undifferentiated cells with the high capacity to undergo self-renewal by asymmetric mitotic division. The main characteristics of stem cells that make them extremely appealing for cell therapy are their capacity for self-renewal. By this way, stem cells keep their ability to multiply while remaining undifferentiated and thus enabling constant. Further wit their differential capacity they are important tool for active replacement of cell population in tissue, and differentiate into variety of distinct cell type. -39-

41 PL 43 STEM CELLS IN MEDICAL TRAINING TUNC AKKOC MARMARA UNIVERSITY FACULTY OF MEDICINE, DEPARTMENT OF PEDIATRIC ALLERGY-IMMUNOLOGY, TURKEY Stem cells can be divided into two main groups by site of origin as embryonic stem cell (ESCs), which are derived from inner mass of blastocytes, and adult stem cells (ASCs), which are obtained from umblical cord blood, bone marrow, peripheral blood, adipose tissue, dental and present specific tissue and organs throughout the adult body. There are special terms which shows the capability of stem cells in differentiation. Most potent one is Totipotent stem cells which capable of originating an entire organism, as they are able to generate extraembriyonic tissue such as placenta. Pluripotent stem cells, in turn, able to differentiate into cells from any of three primary germ layers (ectoderm, endoderm and mesoderm, primordial tissue formed in the early stages of embriyonic development that will later originate all other tissues in the body). Unlike totipotent cells, pluripotent cells cannot grow an entire organism, as they are incapable of generating extraembryonic tissues. Bone marrow hematopoietic stem cells (HSCs) were the first ASCs to be studied and, consequently, are the best characterized. These cell are capable of differentiation into the myeloid and lymphoid components of blood, and their transplantation has long has long been used to great effect in the treatment of bone marrow failure and cancer. Another type of ASC present in the bone marrow, but distinct properties from those of HCSs, was later isolated: mesenchymal stem cells (MSCs), also known as stromal cells. As reported at the time of their discovery by friedenstein in the 970s, MSCs are highly plastic adherentand are similar to fibroblasts. As multipotent stem cells, MSCs can differentiate into cells derived from the mesoderm germ layer, namely chondroblasts, adipocytes and osteocytes. As they inhibit proliferation and cytotoxic action of immune cells, MSCs have been employed in the clinical treatment of several diseases, including graft versus host disease (GVHD) in its acute form. In ClinicalTrials.gov database 3 studies were designed to test MSCs in the treatment of GVHD. PL 44 HYPERCOAGULABILITY IN OVARIAN CANCER: LABORATORY AND CLINICAL PERSPECTIVES SARFRAZ AHMAD FLORIDA HOSPITAL CANCER INSTITUTE, DEPARTMENT OF GYNECOLOGIC ONCOLOGY, UNIVERSITY OF CENTRAL FLORIDA AND FLORIDA STATE UNIVERSITY, COLLEGES OF MEDICINE,USA Cancer represents a major cause of overall mortality, second only to cardiovascular events. Coagulation abnormalities are often encountered in cancer patients, which are typically manifested by a low-grade form of disseminated intravascular coagulation (heightened clotting activation, and therefore considered as hypercoagulable ). Factors that contribute to the activation of coagulation in cancer primarily include non-specific mechanisms such as tissue damage and inflammatory responses, and prolonged immobilization, especially during hospital stay. Furthermore, coagulation may be induced by such treatments as chemo- and/or radio-therapy. A significant number of cancer patients encounter complications of thromboembolic and/or bleeding disorders. Among others, ovarian cancer is a leading cause of death from gynecologic malignancies in women. Unlike breast cancer in which a significant progress has been made for early detection thereby saving lives, a majority of women with advanced-stage ovarian cancer die because early-stages have no obvious symptoms. Furthermore, in the recent past no affordable screening test has been approved that could have proven to be effective in the early diagnosis of the disease. Ovarian cancer patients are significantly more likely to develop a blood clot and associated thromboembolic episodes. One would expect that patients with this devastating disease to have a significantly higher level of clotting and platelet activation than the subjects with benign tumors and healthy volunteers. There are several crucial laboratory markers/tests that can potentially predict the hypercoagulability in a given subject/specimen. The hypercoagulability may be best correlated with the highest levels of the activation markers in patients with advanced-stage and recurrent disease. Lower levels of clotting activation can be expected in patients with ovarian cancer that are treated with polypharmocologic low-molecular weight heparins (LMWH) and designer heparinomimetics, thereby minimizing the potential of hypercoagulable state. These understandings may improve the rationale for novel anticoagulant therapy in select patients, and point the way to more targeted use of LMWH in studies designed to prolong survival and delay/prevent the disease progression in women with ovarian cancer. This presentation will provide an objective account of the laboratory and clinical perspectives that appropriate pre-operative coagulation and platelet activation markers analysis in patients with ovarian cancer may be helpful towards the assessments of the relative risk of thromboembolic events. -40-

42 PL 45 GENE SILENCING MOLECULES AND USING IN THERAPY EMINE SALVA DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, FACULTY OF PHARMACY, INONU UNIVERSITY, MALATYA, TURKEY The knockdown of genes is an important research area in pharmaceutical biotechnology. The down-regulation of genes can be achieved either at the transcriptional or post-transcriptional levels. The sequence-specific gene silencing effect is known as RNA interference (RNAi). RNAi is a highly promising technology using in the gene therapy applications to inhibit the expression of pathologically relevant genes and can be very useful for the development of new drugs based on a gene inhibition expression effect. There are four major anti-mrna strategies; firstly single-stranded oligodeoxynucleotides (ODNs) with 8-0 bases in length that inhibit the translation of mrna into protein through Watson-Crick hybridization to targeted mrnas; secondly ribozymes with around 30 nt as RNA cleaving pharmaceuticals; thirdly micrornas, naturally occuring small non-coding RNA molecules with 0-4 nt that function post-transcriptional regulation of gene expression by binding to the 3 untranslated regions of their target mrnas and finally the sirnas that able to recognize the target mrna with a high specificity through a base pairing complementary sequence process resulting in the degradation of the target mrna by intracellular nucleases. The therapeutic applications of antisense molecules are as antiviral and anticancer agents, in central nervous system therapeutics, in inflammation or cardiovascular therapeutics. Compared to the conventional drugs (e.g., low molecular weight inhibitors, therapeutic antibodies), gene silencing molecules can be specifically targeted and inhibited in protein expression in cell and also, the synthesis of these molecules does not require cellular expression system, complex protein purification or refolding and is relatively uncomplicated. Therefore nucleic acid-based strategies may offer novel therapeutic approaches in various pathologies including viral diseases and cancer. The efficient gene delivery becomes a primary prerequisite for gene silencing in mammalian systems but there are some challenges which restrict its application. First challenge is the potential for an off-target effect. Second challenge is immune stimulation during antisense therapy. Delivery of antisense molecules during the therapy is also an important challenge in therapy. To overcome of these challenges, an appropriate delivery systems are needed. Viral and non-viral delivery systems protect antisense molecules from degradation and facilitate uptake by target cells. The development of suitable carrier systems for delivery of antisense molecules raise considerable hope to bring into clinics novel tharapeutic RNAi-based concepts in human. PL 46 CHEMOTHERAPY RESISTANCE: CANCER GENETICS ON BEHALF OF CLINICAL THERAPY BETUL KARADEMIR DEPARTMENT OF BIOCHEMISTRY, MEDICINE FACULTY / GENETIC AND METABOLIC DISEASES RESEARCH AND INVESTIGATION CENTER, MARMARA UNIVERSITY, ISTANBUL, TURKEY Proteasomal degradation is crucial to prevent the accumulation of cellular damage. The removal of the damage is a required process for healthy organisms to keep the integrity while in cancer cells this situation may induce drug resistance. Regarding chemotherapy for the cancer treatment, degradation mechanisms such as proteasomal system and autophagy have been focused recently and proteasomal inhibition in cancer cells have been shown to induce autophagy. This induced pathway may prevent the cancer cells from death or can cause autophagic cell death which is an important reason for chemotherapy resistance. There are many preclinic studies to improve the results and on the other hand heat shock proteins are accepted to be protective which may bring new approach. In our laboratory, several cancer cell lines have been tested from different aspects of proteasomal activity. HCT6 colon cancer cell line was used to test the role of HSP70 and proteasome inhibition on autophagic cell death. In this direction, heat shock treatment has been applied to the cells which is also an applied process for cancer patients. Cell viability, proteasome activity, degradation of long-lived proteins, and the expressions of HSP70, LC3, beclin, caspase 9 and PARP have been analysed. Additionally, mouse hippocampal cell line is used to test the proteasomal activity in relation to heat shock proteins which highlighted another important point for the chemothrapy resistance with antioxidant gene expressions. Different breast cancer cell lines have also confirmed the role of proteasomal degradation in the failure of chemotherapy. Supported by TUBITAK COST-CM00-0S8-4-

43 PL 47 NANOSCALE DRUG DELİVERY SYSTEMS AND THE BLOOD-BRAIN BARRIER YILMAZ CAPAN HACETTEPE UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, TURKEY Drug delivery to the brain poses a major challenge due to the blood brain barrier (BBB). Thus, several strategies have been developed to overcome the BBB and to achieve successful brain drug delivery. Certain endogenous molecules, such as insulin or transferrin, do cross the blood-brain barrier via a process of receptor-mediated transcytosis (RMT). Our approach is to describe the development of a chitosan nanoparticle carrier system, functionalized with poly(ethylene glycol) (PEG) and monoclonal antibody targeted to the brain for the delivery of a caspase-3 inhibitor and basic fibroblast growth factor (bfgf). The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. On the other hand, growth factors (e.g. bfgf) suppress cell death by acting at several points on death pathways and, additionally, promote regeneration. These features make them promising agents for treatment of the neurodegenerative diseases. However, these large peptides also cannot penetrate the brain tissue when systemically administrated. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (SA)-biotin (BIO) technology, we describe here the design of chitosan (CS) nanospheres conjugated with PEG bearing the CD 7 monoclonal antibody whose affinity for the transferrin receptor (TfR) may trigger receptor-mediated transport across the BBB. These functionalized CS-PEG-BIO-SA/CD7 nanoparticles (NPs) were characterized for their particle size, zeta potential, drug loading capacity, and release properties. Fluorescently labeled CS-PEG-BIOSA/CD 7 nanoparticles were administered systemically to mice in order to evaluate their efficacy for brain translocation. The results showed that an important amount of nanoparticles were located in the brain, outside of the intravascular compartment. These findings, which were also confirmed by electron microscopic examination of the brain tissue, indicate that this novel targeted nanoparticulate drug delivery system was able to translocate into the brain tissue after i.v. administration. Consequently, these novel nanoparticles are promising carriers for the transport of the anticaspase peptide Z-DEVD-FMK and bfgf into the brain. PL 48 POLY(LACTIC-CO-GLYCOLIC ACID) BASED DRUG DELIVERY DEVICES FOR TISSUE ENGINEERING AND REGENERATIVE MEDICINE OYA KERIMOGLU MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY HAYDARPAŞA ISTANBUL, TURKEY Poly(D,L-lactide-co-glycolide) (PLGA) is the most frequently used biodegradable polymer for developing nano/microparticles encapsulating therapeutic drugs in controlled release (CR) applications. PLGA based drug delivery devices have several advantages over the conventional devices. One of the advantage is the extended release rates of drugs up to days, weeks or months. Other reasons for the widespread use of PLGA are its biodegradability, its biocompatibility, and the fact that PLGA has been approved by FDA (Food and Drug Administration). PLGAs are commercially available with very different phys ico-chemical properties, and that the drug release profile can be tailored by selecting PLGAs with the appropriate properties, such as molecular weight (Mw) and the lactide: gycolide ratio. Numerous active pharmaceutical ingredients such as anti-cancer drugs, analgesics, antibiotics and macromolecular drugs such as proteins, peptides, genes, vaccines, antigens, human growth factors, vascular endothelial growth factors etc., are successfully incorporated into PLGA or PLGA based drug delivery devices. PLGA has been used by several research ers in tissue engineering, vascular engineering, nerve regeneration, cartilage tissue engineering and bone tissue engineering. According to various research, PLGA has been shown to be a successful biode gradable polymer as a controlled release system and a drug delivery device for tissue engineer ing and regenerative medicine. -4-

44 PL 49 MAJOR CHANGES IN CLINICAL PHARMACY EDUCATION AND PRACTICE SIDNEY J. STOHS FACN, CNS, ATS, FAPHA, DEAN EMERITUS, CREIGHTON UNIVERSITY, OMAHA, USA Major changes have occurred in pharmacy education and practice over the past 60 years. Major changes and advancements have occurred with respect to the kinds and complexities of drugs available. Furthermore, pharmacy has evolved from a practice devoted to compounding and patient care, to dispensing, to clinical pharmacy and drug information management, to pharmaceutical care, and most recently to medication therapy management. Each of these terms and phases will be addressed. Pharmacy education has similarly evolved from an educational system with a heavy focus on laboratory and dispensing skills to a greater focus on drug information, patient care, and disease state and medication therapy management skills. The changes that have occurred in pharmacy education with respect to courses and laboratories now taught will be reviewed. The role of billing for clinical services to a third party payer and its importance to the future of pharmacy will also be considered. PL 50 THE IMPORTANCE OF CLINICAL ROUNDS IN CLINICAL PHARMACY EDUCATION FIKRET VEHBI IZZETTIN CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY, FACULTY OF PHARMACY, TURKEY Clinical pharmacy is defined as that area of pharmacy concerned with the science and practice of rational medication use (). Pharmaceutical care is the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient s quality of life (). Clinical rotation (round) and practice-based education is important to increase the level of knowledge.by increasing the exposure of pharmacist or pharmacy students to patients and medical team in their education, it will help for better understanding of patients, their diseases and drug therapy and will enhance communication skills. In clinical rotation, pharmacy students will gain a knowledge about: general information about disease, sign and symptom, drug therapy, non-pharmacological alternatives, side effect, administration, prevention and treatment of adverse reactions, monitoring, drug-related problems. Introducing clinical rotation to pharmacy education needs reducing the laboratory hours from traditional pharmacy education program. Because the knowledge gains form the laboratories are more product oriented and not used in future pharmacy practice. And this leads to waste of time and energy. The important of clinical rotation will be discussed through case presentation. Clinical rounds are an ideal opportunities for the students to learn and apply these patient oriented services. References - The Definition of Clinical Pharmacy. Pharmacotherapy 008;8(6): Hepler C.D. Strand L.M. Opportunities and responsibilities in pharmaceutical care. American Journal of Hospital Pharmacy, 990 vol 47. PL 5 PATIENT-CENTERED PHARMACY EDUCATION DO WE REALLY NEED IT OR NOT? AKGUL YESILADA ISTANBUL KEMRBURGAZ UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY The rapid development in the pharmaceutical industry has given rise to the introduction of a vast number of ready-made medicinal products to to market, and has diminished the need for compounding of medicines in the pharmacies and restricted the role of pharmacists mostly to the borders of dispensing medicinal products, which resulted the underuse of pharmacy workforce in the health service. In the developed countries this workforce was sucessfully channelized into clinical medication management where pharmacists were educated to be the effective providers of critical information to other health care teams on the benefits, risks and potential adverse reactions between therapeutic agents, with the application of so- called patientcentered education system. Thus, in the last two decades the pharmacists role in the health care service has gained a new formation globally : experts on medicines. By this way the pharmacy profession has emerged as an important contributor for implementing responsible use of drugs in the developed countries. In spite of all these developments, there is still a debate for or against the need for patient centered education in some countries including Turkey. In this presentation the various aspects of transition to patient-centered pharmacy education in Turkey will be discussed with emphasis to FIP,WHO and UNESCO commentary, reports initiatives and action plans. -43-

45 PL 5 ROLE OF COMMUNITY PHARMACIES IN PROMOTING RATIONAL USE OF DRUGS IN DEVELOPING COUNTRIES. A WAY FORWARD AZHAR HUSSAIN DEAN/DIRECTOR (PHARMACY DEPARTMENT), HAMDARD INSTITUTE OF PHARMACEUTICAL SCIENCES, HAMDARD UNIVERSITY, ISLAMABAD, PAKISTAN The use of medicines for prevention, cure or reducing symptoms for illness is widespread in many societies, around the world. In order for health consumers to achieve optimum health outcomes through the quality use of medicines (QUM), it is vital that they have access to safe and effective medicines which are also affordable. Besides that, access to independent and reliable information about medicines and their alternatives is also essential to enable safe and appropriate use. Distribution of medicines relies heavily on community pharmacies and according to an estimate, 80% of the medicines in developing countries are being distributed through this channel due to their easy accessibility. Thus, majority of the population relies on community pharmacies for their health care needs. Community pharmacies in developed world have been extensively utilized in managing chronic diseases and minor ailments successfully. On the other hand, the role of community pharmacies has been ignored in developing countries. These pharmacies often lack adequate facilities, staffing and equipments. Besides this, the dispensers working at these pharmacies are not trained, and yet, are involved in making diagnoses and recommending therapy to the patients along with dispensing of medicines. Thus it becomes important to critically evaluate and design effective pharmacy practice models to be implemented at these community pharmacies which are required to guide researchers and policy makers to look into the situation from a broader perspective to improve current pharmacy practices and provision of pharmaceutical care. Innovative approaches are required to design appropriate interventions, policies and ways for their effective implementation, to utilize the maximum potential of community pharmacies in promoting rational use of drugs. In this presentation role of community pharmacies and effective pharmacy practice models for promoting rational use of drugs will be discussed PL 53 ROLE OF DIETARY SUPPLEMENTS IN DISEASE PREVENTION AND MANAGEMENT SIDNEY J. STOHS FACN, CNS, ATS, FAPHA, DEAN EMERITUS, CREIGHTON UNIVERSTY OMAHA, USA For optimal health optimal nutrition is required, and health and metabolism are limited by nutrients that are deficient and therefore rate limiting. Widespread deficiencies are common for vitamins D, E, A, K, B6, B and folic acid as well as for minerals including magnesium, calcium, iodine, zinc, selenium, and iron. Dietary supplements are products taken by mouth intended to supplement the diet. In the USA they are classified as foods and not drugs. Recent studies have clearly shown that the use of dietary supplements is cost effective, resulting in significant health care cost savings. Examples regarding healthcare cost savings will be provided, and the amounts of vitamins, minerals, and other supplements that should be consumed to enhance and optimize health will be discussed. In addition, information will be provided regarding the use, safety and efficacy of nutritive sweeteners as sugars and FDA approved non-nutritive (non-caloric) sweeteners as sucralose. -44-

46 PL 54 THE CARCINOGENIC RISKS OF ARTIFICIAL SWEETENERS: THE CASES OF ASPARTAME AND SUCRALOSE MORANDO SOFFRITTI, MICHELA PADOVANI CESARE MALTONI CANCER RESEARCH CENTRE, RAMAZZINI INSTITUTE, BOLOGNA, ITALY Nowadays, after saccharine, aspartame (APM) is the most used artificial sweetener in the world. APM is used on more than 6,000 products and, among them, in over 500 drugs. The major consumers are children and women in childbearing age. Their daily consumption has been estimated to be.5-5 mg/kg b.w. APM is metabolized both in humans and rodents, by intestinal tract into phenilalanin, aspartic acid and methanol. APM is not considered genotoxic based on in vitro and in vivo tests. Epidemiological studies did not show an increased carcinogenic risk, except in one study which showed an association of increased risk of non-hodgkin s lymphoma and multiple myeloma in man who consumed diet soda containing APM. Experimental carcinogenicity studies performed on rats and mice in early 70 by the industry producing APM, and on transgenic mice by the US National Toxicology Program did not show any carcinogenic effect. Overall we believed that the safety of APM concerning the potential long-term toxic effects, in particular the carcinogenic ones, was not been demonstrated by these studies. For these reasons we started a project encompassing several experiments on rats and mice in which APM was administered in feed at various doses, to a large number of rats or mice per group per sex, starting the treatment at different ages and keeping the animals under observation until spontaneous death. In the first experiment we demonstrated that APM, administered from 8 weeks of age for the life-span to Sprague-Dawley rats, induced a significant increased incidence of lymphomas/leukemias and of neoplastic lesions of the renal pelvis and ureter in females, and a significant increased incidence of malignant schwannomas of the peripheral nerves in males. In a second experiment we demonstrated that APM, administered from fetal life until spontaneous death, induced a significant increased incidence of lymphomas/leukemias in males and females, and of mammary cancer in females. Furthermore this study demonstrated an increase of the carcinogenic effects. The oncological results of a third study, performed on Swiss mice treated with APM from fetal life until spontaneous death, demonstrated a significant increased incidence of hepatocellular carcinomas and alveolar/bronchiolar carcinomas in males. Concurrently with the APM mice study, we performed an experiment on mice to test the potential carcinogenic effects of Sucralose, a widely used artificial sweetener in Europe and USA. Preliminary results of this study will be presented during the conference. PL 55 PROBIOTICS: IS FOOD A GOOD CARRIER DILEK HEPERKAN ISTANBUL TECHNICAL UNIVERSITY, FACULTY OF CHEMICAL AND METALLURGICAL ENGINEERING FACULTY, DEPARTMENT OF FOOD ENGINEERING Microorganisms especially bacteria can be used for a number of beneficial purposes. Among them, some are more prominent like Lactobacilli and Bifidobacteria as health promoting to the host. Probiotics are living microorganisms which have several beneficial properties such as improving intestinal tract health, producing antimicrobial substances, enhancing the immune response, reducing symptoms of lactose intolerance, enhancing the bioavailability of nutrients, and decreasing the prevalence of allergy in susceptible individuals. Prebiotics are substances that pass through the gastrointestinal tract without being digested such as inulin, other fructo-oligosaccharides and even almonds. They serve as substrates for the probiotic organisms to enhance their activity and survivability in the colon. A variety of food products containing probiotics, prebiotics and synbiotics are considered as functional foods and have increasing interest in the public. In this presentation the importance of probiotics, the role of prebiotics, factors affecting the growth and activity of probiotic organisms, their beneficial role on the host, potential foods which carry probiotic microorganisms will be discussed in detail. -45-

47 PL 56 RISK FACTORS AND ASSESSMENT OF BACTERIAL PATHOGENS IN FOOD B. IREM OMURTAG KORKMAZ DEPARTMENT OF NUTRITION AND DIETETICS, FACULTY OF HEALTH SCIENCES, MARMARA UNIVERSITY Consumers exposure to bacterial pathogens and their food consumption habits are strictly related to each other. Risk factors contributing to foodborne illnesses show also similarities in-between countries. Due to the growing food sector and increased health concerns, priority of food security issues became more important since last decades. In this concept most critical contamination routes to be considered are; carefully handling of food, differences of consumers habits in rural and urban regions, meat species used for a food, prevalence and concentration of a pathogen in raw meat, sufficient heat treatment, amount of meat and other raw components per portion, and frequency of consumption of a food item. These factors can be evaluated principally on the basis of the risks posed by a pathogen and thus potential problems might be predicted by ranking of food. Accordingly a previous risk assessment model of Omurtag et al. (03) was indicated that amount of contaminated meat at serving stage and also foods with high frequency of consumption was presumed to support possible transmission ways of contaminated food to consumer. Hence it is clear that risks associated with foodborne pathogens have to be assessed by considering several risk factors and therefore providing scientific data on the concentration of pathogens in different food items are considered to be useful. Reference: Omurtag I., Paulsen P., Hilbert F. & Smulders F.J.M. (03). The risk of transfer of foodborne bacterial hazards in Turkey through the consumption of meat; risk ranking of muscle foods with the potential to transfer Campylobacter spp., Food security, 5():7-7. PL 57 DRUG TRANSPORTERS: CIRCADIAN RHYTHMS AND THERAPEUTIC IMPLICATIONS ALPER OKYAR ISTANBUL UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL Circadian rhythms (~4h period) have been shown for most biological variables in living organisms and are generated by molecular clocks involving clock genes. The molecular clocks are coordinated by the suprachiasmatic nuclei along the ~4h and orchestrates the circadian timing system (CTS). The CTS generates daily rhythms in cellular and organism physiology and adjusts them to environmental cycles (). The main function of the CTS is to coordinate bodily and cellular functions, drug pharmacodynamics (PD) and pharmacokinetics (PK) over the 4h. Circadian changes modulate phase I, II and III drug metabolism, detoxification and disposition processes. Some drugs are not only metabolized, but also transported via carriers, e.g., for exsorptive transport through ATP-binding cassette (ABC) transporters in particular P-glycoprotein (P-gp), is the most outstanding one among ABC transporters, as it confers the strongest resistance (MDR) to the variety of antineoplastics. Furthermore, P-gp is expressed in many tissues and is responsible for absorption, distribution and excretion of various compounds. Recently, it was reported that circadian rhythms may influence the PK of drugs and play a role in the pharmacokinetic processes when affected by ABC carriers mediated efflux. This is particularly relevant for anticancer drugs, with a narrow therapeutic index (, 3). Indeed, circadian timing modifies the toxic effects of 40 anticancer medications in rodents and in patients. The mechanisms of drug detoxification involve the cellular efflux of medications and/or their metabolites via transporters. This detoxification rhythm can importantly contribute to host tolerability for some anticancer drugs such as irinotecan, docetaxel, doxorubicin and methotrexate whose efflux involves ABC s. However, we should consider also that several mechanisms jointly account for the chronopharmacology of antineoplastics. The challenge is to identify the theoretically optimal chronotherapeutic schedules that will best spare healthy tissues from toxic insults in an individual patient (, 3). References: - Lévi F, Schibler U. Annu Rev Pharmacol Toxicol 007; 47: Lévi F, Okyar A. Expert Opin Drug Deliv 0; 8: Lévi F, Okyar A et al. Annu Rev Pharmacol Toxicol 00; 50:

48 PL 58 BLAST INJURY INDUCED FUNCTIONAL AND STRUCTURAL CHANGES IN BRAIN NIHAL TUMER PHARMACOLOGY & THERAPEUTICS UNIVERSITY OF FLORIDA AND GERIATRIC RESEARCH EDUCATION & CLINICAL CENTER, VETERANS AFFAIRS MEDICAL CENTER, USA Background: Overpressure blast-induced brain injury (OBI) is a common problem for military population. It leads to progressive pathophysiological changes in brain. Therefore, we investigated the structure and function of the basilar artery (BA) following OBI. Methods: Male Sprague Dawley rats ( g) were divided into Control (Naive), single OBI [30 psi peak pressure, - ms duration], and repeated (every three days) OBI (r-obi). Rats were sacrificed 4 h post injury; brain tissues were taken. BA was cannulised in the pressurized system and vascular responses to KCl, acetylcholine (ACh) and diethylamine (DEA)-NONO-ate evaluated. Cortex and cerebellum were used for immunohistochemistry and assessment of oxidative stress and inflammatory markers. Results: The neurological status was impaired in OBI and r-obi groups (4.6±.5, 3.7±.4 respectively vs 0.66±0.5 in control). A significant increase was detected in malondialdehide (MDA), an index for lipid peroxidation levels in OBI and r-obi groups compared with control in cortex (p<0.05, p<0.05, respectively) and cerebellum (p<0.0, p<0.00, respectively). A significant decrease was detected in glutathione (GSH) levels in r-obi groups compared with control group in cortex (p<0.0) and cerebellum (p<0.05). Myeloperoxidase (MPO) activity-an index for neutrophil infiltration was significantly (p< ) elevated in r-obi. Additionally, tissue thromboplastic activity, a marker for coagulation, was significantly increased in both regions, indicating a tendency for bleeding. Edema and protein levels of nerve growth factor (NGF) and nuclear factor kappa B (NFKB) were significantly (p<0.0) increased in cortex after r-obi. Furthermore, the glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule (Iba) immunoreactivity also demonstrated injury in the cortex. Endothelin contractility was increased and ACh relaxation was decreased in BA in both injury groups. However, impaired DEA-induced dilation and increased wall thickness to lumen ratio were observed only in the r-obi group. Conclusion: These findings indicate that single OBI causes endothelium-dependent and -independent alterations in BA function and additionally, r-obi induced structural changes in the artery wall. The mechanism may be a result of the increased oxidative stress and concomitant decrease in antioxidant levels in cortex and cerebellum. PL 59 METABOLITES FRIENDS OR ENEMIES FOR DRUG DEVELOPMENT? MERT ULGEN ACIBADEM UNIVERSITY INSTITUTE OF HEALTH SCIENCES,ISTANBUL, TURKEY Drug metabolism is an important process in establishing the safety and efficacy of a new drug molecule. Therefore, metabolism studies are carried out in the drug development stage to evaluate a series of compounds in terms of their metabolic stability and reactive toxic intermediates. The aim is to provide data for registration of the drug to be marketed. The identification of metabolites plays important roles in various phases of drug development. In some cases, active metabolites are found to have superior pharmacological properties than the parent molecules thereof and they may be candidates of new commercial products. Again, most of the pro-drugs having active metabolites were incidentally explored at the end of the drug development stage. If a toxic metabolite is identified, the protection of the functional groups involved is essential which requires re-design of the parent molecule. Many drugs can be metabolised to reactive products and these intermediates may react with cellular components ie DNA, nucleic acids, proteins and sugars in the body to form potential toxic products and they produce metabolite related toxicity. In the present lecture, the beneficial and detrimental aspects of drug metabolism will be discussed with specific examples in terms of drug development strategies and the functional groups of potantial toxic properties will be evaluated. -47-

49 PL 60 TWENTY-FOUR YEARS OF EXPERIENCE IN THERAPEUTIC DRUG MONITORING:PAST, PRESENT, AND FUTURE GONCAGUL HAKLAR DEPARTMENT OF BIOCHEMISTRY, SCHOOL OF MEDICINE, MARMARA UNIVERSITY ANDMARMARA UNIVERSITY PENDİK RESEARCH AND EDUCATION HOSPITAL, BIOCHEMISTRY LABORATORY, ISTANBUL, TURKEY Therapeutic drug monitoring is an important field in clinical biochemistry as blood levels of many of the therapeutic drugs administered to patients must be frequently determined, both because of the possible toxic side effects of many of these medications and because, often, lack of patient compliance results in subtherapeutic levels of the drug, requiring intervention. Additionally, it is important for the physician, when initiating drug therapy, to ascertain when the blood levels of the drug have achieved a stable therapeutic level. It becomes important, therefore, to understand the pharmacokinetics, on which drug therapy is based. The techniques involved in detecting the presence and/or the level of particular drugs, whether they are drugs of abuse or therapeutic drugs, are of two basic types: immunochemical and chromatographic. Much drug testing today is performed using immunoassays, namely the enzyme-mediated (or multiplied) immunologic technique (EMIT) and fluorescence polarization immunoassay (FPIA). The major methods for chromatographic techniques are thin-layer chromatography (TLC), highperformance liquid chromatography (HPLC), and gas chromatography mass spectroscopy (GC-MS) and liquid chromatography mass spectroscopy (LC-MS). We measure the concentration of cardiac glycosides, anticonvulsants, immunosuppressives, drugs used in the treatment of mania and depression, and chemotherapeutic agents for therapeutic drug monitoring in serum or whole blood. Furthermore, blood or urine level of the major drugs of abuse including cocaine, the opiates, amphetamines, benzodiazepines, barbiturates, and cannabinoids are also measured. PL 6 ENSURING BIOANALYTICAL PRINCIPLES ON BA/BE STUDIES SEDA UNSALAN NOBEL ILAC TURKEY The global generics drug market has grown substantially in recent years. Given the rapid progress of the sector, organisations must critically manage and assess bioequivalence studies (BE) that are mandatory when bringing new generic drugs to market. Bioavailability (BA) and BE studies play a major role in the drug development phase for both new drug products and their generic equivalents. Bioanalytical part is the most important part of the BA/BE studies. Bioanalytical method validation employed for the quantitative determination of drugs in biological fluids play a significant role in the evaluation and interpretation of BA, BE, pharmacokinetic and toxicokinetic study data. The quality of these studies is directly related to the quality of the underlying bioanalytical data. It is therefore important that guiding principles for the validation of these analytical methods be established and disseminated to the pharmaceutical community. A series of conferences and workshops on bioanalytical method validation and study sample analysis was started in early 990s, initiated by several scientific associations and supported by the US Food and Drug Administration. This approach resulted in the current document FDA Guidance for Industry Bioanalytical Method Validation, published in May 00 (FDA, 00). This document has been widely adopted as the standard reference for validation and routine drug analysis by the global bioanalytical community. In following years, several workshops and conferences were held with the aim of clarification of specific parts of the established Guidance and subsequent improvements in method validation. This included discussion of topics such as calibration curves and QC ranges, determination of metabolites, incurred sample re-analysis, and documentation. The need for a Guideline on validation of bioanalytical methods specifically applicable for studies in the European Unionis obvious. As a consequence, a concept paper on the Need of a Guideline for the Validation of Bioanalytical Methods was released in 008 by the Committee for Medicinal Products for HumanUse (CHMP) that came into effect in 0. References: Viswanathan CT et al., (007). Workshop/Conference Report Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays. The AAPS Journal 9 () Article 4 (http://www. aapsj.org). Shah VP and Bansal S (0). Historical perspective on the development and evolution of bioanalytical guidance and technology. Bioanalysis 3(8), FDA- Guidance for industry: bioanalytical method validation. US Department of Health and Human Services FDA, Center for Drug Evaluation and Research (00). 4 EMA- Guideline on bioanalytical method validation. July 0 EMEA/CHMP/EWP/97/009 Committee for Medicinal Products for Human Use (CHMP) -48-

50 PL 6 PHARMACY MANAEGEMENT: TODAY AND TOMORROW NAZLI SENCAN YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, PHARMACY MANAGEMENT AND SOCIAL PHARMACY DEPARTMENT, ISTANBUL, TURKEY There are countless books, presantations and works on both management and pharmacy, although the works on pharmacy management is still improving in all around the world. Some cultures are dedicated and some are learning the importance of pharmacy management on pharmacutical care and pharmaceutical services.pharmacy management focuses on factors, processes and outcome of pharmacy practice. Time, human resourse, financial, marketing, personal, innovation, risk, environmental, decision making, education and etc. management are some of the main topics of pharmacy management. Also social, ethical and lgal issues like inter and multicultural patient management, influence of culture on adharence, understanding geriatric patients, management of waste pharmaceuticals are some of the research concepts of pharmacy management. In this presantation, the researches done and published through out the world and Turkey will be summerised and future needs and works will be proposed. The main subjects are common priorities of health care givers like ; pharmacovigilance management and knowledge, smoking habbits, internships, drug advertisements, rational drug use, pharmacoeconomics, polypharmacy, geriatric patient care, compliance, dental care, pharmaceutical waste, patient satisfaction, pharmacists commitment to work, gender and pharmaceutical services, disabeled patients, financial loss of pharmacies and etc. It is obvious that pharmacy management perspective leads pharmacists to add value to public health. PL 63 THE IMPACT OF HEALTH LITERACY ON DRUG USE OF THE COMMUNITY HAYDAR SUR MD, PHD, PROFESSOR, BIRUNI UNIVERSITY FACULTY OF HEALTH SCIENCES Irrational use of medicines is a major problem worldwide. WHO estimates that more than half of all medicines are prescribed, dispensed or sold inappropriately, and that half of all patients fail to take them correctly. The overuse, underuse or misuse of medicines results in wastage of scarce resources and widespread health hazards. WHO defines rational use of drug as Rational use of drugs requires that patients receive medications appropriate to their clini- cal needs, in doses that meet their own individual requirements for an adequate period of time, and the lowest cost to them and their community. (WHO, 985) and advocates key interventions to promote more rational use:. Establishment of a multidisciplinary national body to coordinate policies on medicine use. Use of clinical guidelines 3. Development and use of national essential medicines list 4. Establishment of drug and therapeutics committees in districts and hospitals 5. Inclusion of problem-based pharmacotherapy training in undergraduate curricula 6. Continuing in-service medical education as a licensure requirement 7. Supervision, audit and feedback 8. Use of independent information on medicines 9. Public education about medicines 0. Avoidance of perverse financial incentives. Use of appropriate and enforced regulation. Sufficient government expenditure to ensure availability of medicines and staff (). -49-

51 PL The 6 dimensions PHARMACY of MANAEGEMENT: the problem include TODAY both AND service TOMORROW providing and utilizing sides as well as health system managers and policy makers. WHO recommends public education as a major solution options (,).Especially low level of health literacy among health service utilizers is one of the most important reasons of irrational use of medicines (). Health literacy has been defined in many different ways since it was first introduced as a term and concept. A broad and inclu- sive definition developed in 0 by the European Health Literacy Consortium: Health literacy is linked to literacy and entails people s knowledge, motivation and competences to access, understand, ap- praise and apply health information in order to make judgements and take decisions in every- day life concerning health care, disease prevention and health promotion to maintain or improve quality of life during the life course (3). Health literacy is a key determinant of health. Literacy is a stronger predictor of an individual s health status than income, em- ployment status, education level and racial or ethnic group (3).Low level of health literacy causes difficulties in the diagnosis and treatment stages of service use and sometimes it makes the treatment impossible. One of the most important results of this obstacle is related with use of prescribed drugs. Low ability to perceive the potential of treatment, misunderstanding and misinterpretation of progresses about disease are all outcomes of low health literacy. Despite the compatibility of health liter- acy to literacy level in general, it is not uncommon to have difficulties with literate people in terms of health services and use of drugs (4). Development of new strategies and policies aimed to increase the health literacy level in community will certainly provide great contribution to control irrational drug use. This success will give benefits to both health of the community and decrease the overall drug expenditures. References:. (date of access: ). Ambwani S., Mathur AK. Ratıonal Drug Use, Health Administrator Vol : XIX Number : Health literacy The solid facts, Editors: Ilona Kickbusch, Jürgen M. Pelikan, Franklin Apfel & Agis D. Tsouros, WHO European Regional Office Publication, Copenhagen, Sur H. Gene Bir Moda: Sağlık Okuryazarlığı. SD Platform Sayı:

52 PL 64 BENZENE, A MULTIPOTENTIAL CARCINOGEN MYRON A. MEHLMAN MT. SINAI SCHOOL OF MEDICINE, NEW YORK, NY Benzene is the most widely studied chemical in the world. Benzene is present in many household products and in occupational settings using paint, organic solvents, printing, and in gasoline stations, petrochemical plants, and in shoe manufacture. Workers and all these fields are exposed to benzene. Over 6,000 products and chemicals were analyzed for benzene content. Benzene is extremely toxic and causes all types hematopoietic and lymphoreticular tumors. Toxicity of benzene has been known since the 7 th century. Benzene poisoning in humans is a product of degree of individual susceptibility, duration of exposure, and concentration, which has a relative but not an absolute importance. The only safe concentration is zero (Hunter, F. 939). Professor Mustafa Aksoy from Turkey and his coworkers are world-recognized scientists in the studies of the carcinogenicity of benzene. In addition to all types of leukemias and lymphomas, benzene has also been shown to cause lung, liver, stomach, colon, kidney, urothelial, esophageal, nasopharyngeal and lymphosarcomatous tumors. Benzene biomarkers of exposure and intermediate effects are dose-dependent. MDS is found in excess in less than 0 ppm of exposure, and peripheral blood cell counts can be decreased at less than ppm. Genetically defined subgroups with greater sensitivity to benzene are present in the population. PL 65 MUCOSAL NANOVACCINOLOGY H. OYA ALPAR KEMERBURGAZ UNIVERSITY ISTANBUL & UCL LONDON Conventional vaccine delivery presents problems that are related both to patient compliance and to the adjuvants employed. A new generation of vaccine antigens are being identified and produced in the form of subunits and synthetic peptides, which although offering the advantage of safety, are in many cases weakly immunogenic. Therefore, there is an urgent need for pharmaceutically acceptable delivery systems and adjuvants for these antigens and non-parenteral administration for immunological, practical and economic reasons. To this end, biodegradable particles show particular promise. Particulate polymeric carriers made from biodegradable synthetic polymers such as polyesters offer advantages in uniformity and flexibility. During our earlier studies, we have demonstrated that microsphere-associated (adsorbed or encapsulated) vaccine antigens and plasmid DNA can lead to significant immune responses, not only through parenteral delivery, but also through mucosal surfaces, especially through the nasal route and also through the skin and that the responses induced can be optimised through formulation. These studies illustrated the importance of particle characteristics such as hydrophobicity, size and surface charge, as well as polymer type, molecular mass and crystallinity, on the modulation of immune response obtained. In addition, these responses may also be increased by the addition of bioadhesives. We have also conducted an extensive investigation into the uptake and trafficking of radio / fluorescent dye labelled microspheres following intranasal application. These studies showed that, in addition to particle transference into mucosal inductive sites, such as NALT, we also have observed immunologically significant translocation of micro-nano particulate material into systemic inductive sites, such as the spleen which is a prerequisite for the induction of protective immunity. Early publications from our group show the ability of mucosally administered microencapsulated recombinant subunit antigens derived from Y. pestis, to completely protect experimental animals from challenge with virulent Plague causing bacteria. For the same microsphere preparation, when delivered intra-tracheally in a comparative study, which also investigated i.m. and i.n. routes of delivery, mucosal routes gave equivalent or better immune responses than the parenteral route. However, our work has not been restricted to just one clinically relevant vaccine but many others. For example as well as particles containing a recombinant fusion protein, toxin F heavy chain (MBP- FHc) and subsequently with anthrax vaccine (using different types on rpa protective antigen)-microsphere formulations, following protection studies engendered solid protection in mice immunised i.n or i.m or both (combined) against a lethal challenge with the toxin and the organism respectively. In the case of B.anthracis the protection level was both formulation and adsorbtion - method dependent. Again, in the context of clinically relevant antigens, I will also discuss the formulation of PLA, PCL nanoparticules, surface modified with enhancers and adhesive polymers carrying encapsulated or adsorbed S.equi antigens (extract vs. recombinant SeM protein) as a new strategy, to control strangles. Also HepB hybrid cationic PLA-PEG nanoparticles to elicit strong humoral and cellular immunity after only a single mucosal or parenteral administration to replace conventional Alum-HBsAg vaccine to develop improved vaccines with a reduced dosing schedule, effective via a non-evasive route, and therapeutic vaccines for chronic hepatitis B virus carriers. In testing various chitosan based nanocarriers both for immunisation and DNA transfection studies the low MR chitosan/dna polyplexes gave the highest and most reproducible transfection efficiencies. The low MR chitosan polyplexes/gwiz were also successful in eliciting an immune response, suggesting that they hold promise in the field and warrant further investigation. These data will be discussed in the context of particle engineering and mucosal administration of nanoparticulate vaccine carrier systems. -5-

53 PL 66 BIOTECHNOLOGICAL INDUSTRY IN TURKEY AND THE BIOSMILARS AS THE NEW DRIVING FORCE CEM KOÇAK KOÇAK FARMA Biotechnological products present the fastest growing segment in the pharmaceutical industry. The terms biotechnology and biopharmaceutical describe many complex and important products, technologies, R&D, and industries. In this presentation the current status of Biotechnological and Biosimilar products in Turkey are summarized as well as the opportunities in this area in Turkey. The consumption of biotechnological and biosimilar products increase constantly. Since the approval of first biosimilar in 006 in EU, biosimilar present the greatest opportunity of growth for the pharmaceutical companies worlwide. Turkish government is supporting local manufacturing of biotechnological products with several incentives. PL 67 LEPTIN RESISTANCE: PREDISPOSING FACTOR IN OBESITY AND INFLUENCE WITH AGE: PHILIP J. SCARPACE UNIVERSITY OF FLORIDA, GAINESVILLE, FL. Obesity is occurring at epidemic rates with frightful health consequences. Our hypothesis is that leptin resistance is an important causative factor in both diet-induced and age-related obesity. We demonstrated that both types of obesity are associated with leptin resistance and this resistance resides within the first order hypothalamic neurons that contain leptin receptors, and provided strong evidence that the leptin receptor-signaling cascade is impaired. Leptin is produced in white adipose tissue in proportion to amount of fat tissue, and it was generally believed that the elevated leptin associated with obesity was simply a consequence of the increased adiposity. Our data indicate that the elevated leptin with obesity, whether diet-induced or age-related, is not just a consequence of obesity, but also one independent factor that predisposes animal to exacerbated highfat induced obesity. Moreover, we demonstrated that chronic treatment with leptin worsen rather than lessens the obesity. Thus, an increase in obesity elevates leptin levels inducing leptin resistance, which in turn, exacerbates the obesity, leading to ever-escalating cycle of increasing obesity Aged rats with adult onset obesity are leptin resistance, and aged rats with leptin resistance gain more weight on a high fat diet than younger leptin responsive rats. Consumption of high-fat diet in young rats leads to weight gain that is a mixture of an increase in both lean and fat mass. In contrast, high-fat feeding in aged rats not only results in greater absolute increase in weight gain, but the entire increase in weight is due to an increase in fat mass. The availability of highly palatable food is just as alluring to adults as to younger individuals, but our findings suggest that the consequences of consumption this high-fat food may be more dire in the aged population. -5-

54 PL 68 MECHANISM OF ACTION OF INPP4B TUMOR SUPPRESSOR IN ENDOCRINE CANCERS AGOULNIK IU, DERYUGINA EI, LIN D, LOPEZ SM, SUAREZ E, HODGSON MC, BINGOL-OZAKPINAR O, URAS F, WANG Y FIU HERBERT WERTHEIM COLLEGE OF MEDICINE, DEPARTMENT OF CELLULAR BIOLOGY AND PHARMACOLOGY, USA Dysregulation of phosphatidyl inositol signaling occurs in many cancers. Phosphoinositides are produced by a large number of phosphatidylinositol kinases and dephosphorylated by lipid phosphatases, such as tumor suppressors Inositol Polyphosphate 4-phosphatase type II (INPP4B) and PTEN. INPP4B has recently emerged as a potential tumor suppressor in prostate, breast, ovarian, and other cancers. We and other groups have shown loss of INPP4B protein and mrna with cancer progression to metastasis. Efforts are underway to characterize INPP4B catalytic activity and determine signaling pathways regulated by this tumor suppressor. INPP4B contains an N-terminal C-lipid binding domain and a C-terminal phosphatase domain, which contains a dual specificity phosphatase motif. We show that INPP4B can dephosphorylate both lipid and phospho-tyrosine substrates. Both of these activities are potentially important for INPP4B tumor suppressor function. Using cell based assays we discovered that loss of INPP4B leads to activation of several oncogenic signaling pathways that regulate proliferation and invasion. Our data suggests that INPP4B and PTEN tumor suppressors perform distinct functions in epithelial cells and loss of INPP4B has different consequences on tumor progression compared to loss of PTEN. PL 69 PROFESSIONAL PRACTICE AND COMPETENCY STANDARTS IN PHARMACY LEVENT ÜSTÜNES EGE UNIVERSITYFACULTY OF PHARMACY DEPARTMENT OF PHARMACOLOGY, BORNOVA, İZMİR The primary responsibility of a pharmacist is to ensure safe and effective use of medicines through the provision of pharmaceutical care in the scope of clinical pharmacy. Competencies refer to the knowledge, skills, attitudes and behaviours that an individual develops through education, training and work experience. Taken together, these professional acquirements form a framework which provides a pattern to describe the required competencies and appropriate code of conduct for a pharmacist s daily practice. Competency standards focus on key aspects of performance and express how a competent professional would act, in terms of attitudes, behaviors and observable results. Therefore the competency standards are embedded in every aspect of a pharmacist s professional life. On the other hand, complementing the compentency standards, professional practice standards relate to the systems, procedures and information used by pharmacists to achieve a level of conformity and uniformity in their practice. Professional standards allow the pharmacy profession to qualitatively and quantitatively measure the extent to which a pharmacist complies with his/her ethical and legal commitment to the community to ensure safe and effective delivery of pharmacy services, irrespective of the setting in which he/she practices. As health-care professionals, pharmacists play an important role in improving access to health care and in closing the gap between the potential benefit of medicines and the actual value realized. This makes pharmacists an indispensable part of any comprehensive health system. In addition, the increasingly complex and diverse nature of pharmacists roles in the health-care system demands an unceasing observance of the competence of pharmacists as health-care professionals who need to have up-to-date skills and expertise. In this sense, professional practice and competency standards in pharmacy are vital to provide guidelines for the pharmacists to improve access to health care, assist health promotion and ensure effective use of medicines for their patients. Fulfilling these standards is a requisition for every pharmacist to be fully capable of performing their profession in the most effective and beneficial manner, both for the patients they serve and for the society overall. -53-

55 PL 70 NEW TRANSLATİON MODELS TO LİNK OMICS TO HEALTH INNOVATİON: MİCRO-GRANTS FOR BİG DATA VURAL ÖZDEMİR FACULTY OF COMMUNICATIONS AND THE OFFICE OF THE RECTOR, INTERNATIONAL TECHNOLOGY AND INNOVATION POLICY, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY Translation of data-intensive OMICS technologies such as genomics, proteomics and metabolomics to concrete health innovations is at the epicentre of the research and development agenda. Yet the current translational research paradigms are based on the traditional science push model of translation, and rarely consider the science pull model of translation whereby the user communities and other societal stakeholders are included early on in the design stage of science and knowledge-based innovations. We often under-appreciate the important contributions made by citizen scholars and lead users of innovations to design innovative products and co-create new knowledge. We believe there are a large number of users waiting to be mobilized so as to engage with Big Data-driven pharmacy research and practice as citizen scientists-only if some funding were available. Yet many of these scholars may not meet the meta-criteria used to judge expertise, such as a track record in obtaining large research grants or a traditional academic curriculum vitae. We propose a novel idea and action framework to link OMICS to truly novel (disruptive) health innovations: micro-grants, each worth $000, for genomics and Big Data. Though a relatively small amount at first glance, this far exceeds the annual income of the bottom one billion -the.4 billion people living below the extreme poverty level defined by the World Bank ($.5/day). We describe two types of micro-grants. Type micro-grants can be awarded through established funding agencies and philanthropies that create micro-granting programs to fund a broad and highly diverse array of small artisan labs and citizen scholars to connect genomics and Big Data with new models of discovery such as open user innovation. Type micro-grants can be funded by existing or new science observatories and citizen think tanks through crowd-funding mechanisms described herein. Type micro-grants would also facilitate global health diplomacy by co-creating crowd-funded micro-granting programs across nation-states in regions facing political and financial instability, while sharing similar disease burdens, therapeutics, and diagnostic needs. Our hope is that the micro-grants will spur novel forms of disruptive innovation and genomics translation by artisan scientists and citizen scholars alike. -54-

56 ORAL PRESENTATIONS -55-

57 OP DEGRADATIVE ACTIVITIES OF ANTIBIOTIC-RESISTANT STAPHYLOCOCCUS SAPROPHYTICUS, BACILLUS PUMILUS, GRACILIBACILLUS DIPSOSAURI AND IDIOMARINA LOIHIENSIS PINAR CAGLAYAN, MERAL BIRBIR, AYSE OGAN, CRISTINA SáNCHEZ-PORRO 3, ANTONIO VENTOSA 3 DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, GOZTEPE, ISTANBUL, TURKEY DIVISION OF BIOCHEMISTRY, DEPARTMENT OF CHEMISTRY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, GOZTEPE, ISTANBUL, TURKEY 3 DEPARTMENT OF MICROBIOLOGY AND PARASITOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF SEVILLA,SPAIN Proteolytic and lipolytic activities of five moderately halophilic bacteria isolated from salted skins were screened on media containing % (w/v) gelatin and % (v/v) Tween 80, respectively. Then, these isolates were characterized using partial 6S rrna sequence analysis. Antibiotic susceptibilities of these isolates to gentamicin (0 µg), kanamycin (30 µg) and nalidixic acid (30 µg) were examined. Protease and lipase activities of the isolates and their mix culture were determined by the casein digestion assay at 80 nm and measuring the hydrolysis of p-npb to p-nitrophenol at 405 nm, respectively. All isolates showed both positive protease and lipase activities. According to phylogenetic analysis based on 6S rrna gene sequence comparison, moderately halophilic bacterial strains isolated from the skins were identified as Staphylococcus saprophyticus, Bacillus pumilus, Bacillus licheniformis, Gracilibacillus dipsosauri and Idiomarina loihiensis. Protease activities of Gracilibacillus dipsosauri, Staphylococcus saprophyticus, Bacillus pumilus, Idiomarina loihiensis and Bacillus licheniformis, and the mixed culture were found respectively as.6,.0,., 3.0,.6 and 3.5 u/min. Lipase activities of Gracilibacillus dipsosauri, Staphylococcus saprophyticus, Bacillus pumilus, Idiomarina loihiensis and Bacillus licheniformis and the mix culture were found as 64, 93, 87, 77, 55 and 93 µm/ ml, respectively. While Idiomarina loihiensis exhibited the highest protease activity, Staphylococcus saprophyticus displayed the highest lipase activity. All isolates exhibited resistance against gentamicin (0 µg) kanamycin (30 µg) and nalidixic acid (30 µg). Due to destructive effects of these isolates on the preserved skins, effective treatment procedures should be applied to preservation salt to exterminate these destructive antibiotic-resistant microorganisms. OP EFFECT OF USING ANTIBACTERIAL AGENT, DIRECT AND ALTERNATING ELECTRIC CURRENTS TO KILL BACTERIA IN HIDE CURING AND PRE-SOAKING LIQUORS EMINE VURAL GENC, YASAR BIRBIR, MERAL BIRBIR 3 INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY, ISTANBUL, TURKEY 3 DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY Prevention of bacterial activity during brine curing and pre-soaking processes on hides is very important to improve leather quality. In this study, efficacy of different concentrations of potassium dimethyldithiocarbamete on the mixed culture of bacteria at different exposure times were investigated. In addition, the effect of combined electric current treatment using both.5 A direct and A alternating electric currents, followed by 40 mg/00 ml of test antibacterial agent treatment on the mixed bacterial culture was examined. Mixed culture of bacteria containing proteolytic Bacillus mycoides and Aerococcus viridans, lipolytic Staphylococcus xylosus and Enterobacter sakazakii were used. 700 ppm of the test agent was inadequate to kill the bacteria in the mixed culture with a period of 6 hours. However, 400 ppm, 800 ppm and 5600 ppm completely inactivated the bacteria in the same period of 6 hours, while 00 ppm and 400 ppm inactivated these microorganisms in 4 hours and ppm in 3 hours, respectively. The bacteria in the mixed culture treated with electric current were completely exterminated after hours of exposure to 00 ppm test agent. Bacterial cell count of the mixed culture was reduced to a low level via min electric current treatment and the remaining microorganisms were then killed easily by the test agent. In conclusion, this treatment system may be applied in hide brine curing and pre-soaking processes to more efficiently kill the microorganisms in these liquors. -56-

58 OP 3 PROS AND CONS OF PILUS: A TARGET FOR ANTIVIRULENCE THERAPEUTICS AND AN UNLIKELY PLAYER IN THE FIGHT AGAINST CANCER MERVE SUZAN ZEDEN, SCOTT HULTGREN, ENDER VOLKAN CYPRUS INTERNATIONAL UNIVERSITY, CYPRUS WASHINGTON UNIVERSITY IN ST. LOUIS, SCHOOL OF MEDICINEN,ABD Pili are filamentous, polymeric protein appendages assembled by bacteria. P- and type- pili, assembled by uropathogenic Escherichia coli via the chaperone-usher pathway, are virulence factors in urinary tract infections (UTIs). These appendages are required to bind host surfaces and establish infection; so their inhibition is a way to prevent infection. Antivirulence therapeutics named pilicides are bicyclic -pyridones designed to inhibit P-pilus biogenesis. Using SDS-PAGE and Western blotting, our studies indicate that certain pilicides are involved in blocking the polymerization of P-pilus subunits (PapE) that form the tip section of the pilus. These pilicides likely induce non-productive aggregation of PapDE subunits as demonstrated by Western blotting analysis. Type- pili are also involved in UTIs by binding to mannose moieties on bladder surface and invading host tissues. In addition to binding mannose, type- pili were shown to mediate binding with β and α3 integrins that are highly expressed on MDA-MD-3, highly metastatic human breast cancer cells. Upon co-culturing Type- piliated or unpiliated Escherichia coli with MDA-MD-3 cells and carrying out toxicity assays, we have observed a significant increase in cancer cell death when MDA-MD-3 cells were incubated with piliated bacteria rather than unpiliated bacteria. Interestingly, this significant pili-mediated toxicity was specific to highly metastatic MDA-MD-3 cells as lowly metastatic MCF7 cells did not experience significantly increased killing, suggesting that pili may have a role in targeting metastatic tumor cells. These findings indicate that studies on chaperone-usher pili can help improve our approaches of designing therapeutics for treatment of both infection and cancer. OP 4 LIFE SPAN EFFECT DIFFERNT INFUSIONS OF VERBASCUM TRICHOSTYLUM ON CAENORHABDITIS ELEGANS EXPOSED TO CHRONIC HEAT STRESS HASAN KILICGUN FACULTY OF PHARMACY ERZINCAN UNIVERSITY, ERZINCAN, TURKEY Aging is commonly defined as the accumulation of diverse deleterious changes occurring in cells and tissues with advancing age that are responsible for the increased risk of disease and death (). Extracts of plant adaptogens such as Eleutherococcus senticosus and Rhodiola rosea can increase stress resistance and life span in several model systems. In this study it was aimed to investigate whether Verbascum trichostylum, which is endemic to Eastern Anatolia of Turkey, has any effect on lifespan of the nematode C. elegans in a dose-dependent way under chronic heat treatment at 6 C or not. For this purpose 0.0mg/mL 0.mg/mL, mg/ml, 0 mg/ml Verbascum concentrations were prepared and mixed with Escherichia coli OP50 bacteria which is only feding source of Caenorhabditis elegans. Differnt concentrations of Verbascum trichostylum were able to increase stress resistance in C. elegans against chronic heat stress treatment at 6 C. The most promising increase against chronic oxidative stress conditions and lifespan were observed at the concentrations of mg/ml. Whereas, at 0 mg/ml concentrations tested a lifespan shortening effect was observed. Based on these observations, this study indicates that Verbascum trichostylum can be thought as an adaptogen. Because it was experienced as mild stressors at the lifespan-enhancing concentrations and thereby induce increased stress resistance and a longer lifespan.the obtained findings are thought that verbascum has a significant potential for aging as well as the treatment of aging related diseases..harman. D. The free radical theory of aging. Antioxid Redox Signal. 003;5:

59 OP 5 VALIDATED METHODS IN BIOALALYSIS SOMAIEH SOLTANI, AFSANEH FARJAMI PHARMACY FACULTY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, IRAN Bioanalytical method(s) development is of great importance during the process of drug discovery, development, marketing approval and clinical application and has significant impact in the pharmacokinetic and pharmacodynamic interpretations and decision makings. In the present study the application of approved guidelines (i.e. ICH, FDA and USP) in bioanalytical method development during the past decade has reviewed. The frequency of non-validated methods or partially validated ones versus full validated methods are studied and guidelines application trend is discussed. According to the results miss application of the guidelines and non validated methods are among the most challenging issues of the bioanalytical method development. It seems that these methods should be reviewed according to the proper validation aspects more carefully before publication. OP 6 THE ROLE OF GAS6/TAM SIGNALLING IN DIFFERENTIATION OF MESENCHYMAL STEM CELLS NESE ERIZ, OZLEM BINGOL OZAKPINAR, NAZIYE OZKAN, FIKRIYE URAS MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY GAS6 (Growth arrest-specific 6) is a protein vitamin K-dependent protein and is expressed in certain tissues. GAS6 is a ligand of Tyro3, Axl and Mer (TAM receptors). In this study, we aim to investigate the effects of GAS6 during differentiation of the mesenchymal stem cells. Adipose tissue removed during a liposuction procedure was used as starting material. Mesenchymal stem cells isolated from adipose tissue were analyzed by flow cytometry. Then adipogenic, chondrogenic or osteogenic differentiation was achieved using the appropriate differentiation mediums. In parallel with these experiments, the cells were incubated with varying doses of GAS6 added to the medium. RNAs of TAM receptors were subjected to Real-time-PCR analyses. In addition, cells were checked morphologically by staining with suitable dyes to determine the possible effects of GAS6. During chondrogenic differentiation, TAM receptors are expressed in high amounts and these increases were statistically significant (p <0.00, 0.0 and 0.00, respectively). On the other hand, only the Mer receptor was found to be expressed highly during adipogenic differentiation (p<0.00). It was found that osteogenic differentiation was inhibited by addition of GAS6; whereas adipogenic differentiation was increased. Chondrogenic differentiation was decreased significantly, according to the dosage of GAS6 (p<0.00). The findings obtained in this study revealed that GAS6/TAM system has a role on mesenchymal stem cell differentiation in terms of the three differentiation modes: adipogenic, osteogenic and chondrogenic. OP 7 THE PLASMA LEVELS OF GAS6 IN RECURRENT PREGNANCY LOSSES MUSTAFA EROGLU, OZLEM BINGOL OZAKPINAR, LALE TURKGELDI, SADIK SAHIN, DILSAD HERKILOGLU, FIKRIYE URAS ZEYNEP KAMIL GYNECOLOGIC AND PEDIATRIC TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY During the implantation period, a significant portion of embryos are lost and eventually less than half of clinically established pregnancies end as full-term pregnancies without obstetrical complications. Recurrent pregnancy losses (RPL) are thought to have multiple etiologies including autoimmune and cellular immune abnormalities and maternal thrombophilic disorders. Growth arrest-specific 6 (GAS6) is a novel vitamin K dependent protein and has a role in inflammation. The aim of the current study is to investigate the association of plasma GAS6 levels with RPL. We collected blood samples from 8 women with RPL. Also blood samples of 66 women having had at least one live birth were collected as the control group. Patient and control groups plasma GAS6 levels were measured with an ELISA kit (R&D), which were optimized by us in our own laboratory. We used Unpaired T test for GAS6 levels. P<0.05 was taken as statistically significant. The plasma levels of gas6 were significantly higher in patients with RPL than those of the control group (.6±4.4 ng/ml and 0.57±3.7 respectively, p<0.0). The preliminary results show that there is a relation between RPL and plasma GAS6 levels. Inhibition of GAS6 would be an appropriate therapeutic target to slow down the progression of RPL. -58-

60 OP 8 CYTOKINE LEVELS AND PLATELET FUNCTIONS IN PREECLAMPSIA SADIK SAHIN, OZLEM BINGOL OZAKPINAR, AYSIN TULUNAY 3, MUSTAFA EROGLU, ENVER CIRACI, FIKRIYE URAS, SERMIN TETIK ZEYNEP KAMIL GYNECOLOGIC AND PEDIATRIC TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY 3 MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HEMATOLOGY AND IMMUNOLOGY, ISTANBUL, TURKEY The aim of this study is to evaluate the hypothesis that preeclampsia is associated with increased systemic inflammatory responses. We also determine whether there was a correlation between these markers with severity of preeclampsia and platelet functions. Forty-one patients diagnosed with preeclampsia were recruited into our study. Preeclamptic patients were grouped as severe (n=3) and mild (n=8). All patients were in the third trimester of the pregnancy and the values obtained were compared to controls (N=30) who were in the third trimester of uncomplicated normal pregnancy and not affected by either preeclampsia or gestational hypertension. Cytokine levels of interleukin-8 (IL-8) and IL-0 in plasma from women with preeclampsia or from healthy pregnant women were analyzed with ELISA. Aggregation and activation response of platelets to agonist adenosine-5-difosphate (ADP) was determined. Plasma IL-8 levels were significantly higher in severe preeclamptics (p<0.05). There was no significant difference between mild preeclampsia and the controls (p>0.05). IL-0 levels were significantly lower in severe preeclamptic patients compared to normal pregnants and mild preeclamptics (p<0.00 and p<0.05), respectively. Platelet aggregation response to ADP was less in preeclamptics than normal pregnants (p<0.00). Also, CD 6P levels, a marker of platelet activation, were elevated in preeclamptic patients (p<0.05). Negative correlation between the regulatory cytokine IL-0 and pro-inflammatory cytokine IL-8 levels suggests cytokine network disturbance in severely preeclamptic women. This might cause increase in platelet activation, thus decrease in platelet aggregation response to ADP in preeclamptic patients due to exhaustation and turnover of platelets. OP 9 SYNTHESIS, CHARACTERIZATION, PHOSPHATE BUFFER STABILITY, AND ANTIPROLIFERATIVE EFFECTS OF A NOVEL MODIFIED MALEIC ANHYDRIDE CONTAINING COPOLYMER/ANTICANCER DRUG CONJUGATES GULDEREN KARAKUS FACULTY OF PHARMACY CUMHURIYET UNIVERSITY, TURKEY Maleic anhydride (MA) copolymers also known as polyanhydrides, having highly reactive anhydride units, consists of MA and vinyl-based monomers. In our research laboratories poly(maleic anhydride-co-styrene), poly(maleic anhydride-co-vinyl acetate), poly(maleic anhydride-co-methyl methacrylate) and poly(maleic anhydride-co-allyl phenyl ether) were synthesized. Through modification/derivatization/conjugation of these copolymers anhydride ring can be bound, by the ring opening reaction, to amino (-NH) or hydroxyl groups (-OH) of nucleophilic reagents resulted in either ester/carboxylic acid or amide/carboxylic acid (,). Here MAVA was selected as the macromolecular drug carrier for modification through its reactive anhydride group by the systematic addition of biologically active molecules such as noradrenaline, doxorubicin hydrochloride, hydroxyurea, procainamide hydrochloride, cytarabine (3). Structural characterization of the MAVA copolymer and the modified products was carried out by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (H-NMR and 3C-NMR). Their molecular weights were also determined by size-exclusion-chromatography (SEC). All measurements confirmed that anticancer/other agents was successfully covalently bound to the MAVA copolymer backbone. A mechanism was then also suggested for the conjugation reaction. UV-Spectrophotometric measurements, for stability, indicated that conjugates kept its molecular integrity in physiological-body-fluid, PBS (physiological ph 7.40 at 37 ºC). Antiproliferative activities of conjugates were also determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. Two anti-cancer drugs, cisplatin and 5-fluorouracil, were included as positive controls. By comparing with cisplatin, 5-florouracil and also free drug, results showed that conjugates have significant activity against C6 (5-00 µg/ml) and HeLa (75 and 00 µg/ml). Furthermore antiproliferative activities of conjugates were shown to increase depending on the concentration.. Saad GR, Morsi RE, Mohammady SZ, Elsabee MZ. Dielectric relaxation of monoesters based poly(styrene-co-maleic anhydride) copolymer. J Polym Res. 008;5:5-3.. Atıcı OG, Akar A, Rahimian R. Modification of poly(maleic anhydride-co- styrene) with hydroxyl containing compounds. Turk J Chem. 00;5: Karakus G, Akin Polat Z, Yenidunya AF, Zengin HB, Karakus CB Synthesis, characterization and cytotoxicity of novel modified poly[(maleic anhydride)-co-(vinyl acetate)]/noradrenaline conjugate. Polym Int. 03;6:

61 OP 0 GPCR-INTERACTING PROTEINS AND THEIR INDIVIDUAL FUNCTIONAL ROLES LIVIA BASILE, SALVATORE GUCCIONE, GISELLA ALFONSINO 3, DANILO MILARDI 4, MATTEO PAPPALARDO 5 ETNALEAD S.R.L. VIA SAN NULLO 5/I, CATANIA (ITALY) ETNALEAD S.R.L. VIA SAN NULLO 5/I, CATANIA (ITALY); UNIVERSITY OF DEPARTMENT OF DRUG SCIENCES, CATANIA (ITALY) 3 UNIVERSITY OF CATANIA, DEPARTMENT OF DRUG SCIENCES, V.LE A.DORIA 6, I-955 CATANIA (ITALY) 4 INSTITUTE OF BIOIMAGING AND BIOSTRUCTURES-NATIONAL COUNCIL OF RESEARCH CATANIA, (ITALY) 5 UNIVERSITY OF CATANIA, DEPARTMENT OF CHEMICAL SCIENCES,CATANIA (ITALY) Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter and a vasoactive hormone synthesized from the amino acid tryptophan mainly in the enterochromaffin cells of the intestine and in the brain. Based on biochemical and pharmacological criteria, serotonin receptors are classified into seven main subtypes, 5-HT-7, all of which are G-protein-coupled (GPCR), whereas the 5-HT3 subtype represents a ligand-gated ion channel. GPCRs represent the most notable family of validated drug target. The GPCRs structure contains an extracellular N-terminal and intracellular C-terminal, seven transmembrane helices (7TMH) joined by intracellular and extracellular loops. 5-HT-7 receptor is involved in the regulation of important physiological and pathological processes, such as emotions, thermoregulation, circadian rhythmicity, memory processes and smooth muscle relaxation and depression (). Comprising α, β, and γ subunits, the G protein binds to an agonist-activated receptor, and this interaction triggers exchange of GDP for GTP in the GTPase domain of the G protein s α subunit (). Large Scale Molecular Dynamic simulations using an experimentally (in vitro mutagenesis) validated homology model and a Gs-GTP complex were performed to study the preferential interaction between 5-HT-7 and the Gs or G proteins, which probably differs in different pathologies (3). Implicit in the search for the functional relevance of these interactions is the expectation that could serve to address highly selective therapeutic opportunities.. Rosenbaum DM., et al. The structure and function of G-protein-coupled-receptors. NATURE. 009; 459(745): Wess J. G-protein-coupled: Molecular mechanisms involved in receptor activation and selectivity of G-protein recognition; The FASEB Journal. 997; (5): Kvachnina El, et al. 5-HT-7 receptor is coupled to G alpha subunits of heterotrimeric G- protein to regulate gene transcription and neuronal morphology. J Neurosci. 005;5(34): OP NOVEL NANOPARTICLES FOR GENE DELIVERY: PREPARATION, OPTIMIZATION, CELL UPTAKE AND CYTOTOXICITY INVESTIGATION SANAM ARAMI, MOHAMMAD REZA RASHIDI, MAJID MAHDAVI 3, MOHAMMAD SAEID HEJAZI 4 PHARMACEUTICAL BIOTECHNOLOGY DEPARTMENT AND STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN PHARMACEUTICAL CHEMISTERY DEPARTMENT, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 BIOCHEMISTRY DEPARTMENT, FACULTY OF SCIENCE, TABRIZ UNIVERSITY, TABRIZ, IRAN 4 PHARMACEUTICAL BIOTECHNOLOGY DEPARTMENT, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Cancer is one of the most life threatening diseases worldwide and the breast cancer is the top cancer among women. sirna (small interferring RNA) is a single stranded RNA that interferes with the expression of specific genes with complementary nucleotide sequences. sirna functions by causing mrna to be broken down after transcription, resulting in no translation. The porpuse of this study was to prepare novel nanoparticles carrying the sirna strands to cancerous cells. The nanoparticles designed and syntethised as below: The desired nanoparticles should be biocampatible and have positive charge to be safe and can form complexes with sirna. They were syntethised encapsulating a ferricoxide core with polyethyleneglycol-lactide polymer, chitosan and polyethylene imine respectively. The structure had been checked after each step via spectroscopic methods. Size, zeta potential and their ability of comlexation to sirna have been assessed by particle size analyzer, zetasizer and gel retardation assay on agarose gel, respectively. Their toxicity has been avaluated towards MCF-7, human breast cancer cells, using MTT assay in 3 time intervals (4, 48, 7 hours). The results showed that the nanoparticles size was 37.43±.45 nanometers in diameter, and the electric charge was measured +49. mv.the cytotoxicity results didnt show significant cytotoxicity toward the cells, although the survival percent has been reduced while increasing the particle concentration. So, the mentioned particles can be carriers for gene delivery in MCF-7 cells. Detailed tests will be done on their cellular uptake and gene silencing. -60-

62 OP PREPARATION AND IN VITRO- IN VIVO EVALUATION OF TRANSDERMAL FORMULATIONS OF BETAHISTINE SEVINC SAHBAZ, BETUL DORTUNC, MEHMET ZAFER GOREN FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, MARMARA UNIVERSITY, AYDARPASA, ISTANBUL, TURKEY FACULTY OF MEDICINE, DEPARTMENT OF MEDİCAL PHARMACOLOGY, MARMARA UNIVERSITY, BAŞIBÜYÜK, ISTANBUL, TURKEY Betahistin has been used in the treatment of diseases accompanied by impaired peripheral circulation, e.g. Méniѐre s syndrome, to reduce the frequency of episodes of vertigo and tinnitus (). The drug has a short half-life and should be taken three times daily due to the rapid elimination. Contraindication in patients with peptic ulcer history and the difficulty of frequently dosing requires administration ways other than the oral route. In the study, matrix transdermal system formulations of betahistine were prepared. When the drug is given as controlled release system, dosing time interval will be extended, so the patient compliance will be improved. As the dose amount given to the patient is reduced, adverse effects will be seen less and high amount dose loading will be prevented. Besides, the patient can remove the patch easily in case of an adverse effect or whenever he wants (). To prepare the formulations, Eudragit RL 00 and Eudragit RS 00 polymers were preferred which are widely used in controlled release dosage forms. Formulations were prepared using different ratios of these two polymers and a suitable plasticizer and its ratios were optimized. Drug release tests and then, ex-vivo penetration studies from excised human skin were evaluated. In-vivo studies were carried out with Wistar rats in three groups. The blood concentrations of the drug were evaluated and as a conclusion, with transdermal formulations betahistine could be seen at least for hours in the blood.. Weiser M, Strösser W, Klein P. Homeopatic vs Conventional Treatment of Vertigo. Arch Otolaryngol Head and Neck Surg. 998; 4: Hadgraft J. Dermal and Transdermal Delivery. In: Rathbone MJ, Hadgraft J, Roberts MS editors. Modified Release Drug Delivery Technology. New York: Marcel Dekker Inc., 003; p OP 3 CHARACTERIZATION STUDIES OF WELL-DEFINED BLOCK CO-POLYMER ASSEMBLIES GOKCEN YASAYAN, FRANCISCO FERNANDEZ TRILLO, STEPHANIE ALLEN, MARTYN C. DAVIES, CAMERON ALEXANDER DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY SCHOOL OF PHARMACY, UNIVERSITY OF NOTTİNGHAM, NOTTİNGHAM, UK In recent years, synthetic chemistry has expanded the number of amphiphiles that can form vesicular aggregates, with some examples showing improved stabilities when compared to phospholipid vesicles or liposomes.() Among these amphiphiles, polymers offer great potential in the preparation of vesicles, as the correct choice of polymerisation techniques, allows for a wide range of physical, chemical and mechanical properties. In addition, factors such as polymer architecture and molecular weight can be controlled in order to enhance overall properties.() In this study, six types of amphiphilic block copolymer structures derived from poly(phenylacrylamide)-block-poly(4-acrylamidobutanoic acid) with various chain lengths have been characterised. To investigate the ability of amphiphilic block copolymers to self-assemble and the properties of the formed assemblies, firstly a solvent exchange method was used to obtain vesicles and a dye inclusion/release assay was performed using a fluorescence spectrometer. Secondly, these polymeric assemblies were characterised by atomic force microscopy, transmission electron microscopy, dynamic light scattering and zeta potential measurements. Afterwards, the responses of the assemblies to ph changes were investigated; the behaviour of the assemblies at ph 0, ph 7.4, ph 4 and ph was studied by atomic force microscopy, dynamic light scattering and zeta potential measurements. Finally, the effect of adding a polycation, branched polyethylene imine on assemblies was examined by coating assemblies with this polycation; and the properties were investigated by dye inclusion/release assay, atomic force microscopy, dynamic light scattering, and zeta potential studies. School of Pharmacy, UNIVERSITY of Nottingham, Nottingham, UK. Department of Pharmaceutical Technology, Faculty of Pharmacy, Marmara UNIVERSITY, Istanbul, Turkey. References. Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, et al. Polymersomes: Tough vesicles made from diblock copolymers. Science. 999;84(547).. Smart T, Lomas H, Massignani M, Flores-Merino MV, Perez LR, Battaglia G. Block copolymer nanostructures. Nano Today. 008;3(3-4):

63 OP 4 EFFECT OF TAURINE ON CHEMOTHERAPY INDUCED NAUSEA AND VOMITING IN ACUTE LYMPHOBLASTIC LEUKEMIA MINA ISLAMBULCHILAR, MOHAMMADREZA SATTARI, IRAJ ASVADI 3, ZOHREH SANAAT 3, ALI ESFAHANI 3 STUDENT RESEARCH COMMITTEE AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN. HEMATOLOGY AND ONCOLOGY RESEARCH CENTER & DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 HEMATOLOGY AND ONCOLOGY RESEARCH CENTER, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN The purpose of this study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy induced nausea and vomiting in young adults with acute lymphoblastic leukemia. Forty young adults (aged over 6 years) with acute lymphoblastic leukemia were recruited to the study at the beginning of maintenance course of their chemotherapy. The study population was randomized in a double blind manner to receive either taurine or placebo. Life quality and adverse effects were assessed using a questionnaire. Data were analyzed using SPSS software. Of total participants, 43.8% were female and 56.3 % were male. The median age was 9.6±.95 years (ranges: 6-3 years). The results indicated that taurine supplemented patients reported a significant (P<0.05) improvement in chemotherapy induced nausea and/or vomiting after taking taurine during whole study period. Taurine administration significantly improved chemotherapy associated taste and smell alterations compared to the control patients (P<0.05). Moreover, taurine significantly reduced weariness compared to placebo group (P<0.05). In conclusion this study showed that taurine co-administration decreased the chemotherapy associated nausea and vomiting during the maintenance period of treatment in young adults with acute lymphoblastic leukemia. OP 5 INVESTIGATION OF HISTONE LYSINE TRIMETHYLATION OR ACETYLATION IN SPORADIC BREAST TUMORS AND MATCHED NORMAL TISSUES SEHER KARSLI-CEPPIOGLU, GAëLLE JUDES, ASLİHAN DAGDEMIR, MARJOLAINE NGOLLO, FRéDéRIQUE PENAULT-LLORCA, ANDRé LEBERT 3, YVES-JEAN BIGNON, DOMINIQUE BERNARD-GALLON DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF ONCOGENETICS, CENTRE JEAN PERRIN, PLACE HENRI DUNANT, CLERMONT-FERRAND, FRANCE. 3 UNIVERSITY BLAISE PASCAL, INSTITUT PASCAL UMR AUBIèRE, FRANCE Epigenetic alterations are important key factors for cancer development and prognosis. Breast cancer is induced by the accumulation of altered gene regulation. Therefore, we aimed to assess chromatin immunoprecipitation (ChIP) of three modified histones including H3K7me3, H3K9ac, and H3K4ac in breast tumors compared with the normal tissue. In order to identify the regulation of gene expression in 50 tumors and normal tissues, we proposed to follow ChIP with Q-PCR of 7 genes (ERα, ERβ, PGR, BRCA, EZH, P300 and SRC3). In addition, we have evaluated protein levels by western blot. RT-qPCR was used for the quantification of mrna levels. Our results demonstrated that H3K7me3 histone mark has an important role in controlling the gene expression. Gene expression levels of studied H3K7me3-enriched genes were significantly low in breast cancer tumors when compared with normal tissue (p<0.05). Expression levels of ERβ and PGR genes were decreased on H3K4ac mark-enriched sites in tumors (p<0.05). ERβ and PGR genes play a crucial role in determining breast cancer aggressiveness, thus a modified H3K4ac mark would be substantial transcriptional expression of these genes. ERα protein levels in luminal-like tumors were higher than in control tissue samples. We found that EZH protein levels in basal-like tumors were increased. In addition, mrna levels of EZH were higher in tumors than in normal tissue samples. Protein levels of PGR were also increased in tumors and these results were consisted with mrna levels of PGR. We aimed to provide an insight into epigenetic mechanisms of breast cancer with this project. In conclusion, further investigations would reveal new aspects in biomarkers to predict breast cancer aggressiveness and potential epigenetic therapies. -6-

64 OP 6 NOVEL 4-THIAZOLIDINONES AS NON-NUCLEOSIDE INHIBITORS OF HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE GIZEM CAKIR, ILKAY KUCUKGUZEL, RUPA GUHAMAZUMDER, DINESH MANVAR, ESRA TATAR, AMARTYA BASU, BHARGAV A. PATEL 3, TANAJI T. TALELE 3, NEERJA KAUSHIK-BASU MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPAŞA İSTANBUL, TURKEY THE STATE UNIVERSITY OF NEW JERSEY, NEW JERSEY MEDICAL SCHOOL, DEPARTMENT OF BIOCHEMISTRY & MOLECULAR BIOLOGY, USA 3 ST. JOHN S UNIVERSITY, DEPARTMENT OF PHARMACEUTICAL SCIENCES, COLLEGE OF PHARMACY AND HEALTH SCIENCES, QUEENS, USA Hepatitis C virus (HCV) is an important human pathogen of global public health significance with an estimated prevalence of 80 million people world-wide and a predicted 00,000 new-cases each year. The HCV NS5B RNA dependent RNA polymerase (RdRp) is a validated and attractive target for drug discovery. In this study, we report the therapeutic potential of the thiazolidinone scaffold against HCV NS5B RdRp employing 5-(substituted benzylidene)--[[5-aryl-,3,4-thiadiazol--yl]imino]-,3-thiazolidine- 4-ones. We synthesized derivatives of this scaffold (-4) and investigated their anti-hcv potency and anti-hcv NS5B RdRp activity. Of these, compounds -8 bearing,3-thiazolidine-4-one moiety displayed 6-3% anti-ns5b RdRp activity whereas their corresponding arylidene derivatives 9-4, with the exception of compounds 3 and 34 exhibited 70% NS5B inhibition at 50 µm. Among the arylidene derivatives, compound 33 was the most active with an IC50 value of 5.3 µm, whereas the other derivatives of this series displayed between 5-55 µm IC50 values. In antiviral cell based assay, an inverse correlation between the effect of the compounds on cellular viability and their antiviral efficacy emerged with the,3-thiazolidine-4- one moiety bearing compounds -8 exhibiting 68% cellular viability but 35% anti-hcv activty, while the corresponding arylidene derivatives 9-4 displayed 45% cellular viability but 70% anti-hcv activty. We further present a binding interaction analysis of compound 33 within thumb pocket-ii (TP-II) of NS5B with the objective of gaining insight into the compound binding contacts for better inhibitor derivatization. OP 7 IN VITRO SCAVENGING ACTIVITY AND CYTOTOXICITY EFFECT OF GREEN TEA (CAMELLIA SINENSIS) EXTRACTS AGAIN PROSTATE CANCER CELL LINES. SOUMIA LASSED, CLAUDIA DEUS, DJAMILA ZAMA, PAULO OLIVEIRA, FADILA BENAYACHE, SAMIR BENAYACHE UNITé DE RECHERCHE VALORISATION DES RESSOURCES NATURELLES, MOLéCULES BIOACTIVES ET ANALYSES PHYSICOCHIMIQUES ET BIOLOGIQUES (VARENBIOMOL), DéPARTEMENT DE CHIMIE, FACULTé DES SCIENCES EXACTES, UNIVERSITé CONSTANTINE, 5000 CONSTANTINE, ALGéRIE. Prostate cancer has been one of the most frequently diagnosed neoplasis in western countries. Numerous experimental suggest that both dietary and lifestyle factor can act by promoting inflammation and oxidative stress leading to proteins, lipids, DNA damage, associated with prostate cancer initiation and development. Prostate cancer is a suitable target for primary chemopreventive intervention because is a unique malignancy that grows very slowly before symptoms arise. Green tea obtained from the dried leaves of Camellia sinensis plant has been studied extensively for their effect in cancer prevention. It can through their polyphenols antioxidant activity quench ROS and chelae transition metals produced during all the carcinogenesis; however it can also be a source of ROS generation inducing stress and activating apoptotic pathways in cancer cells. In this study, we evaluate the OH. Scavenging capacity of the different green tea extracts (ether, chloroform, ethyl acetate, n-butanol) and their cytotoxicity effect again human prostate cancer cell line, PC-3 and human fibroblasts cell line, BJ using the Sulforhodamine B (SRB) assay. The ether and chloroform extracts showed no scavenging activity on OH., however the butanolic and ethyl acetate extracts observed to have a strong scavenging activity, with IC50 values of 6.7 and 0.57 µg/ml respectively compared to ascorbic acid (positive control), and the half inhibition concentration was 0.3 µg/ml. The SRB assay results of 4 hours treatment obtained showed that the ether extract induce the cell death for both cancer and noncancerous cells at a concentration 50 µg/ml, while the chloroform extract have no effect. The butanolic and ethyl acetate extracts revealed a dose dependent effect in cancer cells. They can inhibit the proliferation of PC-3 cell line with IC50 values of and 36.37µg/ml respectively when the effect was not significant in BJ cell line. The results obtained in the present study suggest that the green tea consumption may prevent from prostate cancer or reduce its development after onset. -63-

65 OP 8 PLASMA GROWTH ARRREST SPECIFIC (GAS6) LEVELS IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS DILVIN GUNEY, AYSIN TULUNAY, FUNDA PEPEDIL, ISIK KAYGUSUZ, CAFER ADIGÜZEL 3, TULIN TUGLULAR, EMEL EKSIOGLU-DEMIRALP 4, FIKRIYE URAS MARMARA UNIVERSITY SCHOOL OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENTS OF HEMATOLOGY, ISTANBUL, TURKEY 3 MEDIKAL PARK HOSPITAL GOZTEPE, DEPARTMENT OF HEMATOLOGY, ISTANBUL,TURKEY 4 MEMORIAL HOSPITAL,TISSUE TYPING AND IMMUNOLGY, ISTANBUL TURKEY GAS6 (growth arrest-specific gene 6) is a vitamin K-dependent protein. Gas6 binds to Tyro3, Axl and Mer tyrosine kinase receptors (TAM receptors). GAS6 is over expressed in various cancers including glioblastoma, lung, gastric, breast, colon, gastric, and ovarian cancer. The objective of this study is to investigate the plasma level of GAS6 in patients with B-Cell chronic lymphocytic leukemia (B-Cell-CLL). B-Cell-CLL patients (grade 0-, according to the classification of RAI), who were not on a drug treatment, were recruited in this study (n= 4, female, 3 male). Their ages were 39 to 79 years (mean= 60.7), and the control group consisted of 4 healthy volunteers (8 female, 6 male), whose age range was 5-78 years (mean= 63.5). EDTA-plasma (platelet poor) was isolated by centrifugation (300 x g) and then human GAS6 ELISA Kit (R&D, Minneapolis, MN, US) was used to assay GAS6 concentration. The concentration of plasma GAS6 in the patient group was ng/ml (mean= 4.85 ± 5.77). In the control group, the range of total plasma GAS6 was between ,8 ng/ml (mean= 6.8±6.8). The concentration of plasma GAS6 in the B-Cell-CLL group was not significantly different than those of the control group (p=0.65). This is a preliminary study with a small group. Future studies will show us whether plasma GAS6 concentrations in patients with CLL are different from the control group or not. Further studies focusing on the molecular mechanism are required to elucidate the actual role of Gas6/ TAM signaling in B-Cell-CLL OP9 THE INVESTIGATION OF ANTIDIABETIC AND IN VIVO ANTIOXIDANT CAPACITY OF FRUITS, BARKS AND LEAVES OF CORNUS MAS L. AYLIN SEPICI DINCEL, ENGIN CELEP, MERAL YUKSEL 3, ERDEM YESILADA FACULTY OF MEDICINE, GAZİ UNIVERSITY, ANKARA DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, UNİVESİTY OF YEDİTEPE, ISTANBUL 3 DEPARTMENT OF MEDİCAL LABORATORY TECHNİCİANS, VOCATİONAL SCHOOL OF HEALTH RELATED SCİENCES, MARMARA UNIVERSITY, ISTANBUL In our country, during our field survey we observed that cornelian cherry (Cornus mas L., Cornaceae), fruits, leaves and bark of branches have been used against diabetes among the country people. In order to evaluate the role of cornelian cherry in the treatment of type- DM, this work had the following aims; to determine the hypoglycaemic effect of cornelian cherry in streptozocin induced diabetes mellitus in rats and to elucidate the mechanism of action of cornelian cherry through evaluating the effects on the serum insulin (ng/ml) concentrations in normal and diabetic animals and as well as on various routine biochemical parameters, AGE (microg/ml), srage (ng/ml) and brain, kidney, liver, heart, tissues of luminol and lusigenin values (rlu/mg tissue) besides serum total antioxidant status (mm). Our study had 9 groups; normoglyceamic control, diabetes, diabetes+reference group, diabetes groups treated with 00 and 00 mg/kg of methanol extraction of fruits, barks and leaves. Another set of study groups were performed for oral glucose tolerance test. Our results revealed that especially leaves (00 mg/ kg) and the fruits (00 mg/kg) have a glucose lowering effects; increasing insulin and total antioxidant status, decreasing AGEs products and could effect the tissue levels of luminol and lusigenin except liver tissue. As conclusion, the above observations have clearly demonstrated that cornelian cherry (Cornus mas L.,Cornaceae) as a folk remedy, exerts effectual hypoglycaemic activity in diabetic animals without inducing apparent toxicity, which confirms the folkloric utilisation. -64-

66 OP 0 SEQUENTIAL INJECTION TECHNIQUE AS A TOOL FOR SAMPLE PRE-TREATMENT IN PHARMACEUTICAL ANALYSIS IVANA ŠRáMKOVá, LUKáš ZAHáLKA, DALIBOR ŠATíNSKý, BURKHARD HORSTKOTTE, HANA SKLENářOVá, PETR SOLICH DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, CHARLES UNIVERSITY,, HRADEC KRáLOVé CZECH REPUBLIC Sequential injection analysis (SIA) is a flow technique based on programmable, bidirectional discontinuous flow. A typical SIA system consists of a multiposition valve, peristaltic or syringe pump, holding coil and a detector, all computer controlled. Solutions of a sample and reagents are aspirated by means of the pump into the connecting holding coil via a specific port of the multiposition valve. After flow reversal towards a detection flow cell, the solutions merge and the signal of the formed reaction product is recorded. The feasibility of SIA makes it an advantageous tool for sample pre-treatment since this step is often tedious and time consuming. Different microextraction methods, both into liquid and onto solid phase, can be performed within a SIA system, as demonstrated here by following novel applications: A. Dispersive liquid-liquid microextraction (DLLME) e.g. in analysis of thiocyanates in human saliva samples (); B. Head-space single-drop microextraction (HS-SDME) for analysis of ethanol in wine (); C. Microextraction by packed sorbent (MEPS) carried out as a sample cleaning procedure prior to HPLC analysis of propranolol in urine. In this work, the benefits and potential of employing SIA in sample pre-treatment, especially regarding the analysis time, reagents, sample and solvents consumption, waste production, automation and simplification, are presented. Acknowledgements The authors gratefully acknowledge the financial support of Zentiva a.s and the Charles UNIVERSITY in Prague project GAUK 40/50/ The work is co-financed by the European Social Fund and the state budget of the Czech Republic. TEAB, project no. CZ..07/.3.00/ Acebal C C, Sklenářová H, Škrlíková J, Šrámková I, Andruch V, Balogh J S, Solich P. Application of DV-SIA manifold for determination of thiocyanate ions in human saliva samples. Talanta 0; 96: 07-. Šrámková I, Horstkotte B, Solich P, Sklenářová H. Automated in-syringe single-drop head-space micro-extraction applied to the determination of ethanol in wine samples. Anal Chim Acta 04; OP DETERMINATION AND PHARMACOKINETICS OF OLANZAPINE IN HUMAN PLASMA BY LC/MS METHOD MEVLUT ALBAYRAK, MEHMET EMRAH YAMAN, ONUR ŞENOL, YUCEL KADIOGLU ATATURK UNIVERSITY FACULTY OF PHARMACY, ERZURUM, TURKEY Olanzapine ( - Methyl-4- ( 4 methyl - piperazinyl ) 0 H thienol [,3 b ] [,5 ] benzodiazepine ), is an atypical antipsychotic drug which is used for the treatment of schizophrenia and bipolar disorder. Several analytical methods in order to determine olanzapine concentration in human plasma samples at therapeutic range could be found in literature. In the present study, a simple, sensitive and rapid liquid chromatography mass spectrometry (LC/MS) method was developed and validated to determine olanzapine in human plasma using irbesartan as internal standard. The validated and proposed method was applied to healthy volunteers for pharmacokinetic study. Extraction of olanzapine from plasma sample was accomplished by a simple liquid-liquid extraction method and the separation of analytes were carried out on a reserved phase C8 column using an isocratic mobile phase mixture and analyzed by MS using positive ion atmospheric pressure chemical ionization and multiple reaction monitoring. The linear concentration range was found as -300 ng/ml. The limit of detection (LOD) and the limit of quantitation (LOQ) were found as 0.8 ng/ml and ng/ml with an acceptable precision, respectively. Inter-day accuracy (relative error) and precision (relative standard deviation) were ranged from.94 to 3.33%, and from.5 to 6.70 %, respectively. The average recovery values of extraction from spiked plasma samples were 94.8 ± 3.%. The validated method has been successfully used to analyze human plasma samples and can be applied to routine clinical studies and pharmacokinetic studies.. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT: Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 996; 4: Cao, J, Zhang, ZJ, Tian, Y, Li, YY, Rui, JZ; Liquid Chromatography-Mass Spectrometry Method for the Determination of Olanzapine in Human Plasma and Application to a Bioequivalence Study. Current Pharmaceutical Analysis 0; 8:

67 OP CLINICAL PHARMACOTHERAPY EDUCATION BY PROBLEM-BASED LEARNING IN CLINICAL PHARMACY COURSES SULE APIKOGLU-RABUS CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY, FACULTY OF PHARMACY, TURKEY In our institution, problem based learning (PBL) has been being performed since 000 at the pharmacy skills laboratory practices of the Clinical Pharmacy course at the 4th year of the education. The students practice basic pharmaceutical care principles through case-based identification and solution of pharmaceutical care issues and therapy monitoring. Surveys questioning the impact of PBL on the students and their attitudes towards the PBL sessions were administered after the whole practice to all of the 4th year students who attended to the full course of the PBL practice. Follow-up surveys questioning the benefits of the PBL sessions while practicing during the Pharmacy Practice courses that took place at the hospital wards, community pharmacies and/or drug industry throughout the 5th year were handled out at the end of the 5th year to the same students. All of the students strongly agreed or agreed that their clinical knowledge improved after PBL sessions. Of the students, 90-97% strongly agreed or agreed that PBL is better than the classical practical and theoretical courses. On the follow-up questionnaires administered at the 5th year 86% of the students strongly agreed or agreed that they used the knowledge, skills and the approach to problem-solving that they earned during the PBL sessions while practicing at the hospital wards; while this rate was 83% for the community pharmacy. The students showed positive attitudes towards PBL that were still present after one-year. OP 3 AN EXAMPLE OF A WORKSHOP ABOUT THE USE OF CREATIVE DRAMA IN PHARMACY EDUCATION FOR DEVELOPMENT OF COMMUNICATION SKILLS OF PHARMACY STUDENTS FILIZ ARIÖZ ÖZDEMIR, GÖKNIL PELIN COŞKUN DEPARTMENT OF ANALYTİCAL CHEMİSTRY, FACULTY OF PHARMACY, MARMARA UNİVERSİTY, ISTANBUL, TÜRKİYE DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, FACULTY OF PHARMACY, MARMARA UNİVERSİTY, ISTANBUL, TURKEY Communication skills and its use is far more important in pharmaceutical profession and these skills can be given to pharmacy students during their education. In recent years, in the field of education and personal development; Creative Drama Method is widely used. This method is based on group work and the individuals of the group, act with a game flow which is a lifestyle, behaviour, concept or an event by using improvization, role playing, theatre and drama technics. The content of this work covers the results of a group work that was done in EPSA (European Pharmaceutical Students Association) Twinnet Project with 5 Serbian and 0 Turkish pharmacy students, a 3 hours of workshop. The first goal of this workshop was to motivate participants to like eachother, increase the group dynamic, preapare the body and the participants for the next stage. In this first stage, games are widely used and this workshop s second stage was the acting stage. The problem or the subject were acted by the participants and creative solutions were expected. In this workshop, the participants were given 4 different subjects and were asked to act them with 5 different groups. Every participant evaluated every groups acts and their feedback were asked. The last stage of this workshop was the evaluation of the whole exercise and the participants were asked to summarize the whole event in few words anonymously. The feedbacks from the participants led us conclude that; -Group individuals friendship, -Learning and comparison of two different country s pharmacy education models and the use of pharmaceutical profession in different areas, 3-Every individual gained experience and creative solutions and they can use these in their further professional life. -66-

68 OP 4 HEALTH PROFESSIONAL STUDENTS KNOWLEDGE ON PHARMACOVIGILANCE (PV) MERI KOLUACIK, ASLI CULDUZ, HANDE SIPAHI 3, CIGDEM KASPAR 4, NAZLI SENCAN YEDITEPE UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF PHARMACY MANAGEMENT AND SOCIAL PHARMACY, FACULTY OF PHARMACY, YEDITEPE UNIVERSITY 3 DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, YEDITEPE UNIVERSITY 4 DEPARTMENT OF BIOSTATISTICS, FACULTY OF MEDICINE, YEDITEPE UNIVERSITY Spontaneous reporting of adverse drug reactions (ADRs) has a critical role on public health. Pharmacovigilance (PV) system tries to minimize the potential health risks, outcomes of medicine consumption for public. The aim the study is to raise the knowledge and awareness of the health care professional students on PV. An education presentaion is prepared by the researchers and approvels and appointments are done via faculty professors. Between February 04 and April 04 trainings have been conducted. The 3rd and 4th class students of the pharmacy, nursing, nutrition and dietetics, physiotherapy and rehabilitation departments have participated. 8 different conference each took 0 minutes and 34 students have participated. A survey was applied, awareness and opinions of the PV before and after the education was measured. The knowledge of PV, reasons for not reporting, appreciated to the education were evaluated. According to results, 50% of students declared that they have never heard PV system. After the training section, 9% of the students reported that PV system/spontaneous reporting is helpful for detection and protection from ADRs. Academic resarchers should not only conduct scientific study but also inform and involve in social interactions so as to promote public health. The results suggest that PV training and education sessions for health care professional students are needed to be increased for the knowledge of PV and to foster positive attitudes toward adverse effects of drugs. -67-

69 -68-

70 POSTER PRESENTATIONS -69-

71 PP 3 THE EFFECT EFFECTS OF COSOLVENTS OF DNA METHYLTRANSFERASE ON MICELLE FORMATION ENZYMES OF AMPHIPHILIC ON AGING-RELATED DRUG AMITRIPTYLINE HUMAN KLOTHO HYDROCHLORIDE GENE EXPRESSION* HASAN TOLGA ÖZÇAM, SINEM GÖKTÜRK DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, GENERAL CHEMISTRY DIVISION, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Several drug molecules such as phenothiazine and benzodiazepine tranquilizers, analgesics, tricyclic antidepressants and nonsteroidal anti-inflammatory drugs display surface activity i.e. amphiphilic behavior (-3). Amitriptyline hydrochloride (AMT) is a pharmacologically active compound and is amphiphilic in nature. It belongs to the family of tricyclic antidepressants and possesses a rigid, almost planar tricyclic ring system and a short hydrocarbon chain carrying a terminal nitrogen atom. In the present study micellization of the amphiphilic drug AMT in the absence and presence of cosolvents have been reported by using conductometric measurements at 98 K. Conductometric measurements were successfully used in determination of critical micelle concentration (CMC) of AMT in aqueous media. The effect of various concentrations of organic solvents such as methanol and ethanol (v/v) on micelle formation of AMP in aqueous solutions has been also studied. From conductivity data the ionization degree (α) and counterion binding parameter (β) have been obtained. It was observed that the presence of cosolvents, diminished the micelle formation of AMT i.e. increased the CMC. Micellization of AMT totally inhibited when cosolvent concentration reached a certain value.. Schreier S, Malheiros S.V.P, de Paula E. Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects. Biochimica et Biophysica Acta 000; 508: Erdinc N, Gokturk S, Tunçay M. A study on the adsorption characteristics of an amphiphilic phenothiazine drug on activated charcoal in the presence of surfactants. Colloids and Surfaces B: Biointerfaces 00; 75: Göktürk S, Var Ü. Effect of pharmaceutically important cosolvents on the interaction of promethazine and trifluopromazine HCl with sodium dodecyl sulfate micelles. Journal of Dispersion Science and Technology 0; 33: Acknowlodgements: This study was financially supported by Research Fund of Marmara UNIVERSITY with the project numbers of SAG-CYLP PP CHEMICAL COMPOSITION AND ANTIMICROBIAL ACTIVITY OF THE ESSENTIAL OIL FROM CULTIVATED SATUREJA HORVATII SILIć (LAMIACEAE) MARINA MILENKOVIC, MIHAILO RISTIC, DMITAR LAKUSIC 3, VIOLETA SLAVKOVSKA 4, BRANISLAVA LAKUSIC 4 DEPARTMENT OF MICROBIOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF BELGRADE, VOJVODE STEPE BELGRADE, SERBIA INSTITUTE FOR MEDICINAL PLANT RESEARCH JOSIF PANCIC, SERBIA 3 INSTITUTE OF BOTANY AND BOTANICAL GARDEN, SERBIA 4 DEPARTMENT OF BOTANY, FACULTY OF PHARMACY, UNIVERSITY OF BELGRADE, SERBIA In this study the chemical composition and antimicrobial activity of the essential oils of Satureja horvatii cultivated plants (Belgrade, Serbia) were characterized. S. horvatii is an endemo-relict species of Montenegro. The essential oils were isolated, from the aerial parts of the plants at different phenological stages, by hydrodistillation and analyzed by GC and GC/MS. Chemical compositions of the S. horvatii oils showed differences between the plants at different phenological stages. The main compounds of the essential oil from plants at the flowering stage were linalool (53.5%), thymol (7.9%), and α-terpineol (8.5%). At the stage of full fruiting the percentage of linalool ( %) and α-terpineol (.8-.3%) increased, while those of thymol ( %) significantly decreased. The antimicrobial activity of tested oils was evaluated against ten standard strains of microorganisms.the working solutions of essential oils (40 μl/ml) were prepared by dissolving the essential oils (EOs) in DMSO and subsequent mixing with Müller Hinton or Sabouraud dextrose broth. The EOs were tested in the final concetration range of μl/ml. All analyzed oils showed the greatest and uniform antimicrobial activity against the yeast (Candida albicans). The essential oil isolated from plant in the flowering stage showed the maximum activity against Staphylococcus epidermidis and Staphylococcus aureus. This oil exhibited moderate activity against the Enterococcus faecalis and weak activity against the other microorganisms. Oils isolated from plants at fruiting stage showed moderate activity against Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa and weak activity against the other microorganisms. Acknowledgement: The authors are grateful to the Serbian Ministry of Science and Technological Development (Project No. 730 and ) for financial support. *This abstract has been presented as poster in Fourth International Meeting on Pharmacy & Pharmaceutical Sciences, Istanbul, Turkey on 8- September

72 PP 3 THE EFFECTS OF DNA METHYLTRANSFERASE ENZYMES ON AGING-RELATED HUMAN KLOTHO GENE EXPRESSION* ELIF ÇAĞLAYAN, KADIR TURAN DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL-TURKEY There are both environmental and genetic factors affecting the aging process. One of the important genetic factors associated with aging is klotho gene. It was shown that Klotho protein encoded by klotho gene has the positive or negative regulatory effects on many metabolic pathways. However, much information about the regulation of klotho gene is not available. In a recently published study, it was reported the results suggesting that the promoter region of human klotho gene could be epigenetically controlled by DNA methylation. Therefore, in this work, it was aimed to reveal the effects of DNMT3A and DNMT3B enzymes on the expression of klotho gene. For this purpose, it was artificially changed the expression level of DNMT3A and DNMT3B in human originated HEK93 cells with sirna transfection or overexpression and investigated by using reporter luciferase gene how klotho gene promoter activity was affected. The results obtained in this research showed that DNMT enzymes have negative regulatory effects on klotho gene promoter organized as a chromatin structure, whereas they are enhancing effect on promoter activity when it was located on plasmid DNA. These results have a great importance to elucidate the functional mechanism of human klotho gene. *This work was supported by a grant from scientific research foundation of Marmara UNIVERSITY (grant number: SAG-C- YLP , 03). PP 4 INVESTIGATION OF THE AFFINITY OF RECOMBINANT SOLUBLE FORM OF HUMAN GLUCAGON RECEPTOR PROTEIN WITH GLUCAGON* ŞULE İBIŞOĞLU, KADIR TURAN DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL-TURKEY The maintenance of the blood glucose level in a narrow range has a vital importance. The human bodies desire blood glucose to be maintained between 70 mg/dl and 0 mg/dl. The significant deviations from these values can cause massive damages in the body. Therefore, the blood glucose level is mainly controlled by particularly insulin and glucagon. Some other factors such as GLP-, GIP, cortisol and growth hormone are also involve in this control. More or less synthesis of glucagon and/or insulin than normal levels in the body or disorders in interactions of these hormones with their receptors lead to a deterioration in blood glucose and ultimately causes type I or II diabetes. The high level of blood glucagon is also important as much as insulin deficiency to diabetes. Therefore, extensive studies are being carried out on glucagon receptor antagonists to block the function of glucagon receptor, having a potential usage in the treatment of diabetes. In this work, we aimed to produce a recombinant soluble form of human glucagon receptor and to reveal the affinity of this protein to glucagon. Therefore, we cloned extracellular domain of human glucagon receptor into the mammalian expression vectors (pcaggs and pcha) and monitored the expression and cellular localization of this proteins in mammalian cells. Immunofluorescence assays showed that, extracellular domain of glucagon receptor is being efficiently expressed in the cells and localized in cytoplasm. The research to reveal the affinity of soluble extracellular domain of glucagon receptor to glucagon by using co-immunoprecipitation and co-localization experiments is going on. *This work was supported by a grant from scientific research foundation of Marmara UNIVERSITY (grant number: SAG-C- YLP , 03). -7-

73 PP 35 THE INVESTIGATION EFFECTS OF OF DNA THE METHYLTRANSFERASE RELATIONSHIP BETWEEN ENZYMES INFLUENZA ON AGING-RELATED VIRUS NS PROTEIN HUMAN AND KLOTHO CELLULAR GENE FACTORS EXPRESSION* WITH YEAST TWO-HYBRID ASSAY* AYŞEGÜL PRINÇAL, KADIR TURAN DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL-TURKEY Influenza A viruses are enveloped viruses classified in Orthomyxoviridae family. These viruses have a genome composed of eight single-stranded, negative sense RNA molecules. NS protein, which is the subject of this work, is encoded on the eighth segment, the smallest segment of the viral genome. It is known that one of the most important functions of the NS protein is to block the host interferon defense mechanisms. In this work, it was aimed to detect of the host cellular proteins related with influenza virus NS protein by using yeast two-hybrid method. Human and avian influenza A virus NS protein was used as a bait and assayed for interaction with the proteins encoded by cdnas of HEK93 cells. Fourteen candidate genes that may be related with the NS protein were determined. Among these genes, the full length sequence of PSMB4 and EEFG gene were cloned in pcha, a mammalian expression vector, to use in research that carried out with mammalian cells in future. The other candidate genes were named as NKG - NKGn. How the specified candidate proteins interact with NS protein and how effect influenza virus replication were not been evaluated within the scope of this work. Elucidation of the action mechanisms of these proteins require detailed studies on each candidate protein, one by one. Data obtained in this works will be base for fighting against viral pathogens. *This work was supported by a grant from scientific research foundation of Marmara UNIVERSITY (grant number: SAG-C- YLP , 03) and The Scientific and Technological Research Council of Turkey (grant number: S58). PP 6 COMPONENTS, ANTIOXIDANT AND IMMUNOSTIMULATORY ACTIVITIES OF HYPERICUM TOMENTOSUM AHMED KABOUCHE, AICHA BOURATOUA, OUASSILA TOUAFEK, MESBAH LAHOUEL 3, SAKINA ZERIZER 4, ZAHIA KABOUCHE UNIVERSITY OF CONSTANTINE, INATAACONSTANTINE, ALGERIA. UNIVERSITY OF CONSTANTINE, DEPARTMENT OF CHEMISTRY, LABORATORY OF THERAPEUTIC SUBSTANCES (LOST), CONSTANTINE, ALGERIA. 3 UNIVERSITY OF JIJEL, FACULTY OF SCIENCES, LABORATORY OF MOLECULAR TOXICOLOGY JIJEL, ALGERIA 4 UNIVERSITY OF CONSTANTINE, FACULTY OF SCIENCES, DEPARTMENT OF BIOLOGY, CONSTANTINE, ALGERIA. The genus Hypericum L. (Clusiaceae) includes numerous species which have been used as medicinal plants for centuries in the treatment of trauma, burns, rheumatism, neuralgia, gastroenteritis, ulcers, hysteria, bedwetting and depression. Pholoroglucinols, isolated from Hypericum species, have reported to possess antidepressant properties. We report here, the isolation of nineteen compounds (a phloroglucinol, flavonoids, phenolic acids, sterols and fatty acids) from the aerial parts of Hypericum tomentosum L. The structures of the identified compounds were established on the basis of physical and spectroscopic analysis, and by comparison with literature data. In vivo and in vitro protective effect of the butanolic extract of H. tomentosum (BEHT) against acute oxidative stress induced by a single dose of 0 mg/kg epirubicin (an anticancer drug) was evaluated in female Wistar rat using kidney and heart cytosolic fraction. Scavenging effect of BEHT, lipid peroxidation (MDA), glutathione (GSH) concentration and Catalase activity were measured. BEHT extract restored the renal and heart functions and clearly shows a protective effect against epirubicininduced oxidative stress. In addition, the immunostimulant potential of the BEHT on the phagocytic activity was measured by the carbon clearance rate test. The BEH exhibited a dose-dependent immunostimulant effect on the reticuloendothelial system. -7-

74 PP 7 DESIGN, SYNTHESIS AND ANTICOAGULANT ACTIVITY OF NEW FLEXIBLE CALIX[8]ARENE SULFONIC ACIDS ZAHIA KABOUCHE, SEIFEDDINE REKKAB, MESBAH LAHOUEL, TAIBI BEN HADDA 3, CAROLINE FELIX 4 UNIVERSITY OF CONSTANTINE, DEPARTMENT OF CHEMISTRY, LABORATORY OF THERAPEUTIC SUBSTANCES (LOST), ALGERIA. UNIVERSITY OF JIJEL, FACULTY OF SCIENCES, LABORATORY OF MOLECULAR TOXICOLOGY,ALGERIA 3 LABORATOIRE DE CHIMIE DES MATéRIAUX, UNIVERSITé MOHAMMED-IER, MOROCCO 4 LABORATOIRE D APPLICATION DE LA CHIMIE à L ENVIRONNEMENT, UMR 5634, UNIVERSITY, FRANCE Calix[n]arenes are macrocyclic molecules, consisting of several phenol units (four to eight) connected via methylene bridges into ortho position with respect to the hydroxy group. They are generally known to possess the properties-ability to complex both metal ions and organic molecules. Functionnalized calixarenes are of particular interest because of their potential uses in complexation electrochemistry, catalysis and in selective enrichment of rare earth metal ions. We report here the synthesis of flexible calix[8]arenes, bearing a propanosulfonic or a butanosulfonic group at the lower ring and the effect of these watersoluble calix[8]arene sulfonic acids by sub-chronic administration on some hematological parameters using blood samples obtained from rat. We investigated whether a change in blood coagulation parameters after natural calixarenes administration in Wistar rats at single dose inhibits platelet aggregation induced by vitamin K or after in vitro incubation of these compounds with rat fresh blood. The investigation of the anticoagulant activity of the synthesized water-soluble calix[8]arene sulfonic acids is justified by the structure activity relationship, which is presented here by the use of POM calculations. PP 8 SYNTHESIS OF NOVEL,3,4-THIADIAZOLE DERIVATIVES FROM L-METHIONINE AND EVALUATION OF THEIR ANTI- INFLUENZA VIRUS ACTIVITY ESRA TATAR, SEDA YALDIZ, İLKAY KÜÇÜKGÜZEL, LIEVE NAESENS MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ISTANBUL, TURKEY REGA INSTITUTE FOR MEDICAL RESEARCH, KU LEUVEN,BELGIUM Influenza viruses are single-stranded, negative-sense RNA viruses that belong to the Orthomyxoviridae family and affect birds and several mammals []. They are categorized as type A, B, and C according to antigenic differences of their nucleoprotein and matrix protein components. Seasonal influenza, also known as the flu, is a highly contagious and acute infection of the upper and lower respiratory tract []. This disease causes substantial morbidity and mortality as well as considerable economic losses during the epidemic periods. Besides, influenza A viruses are notorious for their pandemic potential which is related to reassortment between avian, human and/or swine influenza viruses []. Medications currently used for the prophylaxis and treatment of influenza include the M ion channel blockers (amantadine and rimantadine) and the neuraminidase (NA) inhibitors (oseltamivir and zanamivir) [3]. An important drawback of these antivirals is that, in order to be effective, these drugs must be given within 48 h after onset of symptoms. Besides, oseltamivir and zanamivir are expensive and their synthesis is time-consuming []. During recent years, the emergence of mutant viruses showing resistance to neuraminidase inhibitors (particularly oseltamivir) has been considered as an increasing clinical problem. Whereas antiviral agents play a key role in treatment, influenza prevention mainly depends on vaccination. However, these vaccines require annual updating due to antigenic drift and reassortment of the hemagglutinin (HA) and neuraminidase (NA) genes [4]. Given the drawbacks of current antiviral therapeutics, there is an urgent need for novel influenza virus inhibitors with a unique mode of action., We here present the design and synthesis of a series of novel N-[(S)--[5-(methylamino)-,3,4-thiadiazol--yl]-3-(methylsulfanyl) propyl]benzamide derivatives. Our synthetic protocol yielded the target compounds in five steps starting from L-methionine. All synthesized compounds were checked for purity using chromatographic techniques and elemental analysis; and were characterized by their IR, H NMR and 3C NMR spectral data besides pozitive/negative ion MS/MS (ESI) analyses. Novel,3,4-thiadiazoles were evaluated for antiviral activity against influenza A (HN and H3N) and influenza B virus in Madin- Darby canine kindey (MDCK) cell cultures. The results will be presented in detail. References ] Tintori et.al., Bioorg Med Chem Lett 4 (04) [] Severson et.al., J Biomol Screen 3 (008) [3] Vanderlinden et.al., J Virol 84 (00) [4] De Clercq, Nat Rev Drug Discov 5 (006)

75 PP 9 DEVELOPMENT OF SOME NOVEL THIOUREAS DERIVED FROM,3,4-THIADIAZOLES AND,,4-TRIAZOLES AS ANTITUBERCULAR AGENTS ESRA TATAR, İLKAY KÜÇÜKGÜZEL, Ş.GÜNIZ KÜÇÜKGÜZEL, SEVGI KARAKUŞ, SINEM ÖKTEM-OKULLU, NIHAN ÜNÜBOL, TANIL KOCAGÖZ MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPAŞA İSTANBUL, TURKEY ACIBADEM UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL MICROBIOLOGY, MALTEPE ISTANBUL, TURKEY The data based on WHO s Global Tuberculosis Report 03 [] comprises of.3 million TB deaths, 8.6 million new TB case of which. million are HIV (+) patients. Long-term and relatively low-effective multidrug treatment regimen for TB is not welltolerated moreover severe resistance to first line anti-tb drugs has already been developed. According to the literatüre apprising clinically employed second line antituberculosis drugs; ethionamide, prothionamide, thioacetazone and isoxyl with thioamide and/or thiourea moieties [] and our ongoing efforts [3] to obtain novel thiourea derivatives with antituberculosis activity -[5-(4-aryl)-,3,4-thiadiazole--yl]-3-substituted thioureas, -{3-(methylsulfanyl)--[5-(phenylamino)-,3,4-thiadiazole--yl] propyl}-3-arylthioureas and -[4-aryl]-3-[3-(methylsulfanyl)--(4-phenyl-5-thioxo-4,5-dihydro-H-,,4-triazole-3-yl)propyl] thioureas were synthesized and evaluated against Mycobacterium tuberculosis H37Rv strain. Except for -[5-(4-chlorophenyl)-,3,4-thiadiazole--yl]-3-(4-fluorophenyl)thiourea (KUC06007) and -[5-(4-fluorophenyl)-,3,4-thiadiazole--yl]-3-(4- fluorophenyl)thiourea (KUC0606) with the MIC value of 4 µg/ml each, our compounds showed moderate antituberculosis activity with the MIC values of 8-64 µg/ml. [] WHO s Global Tuberculosis Report 03 [] Nishida et.al, Chem-Biol Interact. 9 (0). [3] Küçükgüzel et.al., Bioorg Med Chem Lett. (00) 703. [4] Küçükgüzel et.al.,eur J Med Chem., 43 (008) 38. PP 0 PREVALENCE OF MYCOPLASMA HOMINIS AND UREOPLASMA UREALYTICUM IN PREGNANT AND NON-PREGNANT WOMEN AND THEIR SUSCEPTIBILITIES TO VARIOUS ANTIBIOTICS YASEMIN ÖZTÜRK, ÖZGE KIZILKALE YILDIRIM, ZEHRA KIPRITÇI, YEŞIM GÜROL, GÜLDEN ÇELIK, MERAL BIRBIR 3, CEM FIÇICIOĞLU DEPARTMENT OF CLINICAL MICROBIOLOGY, YEDITEPE UNIVERSITY HOSPITAL, KOZYATAGI, ISTANBUL, TURKEY DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, YEDITEPE UNIVERSITY HOSPITAL, KOZYATAGI, ISTANBUL, TURKEY 3 DIVISION PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, GOZTEPE, ISTANBUL, TURKEY Mycoplasma hominis and Ureoplasma urealyticum may cause infections of the genitourinary tract in humans. These microorganisms may also cause Bartholin s gland abscess, vaginitis, cervicitis, pelvic inflammation. Furthermore, Mycoplasma hominis may cause meningitis and brain abscess in infants (). Hence, prevalences of both Mycoplasma hominis and Ureoplasma urealyticum were investigated in the 60 pregnant and 56 non-pregnant patients between 8 44 years of age in this study. Identification and antibiotic susceptibilities of Mycoplasma hominis and Ureoplasma urealyticum were performed using AF Genital System (Liofilchem, Italy). The antibiotic susceptibilities of these microorganisms to tetracycline (8 µg/ml), pefloxacine (6 µg/ml), ofloxacin (4 µg/ml), doxycycline (8 µg/ml), erythromycin (6 µg/ml), clarithromycin (6 µg/ml), minocycline (8 µg/ml), josamycin (8 µg/ml) and clindamycin (8 µg/ml) were also investigated using Liofilchem AF genital System. Ureoplasma urealyticum and Mycoplasma hominis were isolated from (8.3%) and 3 (5%) pregnant patients, respectively. Ureoplasma urealyticum was isolated from 9 (6%) non-pregnant patients, but Mycoplasma hominis was not isolated. Mycoplasma hominis resistance in pregnant patients was detected as following; josamycin resistance of 66.6%, tetracycline, erythromycin and ofloxacin resistance of 33.3%. Although in pregnant patients josamycin resistant rate was 8.8% in Ureoplasma urealyticum, ofloxacin and clindamycin resistant rates were 7.3% and 9.09%, respectively. In non-pregnant patients, Ureoplasma urealyticum resistance rates were as follows; josamycin (.%), ofloxacin (.%) and erythromycin (.%). As a conclusion, the prevalence of both Mycoplasma hominis and Ureoplasma urealyticum in pregnant patients was higher than in non-pregnant women..taylor-robinson D, Lamont R. Mycoplasmas in pregnancy. BJOG 0; 8:

76 PP ERADICATION OF ANTIBIOTIC-RESISTANT HIDE MICROORGANISMS USING COMBINED ALTERNATING AND DIRECT ELECTRIC CURRENTS AND ANTIBACTERIAL AGENT MERAL BIRBIR, ESIN YILMAZ, YASAR BIRBIR 3, PINAR CAGLAYAN DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY 3 DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Common use and misuse of antibiotics in human and animals have resulted in the development and spread of antibiotic resistant-gram negative and Gram positive bacteria in different sectors (). Prevalence of antibiotic-resistant bacteria in leather industry may cause health problems for workers. Hence, the aim of the study was to examine resistance of Gram-positive and Gram-negative hide bacteria against amikacin (30 µg), trimethoprim- sulfamethoxazole (5 µg), cefuroxime sodium (30 µg), cefoxitin (30 µg), streptomycin (0 µg), nalidixic acid (30 µg), novobiocin (5 µg), oxolinic acid ( µg), mupirocin (0 µg) and spectinomycin (5 µg) and to determine effective inactivation method which may be used in soak liquor. Mixed culture containing Enterococcus avium, Staphylococcus intermedius, Bacillus lentus, Aerococcus viridans, Enterobacter cloaceae and Pseudomonas putida was used and antibiotic resistance of the mixed culture against the test antibiotics was determined using disc diffusion method. The inactivation effect of a combined electric current treatment using both A direct and.5 A alternating electric currents, followed by.5 g/l of (4% sodium dimethyl dithiocarbamate) treatment on the antibioticresistant mixed culture was examined in a liquid medium containing 3% NaCl and organic substances such as hide-soak liquor. Antibiotic-resistant mixed culture treated with the electric current was completely destroyed after three hours exposure time with.5 g/l of test agent and 7.70 Log0 reduction factor of the mixed culture was detected. In conclusion, electric currents treatment in combination with antimicrobial agent will eradicate antibiotic-resistant microorganisms, hence we suggest using this system in leather industry.. WHO Regional Office for Europe, Tackling antibiotic resistance from a food safety perspective in Europe, 0. Copenhagen: (www.euro.who.int). PP ANTIBIOTIC RESISTANCE OF GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA ISOLATED FROM SALTED HIDES AND THEIR CONTROL USING ANTIBACTERIAL AGENT MERAL BIRBIR, PINAR CAGLAYAN, ESIN YILMAZ DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY Bacterial resistance against various antibiotics may cause important health problems in people working in different industries. Therefore, the goal of the study was to determine resistance of Gram-positive (Enterococcus avium, Staphylococcus intermedius, Bacillus lentus and Aerococcus viridans) and Gram-negative (Enterobacter cloaceae and Pseudomonas putida) bacteria against various antibiotics and to examine their inactivation using commonly applied antibacterial agent in the leather industry. The test microorganisms used in this study were isolated from salted hides and identified with API test kits in previous studies. Antibiotic resistance of the test microorganisms against ceftazidime (30 µg), aztreonam (30 µg), polymyxin B (300 iu) and bacitracin (0.04 iu) were tested using disc diffusion technique. All isolates exhibited resistance against all antibiotics. Then a mixed culture of these antibiotic-resistant microorganisms (07 CFU/mL) was prepared. The test agent containing 4% sodium dimethyl dithiocarbamate was used to inactivate these antibiotic-resistant microorganisms. Fifteen different concentrations of test agent ranging from 0.50 to 7.5 g/l were prepared. The antibacterial effect of different concentrations of the agent against mixed culture was examined using the agar disk diffusion method on nutrient agar containing 3% NaCl. Although inhibition zone diameter of 0 mm belonging to mix culture was observed around the discs containing between g/l of the agent, inhibition zone diameter of 0 mm belonging to mixed culture was observed around the discs containing between g/l of the agent. In conclusion, inhibition zones of antibiotic-resistant test bacteria increased proportionally with the concentrations of antimicrobial agent. -75-

77 PP 3 INACTIVATION OF ANTIBIOTIC-RESISTANT SPECIES BELONGING TO STAPHYLOCOCCUS, BACILLUS, GRACILIBACILLUS AND IDIOMARINA VIA ELECTRIC CURRENT PINAR CAGLAYAN, YASAR BIRBIR, MERAL BIRBIR, CRISTINA SáNCHEZ-PORRO 3, ANTONIO VENTOSA 3 DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, UNIVERSITY OF MARMARA, ISTANBUL, TURKEY DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY, ISTANBUL, TURKEY 3 DEPARTMENT OF MICROBIOLOGY AND PARASITOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF SEVILLA, SEVILLA, SPAIN Salted skins contain proteolytic and lipolytic moderately halophilic bacteria originated from salt, and these microorganisms may cause deterioration of the skins. In this study, we examined antibiotic resistance of protease and lipase positive Staphylococcus saprophyticus, Bacillus pumilus, Bacillus licheniformis, Gracilibacillus dipsosauri and Idiomarina loihiensis against various antibiotics. Resistance of the test isolates against seven different antibiotics was examined using disc diffusion technique. Although all isolates were found to be resistant against amikacin (30 µg), streptomycin (0 µg), spectinomycin (5 µg), polymyxin B (300 iu) and oxolinic acid ( µg), conversely all isolates were susceptible to meropenem (0 µg) and imipenem (0 µg). To prevent growth of antibiotic-resistant bacteria in leather industry and accomplish effective skin preservation, inactivation effect of direct electric current (DC) and alternating electric current (AC) treatments on these test isolates was examined. Four different electric current treatments (0.5A and A of DC and 0.5A and A of AC) were separately applied into brine solutions containing 5% NaCl and mixed culture of test bacteria. Mix culture of test bacteria was killed in min by 0.5A DC and A DC treatment; however, 0.5A AC and A AC treatments eliminated all bacteria respectively in 5 min and 0 min. As a conclusion, AC and DC treatments were found fairly effective to eradicate antibiotic-resistant proteolytic and lipolytic moderately halophilic bacteria in brine curing liquors. Therefore, we highly suggest using this electrochemical disinfection sytem in leather industry. PP 4 ISOLATION AND IDENTIFICATION OF SERRATIA SPECIES ON SALTED HIDES AND SKINS, THEIR SUSCEPTIBILITIES TO VARIOUS ANTIBIOTICS KUBRA ULUSOY, MERAL BIRBIR, PINAR CAGLAYAN INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY Hides and skins may contain pathogenic members of the family Enterobacteriaceae that inhabit animal intestines. The aim of this study was to isolate Serratia species on the salted hides and skins and identify these microorganisms using API 0E test kit (Biomèrieux, France). Proteolytic and lipolytic activities of these microorganisms were investigated and Serratia species susceptibility to different antibiotics were examined. Although four different Serratia species were isolated from the hide samples, six different Serratia species isolated from the skin samples. Serratia species were isolated from three hide and five skin samples. Serratia odorifera, Serratia liquefacicens, Serratia plymuthica and Serratia rubidaea were isolated from both hide and skin samples, but Serratia ficaria and Serratia marcescens were found only on sheep skins. Among the Serratia isolates, Serratia liquefacicens, Serratia rubidaea and Serratia marcescens showed both proteolytic and lipolytic activities. The other Serratia species showed proteolytic or lipolytic activities. Sixty-seven, fifty, eighty-three, thirty-three and thirty-three percent of Serratia species were found to be resistant against ampicilline (0 µg), amoxicillin-clavulanate (30 µg), aztreonam (30 µg), cefoxitin (30 µg) and ceftriaxone (30 µg), respectively. Almost all Serratia species were susceptible to imipenem (0 µg) and meropenem (0 µg), but Serratia ficaria alone was resistant against meropenem. We gather that high frequency of proteolytic, lipolytic and antibiotic-resistant Serratia species on the salted hides and skins may pose health risks to tannery workers and cause hide deterioration. Therefore, effective inactivation treatments should be applied in leather industry to kill pathogenic enteric bacteria. -76-

78 PP 5 CHARACTERIZATION AND ELECTROCHEMICAL INACTIVATION OF ANTIBIOTIC RESISTANT-ACINETOBACTER JOHNSONII ISOLATED FROM SALTED SHEEP SKINS CAN AKPOLAT, YASAR BIRBIR, MERAL BIRBIR 3, ANTONIO VENTOSA 4, PINAR CAGLAYAN, CRISTINA SáNCHEZ-PORRO 4 INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY ISTANBUL, TURKEY 3 DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY 4 DEPARTMENT OF MICROBIOLOGY AND PARASITOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF SEVILLA, SEVILLA, SPAIN Lipolytic halophilic bacteria on salted skins may cause production of unevenly finished leathers. Hence, the prevalence of lipolytic moderately halophilic Acinetobacter johnsonii on the salted sheep skins, its phenotypic characteristics and resistance against various antibiotics were examined. Eleven isolates of Acinetobacter johnsonii were isolated from the two skin samples and characterized with comparative partial 6S rrna gene sequence analysis. Acinetobacter johnsonii grew in the media containing 3-5% (w/v) NaCl and between ph 7 and 9. This microorganism was non-motile, Gram-negative and aerobic rod. It showed positive catalase, negative oxidase reactions, produced NH3 from peptone and hydrolysed Tween 80. HS and indole were not produced and gelatin was not hydrolysed. This isolate was resistant against amikacin (30 µg), tobramycin (0 µg), kanamycin (30 µg), streptomycin (0 µg), aztreonam (30 µg), gentamicin (0 µg), but susceptible to imipenem (0 µg), trimethoprim/sulfamethoxazole (5 µg) and piperacillin/tazobactam (0 µg). Five, three and one minute of A direct electric current treatment were enough to exterminate Acinetobacter johnsonii in the treatment media containing nutrient broth with 3% NaCl, nutrient broth with 5% NaCl and only 5% NaCl, respectively. Ten, five and one minute of A alternating electric current treatment were enough to annihilate Acinetobacter johnsonii in the treatment media containing nutrient broth with 3% NaCl, nutrient broth with 5% NaCl and only 5% NaCl, respectively. In conclusion, direct and alternating electric currents were effective treatment methods to exterminate antibiotic-resistant Acinetobacter johnsonii in leather industry. PP 6 STRUCTURE-ACTIVITY-RELATIONSHIP ON MONOAMINE OXIDASE CATALYZED OXIDATION OF SUBSTITUTED BENZYLAMINES: COMPETING PROTON/HYDRIDE TRANSFER MECHANISMS MEHMET ALİ AKYÜZ, VİLDAN ENİSOĞLU ATALAY, SAFİYE SAĞ ERDEM MARMARA UNIVERSITY CHEMİSTRY DEPARTMENT GÖZTEPE ISTANBUL USKUDAR UNIVERSITY DEPARTMENT OF BİOENGİNEERİNG ÜSKÜDAR ISTANBUL Monoamine oxidase A and B enzymes catalyze the oxidation of neurotransmitter amines and regulate their level. MAO inhibitors are used in the treatment of depression, Parkinson and Alzeimer. This study aims to enlighten the chemical steps of MAO catalyzed amine oxidation because it is crucial for rational design of new selective drugs for the treatment of neurological disorders. As a continuation of our previous computational studies (-3) here we focus on whether MAO-A and MAO-B may have the same or different mechanisms by including their active site aminoacids in the calculations. Oxidation of p-x benzylamines by MAO-A and MAO-B was modelled with quantum chemical DFT method at the ONIOM(B3LYP/6-3+G(d,p):PM6) level and semiempirical PM6 methods. Interestingly, for MAO-A, substituents showed two opposing trends: Log of calculated rate constants of p-x=och3, H, F, CH3, NO, CF3 exhibits a (+) linear relationship with the log of experimental rate constants (R=0.893), which is in line with the proton transfer mechanism. On the contrary, p-x=br, Cl, OH, F, CH3, N(CH3)) exhibit a relationship with a (-) slope, supporting the hydride transfer mechanism. These results suggest that two competing mechanisms are possible for MAO-A monitored by the electronic nature of the substituent. We acknowledge TÜBİTAK for financial support of project: KBAG-3Z66 References. Erdem S. S., Karahan Ö., Yıldız İ., Yelekçi K., Org. Biomol. Chem. 4, 646 (006).. Atalay V. E., Erdem S. S., Computational Biology and Chemistry 47, 8 (03). 3. Akyüz M. A., Erdem S. S., J. Neural Transm. 0, 937 (03). -77-

79 PP 7 IMPROVING ANTIPROLIFERATIVE EFFECT OF SIROLIMUS ON HUMAN T-CELLS USING FUSOGENIC LIPOSOMES HADI VALIZADEH, PARVIN ZAKERI-MILANI, SAEED GHANBARZADEH FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Fusogenic liposomes are unique delivery vehicles capable of introducing their contents directly and efficiently into the cytoplasm. The objective of this study was to evaluate the potential of fusogenic liposomes containing Sirolimus to improve its antiproliferative effect on T- lymphocyte cells. Conventional liposomes containing Sirolimus were prepared from Dipalmitoylphosphatidylcholine (DPPC) and cholesterol using the modified ethanol injection method. To prepare fusogenic liposomes, dioleoylphosphatidylethanolamine (DOPE) was added to the conventional liposome formulation. The liposomes were characterized by their size, zeta potential, encapsulation efficiency percent (EE%) and chemical stability during 6 months. The in vitro release of liposomes, antiproliferative effect and liposome uptake of both types of liposomes with optimized formulations were studied on human T-lymphocyte cells employing the MTT assay and fluorescein isothiocyanate-loaded liposomes. The particle size of the liposomes was evaluated between 38 and 650 nm and mean zeta potential was in the range of to mv. The average EE% of the prepared conventional and fusogenic liposomes were 76.9 % and 80.5, respectively. Liposomal formulations released only 0-0 % of encapsulated drug without any burst effect. In vitro immunosuppressive evaluation on T-cells showed that fusogenic liposomes have the best antiproliferative effects and uptake on T-lymphocyte cell compared to the conventional liposomes. Our results indicated that fusogenic liposomes can be useful carriers for improving the inhibition of T-cell proliferation. PP 8 EFFECT OF OCCUPATIONAL EXPOSURE TO AflATOXINS IN BAKERY WORKERS NIMET EMEL LÜLECI, SEHER KARSLI ÇEPPIOĞLU, TUĞÇE KOÇ, YAŞAR KESKIN, TÜRKAN YURDUN DEPARTMENT OF PUBLIC HEALTH, SCHOOL OF MEDICINE, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, HAYDARPASA-ISTANBUL/ TURKEY Aflatoxins (AFs) are secondary metabolites produced by certain Aspergillus spp. in particular A. flavus and A. parasiticus. AFs (B, B, G and G) are all toxic, mutagenic and carcinogenic compounds and they are major risk factor for hepatocellular carcinoma. Aspergillus spp. grows on grains and other agricultural crops; therefore, ingestion of contaminated foods represents the main route of entry of AFs to the body. Occupational exposure to AFs occurs by inhalation of flour dust generated during the handling and processing of contaminated crops. In this study, AFs exposure in bakery workers was investigated with urinary AF metabolite levels. AFs were isolated from urine using immunoaffinity clean-up followed by derivatization with trifluoroacetic acid and reversed-phase liquid chromatography with fluorescence detection. The isocratic mobile phase consisted of water (5% acetic acid):methanol:acetonitrile (64:8:8). The overall time of analysis was lower than 5 min. for AFs. AFBa (corresponding to AFB) was detected in four (6.45%) of 6 human urine samples examined. However, this study needs to extend in order to understand the relation between the AFs exposure and AF levels in human urine. This work was supported by Research Foundation of Marmara UNIVERSITY (SAĞ-A ). -78-

80 PP 9 DETERMINATION OF LEAD, NICKEL, COBALT AND CHROMIUM LEVELS IN COSMETIC PRODUCTS ZERRIN GÜNGÖR, HANDE SIPAHI, MOHAMMED CHAREHSAZ, BUĞRA SOYKUT, ONUR ERDEM, AHMET AYDIN YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF TOXICOLOGY GULHANE MILITARY MEDICAL ACADEMY, DEPARTMENT OF TOXICOLOGY Evidence of the use of cosmetics has been found in civilization as early as ancient Mesopotamia. Cosmetics are still much preferred by both men and women and have quite a large market share. However, modern cosmetics may contaminated by potentially toxic elements and heavy metals (). The aim of this study was to investigate the concentration of Pb and allergen metals such as Ni, Co and Cr in the most commonly used brands of makeup products, body lotions and nail polish in Turkey. Heavy metal levels were determined by atomic absorption spectrophotometer in total 48 cosmetic products purchased from local markets and large cosmetic stores in Istanbul. According to our results, the levels of Ni generally lower than 0 μg/g, the FDA limit for impurities in color additives (). The highest concentration of Pb was found in pink color of eye shadow compared to three other colors of same brand. Although Cr, Co, Ni and Pb are prohibited by Turkey regulation (3), it was determined that all samples generally include these metals. Despite skin penetration with cosmetic substances is negligible, local effects such as irritation, sensitization, allergy or photoreaction may occur. As a result, althouhg removal of these metals from cosmetics after manufacture is not possible, careful selection of the raw material can improve the quality of the products.. Volpe, M., Nazzaro, M., Coppola, R., Rapuano, F. and Aquino, R. 0. Determination and assessments of selected heavy metals in eye shadow cosmetics from China, Italy, and USA. Microchemical Journal, 0 pp Cosmetic Legislation, TC Sağlık Bakanlığı, Kozmetik Yönetmeliği, 006, Accessed January 03, 3. FDA, Summary of Color Additives Listed for Use in the United States in Food, Drugs, Cosmetics, and Medical Devices, Color Additives Approved for Use in Cosmetics, Part 73, Subpart C: Color Additives Exempt from Batch Certifi cation, 007, Accessed September 03, PP 0 PREPARATION AND CHARACTERIZATION OF THE SKIN CARE PRODUCTS BEARING NIOSOME ENCAPSULATED AESCINE LEMAN CELİK SUREN, NEFISE ÖZLEN ŞAHIN MERSIN UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Aescine, a triterpen saponine mixture, has been used in pharmacy and MEDICINE due to its various therapeutic effects. Recently, aescine has been used in some cosmetic products such as shampoos, body wash foams or skin care products (- 3). Niosomes are non-ionic vesicules prepared employing nanotechnology. Based on the nature of their structure, they can be used to formulate both lipophilic and hydrophilic active substances and allow to obtain the desired effect upon topical administration. Also, they provide targeting and controlled release of active substance. In this project, skin care products of aescine were prepared following its encapsulation in niosomes by nanotechnology and then, in vitro characterization studies including the cell culture test for biological activity were carried out. In conclusion, it was determined that it s possible to obtain optimum cosmetic potency without any significant irritation reaction with aescine encapsulated niosomal skin care products.. Ulbricht C, Tiffany N, Boon H, Basch E. Horse Chestnut. Journal of Herbal Pharmacotherapy. 00; ():

81 PP HIGH GLUCOSE POTENTIATES COLLAGEN-STIMULATED PLATELET AGGREGATION AND APOPTOSIS AZIZE SENER, NAZLI GUL ALTINDIS, OZGE DOGAN, OZGE CEVIK FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, MARMARA UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, CUMHURIYET UNIVERSITY, SIVAS, TURKEY Diabetes mellitus (DM) is associated with various cardiovascular diseases, including platelet hyperactivity, which are major causes of morbidity and mortality in DM. Hyperglycemia stimulates platelet function. However, the effect of acute high glucose on platelet apoptosis is not yet clearly defined. The aim of the present study was to examine effects of acute short-term high glucose on platelet aggregation and apoptosis (Ca(+) mobilization, caspase 3 activation, and Bcl- protein levels) in resting or collagen-stimulated platelets. Washed platelets were incubated for h with 5 mmol/l or 5 mmol/l D-glucose in the presence or absence of collagen. After incubation, mitochondrial reactive oxygen species production (mros), cytosolic Ca(+) concentration, caspase 3 activity and Bcl- protein level were analyzed by fluorometer or ımmunoblotting. Incubation of collagen- stimulated platelets with high glucose caused increases in platelet aggregation, cytosolic calcium concentration, mros level, caspase 3 activity (p<0.05). In addition to that, high glucose significantly reduced Bcl- levels compared to the control group (p<0.05). In resting platelets, it had no significant effects on cytosolic Ca(+) concentration and apoptosis signals. As a result, platelet aggregation, mitochondrial oxidative changes and apoptosis signaling pathway are induced by high glucose in the presence of collagen. High glucose alone does not affect platelet survival in resting platelets. These findings can provide novel therapeutic targets for DM thrombotic complications. PP EFFECT OF INTERLEUKIN β ON PLATELET APOPTOSIS AZIZE SENER, GÖZDE EGEMEN, DERYA OZSAVCI, OZGE CEVIK FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, MARMARA UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, CUMHURIYET UNIVERSITY, SIVAS, TURKEY Platelets are essential for hemostatic process, but they also play an important pro-inflammatory role. They are rich sources of chemokines, cytokines, and growth factors that are packaged in storage granules. After platelet activation, these mediators influence wound repair, and vascular remodeling by signaling target cells and inducing leukocyte accumulation. One of these cytokines is interleukin- beta (IL-β) (). It induces apoptosis in several cell types. However, its effect on platelet apoptosis is unknown. This study investigated the effect of IL-β on induction or inhibition of apoptosis in blood platelets. As indicators of apoptosis, phosphatidylserine translocation, mitochondrial membrane potential and caspase-3 activity were detected in ADP activated platelets. Platelets incubated with ADP (0µM) and ADP plus recombinant IL- β (0 ng/ml ) at 37 C for 30 min. Apoptotic cells were stained with Annexin-V-FITC for phosphatidylserine translocation and JC- dye for mitochondrial membrane potential. They were analyzed by flow cytometry. Interleukin- β induced increases in phosphatidylserine translocation and caspase-3 activity mediated ADP. Mitochondrial membrane potential did not change after IL- β treatment in our in vitro conditions. These results suggest that IL- β can induce apoptosis via death receptor pathway in ADP activated platelets and may contribute to thrombocytopenia associated with inflammation..lindemann S, Tolley ND, Dixon DA Mc Intyre TM, Prescott SM,. Zimmerman GA, Weyrich AS. Activated platelets mediate inflammatory signaling by regulated interleukin, The Journal of Cell Biology, 54: ,

82 PP 3 EXPRESSION OF ADIPONECTIN RECEPTORS IN PANCREAS OF HIGH-FAT FED RATS AZİZE SENER, OZGE DOGAN, NAZLI GUL ALTİNDİS, OZGE CEVİK FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, MARMARA UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY, BİOCHEMİSTRY DEPARTMENT, CUMHURİYET UNIVERSITY, SİVAS, TURKEY Obesity is strongly associated with insulin resistance. Adipose tissue produces small molecules called adipokines, which are important in modulating glucose, lipid metabolism. Adiponectin is a adipokine and promotes insulin sensitivity, decreases inflammation and promotes pancreatic beta cell survival (). Adiponectin acts through two receptors, AdipoR and AdipoR. This study investigated the effects of high fat (HF) diet-induced changes on the serum adiponectin levels and expression of adiponectin receptors (AdipoR and AdipoR) in pancreas. Female rats were fed standart diet or HF (46% energy from fat) for weeks. We used sunflower oil, the rich from n-6 polyunsaturated fatty acids (PUFA), as fat source. HF diet increased body weight and visceral adipose tissue, slightly increased glucose levels and decreased serum adiponectin levels. We observed the marked protein expression of adiponectin receptors AdipoR and AdipoR in rat pancreas. In HF fed rats, protein expression of pancreatic Adipo R and Adipo R significantly increased. In conclusion, pancreas cells is sensitive to circulating adiponectin levels. Protein expression of adiponectin receptors in pancreas was up-regulated by HF induced low adiponectin levels..wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G, Wheeler MB. Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol Chem. 00 9;85(44): PP 4 ANTIDERMATOPHYTIC AND ANTIMYCOBACTERIAL ACTIVITY OF MANNICH BASES OF KOJIC ACID WITH CYTOTOXICITY EVALUATION MUTLU AYTEMİR, GÜLŞAH KARAKAYA, BERRİN ÖZÇELİK HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY GAZİ UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMECEUTİCAL MİCROBİOLOGY The introduction of new oral therapies have improved cure rates of cutaneous mycoses however approximately 0% of the patients with oncomycos are still failing on antifungal therapy (). Tuberculosis caused by Mycobacterium tuberculosis is the leading bacterial cause of death (). The increasing numbers of drug resistance and the lack of sufficient chemical diversity to existing azole antifungal represent a serious challenge for tuberculosis control. Previously, Mannich bases of hydroxypyrone derivatives were synthesized in our laboratory and examined for their anticonvulsant, antibacterial, antifungal and antiviral activities with cytotoxicity (3). Hence we will present the results of a preliminary evaluation of cytotoxicity, antidermatophytic and antimycobacterial activities of thirteen Mannich bases of kojic acid. In vitro antidermatophytic activity of the derivatives against Microsporum gypseum, Trichophyton mentagrophytes var. erinacei and Epidermophyton floccosum will be screened as broth microdilution method. Cytotoxicity will be evaluated by the maximum non-toxic concentrations (MNTCs), which was determined by the method described previously based on cellular morphologic alteration. As for antimycobacterial activity the breakpoint concentrations of the compounds will be determined against standard strains of M. tuberculosis H37Rv and M. avium (ATCC 5769) clinical isolated strains by using the colorimetric resazurin microtiter assay (REMA). This study is supported by TÜBİTAK. Project no: SBAG-3S57. References. Peres, N.T.A., Maranhao, F.C.A, Martinez-Rossi, N.M. Dermatophytes: host-pathogen interaction and antifungal resistance, An Bras Dermatol 00; 85(5): Pavan F.R. et al., Evaluation of anti-mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae), Quim. Nova 009; 3(5): Karakaya, G., Aytemir, M.D., Özçelik B., Çalış, Ü., Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid derivatives, J. Enz. Inh. Med. Chem. 03; 8(3): PP 5 IMPLEMENTATION OF MEDICATION RECONCILIATION AND MEDICATION REVIEW SERVICES CONDUCTED BY PHARMACIST IN HOSPITALIZED ELDERLY PATIENTS AYSU SELCUK, MESUT SANCAR, BETUL OKUYAN, REFİK DEMİRTUNÇ, FİKRET VEHBİ IZZETTİN DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY-FACULTY OF PHARMACY, ISTANBUL, TURKEY DEPARTMENT OF INTERNAL MEDICINE, HAYDARPASA NUMUNE TRAİNİNG AND RESEARCH HOSPİTAL,ISTANBUL, TURKEY The aim of the present study is to implement medication reconciliation service conducted by pharmacist at admission to hospital and retrospectively drive medication review to detect possible medication related problems in hospitalized elderly patients. This study was conducted in internal MEDICINE ward of a research and training hospital between April 4 and June 30, 04. Patients hospitalized with any reason during the present study were eligible if they were 65 years or older, utilized chronically at -8-

83 least one medication before hospitalization, and accepted to participate to the present study. Pharmacist conducted medication reconciliation services to determine any discrepancies between a patient s home medication and medications prescribed on admission to the hospital within 48 hours of admission. Estimated glomerular filtration rate was calculated by The Cockcroft- Gault Equation. Retrospectively inappropriate medication utilization and medication related problems during hospitalization were also investigated by using Beer s Criteria Update 0 and PCNE DRP (Pharmaceutical Care Network Europe Drug Related Problem) Classification V6.; respectively. The frequency of potentially high-risk medication utilization was also determined. The physician s acceptance rate of pharmacist s recommendation during medication reconciliation and medication review was also assessed. A total of a hundred hospitalized elderly patients (mean age, 76,58 ± 8,36 years; 53 female / 47 male) included in the study. The most frequently seen comorbidity was hypertension. When evaluated patients body mass index, it was found that 53% of them were more than normal levels. Estimated glomerular filtration rate was found less than 30 ml/min in 30% of them. 66% of the patients did not take any support for medication utilization. The number of medication usage was increased in 44% of them after hospitalized. Of them, 89% were exposed to polypharmacy and 39% of patients were exposed to hyperpolypharmacy. Inappropriate medication utilization was found in % of them according to Beer s criteria. High-risk medication utilization was found in 74% of them and low-molecular-weight heparin was found the most common utilized highrisk medication in study population. A total of 89 medication related problems were determined and the most frequently determined medication related problems were drug not taken/administered at all and drug-drug interactions; respectively. It was determined clinically significant drug- drug interactions in 36% of them. In medication reconciliation process, 86% of 309 medication discrepancies were found as unintended discrepancies among 74 patients. The physician s acceptance rate of pharmacist s recommendation during medication reconciliation and medication review was found as 84%. As a conclusion, it was found that medication related problems and inappropriate medication utilization at admission would be prevented by medication reconciliation and review services driven by pharmacists. PP 6 DETERMINATION OF CYPC9 POLYMORPHISMS, ADVERSE DRUG REACTION, AND MEDICATION ADHERENCE IN PATIENTS UTILIZED SELECTIVE SEROTONIN REUPTAKE INHIBITORS SEMANUR DENIZ, MESUT SANCAR, BETUL OKUYAN, PINAR ATA, OZLEM BINGOL OZAKPINAR 3, ANIL TALAS 4, TUFAN GUNES 4, MECIT CALISKAN 4, FIKRET VEHBI IZZETTIN CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY DEPARTMENT OF MEDICAL GENETICS, MARMARA UNIVERSITY- FACULTY OF MEDICINE, ISTANBUL, TURKEY 3 DEPARTMENT OF BIOCHEMISTRY, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY 4 DEPARTMENT OF PSYCHIATRY, HAYDARPASA NUMUNE TRAINING & RESEARCH HOSPITAL, ISTANBUL, TURKEY The aim of the study is to determine cytochrome P-450 C9 (CYPC9) enzymes polymorphisms, adverse drug reactions, and medication adherence in patients who were diagnosed with major depression utilized selective serotonin reuptake inhibitors. This study was conducted in outpatient psychiatry clinic between December 0 and May 03. The patients were eligible if they used selective serotonin reuptake inhibitors (sertraline, citalopram or escitalopram) at least four week and were 8 years and older. Demographic and clinical data were collected from the patients who accepted to participate to the present study. Polymorphisms were determined from genomic DNA by using Real-Time Polymerase Chain Reaction method. Toronto Side Effects Scale was used to determine the adverse drug reaction () and also in the four items (Morisky, Green and Levine) adherence scale was used to assess patients medication adherence (, 3). Fifty-three major depression patients (mean of age: 33.5 ±.9 years old; male/female: 7/46) were included in this study. The patients were treated with sertraline (58.5%), escitalopram (37.7%), citalopram (3.8%). The most common adverse drug reactions that patients reported were drowsiness/ daytime somnolence (54.7%), malaise or fatigue (43.4%), sweating (43.4%), nausea (4.5%) and dry mouth (4.5%). Only nine (7%) patients were found high adherent to their medication. When evaluating the CYPC9 polymorphisms of patients, 37.7%, 4.5% and 0.8% of the patients were classified as intermediate, extensive and ultra-rapid metabolizers; respectively. Allele frequencies of CYPC9*7 and CYPC9* was calculated as 4.5% and 7.4%; respectively. When compared with individuals with extensive metabolizers, it was found higher adverse drug reaction scores in individuals with intermediate phenotype and lower adverse drug reaction scores in individuals with ultra-rapid phenotype, but these differences were not statistically significant (p>0.05). Although patients with lower adverse drug reaction scores were more adherent to their medications; no statistically significant difference were found between the groups (p>0.05). The fact that the differences between the groups are not statistically significant is considered to arise from the number of the patients conducted in the study. Largescale studies are needed to put forth more clearly the differences of adverse effects and treatment results depending on the pharmacogenetic characteristics. According to our study population which have a greater rate of intermediate metabolizer and low adherence rate, we believe that the patient counselling and monitoring is critical for these patients on antidepressant therapy. - Vanderkooy JD, Kennedy SH, Bagby RM. (00). Antidepressant side effects in depression patients treated in a naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine. W Can J Psychiatry, 47 (74-80), - Morisky DE, Green LW, Levine DM. (986). Concurrent and Predictive Validity of a Self- Reported Measure of Medication Adherence and Long-Term Predictive Validity of Blood Pressure ControlMed Care, 4(): Yılmaz S. (004). Medication side effects and medication adherence in psychiatric patients Master of Science Thesis in Turkish. Univeristy of Istanbul, Health Science Institute İstanbul, (Consultant: Assoc.Prof.Dr. Sevim Buzlu). -8-

84 PP 7 ASSESSMENT OF KNOWLEDGE AND ATTITUDE TOWARDS OSTEOPOROSIS AMONG WOMEN ATTENDING COMMUNITY PHARMACY SETTINGS BETUL OKUYAN, MEHMET ALI ACAR, BERRA KILIC, HALE KÖME, ERLIASA BAMI, MESUT SANCAR CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the study was to assess the knowledge and attitude about osteoporosis, in women 40 years and older who attend community pharmacy for any reason. This study was carried out within community pharmacies from March to May 04 among subjects who came to community pharmacy for any reason and accepted to participate after being informed about the present study. Participants included were women of 40 years and older that had never been diagnosed with osteoporosis before, and that had not been using any antiresorptive agent. Subjects demographic and clinical data has been collected. The knowledge about osteoporosis was assessed by the OKAT - Osteoporosis Knowledge Assessment Tool (). OKAT was scored from 0 to 0. The study was performed on a total of 9 subjects of a mean average age of 54.6 ± 9.05 years. Of the subjects, 66.% possessed drinking milk and consuming dairy products habits. Meanwhile about 85.0% used to drink more than cups of tea/coffee daily. In addition 83.8% of the participants had smoking habit, while 89.6% were aware that smoking can contribute to osteoporosis. About 95.8% used to drink alcohol once in a while when about 65.0% accepted they knew that alcohol effects bone integrity. It was noticed that BMI (Body Mass Index) of the subjects showed that approximately 7.0% of them were overweight, with 65 participants being obese. Of them, 77.5% tended to think that physical activity is beneficial against osteoporosis, while only 53.% of the subjects accepted to be active in exercising. It was revealed that 74.5% knew some symptoms caused by osteoporosis and 87.0% were conscious that osteoporosis increases the risk for fractures. The total mean score of OKAT was calculated as.9±3.7. At the end of the study it was concluded that the biggest part of women included were aware of osteoporosis as a problem and its high incidence in women. Still more information and advice concerning lifestyle changes, prevention measures and treatment of osteoporosis must be provided, as well as encouragement to modify attitude towards osteoporosis with these changes as soon as possible in order to get less affected by this disorder.. Winzenberg TM, Oldenburg B, Frendin S, Jones G. The design of a valid and reliable questionnaire to measure osteoporosis knowledge in women: the Osteoporosis Knowledge Assessment Tool (OKAT). BMC Musculoskelet Disord. 003 Jul 4;4:7. PP 8 THE ROLE OF PHARMACIST IN DETECTING ANGIOTENSIN CONVERTING ENZYME INHIBITORS INDUCED DRY COUGH AT COMMUNITY PHARMACY SETTING GONCA CÖMERT ATALAY, MESUT SANCAR, BETUL OKUYAN, SULEYMAN ATALAY, FIKRET VEHBI IZZETTIN CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY DEPARTMENT OF SURGERY, HAYDARPASA NUMUNE EDUCATION AND RESEARCH HOSPITAL, ISTANBUL, TURKEY The aim of this study is to determine role of pharmacist in detecting angiotensin converting enzyme (ACE) inhibitors induced dry cough at community pharmacy setting. The study was conducted between January 0 and June 30, 03 at a community pharmacy located in Istanbul. The patients were eligible for the present study if they were 8 years and older, came to community pharmacy for any reason, used ACE inhibitors at least four weeks, accepted to participate after information regarding aim and method of the study. The demographic and clinical data of the patients were collected. The knowledge and attitude about ACE inhibitors were assessed at baseline. If the patients had a dry cough complaint, the pharmacists referred these patients to physicians for further diagnosis and treatment. The changes after all patients who had a dry cough, referring to the physicians by the pharmacist, were questioned after a month by telephone call. Leicester Cough Questionnaire (LCQ) was applied to patients who had dry cough to assess the effect of ACE inhibitors induced dry cough on patients quality of life (). The LCQ was scored from 3 to. Among 70 patients used ACE inhibitors, 56% of patients were female and the mean age of the patients was 58.5±0.7. Among 70 patients, 84% of them did not know the possible adverse drug reaction related to use of ACE inhibitors. In 6 patients out of a total of 70 patients had dry cough complaint while using ACE inhibitors. It is found that 8% of patients who had dry cough did not know that dry cough could be related to ACE inhibitors utilization. The mean total score of LCQ was calculated as 4.40 ( ) in these patients. When evaluating attitude of patients towards dry cough, %85 of them had previously used different medications to eliminate their dry cough complaint. In 4% of them who had dry cough complaint during the therapy with ACE inhibitors and visited the physician after pharmacist consultation, their physician substituted the ACE inhibitors with other agents. However, only 54% of them reported that their dry cough complaint has been relieved after medication modification by their physician. Pharmacists may take more professional responsibility in patients under treatment of ACE inhibitors to eliminate medication related problems, which could be resulted in improvement in patients quality of life.. Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 003 Apr;58(4):

85 PP 9 ASSESSMENT OF PATIENTS KNOWLEDGE AND ATTITUDE TOWARDS METHOTREXATE UTILIZATION HATICE IKRA DUMLU, BETUL OKUYAN, MESUT SANCAR, FIKRET VEHBI IZZETTIN CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of this study is to retrospectively determine the knowledge and attitudes of patients towards methotrexate utilization. A retrospective descriptive study was conducted in rheumatology clinic of a training and research hospital. The patients were eligible for the present study if they were 8 years and older, and accepted to participate after being informed about the present study, using methotrexate for at least four weeks. The questionnaire designed by investigators was applied to patients to assess knowledge and attitudes of patients towards methotrexate utilization. Among 50 participants, 7% of them were female and the mean age of the patients was 5.76 ±.90. The most of the patients were married and had a low education level. When evaluating usage of methotrexate, thirty-eight participants utilized orally, while twelve of them used parenteral dosage form. Most of them utilized methotrexate once a week and more than six months along. In the study 5% of them were not declared correctly a reason for administration of methotrexate and 36% of them did not know what to do if they missed a dose of methotrexate. Most of them (96%) did not know anything about adverse effect of methotrexate. Among nine of fifty patients, who had an indication for contraception, it was determined that 89% of them did not use any contraception method during treatment with methotrexate. Of all participants, 8% used folic acid concurrently with methotrexate treatment. As a conclusion, it was found that participants of the present study have poor knowledge and attitudes towards methotrexate utilization. Pharmacists could be involved in management of patients treated with methotrexate by providing patient education and monitoring. PP 30 EVALUATION OF DRUG BURDEN INDEX AND MEDICATION UTILIZATION IN GERIATRIC PATIENTS AT COMMUNITY PHARMACY MESUT SANCAR, IREM GIRGIN, AYSU SELCUK, SEONKYEONG YANG, FIKRET VEHBI IZZETTIN, BETUL OKUYAN CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the present study was to evaluate medication utilization including determination of polypharmacy and patients knowledge about medication, assessment of physical risk in medication utilization and evaluation of drug burden index among geriatric patients. This study was conducted in community pharmacy located in Canakkale, Turkey between July and August 0. Patients were eligible for the present study if they were 65 years old or older, used at least one medication at least four weeks, they did not take any support for medication utilization, and accepted to participate the present after get required information regarding the aim and method of the study. Patients demographic data and clinical data were collected. Medication utilization physical risk assessment has been evaluated by using sub-scale developed by Lubinga et al. (). Patients medication knowledge and drug burden index have been also evaluated. Of the 00 geriatric patients, 5.5% were years old and 5% of them were females. Of them, 84% were exposed to polypharmacy and 4% of patients were exposed to hyperpolypharmacy. DBI score has been calculated in a total of seventy-five patients. The DBI scores were between 0- in sixty-six patients and were more than one in 9 patients. Of them, 5% had low medication knowledge. When evaluated patients dexterity on usage of dosage form, most of the patients experienced no difficulties during medication utilization. However; only 43% of patients showed fine manipulation skills. It is important to detect and prevent medication related problems in geriatric patients at community pharmacy setting. This will be beneficial to enhance the medication adherence in elderly patients..lubinga SJ, Millar I, Babigumira JB. Pilot evaluation of the psychometric properties of a self-medication Risk Assessment Tool among elderly patients in a community setting. BMC Res Notes. 0; 4:

86 PP 3 DETERMINATION OF DRUG RELATED PROBLEM AND DRUG BURDEN INDEX IN ELDERLY PATIENTS BETUL OKUYAN, ZEHRA AYDINLI, IPEK CELIK, EFE DOGUKAN DINCEL, TUGCE SAY, DILAY YAVUZ, AYSU SELCUK, SEONKYEONG YANG, MESUT SANCAR CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the present study was to determine medication related problems and drug burden index in elderly patients at community pharmacy. This cross-sectional descriptive study was conducted between February and May 04. Patients were eligible for the present study if they were 65 years old or older, they did not take any support for medication utilization, and accepted to participate study. Potentially inappropriate medications were defined as updated 0 Beer s Criteria. Cognitive function has been evaluated by using revised Turkish version of Mini Mental State Examination (rmmse-t) was scored between 0-30 (). Drug burden index have been also calculated. Among 3 elderly patients, 43.% of them were female and the mean age of the patients was 7.50 ± 6.7. The most of the patients were married (74.0%) and had a low education level. The mean of total medication utilized in patients was 5.0±.53 and eighty patients used five and more medication. The mean of rmmse-t score was 3.56± % (n=3) of the patients were prescribed with potentially inappropriate medications. The frequency of DBI exposure was high (76.5%) in elderly patients. The DBI scores were between 0- in eighty-one patient and more than one in 3 patients. As a conclusion, it was found higher rate of drug burden index and polypharmacy in elderly patients in the present study. Pharmaceutical care conducted in community pharmacy would be beneficial in preventing and determining of medication related problems..keskinoglu P, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State Examination (rmmse-t) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 009;4():4-50. PP 3 EVALUATION OF DRUG BURDEN INDEX IN ELDERLY PATIENTS UTILIZED DISPOSABLE INSULIN PEN BETUL OKUYAN, ZEHRA AYDINLI, IPEK CELIK, EFE DOGUKAN DINCEL, TUGCE SAY, DILAY YAVUZ, AYSU SELCUK, SEONKYEONG YANG, MESUT SANCAR CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the present study was to evaluate patients attitude and knowledge about disposable insulin pen utilization and calculate drug burden index among elderly patients at community pharmacy. This cross sectional descriptive study was conducted between February and May 04. Patients were eligible for the present study if they were 65 years old or older, prescribed at least a disposable insulin pen for at least 4 weeks, did not take any support for medication utilization and accepted to participate to the present study. Cognitive function has been evaluated by using revised Turkish version of Mini Mental State Examination (rmmse-t) was scored between 0-30; the score under or less and 8 or less were labelled as cognitive impairment in educated and uneducated elderly; respectively (). The steps for proper administration and storage were evaluated in utilization of disposable insulin pens. Drug burden index have been also calculated. A total of forty-five elderly patients (mean of age: 7.8±5.77 years old; male/female: 7/8) utilized disposable insulin pen were included in this study. Of them, 40% had cognitive impairment according to rmmse-t scores. The DBI scores were between 0- in twenty-eight patients and were more than one in three patients. Most of them were failure to hold needle adequate period before withdrawal of pen needle from skin (80.0%), failure to prime needle (60.0%), failure to store in-use pen at room temperature (53.3%), and failure discard the insulin pen before expire date reported by manufacturer (44.4%). When evaluated discard pen needle after each injection, 84.4% of them stored their disposable insulin pen with needle.although the small sample size is a limitation of the present study, it was concluded that patients cognitive function and drug burden index should be considered when selected disposable insulin pen for elderly and pharmacist would take a role in education and monitoring of disposable insulin pen among elderly patients..keskinoglu P, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State Examination (rmmse-t) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 009;4():

87 PP 33 EVALUATION OF DRUG BURDEN INDEX IN ELDERLY PATIENTS UTILIZED INHALER BETUL OKUYAN, ZEHRA AYDINLI, IPEK CELIK, EFE DOGUKAN DINCEL, TUGCE SAY, DILAY YAVUZ, AYSU SELCUK, SEONKYEONG YANG, MESUT SANCAR CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the present study was to evaluate patients inhalation skills and calculate drug burden index (DBI) among elderly patients utilized metered-dose inhalers, diskuses, turbuhalers and aerolizers at community pharmacy.this cross sectional descriptive study was conducted between February and May 04. Patients were eligible for the present study if they were 65 years old or older, used at least one inhaler device, did not take any support for medication utilization and provided their consent. Patient demographic, clinical and medication data were recorded with face-to-face interview. Cognitive function has been evaluated by using revised Turkish version of Mini Mental State Examination (rmmse-t) was scored between 0-30 (). Patients inhaler use attitudes were evaluated essential steps during inhaler use for each inhaler device. Drug burden index has been also calculated.a total of thirty-seven elderly patients (mean of age: 7.65±5.47 years old; male/female: 0/7) utilized aerolizer (70.7%), metered dose inhaler (54.05%), diskus (.6%), and turbuhaler (0.8%) were included in this study. The number of inhaler utilized by elderly patients was one (48.60%), two (45.90%) and three (5.40%). The mean of rmmse-t score was calculated as 3.6±4.08. Twenty seven elderly patients utilized five or more medications. Among twenty five elderly patients who utilized anticholinergic and sedative medications; DBI index was calculated equal and less than one in twenty two and more than one in three patients. When evaluating patients steps while using their inhaler; only five patients could correctly follow all steps during inhaler utilization. Most of patients were failure to hold their breath for ten second after inspiration and wait a few seconds before next dose. Although present study had a little sample size; our results presented the importance of evaluation drug burden index and cognitive function in elderly patients, who used inhalers which required special skills and had polypharmacy..keskinoglu P, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State Examination (rmmse-t) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 009;4():4-50. PP 34 PROTECTIVE EFFECTS OF FERULIC ACID AND CURCUMIN AGAINST CISPLATIN-INDUCED NEPHROTOXICITY IN RATS ERLIASA BAMI, BETUL OKUYAN, OZLEM BINGOL OZAKPINAR, ZARIFE N. OZDEMIR KUMRAL 3, KUTAY KOROGLU 4, FERIHA ERCAN 4, ZEYNEP CIRAKLI 5, TURGUT SEKERLER, FIKRET VEHBI IZZETTIN, MESUT SANCAR DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY DEPARTMENT OF BIOCHEMISTRY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY 3 DEPARTMENT OF PHYSIOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY 4 DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY 5 DEPARTMENT OF BIOCHEMISTRY, BAKIRKOY DR. SADI KONUK TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY This study aims to evaluate protective effects of phenolic compound ferulic acid and curcumin against cisplatin induced nephrotoxicity in rats. Rats were divided into six groups consisting of six animals: three control groups, one toxicity group, and two treatment groups. Serum saline (ml/kg), ferulic acid (50 mg/kg), and curcumin (00 mg/kg) were administered by oral gavage throughout five days. Single dose (0mg/kg) i.p. cisplatin was administered on the second day of experiment. Kidneys were removed after 7 hours of cisplatin administration within each group. Malondialdehyde (MDA) levels, myeloperoxidase (MPO) levels, and total antioxidant status (TAS) were measured in rat kidney tissues. Ferulic acid and curcumin significantly decreased kidney MPO levels, which had increased as a result of cisplatin administration (p<0.05). Cisplatin caused an obvious decrease in kidney TAS levels, while ferulic acid (50 mg/kg) and curcumin (00 mg/kg) administration significantly increased TAS levels in treatment groups (p<0.05). Although a slight decrease was noticed in kidney MDA levels after treatment with ferulic acid and curcumin when compared to toxicity group, no statistically significant differences were observed (p>0.05). Based on this study we suggest that ferulic acid and curcumin supplementation expelled beneficial effects against cisplatin toxicity on rat kidneys, therefore it appears that both ferulic acid and curcumin may be effective in preventing cisplatin induced nephrotoxicity. -86-

88 PP 35 PROTECTIVE EFFECTS OF FERULIC ACID AND CURCUMIN AGAINST TESTICULAR OXIDATIVE DAMAGE INDUCED BY CISPLATIN IN RATS ERLIASA BAMI, BETUL OKUYAN, OZLEM BINGOL OZAKPINAR, ZARIFE N. OZDEMIR KUMRAL 3, KUTAY KOROGLU 4, FERIHA ERCAN 4, ZEYNEP CIRAKLI 5, TURGUT SEKERLER, FIKRET VEHBI IZZETTIN, MESUT SANCAR DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY DEPARTMENT OF BIOCHEMISTRY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY 3 DEPARTMENT OF PHYSIOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY 4 DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY 5 DEPARTMENT OF BIOCHEMISTRY, BAKIRKOY DR. SADI KONUK TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY The purpose of the present study was to provide information about the protective effects of phenolic compound ferulic acid and curcumin against cisplatin induced toxicity in rat testis. A total of 36 male rats were divided into six groups each consisting of six animals: three control groups, a toxicity group, and two treatment groups. Serum saline (ml/kg), ferulic acid (50 mg/kg), and curcumin (00 mg/kg) were administered by oral gavage for five days. Single dose 0mg/kg i.p. cisplatin was administered on the second day of the experiment. Animals were sacrificed 7 hours due to cisplatin administration and rat testis was removed within each group. Malondialdehyde (MDA) levels, myeloperoxidase (MPO) levels, and total antioxidant status (TAS) were measured in rat testicular tissues. Ferulic acid and curcumin significantly decreased testis MPO levels, which had increased as a result of cisplatin administration (p<0.05). TAS levels depletion was obvious in cisplatin administered testicular tissues, while this situation was significantly reversed in treatment groups by an increase in TAS levels after treatment with ferulic acid and curcumin (p<0.05). A slight improvement in the MDA levels was noticed after treatment with ferulic acid (50 mg/kg), and curcumin (00 mg/kg) when compared to toxicity group, however MDA levels did not differ significantly (p>0.05). The current study showed that ferulic acid and curcumin administrations were able to attenuate testicular oxidative damage induced by cisplatin, leading thus in protective effect on the reproductive system of male rats. PP 36 AN EVALUATION ON BEAUVERIA BASSIANA, ITS MICOTOXINS AND BIOACTIVITY ENGIN KILIC DEPARTMENT OF PHARMASOTIC MICROBIOLOGY, BASIC SCIENCE OF PHARMACY, FACULTY OF PHARMACY, ERZINCAN UNIVERSITY, ERZINCAN, TURKEY Beauveria bassiana occurs naturally in soils throughout the world and it is flamentous fungi. It produces beauvercin, a toxin that weakens the immune system of the hosts. Beauvercin is a cyclıc hexadepsipeptide mycotoxin, which has insecticidal, antimicrobial, antiviral and cytotoxic. İt is a potantial bioagents for pesticides and MEDICINEs. We reviews the important of B. bassiana, the structure of chemical and bioactivity (insecticidal activite, anticancer activity, antibacterial activity, antifungal activity, antiviral activity) of a fungal product beauvercin. Key Word: Fungi, Beauveria bassiana, beauvercin, anticancer activity, antibacterial activity, antifungal activity, antiviral activity, insecticidal activite -87-

89 PP 37 ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF MARRUBIUM VULGARE AND ANACYCLUS PYRETHRUM DIFFERENT EXTRACTS BOUAMRA DALILA, BAKI CHEKIB ARSLANE, BOUCHEBOUR ABDELHAMID, HARZALLAH DAOUD, CRISTANI MARIATERESA 3, FRATANTONIO DEBORAH 3, GINESTRA GIOVANNA 3, NOSTRO ANTONIA 3 LABORATORY OF CHRONIC DISEASES APPLIED PHYTOTHERAPY, FACULTY OF NATURAL AND LIFE SCIENCES, UNIVERSITY FERHAT ABBAS, SETIF, 9000, ALGERIA LABORATORY OF APPLIED MICROBIOLOGY, FACULTY OF NATURAL AND LIFE SCIENCES, UNIVERSITY FERHAT ABBAS, SETIF, 9000, ALGERIA 3 DEPT. DRUG SCIENCES AND HEALTH PRODUCTS, UNIVERSITY OF MESSINA, MESSINA, ITALY In this study, the methanol, hexane and ethyl acetate extracts of both Marrubium vulgare and Anacyclus pyrethrum were investigated for antioxidant and antimicrobial activities. The extracts were evaluated for phenolic content with Folin-Ciocalteau colorimetric method, and the results demonstrated the richness of all extracts in polyphenols with mild concentration differences. The ABTS (,-azobis-3-ethylbenzthiazoline-6-sulfonic acid), DPPH (Diphenyl--picrylhydrazyl), FRAP (Ferric Reducing Antioxidant Power), and ORAC (Oxygen Radical Absorbance Capacity) assays were carried out to evaluate the antioxidant activity of the extracts, and the outcomes of the ABTS, DPPH and FRAP tests showed that Marrubium vulgare hexane extract had the highest antioxidant activity (0.0±0.006 mmol TE/g.; 0.003±0.00 mmol TE/g and 0.40±0.04 mmol Fe+/g. respectively) while the ORAC assay referred the latter to the hexane extract of Anacyclus pyrethrum (0.666±0.0 µmol TE /g). Additionally, the AGE formation assay was performed to assess the glycation inhibitory activity of the extracts, and the results showed that the hexane extract of Marrubium vulgare got the highest activity (IC50 =.4%). The disc-diffusion method, that was performed to investigate the antimicrobial activity, revealed that all the extracts have inhibitory effects on Staphylococcus aureus ATCC 6538 and the ethyl acetate extract of Anacyclus pyrethrum got the best results. PP 38 COMPARATIVE ANALYSIS OF FIVE DIFFERENT GENERIC BRANDS OF PREDNISOLONE TABLET MARKETED IN LIBYA ASMA BEN AHMED, HAJER ALBORAWY, ALAA MASHINA, PRADEEP VELAUTHAM, ABDULMONEM GOBASSA, EMHEMMED ELGALLAL, MOHAMED EL ATTUG* DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, UNIVERSITY OF TRIPOLI, TRIPOLI- LIBYA CENTRE FOR FOOD AND DRUG CONTROL, GURGI, TRIPOLI-LIBYA Generic MEDICINEs have been increasingly used in recent years, primarily as a cost saving measure in healthcare provision. Generic MEDICINEs are typically 0 90 % cheaper than originator equivalents. Physicians often continue to prescribe brandname drugs to their patients even when less expensive pharmacologically equivalent generic drugs are available. Unfortunately Physicians in general and Libyan Physicians in particular tend to prescribe brand-name drugs, even without evidence of their therapeutic superiority. There are several generic brands of Prednisolone are available in the Local market. However, their pharmaceutical quality which affect safety and efficacy is unknown. Hence, prescribing of some generic products may lead to serious health consequences. It is important, from a quality control point of view, to perform a comparative analytical evaluation between trademarked and generic formulations to assure the quality of generics. Therefore the aim of this study was to assess the quality of 5 mg Prednisolone tablets produced by five Pharmaceutical manufacturers from Turkey, United Kingdom, India, UAE and Egypt under different trade names. The quality of five commercial brands of Prednisolone of the same strength from different manufacturer were selected. The physicochemical parameters through the evaluation of uniformity of tablet weight, friability, hardness, thickness, disintegration, microbiological, identification, dissolution and assay of the five brands of prednisolone tablets were assessed using official (Pharmacopeial), non-official methods and in house validated methods. All generic products complied with the official specification the limits for the friability, hardness tests, uniformity of weight and thickness uniformity, except one product from Middle East do not comply with the limits for the friability test which is more than %, hardness was less than 40 N, highest RSD % (3.5 % for thickness) and (3.0 % for uniformity of weight). All generic products complied with microbial tests, absent of microorganisms count and total yeast & mold count. So It can be assumed that it is not as therapeutically effective and is not approved. -88-

90 PP 39 SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW TETRAZOLE DERIVATIVES LEYLA YURTTAŞ, ZAFER ASIM KAPLANCIKLI, GÜLŞEN AKALIN ÇİFTÇİ, HALİDE EDİP TEMEL DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKİŞEHİR, TURKEY DEPARTMENT OF BİOCHEMİSTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKİŞEHİR, TURKEY Tetrazole derivatives possess very interesting pharmacological and biological properties and are reported to exhibit variety of biological activities such as antibacterial, antifungal, antiviral, anticonvulsant, analgesic, anti-inflammatory, antinociceptive, anesthetic, hypoglycemic, antiallergic, antitubercular and anticancer activities. In particular, -substituted tetrazole and 5-thio-substituted tetrazoles have been used in the synthesis of pharmacologically active drugs []. The aim of the present work is to synthese a novel series of tetrazole derivatives and to investigate their potential cytotoxic properties and also anticholinesterase activity on acetylcholinesterase and butyrylcholinesterase enzymes. N-(arylidene)-4-[(-phenyl-Htetrazole-5-yl)thio]butanohydrazide derivatives (3-8) derivatives were synthesized using -methyl-h-tetrazole-5-thiol and ethyl 4-chlorobutanoate as starting materials. The obtained ester compound () was reacted with hydrazine hydrate, then with appropriate aromatic aldehydes to gain final compounds. The structures of the compounds were confirmed by IR, H-NMR, 3C-NMR, mass spectra and elemental analysis. The biological activity studies are in progress.. Kaplancıklı ZA, Yurttaş L, Özdemir A, Turan-Zitouni G, Akalın Çiftçi G, Ulusoylar Yıldırım Ş, Abu Mohsen U. Synthesis and antiproliferative activity of new,5-disubstituted tetrazoles bearing hydrazone moiety. Med Chem Res. 04; 3: PP 40 IN VITRO ANTITUMOR ACTIVITY EVALUATION OF NEW,-DISUBSTITUTED BENZIMIDAZOLE DERIVATIVES LEYLA YURTTAŞ, ŞEREF DEMIRAYAK, GÜLŞEN AKALIN ÇİFTÇI 3 DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKIŞEHIR, TURKEY DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, SCHOOL OF PHARMACY, MEDIPOL UNIVERSITY, ISTANBUL, TURKEY 3 DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKIŞEHIR, TURKEY Since we have worked on,-disubstituted benzimidazole derivatives and their anticancer activities, we have reported some anticancer active,-disubstituted benzimidazole derivatives in a few studies (,). In this study, we have identified the synthesis of new benzimidazole derivatives named -(-aryl--oxoethyl)--(thioamido)benzimidazoles and also their antitumor activity evaluation. The compounds (3a-n) were synthesized according to the procedure described in our previous study (3). The anticancer activity evaluation studies are going on according to the MTT assay, BrdU method, and flow cytometric analysis on C6 and A549 tumor cells.. Demirayak S, Kayagil I, Yurttas L. Microwave supported synthesis of some novel,3-diarylpyrazino[,-a]benzimidazole derivatives and investigation of their anticancer activities Eur J Med Chem. 0;46: Demirayak S, Abu Mohsen U, Karaburun AC. Synthesis and anticancer and anti-hiv testing of some pyrazino[,-a]benzimidazole derivatives. Eur J Med Chem. 00;37: Yurttaş L, Demirayak S, Çiftci GA, Yıldırım ŞU, Kaplancıklı ZA. Synthesis and biological evaluation of some,-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch Pharm Chem Life Sci. 03;346:

91 PP 4 SPECIFIC KILLING OF HIGHLY METASTATIC BREAST CANCER CELLS BY TYPE PILIATED ESCHERICHIA COLI MERVE SUZAN ZEDEN, ENDER VOLKAN CYPRUS INTERNATIONAL UNIVERSITY Pili are filamentous, polymeric protein appendages assembled by bacteria. Type pili, assembled by uropathogenic Escherichia coli (UPEC) via the chaperone-usher pathway, are virulence factors in urinary tract infections (UTIs). Type pili mediate binding with the mannose residues on the bladder surface, to invade the host cells. In vitro studies demonstrated that β and α3 integrins are also key receptors for type piliated UPEC. The function of such integrins seems to be versatile ranging from cell adhesion to migration on extracellular matrix. Interestingly, β and α3 integrins are highly expressed on highly metastatic breast cancer cell lines MDA-MB-3. To test the hypothesis that type piliated UPEC may exert toxicity on MDA-MB-3 cancer cells, we have co-cultured statically grown, normalized, piliated cultures of UTI89 strain of UPEC with a confluent layer of MDA-MB-3 cells for hour. Statically grown, piliated cultures of UTI89 were observed to cause significantly higher death rates (p < 0.0) on MDA-MB-3, when compared with the media control, shaking cultures or the control strain of C600. Tryphan blue assay and microscopic investigations were utilized to observe cancer cell death. Interestingly, this significant type pili-mediated toxicity was specific to highly metastatic MDA-MD-3 cells as lowly metastatic MCF7 cells did not experience significantly increased killing, suggesting that pili may have a role in targeting metastatic tumor cells. These findings indicate that studies on bacterial factors like chaperone-usher pili can help improve our approaches of designing therapeutics for treatment of not only infections but also other diseases like cancer. PP 4 ANTIMICROBIAL ACTIVITY OF VARIOUS MOUTHRINSES AGAINST STREPTOCOCCUS MUTANS, LACTABACILLUS CASEI, L. ACIDOPHILUS AND CANDIDA ALBICANS GÜLBIKE DEMIREL, MÜJDE ERYILMAZ, NURTEN ALTANLAR, GÜRKAN GÜR DEPARTMENT OF RESTORATIVE DENTISTRY, FACULTY OF DENTISTRY, ANKARA UNIVERSITY, ANKARA, TURKEY DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACY, ANKARA UNIVERSITY, ANKARA, TURKEY Mouthrinses are used for several reasons such as to freshen breath, to control dental caries, to prevent gingivitis and to reduce plaque formation on teeth. The main advantage of mouthrinses is their ability to deliver antimicrobial properties to all accessible surfaces in the mouth (, ). The aim of this in vitro study was to determine the antimicrobial activities of commonly used mouthrinses against different oral microorganisms. Six commercially available mouthrinses (Colgate Total, Colgate Pro-argin, Colgate Plax, Listerine, Oral B Pro-expert and Oderol) were used in the study. The antimicrobial activities of mouthrinses against Streptococcus mutans ATCC 575, Lactobacillus casei (RSM:900), Lactobacillus acidophilus ATCC 975 and Candida albicans ATCC 03 were evaluated by disc diffusion and tube dilution methods. Chlorhexidine gluconate was used as positive control. The diameters of the inhibition zones were measured in millimeters and the experiment was repeated twice. According to the results, Colgate Total, Colgate Plax, Oral B Pro-expert and Oderol showed good antimicrobial activity against test microorganisms compare with Colgate Pro-argin and Listerine. We found the chlorhexidine and cetylpyridinium chloride included mouthrinses more active than other products tested. In conclusion, the daily usage of mouthrinses will help to provide oral hygiene.. Silverman S, Wilder R. Antimicrobial mouthrinse as part of a comprehensive oral care regimen. JADA. 006; 37:S-6S.. Chen Y, Wong RWK, Seneviratne CJ, Hagg U, McGrath C, Samaranayake LP. Comparison of the antimicrobial activity of Listerine and Corsodyl on orthodontic brackets in vitro. Am J Orthod Dentofacial Orthop. 0; 40:

92 PP 43 SYNTHESIS, MOLECULAR DOCKING, AND ANTITUMORAL ACTIVITY OF ALNUSTONE-LIKE COMPOUNDS AGAINST ESTROGEN RECEPTOR α-positive BREAST CANCER KAAN KÜÇÜKOĞLU, HATİCE SEÇİNTİ, AYKUT ÖZGÜR, HASAN SEÇEN, YUSUF TUTAR 3 FACULTY OF PHARMACY ATATÜRK UNIVERSITY, ERZURUM FACULTY OF PHARMACY GAZİOSMANPAŞA UNIVERSITY, TOKAT 3 FACULTY OF PHARMACY CUMHURİYET UNIVERSITY, SIVAS Breast cancer is the most common cancer type worldwide among women. In the United States, breast cancer is 4.% of all expected cancer cases and approximately 3,340 new cases and 39,60 deaths will be estimated in 03 (). Alnustone, a nonphenolic diarylheptanoid, was first isolated from Alnus pendula (Betulaceae) and characterized four decades ago (). Recently, it was reported that alnustone exhibited significant antitumor activity against Bel-740 (human hepatocellular carcinoma cells) cell lines (3). New alnustone-like compounds were synthesized by condensating 4-phenyl--butanones and cinnamaldehydes. Condensations of 4-phenyl--butanones and cinnamaldehydes were performed in situ enamination using pyrrolidine and acetic acid in diethyl ether. Ten different alnustone-like compounds differing with aryl substituents were prepared with a variety of yields. The cytotoxic activity of alnustone-like compounds were evaluated against MCF-7 cells and tamoxifen and paclitaxel were used as positive control to compare with the alnustone-like compounds. Cell proliferation assay showed that compounds, 0,, 4, and 7 (Group A) displayed paclitaxel like activity and on the other hand, compounds 5, 6, and 9 (Group B) displayed tamoxifen like activity. And, compounds 5 and 8 (Group C) displayed a transition activity between these drugs. Structure and function of the designed compounds correlates with the biochemical behavior of the breast cancer cell survival. The designed compounds may be developed for drug resistance and may potentially decrease the side effects of the commercially available drugs in the future.. Surveillance, Epidemiology, and End Results Program. National Cancer Institute. html (accessed ). Suga T, Asakawa Y, Iwata N.,7-Diphenyl-,3-heptadien-5-one: a new ketone from Alnus pendula (Betulaceae). Chem Ind (London). 97;7: Li Y, Yang L, Wang C, Chou G, Wang Z. Chemical constituents from seeds of Alpinia katsumadai Hayata and their anti-tumor activity. Shang Hai Zhong Yi Yao Da Xue Xue Bao. 00;4:7-75. PP 44 EVALUATION OF THE CYTOTOXICITY OF SOME HYDRAZONE COMPOUNDS AGAINST FOUR HUMAN CANCER CELL LINES KAAN KÜÇÜKOĞLU, HALISE INCI GÜL, HIROSHI SAKAGAMI FACULTY OF PHARMACY ATATÜRK UNIVERSITY, ERZURUM FACULTY OF PHARMACY MEIKAI UNIVERSITY, JAPAN Hydrazones and Mannich bases are group of compounds which are known to have anticancer and cytotoxic activities (,). Some new hydrazone compounds, N,N-bis[-aryl-3-(pyrrolidine--yl)propylidene]hydrazine dihydrochlorides, were synthesized by condensating corresponding mono Mannich base and hydrazine hydrate in ethanolic acetic acid. Precursor mono Mannich bases were prepared by using acetophenone derivatives, paraformaldehyde, pyrrolidine and hydrochloric acid in ethanol. Seven different hydrazone compounds with different aryl substituent were synthesized in moderate yields. The aryl part was changed as phenyl in R, 4-methylphenyl in R, 4-methoxyphenyl in R3, 4-hydroxyphenyl in R4, 4-chlorophenyl in R5, 3-methoxyphenyl in R6, 4-fluorophenyl in R7. The cytotoxic activity of hydrazone compounds were evaluated against three human oral squamous cell carcinoma cell lines (HSC-, HSC-3, and HSC-4) and human promyelocytic leukemia cells (HL-60) and three normal human oral cell types [gingival fibroblast (HGF), pulp cell (HPC), periodontal ligament fibroblast (HPLF)]. The most powerful compound in this series was 4-methylphenyl derivative compound R which showed cytotoxic activity with mean CC50 = μm against four tumor cell lines and this compound had stronger cytotoxic activity than the reference compound peplomycin. Compound R6, a 3-methoxyphenyl derivative, and compound R5, a 4-chlorophenyl derivative, had significant cytotoxic activities with 40 μm and 64 μm mean CC50 values, respectively. Compound R3 which was 4-methoxyphenyl derivative had the highest tumorspecifity with.4 value. In conclusion, hydrazones synthesized having a pyrrolidine moiety as potential anti-cancer candidate deserved further structural modification and pharmacological evaluation.. Gul HI, Das U, Pandit B, Li PK. Evaluation of the cytotoxicity of some mono-mannich bases and their corresponding azine derivatives against androgen-independent prostate cancer cells. Arzneimittelforschung 006;56: Cocco MT, Congiu C, Lilliu V, Onnis V. Synthesis and in vitro antitumoral activity of new hydrazinopyrimidine-5-carbonitrile derivatives. Bioorg Med Chem. 006;4:

93 PP 45 ACTION OF N,N -BIS[-(4-FLUOROPHENYL)-3-(PIPERIDINE--YL)PROPYLIDENE]HYDRAZINE DIHYDROCHLORIDE ON MITOCHONDRIAL RESPIRATION KAAN KÜÇÜKOĞLU, HALISE INCI GÜL, RENGUL CETIN-ATALAY, YOSRA BARATLI 3, ANNE-LAURE CHARLES 3, MURAT SÜKÜROĞLU 4, MUSTAFA GÜL, BERNARD GENY 3 FACULTY OF PHARMACY ATATÜRK UNIVERSITY, ERZURUM FACULTY OF PHARMACY BILKENT UNIVERSITY, ANKARA 3 FACULTY OF PHARMACY UNIVERSITY DE STRASBOURG, FRANCE 4 FACULTY OF PHARMACY GAZI UNIVERSITY, ANKARA Hepatocellular carcinoma (HCC) is such a cancer type that the treatment options are very limited, the only curative treatment procedure is surgery and HCC cells have high resistance to chemotherapeutic agents (). N,N -Bis[-(4-fluorophenyl)-3- (piperidine--yl)propylidene]hydrazine dihydrochloride which was called P7 in the literature () was synthesized by the reaction of -aryl-3-(piperidine--yl)--propanone hydrochloride with hydrazine hydrate in ethanolic acetic acid. The chemical structure of this compound was confirmed by UV, H NMR, 3C NMR and HRMS spectra. The cytotoxic activity of P7 was tested against human hepatoma (Huh7) and breast cancer (T47D) cells. This compound was found to have more potent cytotoxic activity against Huh7 cells with 8.0 μm IC50 value than the reference compound 5-FU. In addition, the action of P7 on the mitochondrial respiratory chain complexes was measured. Compound P7 inhibited the mitochondrial respiration significantly at 44, 64 and 44 μm concentrations dose-dependantly in liver homogenates. Therefore, inhibition of mitochondrial respiratory chain by the compound P7 suggests that inhibition of mitochondrial respiration may be one of the contributing mechanisms to the cytotoxic activity of P7. The results suggest that P7 deserved further structural modification and pharmacological evaluation as potential anti-cancer candidate.. Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 007;4: Kucukoglu K, Gul HI, Cetin-Atalay R, Baratli Y, Charles A-L, Sukuroglu M, Gul M, Geny B. Synthesis of new N,N -bis[-aryl-3-(piperidine--yl)propylidene]hydrazine dihydrochlorides and evaluation of their cytotoxicity against human hepatoma and breast cancer cells. J Enzyme Inhib Med Chem. 03;Early Online: -7, doi: 0.309/ PP 46 EXTEMPORANEOUS PEDIATRIC SUSPENSION OF SPIRONOLACTONE: FORMULATION AND STABILITY STUDY AMEL CHENAFA, LINDA AOUAD, IMANE SEDIRI, ISMAHAN DJEBBAR DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE, DJILLALI LIABES UNIVERSITY, SIDIBELABBES, ALGERIA FACULTY OF MEDICINE, DJILLALI LIABES UNIVERSITY, SIDIBELABBES, ALGERIA The specialties intended for adults are often inadequate marketed for pediatric use, such as for a galenic form or in the dosage. In industry, the development of a pediatric drug is confronted to various problems. So, the hospital pharmacies have to respond to adaptation needs of pharmaceutical forms for pediatric use. The objective of our work is to develop an oral form of spironolactone for pediatric use since no adapted form to child is commercialized. Therefore an extemporaneous suspension of spironolactone was prepared at the concentration of mg/ml from 5mg tablets and stored in amber glass bottles. Physical and chemical stability was studied in three temperatures: 5 C, 5 C and 40 C and evaluated at 0, 7, 4, 8, 4, 56, 70 and 90 days. The microbiological stability was also conducted at D0, D5 and D30. No organoleptic changes have been detected on the suspension conserved at 5 and 5 C and ph values are around the optimum ph of the spironolactone stability ( 4,5)(). Sheltered from light, the developed suspension of spironolactone remained stable at the temperature of 5 C.. Ana, C. Salgado, M. Luísa Rosa, M.Aida Duarte and António J.Almeida, Stability of spironolactone in an extemporaneously prepared aqueous suspension: the importance of microbiological quality of compounded paediatric formulations, The European Journal of Hospital Pharmacy Science, Volume, 005, P

94 PP 47 DEVELOPMENT OF TWO TRADITIONAL IMPROVED PREPARATIONS BASED ON SPONTANEOUS PLANT IN ALGERIA AMEL CHENAFA, MUSTAPHA CHELGHOUM, DJAHIDA ELGOUTNI, SIHEM HAFDI DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE, DJILLALI LIABES UNIVERSITY, SIDIBELABBES, ALGERIA Anthemis nobilis and Thymus vulgaris are two plants widely used in traditional MEDICINE, and very popular in Algeria for the treatment of inflammatory conditions (Roman chamomile) and bronchitis (thyme) (). Numerous scientific studies have confirmed the pharmacological properties of different extracts of the aerial parts of the two plants. The objective of our study is the valorization of these two spontaneous plants by an adequate galenic formatting of the methanolic extract of chamomile and essential oil of thyme. The quality control of plant material was performed according to the recommendations of the European Pharmacopoeia. The extraction was performed by steam distillation of the leaves of thyme to obtain the essential oil and by Soxhlet for flower heads of Chamomile. Taking into account the physical and chemical properties of raw materials, the choice of the dosage form is focused on a % ointment methanolic extract of chamomile and suppositories 50 mg of thyme essential oil. The results of quality control of plant material are conform to standards. Suppositories obtained have a white and homogeneous color. The resulting ointment is brown, with a smooth appearance without any lumps. The ph is 6.8. The development of these two dosage forms can be part of a broader outreach to drug herbal perspective, and the use of chamomile and thyme, which are two plants available in nature.. Basch E, Catherine U et al. Thyme (Thymus vulgaris L.), Thymol, Monograph from natural stansard. Journal of Herbal Pharmacotherapy 004, Vol. 4(): PP 48 THE FOLK MEDICINAL PLANTS OF ÇATAK (VAN-TURKEY) GIZEM BULUT, ERTAN TUZLACI, RABIA SENA TÜRKER MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY This study was made to reveal the plants used as traditional folk medicine in Çatak (Van) situated in east of Turkey. The specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s) used, the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara University. As a result of identification of the plant specimens, 33 species, used as a traditional folk medicine in Çatak, have been determined. According to the majority of the informants, the plants are mostly used for cold, wound, anthelmintic and kidney stones. PP 49 THE FOLK MEDICINAL PLANTS OF HATAY (TURKEY) GIZEM BULUT, ERTAN TUZLACI, SEÇKIN YATKIN MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY This study was made to reveal the plants used as traditional folk medicine in Hatay situated in south of Turkey. The specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s) used, the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara University. As a result of identification of the plant specimens, 30 species, used as a traditional folk medicine in Hatay, have been determined. According to the majority of the plants which have similar usage the plants are mostly used for wound, stomach ailments, cold and diabetes. -93-

95 PP 50 THE FOLK MEDICINAL PLANTS OF SARIYER (İSTANBUL-TURKEY) ERTAN TUZLACI, GIZEM BULUT, CIHAN ÖNDER MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY This study was made to reveal the plants used as traditional folk MEDICINE in Sarıyer (İstabul) situated in northwest of Turkey. The specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s) used, the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara UNIVERSITY. As a result of identification of the plant specimens, 33 species, used as a traditional folk MEDICINE in Sarıyer, have been determined. According to the majority of the plants which have similar usage, the plants are mostly used for gastrointestinal system diseases, wound, cold and diabetes. PP 5 THE FOLK MEDICINAL PLANTS OF KIZILTEPE (MARDİN-TURKEY) ERTAN TUZLACI, GIZEM BULUT, SÜLEYMAN OK MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY This study was made to reveal the plants used as traditional folk MEDICINE in Kızıltepe (Mardin) situated in southeast of Turkey. The specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s) used, the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara UNIVERSITY. As a result of identification of the plant specimens, 6 species, used as a traditional folk MEDICINE in Kızıltepe, have been determined. According to the majority of the informants, the plants are mostly used for urinary system diseases, heart diseases, shorthness of breath diabetes stomach diseases. PP 5 PREPARATION AND CHARACTERIZATION OF LOVASTATIN POLYMERIC MICROPARTICLES BY COACERVATION METHOD FOR DISSOLUTION ENHANCEMENT SUHAIR AL-NIMRY, MAI KHANFAR FACULTY OF PHARMACY JORDAN UNIVERSITY SCIENCE AND TECHNOLOGY, JORDAN Lovastatin is a highly lipophilic and poorly water soluble drug (BCS class II drugs). Oral absorption of lovastatin is about 30% of the dose. It undergoes extensive first-pass extraction resulting in low and variable bioavailability. The objective was to enhance the dissolution and release of the drug from the dosage form. Polymeric microparticles were prepared by coacervationphase separation method. The method was optimized through studying effects of type of polymer; drug:polymer ratio; type of organic solvent; and concentration of SDS surfactant on particle size, particle size distribution, and in-vitro drug release. Polymeric microparticles were characterized using different techniques. In-vitro drug release into 0.N HCl was evaluated and compared to that from physical mixtures and of unprocessed drug. Microparticles prepared using Eudragit L 00 at a ratio of : (drug:polymer), ethanol as a solvent, SDS at a concentration of 0.5%, were optimum. SEM images and PXRD patterns indicated that the drug was transformed into an amorphous solid. The results of FTIR, DSC and PXRD indicated the absence of any interaction between drug and polymer. Compressibility index and Hausner ratio, indicated that flow properties were enhanced and that addition of glidants can be useful. Release of drug from both polymeric microparticles and physical mixture was enhanced as compared to the unprocessed drug. It was faster and almost complete within 5 min from the polymeric microparticles as compared to that from physical mixture. In conclusion, the optimized microparticles proved to be useful in enhancing the release of the drug 5 folds. -94-

96 PP 53 SIMULTANEOUS DETERMINATION OF B, B, B3, B9, AND B VITAMINS IN APPLE BY HPLC-DAD HALİL İBRAHİM ULUSOY FACULTY OF PHARMACY CUMHURIYET UNIVERSITY, SIVAS, TURKEY Vitamins are organic compounds that promote and regulate essential biochemical reactions within the human body, which is generally unable to synthesize these compounds they have to be obtained from food in trace amounts for growth, health, and reproduction, and the lack of these compounds in the diet results in overt symptoms of deficiency (). The qualitative and quantitative analysis of vitamins in foods, whether inherently present or added during food manufacture, also in plasma, serum, and pharmaceuticals, has become extremely important to the food industry, to assess the nutritional quality of foodstuff, and to the medical and pharmaceutical industries, for protection or control of human health (). A new HPLC method was developed for the simultaneous determination of five water-soluble vitamins, viz. thiamine, riboflavin, nicotinamide, cyanocobalamin, and folic acid in apple samples. Separation was achieved at 40 C on a Inertsil C8 (50 mm 4,6 5 µm) analytical column. Gradient elution was performed by using HO/CH3OH (50/50), ph:3.00 and ph 5.0 phosphate buffers at a flow rate of 0.6 ml/min. Detection was performed with a photodiode array detector at 67 (B, B3), 8 (B9), 44 (B), 36 (B) nm. Each vitamin was quantitatively determined at its maximum wavelength. Spectral comparison was used for peak identification in real samples. Detection limits were in the range of µg ml-. The preparation of apple samples was performed by using microwave extraction system. Extraction recoveries from sample matrices ranged from 94.6% to 04.0%. PP 54 INVESTIGATION ON THE TOXIC POTENTIAL OF TRIBULUS TERRESTRIS IN VITRO GUL OZHAN, MAHMOUD ABUDAYYAK, TARBIN JANNUZZI, BUKET ALPERTUNGA FACULTY OF PHARMACY ISTANBUL UNIVERSITY, TURKEY Tribulus terrestris L. (Zygophyllaceae) has been commonly used to energize, vitalize, and improve sexual function and physical performance in men. This study investigates the potential cytotoxic and genotoxic, and endocrine disrupting activities of T. terrestris in vitro. The whole plant was extracted with water, methanol, and chloroform. The genotoxic potential of T. terrestris extracts at mg/ml was assessed by Comet assay in a rat kidney cell line (NRK-5E) and by Ames assay in Salmonella typhimurium TA98 and TA00 strains. Endocrine disrupting effects of the extracts at concentrations of mg/ml were assessed by YES/YAS assay in Saccharomyces cerevisiae. Cytotoxic activity of the extracts was determined by the MTT test in NRK-5E cells. The different exposure times were used for four tests (3-48 h). The methanol extract of T. terrestris IC50 value was 60 mg/ml. The other extracts did not show cytotoxic effects. In the Comet and Ames genotoxicity assays, none of the extracts possessed genotoxic activities at concentrations of mg/ml. Only the water extract of T. terrestris induced frame shift mutations after metabolic activation. The water extract also showed estrogenic activity by YES/YAS assay in S. cerevisiae at the higher concentrations than 7 mg/ml (higher than.6-fold), while the other T. terrestris extracts had anti-estrogenic properties. T. terrestris had estrogenic and genotoxic activities. The study was useful in determining its toxicological effects and the precautions regarding consumption. PP 55 THE EFFECTS OF AGING ON THE FUNCTIONAL AND STRUCTURAL PROPERTIES OF THE RAT BASILAR ARTERY NIHAL TUMER, HALE ZERRIN TOKLU, JUDY DELP, SEHKAR OKTAY, PAYAL GHOSH, KEVIN STRANG, MICHAEL DELP, PHILIP SCARPACE PHARMACOLOGY AND THERAPEUTICS APPLIED PHYSIOLOGY AND KİNESİOLOGY UNIVERSITY OF FLORIDA, ABD Aging leads to progressive pathophysiological changes in blood vessels of the brain and periphery. The aim of this study was to evaluate the effects of aging on cerebral vascular function and structure. Basilar arteries were isolated from male Fischer 344 cross Brown Norway (F344xBN) rats at 3, 8 and 4 months of age. The basilar arteries were cannulated in the pressurized system (90 cm HO). Contractile responses to KCl (30-0mM) and endothelin- ( M) were evaluated. Responses to acetylcholine (ACh) ( M), diethylamine (DEA)-NONO-ate ( M), and papaverin ( M) were assessed to determine both endothelium-dependent and endothelium-independent responsiveness. Advanced aging (4 months) decreased responses of the basilar artery to both the contractile and relaxing agents; whereas, DEA-induced dilation was significantly higher in the 8 month old group compared with the younger and older groups. The arterial wall-to-lumen ratio was significantly increased in 4 month old rats. Smooth muscle cell count was also decreased in old rats. These findings indicate that aging produces dysfunction of both the endothelium and the vascular smooth muscle in the basilar artery. Aging also alters wall structure of the basilar artery, possibly through decreases in smooth muscle cell number and concomitant hypertrophy. -95-

97 PP 56 INVESTIGATION OF THE PROTECTIVE EFFECT OF CINNAMOMUM CASSIA BARK EXTRACT AGAINST HO-INDUCED OXIDATIVE DNA DAMAGE IN HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND ANTIOXIDANT ACTIVITY SUMRU SOZER KARADAGLI, BORTE AGRAP, FERZAN LERMIOGLU ERCIYAS FACULTY OF PHARMACY EGE UNIVERSITY, IZMIR, TURKEY Cinnamon, one of the most widely used spices in the world, has been shown to have various biological functions including antidiabetic and antitumor activities. Its antidiabetic and antitumor effects were linked with its strong antioxidant activity. In the present study we aimed to investigate the antioxidant activity and possible protective effect of Cinnamomum cassia bark water extract against HO-induced oxidative DNA damage. Viability of lymphocytes was determined by Trypan Blue test. For the evaluation of the antioxidant activity, total phenol and flavonoid contents and,-diphenyl--picrylhydrazyl (DPPH) inhibitory activity of the extract were determined. DNA damage was determined by alkaline comet assay in human peripheral blood lymphocytes. Lymphocytes exhibited >86 % survival up till the concentration of 800 μg/ml of the extract. Total phenol and flavonoid contents were calculated as 0.6 g ± 0.00 gallic acid equivalents/ 00 g dry weight and.5±0.004 g quercetin equivalents/00 g dry weight of the extract, respectively. The extract concentration providing 50 % inhibition of DPPH was found as μg/ml. Cinnamomum cassia bark water extract at 00 μg/ml concentrations caused significant protection against HO-induced oxidative DNA damage in lymphocytes. Our results support the suggestions that Cinnamomum cassia bark water extract could be beneficial as a prophylactic agent in prevention of oxidative stress-related diseases..singh R, Koppikar SJ, Paul P, Gilda S, Paradkar AR, Kaul-Ghanekar R. Comparative analysis of cytotoxic effect of aqueous cinnamon extract from Cinnamomum zeylanicum bark with commercial cinnamaldehyde on various cell lines. Phar Bio 009; 47:74-9..Wondrak GT, Villeneuve NF, Lamore SD, Bause AS, Jiang Tao Z, Donna D. The Cinnamon-Derived Dietary Factor Cinnamic Aldehyde Activates the Nrf-Dependent Antioxidant Response in Human Epithelial Colon Cells. Molecules 00; 5: *This abstract has been presented in Marmara Pharmaceutical Journal 8: 43-48, 04. PP 57 PHYTOCHEMICAL ANALYSIS OF HELIOTROPIUM LASIOCARPUM SUBSP. LASIOCARPUM FISCH. ET MEY. (BORAGINACEAE) MELDA DÖLARSLAN, AYŞE ŞAHİN YAĞLIOĞLU, MURAT TEMIRTÜRK, EBRU GÜL 3, İBRAHIM DEMIRTAŞ DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY 3 DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 800, CANKIRI, TURKEY Heliotropium lasiocarpum subsp. lasiocarpum Fisch. Et Mey. belongs to the family Boraginaceae, the plants of family use decorative plants, spices, and useful for the preparation of dyestuffs. Active agents of the family are mucilage derivatives (arabinose, glucose and galactose), Pyrolizidinalkaloits (Amabilin, Supinidin, Lycopsamin, Intermedin, 7-Asetil-Lycopsamin ve 7-Asetilintermedin). Also, The family contains tannins, saponins, resins, starches, silicic acids, vitamin C and minerals. H. lasiocarpum Fisch. Et Mey. are semi boy grows, perennial and annual herbaceous plants (). This plant acts as an antidote against all deadly poison and uses antipyretic, the gall enhancer and wound healing (). In this study, H. lasiocarpum were collected from Çankırı. This plant were separated as airel parts and root and dried at room temperature (5 C) in the shade. The extracts of these materials which were acetone, chloroform, ethyl acetate and ethanol, extracts, respectively were prepared. The fatty acides of acetone and chloroform extracts by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by the HPLC-TOF-MS were performed. As a result of GC-MS analyzes were detected compounds. The choloroform extract of H. lasiocarpum root and airel parts and the acetone extract of this plant roots were determined linoleic acid the main component. However, the acetone extract of the airel parts were detected linolenic acid. The main component were rosmarinic acid from the ethanol and ethyl acetate extracts of the root; vanillic acid from the ethyl acetate extracts of the airel parts and rutin from the ethanol extracts of the same parts by HPLC-TOF-MS.. Davis, P. H., , Flora of Turkey and the East Aegean Islands, vol. -9, Edinburgh: Edinburgh UNIVERSITY Pres.. Baytop, T Türkiye de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul. -96-

98 PP 58 PHYTOCHEMICAL ANALYSIS, DYESTUFF POTENTIAL AND CYTOTOXIC ACTIVITY OF ANTHEMIS TINCTORIA VAR. TINCTORIA (ASTERACEAE) AYŞE ŞAHİN YAĞLIOĞLU, FERDA ESER, MELDA DÖLARSLAN 3, İBRAHIM DEMIRTAŞ DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND EDUCATION, GAZIOSMANPASA UNIVERSITY, 6040 TOKAT, TURKEY 3 DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY Anthemis species are used in pharmaceutics, cosmetics and food chemistry. Extracts of the plant are used as antiseptic, anti-inflammatory, antibacterial, antispasmodic, sedative agents, soothing the pain and irritation, ulcers and wound healing, treatment of cystitis and dental afflictions in folk medicine(). The plant is also used to dye fabrics for obtain yellow color (). In this study, Anthemis tinctoria var. tinctoria (Asteraceae) was collected from Çankırı. Species identification of the collected materials was performed. The parts of the plant were separated as flowers, stem and roots and dried at room temperature (5 C) in the shade. Ethanol and water extracts of each part were succesfully prepared by maseration method. The analysis of ethanol and water extracts were performed by HPLC-TOF/MS. HPLC-TOF-MS analyzes of the plant were resulted twelve compounds and, chlorogenic acid and apigenin-7-glikozit from water and ethanol extract of the stem; gentisic acid from the water extract of the stem; chlorogenic acid and 4-hydroxybenzoic acid from ethanol extract of the root; gentisic acid and 4-hydroxybenzoic acid from the water extract of the root as the main components. The obtained cytotoxic activities of all extracts were determined by LDH assays against C6 cells. The extracts were detected cytotoxic activities and was found to be less toxic than 5-fluorouracil used as a standard. Dyeing performance of the plant was also studied and the results were evaluated in terms of color strength (K/S). Best color strength values were obtained in the dyeing of cotton fabric (K/S=9.9; K/ S=8.50) fors tem and flowers, respectively.. Mann C., Staba, E. J., (986). The chemistry, pharmacology, and commercial formulations of chamomile. In: Herbs, Spices, and Medicinal Plants: Recent Advances in Botany, Horticulture, and Pharmacology, Vol. (Craker L. E. and Simon J. E., eds.). Oryx Press, Phoenix, AZ, pp Çakılcıoğlu U, Türkoğlu İ, Kürşat M. Harput (Elazığ) ve Çevresinin Etnobotanik Özellikleri, Doğu Anadolu Bölgesi Araştırmaları, 007; -8. PP 59 GC-MS ANALYSIS OF CENTAUREA VIRGATA LAM. (ASTERACEAE) HEXANE AND CHLOROFORM EXTRACTS AYŞE ŞAHİN YAĞLIOĞLU, MELDA DÖLARSLAN, FATIH AVCI, EBRU GÜL 3, İBRAHIM DEMIRTAŞ DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY 3 DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 800, CANKIRI, TURKEY The genus Centaurea L. (Asteraceae) is represented by a diversity of species, distributed in particular in southwest, central and east of the Turkey (). There are traditional uses of the some Centaurea species including antidiarrhoeic, antipyretic, diuretic, choleretic, antiinflammatory and antibacterial effects (). In this study, Centaurea virgata Lam. (Asteraceae) was collected from Çankırı. Species identification of the collected materials were performed. This plant were separated as flowers, steam and root and dried at room temperature (5 C) in the shade. The extracts of these materials were prepared hexane and chloroform, respectively, by maseration methods. The components of hexane and chloroform extracts were determined by GC-MS. As a result of GC-MS analyzes were detected components. The components were obtained as five mono saturated fatty acids, two mono unsaturated fatty acids, two polyunsaturated fatty acids and twelve other compounds. Taraxasterol from the flowers chloroform and the steam hexane extracts (6.44 and % respectively); palmitic acid from the steam and the root dichloromethane extracts (58.57 and % respectively); palmitoleic acid from the root hexane extract (38.7 %) were detected as the main components.. Wagenitz G (986). Centaurea in South-West Asia: Patterns of distribution and diversity, Proc. Royal Soc. Edinburgh 89: -.. Kargioglu M, Cenkci S, Serteser A, Konuk M, Vural G (00). Traditional uses of wild plants in the middle Aegean region of Turkey. Hum. Ecol. 38:

99 PP 60 PHYTOCHEMICAL ANALYSIS OF CRAMBE ORIENTALIS L. (BRASSICACEAE) AYŞE ŞAHİN YAĞLIOĞLU, MELDA DÖLARSLAN, TUĞÇE ÇOŞAR, EBRU GÜL 3, İBRAHIM DEMIRTAŞ DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY 3 DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 800, CANKIRI, TURKEY In the industrial area, Crambe L., which is promising one of the new plant contain percent 35-60% oil in oil the seeds and it also constitutes 57% erucic acid. Crambe L. due to this feature are used in many areas of industry, such as biodiesel, oil industry, machinery industry. Also after oil remaining portion is an important food source for animals (). In this study, Crambe orientalis L. (Brassicaceae) were collected from Çankırı. Species identification of the collected materials were performed. This plant were separated as flowers, leaves and stems and dried at room temperature (5 C) in the shade. The extracts of these materials which were acetone, chloroform, ethyl acetate and ethanol, extracts, respectively were prepared. The fatty acides of acetone and chloroform extracts by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by the HPLC-TOF/ MS were performed. As a result of GC-MS analyzes were detected compounds, palmitic acid and linolenic acid as the main component. The 6 different phenolic compounds were determined from HPLC-TOF-MS and were obtained 4-hydroxybenzoic acid and rutin as the main components.. Baytop, T Türkiye de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul. PP 6 GC-MS ANALYSIS OF THYPHA SHUTTLEWORTHII W. D. J. KOCH & SOND. (TYPACEAE) HEXANE AND DICHLOROMETHANE EXTRACTS AYŞE ŞAHİN YAĞLIOĞLU, MELDA DÖLARSLAN, EDA KIYMAZ, SELIN KÖKEN, EBRU GÜL 3, İBRAHIM DEMIRTAŞ DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY 3 DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 800, CANKIRI, TURKEY The root portion of Typha shuttlewortthi W. D. J.Koch & Sond. (Typaceae) is used urine enhancer and as urinary tract antiseptics in infusion. If the flower parts is used hernia and at treatment of burns as ointment which prepared with rancid oil (). In this study, Thypha shuttleworthii W. D. J.Koch & Sond.(Typaceae) was collected from Çankırı. Species identification of the collected materials were performed. This plant were separated as flowers, steam and root and dried at room temperature (5 C) in the shade. The extracts of these materials were prepared hexane and dichloromethane, respectively, by maseration methods. The components of hexane and dichloromethane extracts were determined by GC-MS. As a result of GC-MS analyzes were detected 4 components. The components were obtained as eight saturated fatty acids, two polyunsaturated fatty acids and thirty two other compounds. Palmitic acid (7.79 %) from the root dichloromethane, Sitosterol (0.7 %) from the root hexane extracts; lupeol and beta-amyrin from the flower dichloromethane extracts (48.7 and 8.68 % respectively) were detected as the main components.. Baytop, T Türkiye de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul. -98-

100 PP 6 PHYTOCHEMICAL ANALYSIS AND SOIL PROPERTIES OF CARDARIA DRABA (L.) DESV. SUBSP. DRABA (L.) DESV. (BRASSICACEAE) AYŞE ŞAHİN YAĞLIOĞLU, MELDA DÖLARSLAN, DUYGU GÜNEŞ, EBRU GÜL 3, İBRAHİM DEMİRTAŞ DEPARTMENT OF CHEMİSTRY, FACULTY OF SCİENCE, CANKİRİ KARATEKİN UNIVERSITY, 800 CANKİRİ, TURKEY DEPARTMENT OF BİOLOGY, FACULTY OF SCİENCE, CANKİRİ KARATEKİN UNIVERSITY, 800 CANKİRİ, TURKEY 3 DEPARTMENT OF FOREST ENGİNEERİNG, FACULTY OF FOREST, CANKİRİ KARATEKİN UNIVERSITY, 800, CANKİRİ, TURKEY Cardaria draba (L.) Desv. subsp. draba (L.) Desv. (Brassicaceae) is used as suppressors of gas and gain energy. Also, the plants young leaves are eaten salad (, ). This plant is perennial and known as Kediotu, Kır teresi and Yabanı Tere between people (). In this study, C. draba (L.) Desv. were collected from semi-aired soils which shows medium coarse (clay loam, sandy clay loam, loam), high acidic ( ph) and rich soil organic matter properties in Çankırı. Species identification of the collected materials were performed. This plant were separated as flowers, root and airel parts and dried at room temperature (5 C) in the shade. The extracts of these materials which were acetone, chloroform, ethyl acetate and ethanol extracts, respectively were prepared by maseration methods. The fatty acides of acetone and chloroform extracts by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by the HPLC-TOF/MS were performed. As a result of GC-MS analyzes were detected 3 compounds and palmitic acid as the main component. The 9 different phenolic compounds were determined from HPLC-TOF- MS and were obtained kaempferol, rutin, 4-hydroxybenzaldehyde ve 4 hydroxy benzoic acid as the main components..deniz L, Serteser A, Karlıoğlu M. Uşak Üniversitesi ve Yakın Çevresindeki Bazı Bitkilerin Mahalli Adları ve Etnobotanik Özellikleri, AKÜ Fen Bilimleri Dergisi, 00; 0: Çakılcıoğlu U, Türkoğlu İ, Kürşat M. Harput (Elazığ) ve Çevresinin Etnobotanik Özellikleri, Doğu Anadolu Bölgesi Araştırmaları, 007; -8. PP 63 MOMORDICA CHARANTIA CAN BE UPREGULATE ESTROGEN RESEPTORS ESRα/ESRβ GENE LEVELS IN OVARIECTOMY RATS OZGE CEVIK, HIKMET AKPINAR, RABIA OBA FACULTY OF PHARMACY MARMARA UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY CUMHURIYET UNIVERSITY, SIVAS, TURKEY Changes resulted by the decrease in 7-β Estradiol (E) and its replacement with Estrone hormone in menopause, both cause quality of life to reduce and various diseases to appear. Studies carried out recent years prove that, hormone replacement therapy has resulted in pathological consequences, and these studies recommend the use of alternative herbal approaches. In this study, we aimed at investigating the antioxidant effect of Momordica charantia (Bitter melon) on experimental ovariectomized rats and the changes in estrogen receptor gene levels (ESR-α, ESR-β). In the study, overectomy model was composed by ligaturation and applied fruit extract of Momordica charantia (MCE, g/kg orally) for 30 days. Serum E levels were observed by ELISA, tissue cytokine levels (TNF-alpha, IL-6, IL-0) and NF-kB protein expressions were measured by western blotting. Estrogen genes ESR-α, ESR-β were observed by RT-PCR. In our findings, serum E decreased in overectomy group (p<0.05) and reduced by the application of MCE (p<0.05). MCE suppressed pro-inflammatory cytokines as TNF-α and IL-6 in uterus tissue (p< ). On the other hand, the IL-0 levels were up regulated with MCE treatment (p<0.0). While ESR-α, ESR-β gene were reduced in overectomy, increase was observed by means of MCE application (p< ). In consequence; Momordica charantia plant has displayed an effect on ovariectomized rats in both gene and protein level, by the effect of phytoestrogen and antiinflammatory; and it may contribute to the development of new medicine that can be used in the period of menopause. -99-

101 PP 6 64 PHYTOCHEMICAL ANTIOXIDANT AND ANALYSIS ANTI-APOPTOTIC AND SOIL EFFECT PROPERTIES OF MOMORDICA OF CARDARIA CHARANTIA DRABA (L.) ON DESV. UTERUS SUBSP. TISSUE DRABA IN OVARIECTOMY (L.) DESV. RATS OZGE CEVIK, HIKMET AKPINAR, RABIA OBA CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY Aging and hormonal regulation differences can trigger oxidative stress which is mainly due to an increased production of oxygen free radicals and a suppression of antioxidant defensive. Momordica charantia (MC) is composed of special biologically active chemicals. The present study was designed to investigate the effect of MC on anti-apoptotic proteins and oxidative stress status on a postmenopausal rat model. In the study, overectomy model was composed by ligaturation method and gavage with g/kg fruit extract of Momordica charantia (MCE) applied on the rats during 30 days. Oxidative stress markers (8-OHdG,MDA,GSH,SOD,MPO) were measured. For apoptotic status in tissue were analyzed pro-caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, Bcl- by western blotting. In our findings, increasing serum 8-OHdG levels on ovariectomized rats were reduced by MCE application. It was observed that the MCE increased SOD,GSH considerably that had been reduced in overectomy; and reduced increasing MDA,MPO (p< ). Concerning extrinsic and intrinsic apoptosis, the caspase-3 protein expression levels increased in OV group rat uterine tissue (p<0.05) and decreased with MCE treatment (p<0.0). At the same time, our data showed that pro-caspase-9 protein expression in the OV group elevated (p<0.05) while this increase was reversed with MCE treatment (p<0.0). MCE treatment Bcl- protein expression was higher than that in OV group (p<0.0). This study showed that MC fruit extract has a potential antioxidant effect as radical scavenging activity of the extract against radicals which include bioactive molecules. In addition to MCE treatment decreased uterine apoptotic stimulation in ovariectomy rats. PP 65 ESTROGENIC EFFECTS OF MOMORDICA CHARANTIA IN HISTOLOGICAL CHANGES ON UTERUS TISSUE RABIA OBA, HIKMET AKPINAR, OZLEM TUGCE CILINGIR, ZARIFE NIGAR OZDEMIR 3, SULE CETINEL, OZGE CEVIK 4 MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY 3 MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHYSIOLOGY 4 CUMHURIYET UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY Estrogens are 8-carbon steroid hormone which are very high hormone levels in reproductive aged-women. The amount of estrogen produced by the ovary is a significant downward after menopause. In recent years there has been increased the use of phytoestrogens in the treatment of menopause. In this study, we aimed at investigating the effect of Momordica charantia (MC) and structural changes of uterus tissue on experimental ovariectomized rats. In the study, overectomy model (OV) was used and MCE applied with gavage (g/kg) for rats. The weight of the rats was recorded every the third day and uterine weight was measured after the decapitation. Uterus tissue samples were fixed in 0% formaldehyde and hematoxylin-eosin staining were performed for light microscopic evaluations. It is known that body weight is inversely to relation with uterine weight in ovariectomy. Uterine/BW ratio decreased in the OV group (p<0.00) and reversed with MCE (p<0.05). In overectomized rats we detected cell infiltration related with the loss of cytoplasm in epithelial cells. Irregular endometrial stroma was detected in estradiol applied group. Compare with overectomized group epithelial cells have more regular morphology and less cell infiltration were observed. In comparison with the overectomized group, MCE applied group has more regular surface epithel and uterus glands which are more like control group. In contrast with overectomized group very less amount of neutrophil infiltration has observed. MC suppressed cell damage in uterus tissue in ovariectomized rat which has therapeutic potential to prevent the development of cell degenerative complications. -00-

102 PP 66 MOMORDICA CHARANTIA AND ESTRADIOL IMPACT OXIDATIVE STRESS RESPONSES ON LIVER IN OVARIECTOMIZED RAT RABIA OBA, HIKMET AKPINAR, ZARIFE NIGAR ODEMIR, OZLEM TUGCE CILINGIR 3, SULE CETINEL 3, OZGE CEVIK 4 MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHYSIOLOGY 3 MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY 4 CUMHURIYET UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY The lack of protective action of estrogens (E) is known to cause serious metabolic disturbances, and oxidative stress is thought to be one of the suspected mechanisms. To estimate the impact of MCE Estrogen deficiency on the oxidative and antioxidative status in the liver of the ovariectomized rats. Female rats were separated into four groups: (i) sham ; (ii) ovariectomy (OV) rats; (iii) OV+E (50 µg/kg, im) and (iv)ov+mce (g/kg, orally). The histopathological assessment of the liver was performed using hematoxylin and eosin staining. Histological preparations were evaluated in the light microscope. The tissue levels of oxidative status markers such as MDA,GSH,SOD, CAT, GST and MPO levels were measured in liver. Liver GSH and CAT levels were significantly increased in MCE or EST treated rat when compared to OV. SOD and GST increasing were not significantly. The levels of MDA were significantly increased in OV group. EST or MCE treated rats had significant reductions in MDA levels in liver compared to sham. There was no big changing in MPO levels for each group. OV group, hepatic tissue showed extensive cytoplasmic lacking and activated Kupffer cells. Necrosis, hepatocyte apoptosis, nonparenchymal cell apoptosis, and macroscopic and microscopic peliosis were markedly reduced or minimized in MCE treated rats. In summary, MCE treatment also induced antioxidant molecules/enzymes and inhibited lacking of estradiol-mediated increase in oxidative damage in liver tissues. Decreased oxidative stress, and increased cell regeneration and formation in MCE rats suggested a protective role of phytoestrogen against oxidative stress induced ovariectomized degeneration. PP 67 EVALUATION OF ESTROGENIC EFFECTS OF MOMORDICA CHARANTIA ON THE KIDNEY OF OVARIECTOMIZED RATS RABIA OBA, HIKMET AKPINAR, ZARIFE NIGAR OZDEMIR, OZLEM TUGCE CILINGIR 3, SULE CETINEL 3, OZGE CEVIK 4 MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHYSIOLOGY 3 MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY 4 CUMHURIYET UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY Momordica charantia (MC) is a medicinal plants that have served through the ages as the mainstay in the treatment of variety of diseases and preservation of human health. Estrogen (E) has been demonstrated to exert beneficial effects on kidney. Consequently, the aim of the present study is to investigate the estrogenic effects of MC fruit extract (MCE) on the kidney of rats. Female rats were separated into four groups: (i) sham ; (ii) ovariectomy (OV) rats; (iii) OV+E (50 µg/kg, im) and (iv) OV+MCE (g/kg, orally). A structural change in kidney was examined on the light microscope by means of H&E staining. The tissue levels of oxidative status markers such as MDA,GSH,SOD, CAT, GST and MPO levels were measured in kidney. Kidney MDA levels increased in OV and decreased with MCE or EST treatment. SOD, GST and MPO levels were not significantly different among treatment with OV. GSH and CAT levels increased with MCE or EST treatment in OV rats. Control animals showed normal kidney histology. The glomeruli were well demonstrated with normal bowman space. OV kidney showed atrophy of the glomeruli and the tubules were fairly preserved. Administration of the extracts and EST improves cellular regeneration which is quite prominent in OV. The histopathological findings indicated that there were no histopathological lesions observed in the OV experimental groups treated with MCE fruit extract. From this study, we inferred that Momordica charantia administered in OV rats have antioxidant and protective properties that could prevent damage to the kidneys. -0-

103 PP 68 PROTECTIVE EFFECTS OF POLYGONUM COGNATUM MEISSN AGAINST STZ INDUCED DIABETES ON PANCREATIC TISSUE OZGE CEVIK, RABIA OBA 3, OZLEM TUGCE CILINGIR, SULE CETINEL, OZLEM OZAKPINAR 3, HALIL AKSOY 3, DERYA OZSAVCI 3, AZIZE SENER 3 CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL, TURKEY 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY Diabetes mellitus is major endocrinological problem for worldwide. It is known that pancreatic beta-cell dysfunction involve in diabetes and this condition produce oxidative stress. Medicinal plants play an important role in the treatment of diabetes mellitus and there are many and different therapeutic strategies in the management of diabetes. To investigate the role of Polygonum cognatum meissn (PCM) plants in the progression of pancreas in type diabetes, we evaluated STZ induced diabetic rat model. Cytotoxicity of PCM different concentration (,, 4, 8 and 6 mg/ml) were measured with MTT assay in NIH- 3T3 mouse fibroblast. Diabetes was induced in rats using single dose of 45 mg/kg STZ and PCM was studied orally g/kg for 0 days. Pancreatic tissue MDA, MPO, GSH and SOD levels was elevated in diabetic rats. Tissue damages were observed from H&E staining examination. MTT assay showed that the lower dosed PCM was found more effective for cell viability. Oral administration of PCM to diabetic rats resulted in a decrease in the levels MDA (p 0.00) and MPO levels (p 0.00) compare to diabetes group. PCM also resulted in the incerases of SOD and GSH coming to near control (p ). These results indicate that PCM ameliorated the diabetes-induced changes in oxidative stress. PCM can contribute to development a new therapeutic target for diabetes mellitus. PP 69 ANTIOXIDANT EFFECTS OF POLYGONUM COGNATUM MEISSN ON RAT LIVER TISSUE IN STZ INDUCED DIABETIC MODEL RABIA OBA, OZLEM TUGCE CILINGIR, SULE CETINEL, OZGE CEVIK 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL, TURKEY 3 CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY Diabetes mellitus is known that a metabolic disorder and characterize by hyperglycemia, abnormal lipid, and protein metabolism. Whatever the complication can be insulin targeting tissue mainly in liver, skeletal muscle, and adipocytes in early stage of diabetes. In this study we investigated effects of Polygonum cognatum meissn plants on liver tissue in diabetic rats. PCM aqueous extract was prepared by fresh leaves. Diabetes was induced in rats using single dose of 45 mg/kg streptozotocin (STZ) and rats selected randomly as control, diabetes, PCM groups. PCM was given orally g/kg dose for 0 days to STZ-induced diabetic rats. End of 0 days rats liver tissues collected for analysis MDA, MPO, GSH and SOD levels. Liver tissue histopathological changes were observed with haematoxylin-eosin staining. Liver MDA (p 0.0) and MPO (p 0.00) levels were decreased versus to diabetes groups. The elevated liver levels of GSH, which is a small peptide that is an indicator of anti-oxidative status, were significantly increased in diabetic rats applied PCM group. Similarly, the Liver SOD activity was also improved in PCM group versus to diabetic groups (p 0.05), there was no significantly changing versus to control groups. Histological data showed that PCM has a effective on hepatic proliferative and regenerative response. These results from the scientific basis supporting the oral administration of PCM extracts to the diabetic rats slightly improved antioxidant molecules and also alleviated various oxidative stress indices of the liver of the diabetic rats. -0-

104 PP 70 EFFECT OF POLYGONUM COGNATUM ON HISTOLOGICAL STRUCTURE OF KIDNEY IN STZ-INDUCED DIABETIC RATS RABIA OBA, OZLEM TUGCE CILINGIR, SULE CETINEL, OZGE CEVIK 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL, TURKEY 3 CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY Complementary and alternative therapy is treatments that are more popular studies for diabetes metabolism in animal models. Diabetes has long-term complication affecting the retina, kidney, and nervous system; thirty percent of diabetic patients develop nephropathy. The aim of our study was the screening for oxidative status on kidney tissue model used Polygonum cognatum meissn treatment in diabetic rats. PCM was collected and aqueous extract prepared with homogenization from fresh leaves. Rats were orogastrically treated with PCM (g/kg) throughout a 0-day interval after diabetes, which was induced by intraperitonal administration of STZ (45 mg/kg). Control and diabetic group was orally administered only isotonic saline. End of 0 days of PCM administration, rats kidney tissues collected and was stored at -800C until for the detection of MDA, MPO, GSH and SOD levels. Assessment of kidney damages was stained with hematoxylin and eosin for general morphology analysis. The levels of MDA, which is a major degradation product of lipid peroxidation, were significantly decreased in PCM group with respect to diabetic group (p 0.0). However, in the diabetic group, treated with PCM, diabetes-induced increases in MPO activity were significantly inhibited (p 0.00). The GSH and SOD levels were significantly increased in diabetic rats with PCM treatment (p<0.00). By HE staining the diabetic groups showed serious histological modifications. PCM rats kidney had alterations in organized tubular structure, decreasing tubular vacuolization and increasing regeneration. These findings emphasize that PCM is not only antioxidant effects but may also provide therapeutic targets to the prevention of diabetic complications. PP 7 REGULATION OF INSULIN RECEPTOR SUBSTRATE (IRS) GENES IN THE PANCREAS OF DIABETIC RATS SUBMITTED TO POLYGONUM COGNATUM MEISSN OZGE CEVIK, RABIA OBA CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling and mediate different biological signals such as growth, survival, and metabolism. The objective of the present study was to evaluate anti-diabetic effects of Polygonum cognatum meissn (PCM) in type diabetic rats. Rats were made diabetic using single dose streptozotocin (45 mg/kg)and PCM applied for 0 days. Rats were monitored for 0 day for adverse side effects, blood glucose, and insulin requirements and were sacrificed under anesthesia, and the pancreas was immediately removed and placed into cold lysis buffer for protein and gene analyses. Western blotting, RT-PCR and ELISA assay analyses were completed to evaluate protein and gene levels. Circulating serum glucose concentrations decreased (p 0.05)and insulin concentrations increased (p 0.0) in diabetic rats treated with PCM. Expression of Bcl- protein in the pancreas was greater in diabetic rats treated PCM, as compared with diabetic rats (p 0.0). PI3-kinase expression reduced in pancreases tissue of diabetic rats (p 0.05) compare to control while in PCM treatment groups was not significantly changes. Phopsho-AKT activation was increased with PCM administration. A significant decrease in IRS- (p 0.0) and IRS- (p 0.05) gene levels were observed in the diabetic pancreas. On the other hand IRS- gene level was increased with PCM administration (p 0.00) but IRS- was not change. Taken together, these data indicate that PCM trigger to IRS- mediating metabolic effects of insulin in pancreas tissue, and upregulation of IRS in β cells could be prevent or treat for β cell failure and many forms of diabetes. -03-

105 PP 7 INHIBITION OF PANCREATIC LIPASE BY CULINARY PLANT EXTRACTS DAMLA ANBAR, AYŞE OGAN, CİHAN GÜNDÜZ, ÖZKAN DANIŞ, MUSTAFA MUHLİS ALPARSLAN, MUSTAFA BULUT, SEDA YILMAZ, ÜMİT SALAN FACULTY OF PHARMACY MARMARA UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY CUKUROVA UNIVERSITY, ADANA, TURKEY Obesity is a strong risk factor for various diseases, such as hypertension, arteriosclerosis and diabetes ().Therefore, an effective way to prevent obesity is to inhibit fat absorption from intestines. Pancreatic lipase (PPL) is a key enzyme for lipid absorption. Only a few substances such as orlistat (tetrahydrolipstatin) interact directly with lipases but, causes unpleasant side effects on gastrointestinal system and kidneys (). One of the approaches to reduce obesity is treatment with natural products. Many plants have been reported to inhibit lipase activity which is attributable to the presence of secondary metabolites such polyphenols, benzopyrones whose members include flavonoids, saponins, coumarins etc. are active inhibitors of PPL (3). In our study using porcine pancreatic lipase, a series of plants were screened for their pancreatic lipase) inhibitory activities and compared to lipase inhibitory activities of coumarin derivatives synthesized in our laboratory According to the results; green tea, green apple and avocado extracts had the highest antilipase activities however coumarin derivaties displayed no considerable antilipase activities.. Kopelman PG. Obesity as a Medical Problem. Nature. 000;404: Ballinger A, Peikin SR. Orlistat: Its Current Status As an Anti-Obesity Drug. Eur J of Pharmacol. 440;00: de la Garza AL, Milagro FI, Boque N, Campion J, Martinez JA. Natural Inhibitors of Pancreatic Lipase as New Players in Obesity Treatment. Planta Med.0;77: PP 73 EVALUATION OF DNA DAMAGE IN PETROL STATION PUMPERS OCCUPATIONALLY EXPOSED TO PETROL VOLATILE PINAR SINEM OMURTAG, NEBAHAT AKDEMIR, AYFER TOZAN-BECEREN, GÜLDEN ZEHRA OMURTAG 3, SEMRA ŞARDAŞ DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND LETTERS, ISTANBUL TECHINICAL UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY 3 DEAN OF MARMARA UNIVERSITY, ISTANBUL,TURKEY According to the International Agency for Research on Cancer (IARC), exposure of petrol volatile is classified as human carcinogen. Petrol station workers are potentially exposed to a wide range of petroleum-derived such as hydrocarbons and chemical substances. Benzene, toluene and xylene are produced by distillation in the aromatic units and used as raw materials for petrol and petrochemical products. This study deals with evaluation of the genotoxic effects of occupational exposure to benzene, toluene and xylene in the petroleum station workers in Istanbul, Turkey. The workers in petrol station who were volunteers for this study (n=5) were selected randomly and controls (n=4) from the general population with no history of occupational exposure. The comet assay was used to evaluate effects of occupational exposure to petrol volatile on DNA damage (). In the light of the results, it can be said that exposure to petrol and petroleum products have a potential to give genotoxic damage. To support these results other methods can be used with Comet assay technique to evaluate the DNA damage coming from petroleum derivatives.. Karabıyık L, Şardaş S, Polat U, Kocabaş NA, Karakaya AE. (00). Comparison of genotoxicity of sevoflurane and isoflurane in human lymphocytes studied in vivo using the comet assay. Mutat Res, 49:

106 PP 74 INVESTIGATION OF ANTIOXIDANT S ANTIMUTAGENIC EFFECTS BY THE AMES TEST AYFER TOZAN-BECEREN, BETÜL SARIKAYA, GÜLDEN ZEHRA OMURTAG, SEMRA SARDAS DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Nowadays, several test systems have been developed in order to observe the mutagenic effects of chemical agents which play crucial roles in human health. The Ames Test is one of these test systems. With the Ames Test, some bacterial mutants have been discovered to investigate the mutagenic effects of the chemicals. Various strains of Salmonella typhimurium are one of the groups of the bacterial mutants in question. The aim of this study is to investigate possible antimutagenic effect of Pelargonium sidoides which have an antioxidant effect towards carcinogenic substance called -Aminofluorene by Ames/ Salmonella/Microsome test kit in the absence and presence of metabolic activation. TA 98 and TA 00 strains were used in these experiments. TA 98 is designed for frame-shift mutagens and TA 00 is designed for base-pair mutagens. The antimutagenic activity was screened in two groups with or without S9 metabolic activation. The results were evaluated the mean average values and compared with positive and negative controls. In conclusion, it was shown that Pelargonium sidoides have antimutagenic effect towards TA 98 and TA 00 without S9 metabolic activation (p>0.05) but have no antimutagenic effect towards TA 98 and TA 00 with S9 metabolic activation (p<0.05). PP 75 SYNTHESIS OF NOVEL HYDRAZIDE-HYDRAZONES DERIVED FROM TOLMETIN AS ANTICANCER AGENTS DERYA KOÇ, PELİN ÇIKLA-SÜZGÜN, ÖZLEM BİNGÖL-ÖZAKPINAR, DERYA ÖZSAVCI, Ş.GÜNİZ KÜÇÜKGÜZEL MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPAŞA İSTANBUL, TURKEY. MARMARA UNIVERSITY, FACULTY OF PHARMACY,DEPARTMENT OF BIOCHEMISTRY, HAYDARPAŞA İSTANBUL, TURKEY Tolmetin ([-methyl-5-(4-methylbenzoyl)-h-pyrol--il]acetic acid), is a non-steroidal anti-inflammatory drug which acts by inhibiting prostaglandin synthesis [,]. Tolmetin, reported antitumor effect on colon cancer [3] and investigated for biochemical modulator of anticancer drugs [4]. Tolmetin is used as a starting compound for the synthesis of [-methyl-5- (4-methylbenzoyl)-H-pyrol--yl]acetic acid hydrazide and related hydrazide-hydrazones. A novel series of new tolmetin hydrazide derivatives, -[-methyl-5-(4-methylbenzoyl)-h-pyrol--yl]-n-[(substitutedphenyl/5-nitro--furyl)methylidene] acetohydrazide hydrazones have been synthesized in this study. The characterization of these compounds were identified by the help of elemental analysis, UV, IR and H-NMR spectral data while the purities of them were proved with elemental analysis and TLC. Tolmetin and -[-methyl-5-(4-methylbenzoyl)-h-pyrol--yl]-n-[(,6-dichlorophenyl)methylidene]acetohydrazide [4g] (SGK 47) were evaluated for cell viability and growth inhibition by HCT-6 (ATCC, CCL-47) and HT-9 (ATCC, HTB-38) of MTT assay and cytotoxicity at different doses (0-6-0-M). Compound 4g exhibited anticancer activity with IC50 value 76 µm against colon cell line HT-9 and did not displayed cytotoxicity towards NIH3T3 rat fibroblast cell compared tolmetin. Apoptosis levels of compound 4g were determined. -05-

107 PP 76 RHEOLOGICAL EVALUATION OF DICLOFENAC DIETHYLAMINE CONVENTIONAL GEL, EMULGEL, AND A NANOEMULSION-BASED GEL FORMULATION RANIA HAMED AL-ZAYTOONAH UNIVERSITY OF JORDAN The objective of this study was to prepare a nanoemulsion-based gel formulation (nanogel) of diclofenac diethylamine amine (DDEA) in.5%w/w Carpobol 934 as a potential vehicle for transdermal drug delivery and to compare the rheological properties of DDEA nanogel with those of a conventional DDEA gel and emulgel. Twenty-seven o/w nanoemulsion formulations containing.6%w/w DDEA were prepared. Nanoemulsions were evaluated for thermodynamic stability and characterized for mean droplet size (MDS) and polydispersity index (PDI). The optimized DDEA nanoemulsion, and DDEA conventional gel and emulgel were dispersed in.5%w/w Carpobol 934. Oscillatory rheological analysis of the gels was performed where the storage modulus G and loss modulus G were determined over a frequency range of -00 rad/sec. Based on the pseudo-ternary phase diagram and solubility studies, the optimized DDEA nanoemulsion was composed of.6%w/w DDEA, 0%w/w oleic acid, 55%w/w Smix (Tween 0:ethanol, :), and 34%w/w distilled water. MDS of nanoemulsions was ~0 nm with an average PDI of 0.5. DDEA gel, emulgel and nanogel exhibited elastic behavior where G dominated G at all frequencies. Conventional gel exhibited higher G and G values than emulgel, which indicated the formation of a strong gel network. Nanogel exhibited the lowest rheological properties. DDEA conventional gel, emulgel, and nanogel dispersed in.5%w/w Carpobol 934 exhibited different rheological properties with nanogel exhibited the least elastic and viscous properties. Understanding these properties is crucial to predict the in vitro permeation of drugs from these systems and their potential to enhance skin penetration. PP 77 THE EFFECT OF POLYMER PROPERTIES ON THE IN VITRO RELEASE OF QUETIAPINE FUMARATE, A BCS CLASS II DRUG, FROM A CONTROLLED RELEASE MATRIX TABLETS RANIA HAMED, LINA HAMMAD, AIMAN ABBAS AL-ZAYTOONAH UNIVERSITY OF JORDAN HIKMA PHARMACEUTICALS The aim of this study was to prepare oral controlled release matrix tablets (MT) of BCS class II drug, Quetiapine Fumarate (QF), using a range of release controlling polymers with different properties, and to correlate these changes with the rheological properties of the polymer gels and the in vitro release of the drug. Two sets of MT were prepared: () MT composed of different blends of the hydrophilic hydroxypropylmethylcellulose (HPMC) polymer of different viscosity grades (HPMC K00LV and HPMC K4M), and () MT composed of various blends of HPMC K00LV polymer with the hydrophobic polymer, polyethyleneglycol behenate (GB HD5 ATO). The in vitro release of QF from the MT and rheological characterization of gels following tablet hydration were assessed. For hydrophilic MT, as the proportion of the more viscous HPMC K4M increased, time for 50% and 90% QF release decreased significantly. QF release from MT containing a combination of HPMC K00LV and GB HD5 ATO, was higher than that of the hydrophilic MT. QF release from the hydrophilic HPMC MT tablets was found to correlate with the storage modulus G and loss modulus G of the gel formed from their hydration. The hydrophilic gel G and G values were found to be 00-fold higher than the gel formed from the hydration of HPMC:GB HD5 ATO blends, which explains the lower release rates from hydrophilic MT. QF release rate from MT is affected by polymer properties and correlated with the rheological properties of the gels formed from polymer hydration. -06-

108 PP 78 THE USE OF PERFORMANCE ENHANCING DRUGS IN 6- AGE GROUP ALPINE DISCIPLINE SKIERS AND SOCCER PLAYERS İ.BANU AYÇA, ŞINASI ÜNAL, ATILA ABDULLAHI MARMARA ÜNİVERSİTESİ BEDEN EĞİTİMİ VE SPOR YÜKSEKOKULU, ISTANBUL, TURKEY 55 soccer players and 5 Alpine discipline skiers living in the Macedonia were randomly surveyed regarding their knowledge and usage certain medications for the purpose of enhancing their sports performance.results were evalated in the sense of frequency(f) and percentage distiribution (%) by using SPSS 5.0 package program. 7.7%(f:40) of soccer players and 80.0%(f:0) of skiers though that drugs have a positive effects on sports performance. The soccer players and skiers were asked to name the drugs that could be used performance enhancement ; the soccer players 63.6%(f:35) replied as vitamins,4.5%(f:8) replied as anabolic steroids; the skiers 60%(f:5) replied as anabolic steroids,36%(f:9) replied as vitamins and central nervous system stimulants.the soccer players and skiers reported that to use vitamins (B,B,B6,B and C vitamin) as orally and injectable form. 7.3% (f:5) soccer players and 6.0%(f:4) skiers reported to use drugs for enhancing their performance. Among the drug used players ; 86.7%(f:3) soccer players and 50%(f:) skiers reported to use drugs one a day for the whole year.80%(f:44) soccer players and all of the skiers (f:5) thought that drugs have side-effects.56.4%(f:3) soccer players and 56% (f:4) skiers thought that the main potential side-effects of the drug used were reported as dependency. 76.4%(f:4) soccer players and 84%(f:)skiers thought that drug used in sports have the main effects of increasing endurance.the results of the questionnaire suggests that drug-use with the aim of performance-enhancement was not common among 6 to age group the soccer players and skiers,and they were not adequately informed on the effects and side-effects of the drugs. PP 79 ASSESMENT OF ENERGY-DRINK AND VITAMIN SUPPLEMENT UTILIZATION PROFILE OF 0-4 AGE GROUP CHILDREN FROM DIFFERENT SPORTIVE BRANCHES İ.BANU AYÇA, VOLKAN ŞIRINOĞLU MARMARA ÜNİVERSİTESİ BEDEN EĞİTİMİ VE SPOR YÜKSEKOKULU,ISTANBUL,TURKEY TEŞVIKIYE SPOR KLUBÜ,ISTANBUL,TURKEY The aim of this study was to assess the ergojenic aid, energy-drink and vitamin-mineral combination supplement utilization profile of 0-4 age group children. It was conducted on 60(5 girl and 45 boy)children from 6 different (tennis,swimming,waterpolo,track and field,basketball,volleyball) sportive branches.the players were asked to fill in a standart questionnaire, where information about their utilization profiles of energy-drinks, ergojenic aid and multivitamin-mineral combination supplements were sought trough various questions. Results were evaluated in the sense of frequency(f) and percentage distribition(%) by using SPSS 5.0 package program. Among the 5 girl players ; 3% (f:36)reported to use multivitamin-mineral combination supplements, 6.5% (f:9) reported to use ergojenic aid and.7% (f:) reported to use protein powder % (f:97) of the girl players reported to consume energy-drinks.49.5%(f:48) of them reported to make their choices according to the taste; while,7.5% (f:7) made their choices according to the ingredients. Among the 45 boys ; 37.93%(f:55) to use multivitamin-mineral combination supplements, 3%(f:45) reported to use ergojenic aid,.%(f:3) reported to use protein powder. 9.4% (f:34) of the boy players reported to consume energy-drinks. 56% (f:75) of them reported to make their choices according to the taste; while,.9% (f:6) made their choices according to the ingredients. All users of vitamins; they reported to use multivitamin-mineral combination supplements once a day for every month or reported to use them one a day throught the training days.the results of the questionnaire suggest that energy-drinks and multivitaminmineral combination use were common among children players.they must be informed on the effects, adverse effects of these supplements. -07-

109 PP 80 EVALUATION OF DRUG, NUTRITIONAL SUPPLEMENT AND VITAMIN USAGE HABITS OF AMATEUR GOLF PLAYERS WHO ARE MEMBER OF GOLF CLUB İ.BANU AYÇA, ŞEHMUS IŞIK MARMARA ÜNİVERSİTESİ BEDEN EĞİTİMİ VE SPOR YÜKSEKOKULU,ISTANBUL, TURKEY KEMER GOLF&COUNTRY CLUBS, ISTANBUL, TURKEY A survey was applied on 50 (5 female, 5 male) amateur golf players who are member of a golf club in İstanbul and it was aimed to evaluate their drug, nutritional supplement and vitamin usage habits. Results were evaluated in the sense of frequency (f) and percentage distribution (%) by using SPSS 5.0 package program. 40% (f:0) of amateur golf players think vitamins positively effect performance at golf. 5% (f:6)of participants stated they use nutritional supplement % (f:4) of them reported to use amino acid/protein powders. 76.9% (f:0) of nutritional supplement users stated the reason for using is muscle hypertrophy and to prevent injuries. All of the players reported to use vitamin, 0% (f: 0) of them stated vitamins regulate metabolic cases, 6% (f: 8) stated vitamins enhance immune system. They stated that the reason for using vitamins is to gain resistance against diseases 36% (f:8). Factors which have effect on choice of trademark are 40% (f: 0) product ingredient.60% (f: 30) of participants stated they obtain vitamin from pharmacy. 40% (f: 0) of participants stated they use vitamin a few days in a week, 8% (f: 4) stated they use regularly. In case of any health problem, 38% (f: 9) of participants stated that they use drugs which they have used in similar occasions before. 74% (f: 37) of participants stated they bought product from herbalists. As a result ; amateur golf players do not have sufficient knowledge about performance enhancing drugs at golf sport, however they use vitamins commonly which they believe to have positive effect on performance. PP 8 PLANTS USED FOR LITHOTRIPSY IN TRADITIONAL MEDICINE SHAMIM SAHRANAVARD, SOMAYEH ESMAEILI TRADITIONAL MEDICINE AND MATERIA MEDICA RESEARCH CENTER, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN DEPARTMENT OF TRADITIONAL PHARMACY, SCHOOL OF TRADITIONAL MEDICINE, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN The prevalence and incidence of kidney stones is increasing globally. Kidney stone formation is usually due to genetic and environmental factors (). The introduction of new techniques for removing stones has improved the management of urolithiasis, but recent studies show that they associated with several adverse effects (). Some herbal remedies have long been used to treat urinary stone disease, therefore might be an alternative treatment with an effective, safe and culturally acceptable nature of urinary stones (3). In this study, we investigated plants used in breaking the calculi in the most famous Iranian traditional medicine books including Canon, al-hawi, al-abniah an Haqaeq al Adwia and Tuhfat al-mu minin and selected those which were effective in managing this condition. Seventeen plants were identified as herbal remedies to treat urolithiasis by breaking stones.the plants were identified by matching their names with scientific names using different comprehensive glossaries. We also searched scientific literature for pharmacological evidence of their effectiveness. Data showed that eight different genera of these plants have been pharmacologically investigated and exhibited significant anti-urolithiasis activity. - RomeroV, Akpinar V, Assimos D.G.Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors. Rev Urol. 00; (-3): Ghalayini IF, Al-Ghazo, Harfeil M.N.A. Prophylaxis and therapeutic effects of raspberry (Rubus idam.aeus) on renal stone formation in Balb/c mice. International Braz J Urol. 0; 37 (): Guerocak S, Kuepeli B. Consumption of Historical and Current Phytotherapeutic Agents for Urolithiasis: A Critical Review. J Urol. 006; 76:

110 PP 8 PLANTS USED FOR LITHOTRIPSY IN TRADITIONAL MEDICINE SAEEDEH GHAFARI, SHAMIM SAHRANAVARD, SOMAYEH ESMAEILI TRADITIONAL MEDICINE AND MATERIA MEDICA RESEARCH CENTER, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN DEPARTMENT OF TRADITIONAL PHARMACY, SCHOOL OF TRADITIONAL MEDICINE, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN The prevalence and incidence of kidney stones is increasing globally. Kidney stone formation is usually due to genetic and environmental factors (). The introduction of new techniques for removing stones has improved the management of urolithiasis, but recent studies show that they associated with several adverse effects (). Some herbal remedies have long been used to treat urinary stone disease, therefore might be an alternative treatment with an effective, safe and culturally acceptable nature of urinary stones (3). In this study, we investigated plants used in in the most famous Iranian traditional medicinebooks including Canon, al-hawi, al-abniah an Haqaeq al Adwia and Tuhfat al-mu minin and selected those which were effective in managing this condition. Seventeen plants were identified as herbal remedies to treat urolithiasis by breaking stones.the plants were identified by matching their names with scientific names using different comprehensive glossaries. We also searched scientific literature for pharmacological evidence of their effectiveness. Data showed that eight different genera of these plants have been pharmacologically investigated and exhibited significant anti-urolithiasis activity. - RomeroV, Akpinar V, Assimos D.G.Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors. Rev Urol. 00; (-3): Ghalayini IF, Al-Ghazo, Harfeil M.N.A. Prophylaxis and therapeutic effects of raspberry (Rubus idam.aeus) on renal stone formation in Balb/c mice. International Braz J Urol. 0; 37 (): Guerocak S, Kuepeli B. Consumption of Historical and Current Phytotherapeutic Agents for Urolithiasis: A Critical Review. J Urol. 006; 76: PP 83 5-HTTLPR&BDNF VAL66MET POLYMORPHISMS AND MAJOR DEPRESSION PATIENTS TREATED WITH CITALOPRAM ZUHAL UÇKUN, HATICE ÖZDEMİR, BORA BAŞKAK 3, ERGUVAN TUBA ÖZEL KIZIL 3, HALISE DEVRIMCI ÖZGÜVEN 3, SINAN SÜZEN 3 DEPARTMANT OF TOXICOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF MERSIN, MERSIN, TURKEY DEPARTMANT OF PSYCHIATRY, FACULTY OF MEDICINE, UNIVERSITY OF KIRIKKALE, KIRIKKALE,TURKEY 3 DEPARTMANT OF PSYCHIATRY, FACULTY OF MEDICINE, UNIVERSITY OF ANKARA, ANKARA, TURKEY The aim of this study was to determine the relationship between 5-HTTLPR&BDNFVal66Met polymorphismsand the response to citalopram (CIT, 0-40 mg/day) in major depression patients. Fourty-six patients with major depression were determined according to Diagnostic and statistical manual of mental disorder-iv criteria (DSM-IV) and were genotyped for 5-HTTLPR&BDNF Val66Met polymorphism using PCR and PCR-RFLP techniques, respectively. Clinical response to CIT was determined by 7 items Hamilton rating scale (HAM-D). For 5-HTTLPR&BDNF Val66Met, the results were obtained 36 (78%) subjects for treatment response (R+) and 0 (%) subjects for treatment nonresponse (R-). There were statistically not difference in between R+ subjects and R- subjects. In terms of odds ratio,odds ratio for LL + LS genotypes versus SS genotypes and L allele versus S allele were,333 (95% CI , p>0.05), and.57 (95% CI , p>0.05), respectively. Also, odds ratio for Val/Met + Met/Met genotypes versus Val/Val genotype and Met allele versus Val allele were.857 (95% CI , p>0.05), and.888 (95% CI , p>0.05), respectively. In spite of statistically insignificant data, it could be reached predictive information that subjects having L allele might have better in response to CIT treatment than those having S allele, and that subjects having Met allele might have better in response to CIT treatment than subjects having Val allele. (This study was supported by The Scientific and Technological Research Council of Turkey, Project No: 09S47). -09-

111 PP 84 THE RELATIONSHIP BETWEEN CYPC9 PHARMACOGENETICS AND DOSE-RELATED ADRS ZUHAL UÇKUN DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MERSIN UNIVERSITY, MERSIN, TURKEY The aim of this study is to investigate the relationship between variations in CYPC9 gene and dose-related adverse drug reactions. Adverse drug reactions (ADRs) are a major clinical problem among patients used drugs all over the world. ADRs are widespread causes of hospitalization, morbidity and mortality. Most of ADRs are preventable, especially dose-related. Impaired drug metabolism is a primary cause of ADRs. Recently, there has been a great deal of interest in the role of CYP450 genes polymorphisms in the pathogenesis of ADRs. CYPC9 enzyme metabolizes approximately 5% of clinical drugs. The CYPC9 gene encoding CYPC9 enzyme consists of nine exons encoding a protein of 490 amino acids. To date, at least 56 allelic variants (*B through *58) of the CYPC9 gene have been described. Functionally important variant alleles of CYPC9 gene are*b,*, *3, *4, *5,*6, * and *3. The two most common allelic variants in the CYPC9 gene are CYPC9* and CYPC9*3, which lead to poor metabolism phenotypes. CYPC9* and CYPC9*3 encode enzymes which are about and 5% as efficient as the wildtype, respectively. Changes in metabolic activity caused by genetic variants in CYPC9 play a major role in pathogenesis because of ADRs. Patients with low enzyme activity are at risk of ADRs, particularly for CYPC9 substrates with a narrow therapeutic index. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, particularly during the initial phase of treatment. Therefore, in order to avoid ADRs, it can be important to know genotype and phenotype. PP 85 PREPARATION AND CHARACTERIZATION OF OXACEPROL LOADED PLGA (POLY-LACTIDE-CO-GLYCOLIDE) NANOPARTICLES EMİNE ALARÇİN, ÇAĞLAR DEMİRBAĞ, SEHER KARSLI ÇEPPİOĞLU 3, OYA KERİMOĞLU MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTİCAL TECHNOLOGY, İSTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTİCAL CHEMİSTRY, İSTANBUL, TURKEY 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTİCAL TOXİCOLOGY, İSTANBUL, TURKEY Oxaceprol is an amino acid derivative, which has been used for several years for the symptomatic treatment of degenerative and inflammatory joint disease in Europe without serious side-effects (). Nanoparticles have been extensively used as drug delivery systems for a variety of drugs, to regulate the drug release speed, increase the permeability of the biological membrane, change the distribution of drugs in the body and improve bioavailability (). PLGA is also one of the most successfully used biodegradable nanosystem for the development of nanomedicines because of its excellent biocompatibility and biodegradability (3). The aim of this study was to encapsulate oxaceprol in PLGA nanoparticles for intra-articular injection using a water-in-oilin-water emulsification method and characterize the oxaceprol loaded and free nanoparticles by particle size distribution, zeta potential and surface morphology. Particles were sized by laser diffractometry using a ZetaSizer Nano ZS 3600 Malvern. The surface morphology of the nanoparticles was determined by a scanning electron microscobe. The influence of the formulation parameters (amount of stabilizer, polymer:drug ratio, stirring speed) on particle size, zeta potential and surface morphology were investigated. Oxaceprol loaded PLGA nanoparticles were successfully prepared. The nanoparticles exhibited spherical shape and particle size changed by different polymer ratio, drug ratio, amount of stabilizer and stirring speed of the emulsion. Krüger K, Klasser M, Mössinger J, Becker U. Oxaceprol a randomised, placebo-controlled clinical study in osteoarthritis with a non-conventional non-steroidal anti-inflammatory drug. Clinical and Experimental Rheumatology 007; 5: Mo L, Hou L, Guo D, Xiao X, Mao P, Yang X. Preparation and characterization of teniposide PLGA nanoparticles and their uptake in human glioblastoma U87MG cells. International Journal of Pharmaceutics 0; 436: Merlin JPJ, Venkadesh B, Hussain R, Rajendra Prasad N, Shibli, Anupama VR, Rajan SS. Paclitaxel loaded poly-d,l-lactide-co-glycolide nanoparticles: Enhanced anticancer effect in non-small cell lung carcinoma cell line. Biomedicine&Preventive Nutrition 03;3:

112 PP 86 A NEW VALIDATED HPLC-DAD METHOD FOR THE SIMULTANEOUS DETERMINATION OF SIX FLAVONOIDS IN FOUR SCUTELLARIA SPECIES HILAL BARDAKCI, EBRU TÜRKÖZ ACAR, HASAN KIRMIZIBEKMEZ FACULTY OF PHARMACY YEDITEPE UNIVERSITY The genus Scutellaria L. which belongs to the family Lamiaceae, encompasses about 350 species []. 6 species of Scutellaria grow wild in the flora of Turkey []. Antitumor, antiangiogenic, hepatoprotective, antioxidant, anticonvulsant and neuroprotective effects of several Scutellaria species have been reported. The chemical composition of Scutellaria species have also been studied since 889 and over 95 phytoconstituents have been isolated []. In this study we have developed a simple, sensitive, precise, accurate and a validated reversed phase high performance liquid chromatographic method for the simultaneous determination of common flavonoids of Scutellaria genus (scutellarein 7-O-β-D-glucopyranoside, hispidulin 7-O-β-D-glucuronopyranoside, apigenin 7-O-β-D-glucopyranoside, hispidulin 7-O-β-D-glucopyranoside, luteolin, apigenin) in MeOH extract of the aerial parts of S. hastifolia, S. velenovskyi, S. orientalis ssp. pinnatifida and S. albida ssp. albida. The method involved the use of Zorbax XDB C8 column (4.6 x 50 mm, 3.5 µm) at 5 C with the mixture of ACN and water gradient (5-50% ACN in 30 min.), constant flow rate 0.8 ml/min) as a mobile phase and detection at 340 nm. Calibration plots were linear in the range of 5-0 µg/ml for scutellarein 7-O-β-D-glucopyranoside and for apigenin 7-O-β-D-glucopyranoside, 5-75 µg/ml for hispidulin 7-O-β- D-glucuronopyranoside - 75 µg/ml for hispidulin 7-O-β-D-glucopyranoside, aglycones apigenin and luteolin. The amounts of above phytoconstituents varied among the species. This method can be used for the determination of flavonoids which constitute one of the major chemical classess of the genus Scutellaria.. Shang X., He X., He X., Li M., Zhang R., Fan P., Zhang Q., Jia Z., The genus Scutellaria an ethnopharmacological and phytochemical review, J Ethnopharmacol 00; 8, Edmonson J.R. Scutellaria L. In Flora of Turkey and East Aegan Islands Davis P.H. (ed.) Edinburgh UNIVERSITY Press. Edinburgh. pp (98). PP 87 IN VIVO MODELING STUDY TO DETERMINE THE EFFECT OF CONVOLVULUS SPECIES AS A POTENTIAL DRUG SEVILAY CENGIZ, GÜLTEN TAŞDELEN, RAMAZAN MAMMADOV PAMUKKALE UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, DENIZLI, TURKEY PAMUKKALE UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF BIOLOGY, DENIZLI, TURKEY Convolvulus galaticus was used in the present study, since there have been some literatures about Convolvulaceae family which point out their pharmaceutically important characteristics such as prevention of memory and nervous system problems, activation of intestines, and inhibition of tumor growth (-3). The effects of C.galaticus ethanol extract as a potential drug source on the blood parameters and liver/kidney antioxidant enzyme activities of Wistar type female rats were determined in in vivo conditions. All the rats studied (A: control group; B, C: groups which include %0.5 and % C.galaticus extract in their diet, respectively) were fed for one month and sacrificed under anesthesia at the end of this period. Results show that liver SOD, CAT and GPx activities of group B decreased significantly (from 8.63 to.70, 0.69 to 4.88 and. to 0.73 U/ mg protein, respectively), however they increased again in group C (from.70 to 7.46, 4.88 to 6. and 0.73 to 0.8 U/mg protein, respectively). The statistically significant difference was observed between the LPO levels of group A and B (p<0.05). The increase in SOD activity may reduce the liver damage, and therefore no significant difference between the LPO levels was observed between the groups A and C. Besides, AST results are compatible with both these observations. The ethanol extract of C.galaticus causes no significant damage on kidney, LPO and urea results were also consistent with this observation. Eventually, it can be concluded that the specified doses of C.galaticus can be used for further experiments. References ) Liu L-F, Durairajan SSK, Lu J-H, Koo I, Li M. In vitro screening on amyloid precursor protein modulation of plants used in Ayurvedic and Traditional Chinese MEDICINE for memory improvement. J. Ethnopharmacol. 0; 4: ) Bihaqi SW, Sharma M, Singh AP, Tiwari M. Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain. J. Ethnopharmacol. 009; 4: ) Sadeghi-Aliabadi H, Ghasemi N, Kohi M. Cytotoxic effect of Convolvulus arvensis extracts on human cancerous cell line. Res. Pharm. Sci. 008; 3():

113 SEVILAY CENGIZ PAMUKKALE UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, DENIZLI, TURKEY There has been a rapid increase in the number of cancer cases in recent years and natural products are gaining importance in treatments as a result of many side effects of currently used drugs. According to the report of WHO, even more than 50% of drugs used in clinical applications and 60% of drugs in cancer treatment are of natural origin (). Although a lot of investigations are found in the literature which evaluates the potential of terrestrial organisms as pharmaceutical raw materials, there are only a few studies for aquatic organisms. It was shown that there are significant structural and chemical differences between the secretions of terrestrial organisms and marine organisms that evolved to secrete active metabolite to cope with extreme pressure, temperature, salinity, etc (,3). Despite intensive research on marine organisms, there are only 3 components currently used in clinical applications. The main problem that limits the conversion of potential components to end products is ensuring sustainable sources. Microalgae species are very important sources with its rich content of active metabolites and easy cultivation conditions (3). More than 50% of microalgal species are capable of killing the cancer cells through the bioactive metabolites by influencing the cell signaling system (). These features of the microalgae may be a proof that it can be a promising source in developing cancer treating drugs. These investigations may be supported by collecting the obtained results in related databases in order to reevaluate by all researchers interested in the subject. References ) Sithranga Boopathy N, Kathiresan K. Anticancer Drugs from Marine Flora: An Overview. Journal of Oncology, 00; doi:0.55/00/486. ) Hussain Md. S, Fareed S, Ansari S, Sajid Khan M. Marine natural products: A lead for Anti-cancer. Indian Journal of Geo- Marine Sciences, 0; 4(): ) Jimeno J, Faircloth G, Fernández Sousa-Faro JM, Scheuer P, Rinehart K. New Marine Derived Anticancer Therapeutics A Journey from the Sea to Clinical Trials. Mar. Drugs 004; :4-9 PP 89 OPIOID MEDIATED ANTINOCICEPTIVE ACTIVITY OF AGOMELATINE MERVE KASAP, ÖZGÜR DEVRIM CAN ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY Agomelatine is a new antidepressant drug with anxiolytic properties, acts through a unique mechanism of action, as a melatonin MT and MT receptor agonist and a 5-hydroxytryptamine (5-HT)C receptor antagonist. This study was planned to investigate possible antinociceptive effect of agomelatine on acute nociceptive stimulus. Hot plate, tail-clip and writhing tests were performed with this purpose. Agomelatine administrated at 40 mg/kg, increased the reaction time of animals both in hotplate and tail-clip tests, suggesting the anti-nociceptive activity which is related to both supraspinal and spinal mechanisms. This drug also reduced the number of acetic acid induced writhing behaviors indicating the presence of peripherally mediated anti-nociceptive activity, as well as centrally mediated ones. Anti-nociceptive activity of agomelatine seems to be unrelated with probable motor impairment, which may interfere with the test results and give false positives because the Rota-rod tests showed no significant effect on the motor coordination of animals. Anti-nociceptive effect of agomelatine disappeared by naloxone (5.48 mg/kg, i.p) pre-treatment in all of the tests indicating that some opioidergic mechanisms were involved in the observed pharmacological activity of agomelatine. Further studies are needed to clarify responsible opioid receptor subtypes. --

114 PP 90 SYNTHESIS AND ANTICHOLINESTERASE INHIBITORY ACTIVITY OF SOME NOVEL BENZIMIDAZOLE DERIVATIVES ÜMIDE DEMIR ÖZKAY, NAFIZ ÖNCÜ CAN, YUSUF ÖZKAY 3 ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKIŞEHIR, TURKEY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, ESKIŞEHIR, TURKEY 3 ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKIŞEHIR, TURKEY Alzheimer s disease (AD) is the most common cause of dementia for older people. Its treatment is based on the use of cholinesterase inhibitors. The pathogenesis of AD is caused by decreasing the acetylcholine (ACh). In the brain, acetylcholinesterase (AChE) terminates the activity of ACh by hydrolysing it to acetic acid and choline (). In the present study some new benzimidazole derivatives were synthesized in order to investigate their inhibitory potency against AChE and butrylcholineesterase (BChE). Structures of the target compounds were confirmed by spectral data and elementary analysis. Elman s colorimetric method [] was used in enzymatic studies. Synthesized compounds showed low inhibitory potency against BChE. On the other hand AChE inhibitory potencies of some compounds in the series were comparable with that of reference drug donepezil.. Masoud MS, Ali AE, Ghareeb DE, Nasr NM. Synthesis and characterization of cephradine metal complexes as Alzheimer disease therapeutic agent: An in vitro kinetic study on acetylcholinesterase and monoamine oxidase. J. Chem. Pharm. Res. 03;8: Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 96;7: PP 9 THE PLACE OF HERBAL PRODUCTS IN MALATYA PHARMACIES NARİN SADIKOĞLU DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, İNÖNÜ UNIVERSITY, MALATYA, TURKEY Nowadays, herbal products are sold often in spice shops, markets and on the internet. Their place in the pharmacy and in particular to investigate about the situation in Malatya in 03, pharmacists who located in the city of Malatya pharmacies were interviewed. Questionnaire survey of pharmacists who accept the offer of 5 based on the information we have, that there is not given enough attention to herbal medicine and -3 kinds of products as per the pharmacy is found to exist. Because it is not approved by the Ministry of Health, pharmacists does not want to keep herbal products in pharmacies. Pharmacists have expressed, especially the use of herbal tea is not controlled and is causing many side effects and they do not want to take this responsibility, provided the use is controlled and approved by the Ministry of Health, they would have at the pharmacy. PP 9 GAS6 HAS A MITOGENIC EFFECT ON MEGAKARYOPOIESIS OZLEM BINGOL OZAKPINAR, ANNE-MARIE MAURER, CAFER ADIGUZEL 3, FIKRIYE URAS MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF HAEMATOLOGY, İSTANBUL, TURKEY 3 MEDICAL PARK HOSPITAL, İSTANBUL TURKEY Megakaryopoesis is characterized by a set of cellular events in the formation of mature megakaryocytes from hematopoietic stem cells (HSC). Giving the patient ex vivo megakaryocyte-differentiated progenitor cells rather than short-lived platelets might be a good strategy. This study was intended to assess possible effects of GAS6 on megakaryopoeisis. Material and Methods: CD34+ HSCs were isolated from peripheral blood of healthy donors. These cells were differentiated into megakaryocytes with a two-stage liquid culture method for days. During differentiation of these cells 00, 50 and 500 ng/ml GAS6 protein were added to medium (n=5). Also, cells were treated with GAS6 antibody of 4 ng/ml and 8 ng/ml concentration in parallel experiments (n=). Cells taken at days 7 and 4 of culture were analyzed by flow cytometry. It was detected that CD34 + cell ratio decreased significantly at 50 ng/ml and 500 ng/ml GAS6 concentrations (p <0.05) on day 7. In addition, CD 34+/CD 4+ cells ratio was increased significantly at 50 ng/ml GAS6 concentration. In parallel to these findings, GAS6 antibody was noted to inhibit the proliferative effect when added to the medium in the early stages. In the light of these findings, it could be argued that GAS6 is a growth factor for maintaining ex vivo expansion of MPH by increasing the number of CD34+ cells. Furthermore, a good approach might be to substitute megakaryocyte-differentiated progenitor cells instead of platelets. In clinical practice of MPH, these results are promising. -3-

115 PP 93 CURCUMIN PREVENTS UTERI ISCHEMIA-REPERFUSION INJURY VIA ITS ANTIOXIDATIVE AND ANTIAPOPTOTIC EFFECTS OZLEM BINGOL OZAKPINAR, BETUL FEYZA ULUSOY, TURGUT SEKERLER, SADIK SAHIN, NAZIYE OZKAN 3, ANNE-MARIE MAURER 4, FIKRIYE URAS MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY ZEYNEP KAMIL GYNECOLOGIC AND PEDIATRIC TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY 3 MARMARA UNIVERSITY, VOCATIONAL SCHOOL OF HEALTH SERVICES, İSTANBUL, TURKEY 4 MARMARA UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF HAEMATOLOGY, İSTANBUL, TURKEY Curcumin is a major chemical component produced from the rhizome of the plant Curcuma longa. It has been demonstrated that curcumin functions as an antioxidant, anti-inflammatory, antiproliferative, antiangiogenic and anti-atherosclerotic, and protects ischemia-reperfusion injury in various tissues. Ischemia-reperfusion (I/R) injury has detrimental effects on transplanted organs including uteri. The major consequence of I/R injury is oxidative stress leading to the generation of reactive oxygen species (ROS). Uterine transplantation (UT) has been gaining popularity around the world in the past few years. The aim of the present study was to examine the antioxidative and antiapoptotic effects of curcumin on uterine I/R injury induced by distal abdominal aortic occlusion in rats. For this purpose, the rats were randomized into three groups of seven rats each. Group I (the control group) consisted of rats that did not receive any treatment, group II (the uterine I/R injury group) of rats exposed to 0.5 hour of ischemia and hour of reperfusion, group III (curcumin group) of rats that received intraperitonealy curcumin (00 mg/kg) 0.5 hour before the induction of I/R. Then, the rat uterine tissue levels of MDA, TAC, caspase-3, 8 and 9 were measured. Furthermore, the rat uterine specimens were histologically evaluated. Biochemical analysis results showed that curcuimin decreased the MDA and caspase-3 and 9 levels, and increased the uterine tissue levels of TAC. The results of the present study demonstrate that curcumin has protective effects against uterine I/R injury, and these protective effects may be due to its antioxidant, antiapoptotic and antiinflammatory properties. PP 94 ANALYSIS OF PHARMACISTS PERCEPTION AND ATTITUDES TOWARDS GENERIC DRUGS AND GENERIC SUBSTITUTION IN ALGERIA ACHOURI MOHAMED YACINE, ALLEG ABDELATIF OUSSAMA, MOULAI MOHAMED CHERIF LOUAZZANI, MOHAMED ADIL SELKA DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE SID BEL ABBES, ALGERIA This study aims to assess the perception and attitudes of community pharmacists in Sidi-Bel-Abbes (North of Algeria) towards generic drugs. This is a descriptive and cross-sectional survey, conducted between st April 04 and 30st May 04. The target population consisted of 8 pharmacists practicing in pharmacies in Sidi-Bel-Abbes. Data collection was conducted through a questionnaire consisting of thirteen (3) items. Fifty six (67%) of community pharmacists in the town of Sidi-Bel-Abbes believe that generics have a lower quality compared to the originator. 5 respondents (6%) were in no apprehension towards generics and 63% believe that the generics substitution has led to change the relationship between a pharmacist and patient. In order to promote the practice of generic medicines in Qatar, an educational program should be implemented in Algeria. -4-

116 PP 95 DETERMINATION OF MAJOR PHENOLIC COMPOUNDS OF POMEGRANATE WINES WITH REVERSE PHASE HPLC-DAD METHOD CAGLAR DEMIRBAG, SERAP AYAZ SEYHAN, GULER YALCIN, NESE ERDINC MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY Pomegranate (Punica granatum L.) is an edible fruit and it has been used as a medicine in many different cultures. Many phytochemicals have been identified in pomegranate leafs, flowers and fruits. These phytochemicals are classified as ellagitannins, gallotannins, ellagic acid derivatives, catechin, procyanidin, anthocyanins, anthocyanidins, flavanols, organic acids, fatty acids, triglycerides, steroids, terpenoids and alkaloids (). Pomegranate was used for the treatment of diseases such as oral aphthae, ulcers and diarrhea in India, China and Middle East in ancient times. Nowadays there are many studies on therapeutic activity of pomegranate due to the variety of antioxidant compounds content and the studies have been reported that extracts from different parts of plant has therapeutic activity (). We have developed a reverse phase HPLC-DAD method for the determination of major phenolic compounds in pomegranate which are produced in Turkey. The HPLC analysis were carried on C8 column and gradient elusion of Acetonitrile: Phosphate Buffer mobile phase system were used. We have experienced some stability problems with one of the analysed ellagitannins. The future goal of this study is to solve stability problem and apply the method to some pomegranate wine brands which are produced in Turkey.. Özkal N, Dinç S. (993). Punica granatum L. (Nar) Bitkisinin Kimyasal Bileşimi ve Biyolojik Aktiviteleri. Ankara Ecz Fak Der, (-): Noda Y, Kaneyuki T, Mori A, Packer L. (00). Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyaniding, and pelargonidin. J Agric Food Chem, 50 ():66 7. PP 96 ANTIBACTERIAL ACTIVITY OF THE ESSENTIAL OIL OF ORIGANUM GLANDULOSUM ON BACTERIAL STRAINS OF HOSPITAL ORIGIN MOST IMPLICATED IN NOSOCOMIAL INFECTIONS LARDJAM ABDERRAHMENE, MAZID RYM, BOUDGHENE STAMBOULI YASMINE, IZAROUKEN ASSIA, DALI YAHIA, DJEBLI NOUREDDINE, TOUMI HOUARI DEPARTMENT OF PHARMACY ORAN ALGERIA Origanum glandulosum is an aromatic plant, common in Algeria and widely used by local people for its medicinal properties. The essential oil from this plant, which grows in the west of Algeria, was studied to evaluate and determine its antibacterial activity. The extraction of the essential oil was performed by water steam distillation; the yield obtained from the aerial parts (.78%) is interesting, its chromatographic profile revealed by TLC showed the presence of phenolic compounds thymol and carvacrol. The evaluation of the activity of the essential oil of Origanum glandulosum on bacterial strains of hospital origin, ATCC, MRB, and HRB, most implicated in nosocomial infections (Staphylococcus aureus ATCC 593, Staphylococcus aureus ATCC 43300, Enterococcus faecalis ATCC 9, Escherichia coli ATCC 59, Pseudomonas aeruginosa ATCC 7853, Staphylococcus aureus resistant to meticillin, Enterococcus faecium, VA R and R TEC, Acinetobacter baumanii, IMP R and R CAZ, Klebsiella pneumonia carbapenemase-producing) by the method of aromatogramme and microatmosphere, shows that the antibacterial potency of this oil is very high, expressed by significant inhibition diameters on all strains except Pseudomonas aeruginosa, and low MICs and is characterized by a bactericidal action. -5-

117 PP 97 DETERMINATION OF CADMIUM, LEAD AND SELENIUM CONCENTRATIONS IN TURKISH HERBAL TEAS DILEK BILGIC ALKAYA, SERAP KARADERI, GULBIN ERDOGAN, AYSEN KURT CUCU MARMARA UNIVERSITY The use of herbal teas is now widespread in our community. The presence of heavy metals and trace elements in the herbal teas has received special attention because they are directly related to health. The main sources of heavy metals in plants are their growth media, nutrients, agro inputs and soil. Other sources may include pesticides and fertilizers. Elevated heavy metal levels cause damage to plants such as delayed flowering, lower chlorophyll content and reduction in the number and quality of shoots. Owing to the importance of heavy metals present in herbal teas, this study was carried out to determine their concentrations and reliability of usage of these plants. Ten different brand teas purchased from herbalist. Concentration of three elements Pb, Cd and Se were measured in ten samples of different species of teas using flame and electrothermal atomic absorbtion spectrophotometry after microwave digestion method. The samples were digested with concentrated HNO3 in closed Teflon PFA vessels in a microwave oven. Metal concentrations in several samples were in excess of FAO/WHO and Turkish Regulations, indicating that consumption of these irrigated foods may represent an important exposure pathway to humans. Also passing time to blood of metals in teas are compared at, 5 and 0 minutes and it has been seen that amount of metal has been increased when the passing time to blood has been increased. References.Antun Kucak and Maja Blanusa.Validation of microwave digestion method for determination of trace metals in mushrooms. Arh hig rada toksicol, Vol. 49 (4), , (998).. I. Baranowska, K. Srogi, A. Włochowicz, K. Szczepanik. Determination of Heavy Metal Contents in Samples of Medicinal Herbs. Polish Journal of Environmental Studies Vol. (5), , (00). PP 98 GLYCATED TRANSFERRIN INDUCED OXIDATIVE STRESS IN HUMAN PLATELETS BAHAR GOKER, OZGE CEVIK, OZLEM OZAKPINAR, HALIL AKSOY, DERYA OZSAVCI, AZIZE SENER MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY Iron is essential for life in cells and soluble iron can generate reactive oxygen species (ROS). Non-enzymatic glycosylation of a variety of transferrin (TrF) proteins has been shown that release to iron and produce occur in different diseases advanced glycation end products (AGEs). The aim of this study is to determine the effects of in vitro glycation of TrF in human platelets. Human commercial apo-trf was dissolved in PBS and incubated with different concentration glucose (0, 5.6,.,, ve 33,3 mmol/l) under sterile conditions at 370C for 0 days. After incubation, protein glycation were determined by NBT reduction assay. Human platelet was isolated from healthy volunteers and suspended with HEPES buffer. Platelets were incubated with different concentration glycated transferrin (g-trf) with/without ADP. Then some oxidative stress marker (MDA, GSH, SOD, NO) were measured with ELISA. Platelet MDA levels were increased high concentration g-trf compare to control and TrF group (p ). GPx levels decreased with incubated high concentration g-trf compare to control and TrF group (p ). However, there was no significant change in platelets GSH and SOD levels compare to TrF group. NO level was decreased in dose dependent g-trf incubated platelets (p ). The results reported here clearly demonstrate that in vitro glycated transferrin causes platelet oxidative stress and apoptosis induction resulting in the formation of AGEs and free iron releasing. -6-

118 PP 99 ROLE OF THE GLYCATED TRANSFERRIN ON ACTIVATION AND APOPTOSIS OF HUMAN PLATELETS OZGE CEVIK, BAHAR GOKER CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL,TURKEY Transferrin receptor (TFR) is an essential protein that cell surface receptor for transferrin (TrF) circulation and involved in iron uptake and the regulation of cell growth. Protein glycosylation s can modify structure properties and plays an important role in receptor ligand and cell cell interactions. In this study the interaction between the platelet transferrin receptor and the platelet activation with glycated transferrin (g-trf) protein was investigated. G-TrF was produce with different concentration glucose (0, 5.6,.,, ve 33,3 mmol/l) in commercial apo-trf. TrF modifications were determined using HPLC and protein glycations were determined by NBT reduction assay using control as BSA. Human platelet was isolated from healthy volunteers and suspended with HEPES buffer. Platelets were incubated with different concentration glycated transferrin (g-trf) with/ without ADP. Then detection for TFR binding and p-selectin (CD6p) binding for activation of platelets were measured using flow cytometer (FACS). At the same time platelet caspase-3 activity was determined by ELISA. Incubation of platelets with the g-trf elicited protein modification in a dose- and time-dependent manner. In FACS data showed that ADP activated platelets were high binding with TFR receptor compare to non-activated platelets (p 0.00). Importantly, FACS analysis revealed significant up-regulation of CD6p binding in platelets following dose dependent g-trf incubation (p 0.0). Platelet Caspase-3 activity were increased with dose dependent g-trf groups (p ). We show that platelets have TFR receptor for iron regulation and cellular function and g-trf production may promote proapoptotic events in blood circulation. PP 00 PROTEOMIC PERSPECTIVE FOR HUMAN PLATELETS INTERACTION WITH GLYCATED TRANSFERRIN OZGE CEVIK, AHMET TARIK BAYKAL, BAHAR GOKER 3 CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY MEDIPOL UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL BIOCHEMISTRY, ISTANBUL, TURKEY 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY Platelets are enucleate cells that are considered as a crucial role in hemostasis. Glycosylation of proteins is known that posttranslational modification, strongly influencing many of their functional aspects, including cellular localization, turnover and protein quality control. To investigate platelet protein expression induced by glycated transferrin (g-trf), washed human platelets were incubated in HEPES buffer with g-trf and/or ADP. D-PAGE and LC/MS/MS applied to examine the platelet proteins expression analysis. Platelets washed with ammonium bicarbonate buffer and total protein was quantified. The first dimension separation was performed on an isoelectric focusing using ph 3-0 and ph 5-8 strips. Second dimension, strips were applied directly to 0% SDS-polyacrylamide gels and used silver staining. After the spot selection, specific trypsin digested peptides were analyzed in mass spectrometry. Spot analysis showed that, especially membrane structural proteins and cytoskeletal proteins were changed with g-trf incubation in platelets. Activated platelets by g-tfr causes dramatic changes in their morphology. Modification of specific platelet proteins after activation appears can be related to both changes in cytoskeleton structure and granule contents. Our data support the hypothesis that g-trf interacts with platelet transferrin receptors and triggered platelet functions as structural proteins. This result is preliminary and all proteins need to be confirmed starting point for studying the protein signaling pathways. -7-

119 PP 0 SYNTHESIS AND BIOCHEMICAL MECHANISM EVALUATION OF NEW BENZIMIDAZOLE DERIVATIVES BEARING PYRIDYL/PYRIMIDINYL PIPERAZINE MOIETY GULSEN AKALIN CIFTCI, HALIDE EDIP TEMEL, LEYLA YURTTAS ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF BIOCHEMISTRY, ESKISEHIR, TURKEY ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY Benzimidazoles are bioactive compounds which they have broad range of pharmacological activities such as antifungal, anti-helmintic, anti-hiv, antihistaminic, antiulcer, cardiotonic, and antihypertensive (). In recent years, they have attracted particular interest due to their anticancer activity or as potential in vitro anticancer agents (,3). In this study -[-oxo-- (4-substituted phenyl)ethyl]benzimidazol--yl)methyl 4-(pyridyl/pyrimidin--yl)piperazine--carbodithioate derivatives (a-n) were synthesized and were identified using IR, H-NMR, 3C-NMR, and MS data. Intermediate products were prepared with the reaction of -(chloromethyl)benzimidazole and sodium salts of 4-(-pyridyl/pyrimidinyl)piperazine-- dithiocarbamic acids in acetone at room temprature with stirring (a, b). Final compounds (a-l) were gained with the reaction of the obtained compounds a and b and α-bromoacetophenone derivatives in acetone. Anticholinesterase activities of the final compounds will be evaluted with Ellman method. Furthermore, cytotoxic activity of these compounds will be measured bty MTT method.. Chawla A, Ramandeep K, Goyal A. Importance of microwave reactions in the synthesis of novel benzimidazole derivatives: A review. J Chem Pharm Res. 0;3: Husain A, Rashid M, Mishra R, Parveen S, Shin DS, Kum D. Benzimidazole bearing oxadiazole and triazolo-thiadiazoles nucleus: Design and synthesis as anticancer agents. Bioorg Med Chem Lett. 0;: Yurttaş L, Demirayak S, Akalın Çiftci G, Yıldırım ŞU, Kaplancıklı ZA. Synthesis and biological evaluation of some,-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch Pharm Chem Life Sci. 03;346: PP 0 EVALUATION OF ANTICHOLINESTERASE AND CYTOTOXIC PROPERTIES OF NEW MORPHOLINE DITHIOCARBAMATE DERIVATIVES BEARING BENZIMIDAZOLE MOIETY HALİDE EDİP TEMEL, GÜLŞEN AKALIN ÇİFTÇİ, LEYLA YURTTAŞ ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF BİOCHEMİSTRY, ESKİŞEHİR, TURKEY ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, ESKİŞEHİR, TURKEY In this present study, new morpholine dithiocarbamate derivatives bearing -(-aryl--oxoethyl)--substituted benzimidazole moiety were synthesized and their potential anticholinesterase and cytotoxic properties were investigated. Benzimidazole scaffold is an important pharmacophore that has been extensively utilized as a drug in medicinal chemistry for years (). Among them -(-aryl--oxoethyl)--substituted benzimidazole derivatives have a particular interest as a result of studies which we have been reported before with satisfactory anticancer activity results (,3). Additionally, gefitinib, a recent morpholine carrying anticancer drug, is expected to play a significant role in designing and synthesizing new drugs (4). In this manner, we have synthesized benzimidazole and morpholine including compounds (a-l). The structures of the final compounds were elucidated by IR, H-NMR, 3C-NMR, and MS spectroscopy. Final compounds were achieved with the reaction of (benzimidazol--yl) methyl morpholine-4-carbodithioate and α-bromoacetophenone derivatives in acetone at room temprature with stirring. The anticholiesterase and cytotoxic activity studies are in progress.. El-Nassan HB. Synthesis, antitumor activity and SAR study of novel [,,4]triazino[4,5-a]benzimidazole derivatives. Eur J Med Chem. 0;53:-7.. Demirayak S, Kayagil I, Yurttas L. Microwave supported synthesis of some novel,3-diarylpyrazino[,-a] benzimidazole derivatives and investigation of their anticancer activities Eur J Med Chem. 0;46: Yurttaş L, Demirayak S, Akalın Çiftci G, Yıldırım ŞU, Kaplancıklı ZA. Synthesis and biological evaluation of some,-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch Pharm Chem Life Sci. 03;346: Surve P, Ravindran S, Acharjee A, Rastogi H, Basu S, Honrao P. Metabolite characterization of anti-cancer agent Gefitinib in human hepatocytes. Drug Metab Lett. 03;7:

120 PP 03 SYNTHESIS AND BIOCHEMICAL MECHANISMS OF BISTHIAZOLE DERIVATIVES ACTION GÜLHAN TURAN-ZİTOUNİ, MEHLİKA DİLEK ALTINTOP, AHMET OZDEMİR, HALİDE EDİP TEMEL, GÜLŞEN AKALIN ÇİFTÇİ, ZAFER ASIM KAPLANCİKLİ ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, ESKİŞEHİR, TURKEY ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF BİOCHEMİSTRY, ESKİŞEHİR, TURKEY Thiazoles are thus important molecules. They exhibit a variety of activities such as antimicrobial, antiretroviral, antineoplastic antithrombotic including anticholinesterase. Recently the applications of thiazoles were found in drug development for the treatment of allergies, hypertension, inflammation, schizophrenia, bacterial, HIV infections and more recently for the treatment of pain (,). Thus bisthiazole has been a hot topic of investigations. We aimed to investigate the therapeutic values of bisthiazole derivatives. 3,3-Dimethoxy-N4,N4-bis(4-phenylthiazol--yl)biphenyl-4,4-diamine derivatives (-0) were synthesized via the ring closure of,-(3,3-dimethoxybiphenyl-4,4-diyl)bis(thiourea) (A) with phenacyl bromides. Each derivative was also evaluated for their cytotoxic activity by MTT method and ability to inhibit AChE and BuChE using a modification of Ellmans spectrophotometric method. Compound 8 can be identified as the most potential anticholinesterase agent due to its inhibitory effects on AChE and BuChE with IC50 values of 5.86 ± 0.9 µg/ml and ±.9 µg/ml, respectively.. Turan-Zitouni G, Ozdemir A, Kaplancikli ZA, Altintop MD, Temel HE, Çiftçi GA. Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors. J Enzyme Inhib Med Chem. 03;8(3): Siddiqui N, Arshad MF, Ahsan W, Alam MS. Thiazoles: a valuable insight into the recent advances and biological activities. Int J Pharm Sci Drug Res 009;: PP 04 SYNTHESIS, CHARACTERIZATION AND IN VITRO ANTIBACTERIAL ASSESSMENTS OF A POLY[MALEIC ANHYDRIDE-ALT- ACRYLIC ACID]/ACRIFLAVINE CONJUGATE GULDEREN KARAKUS, HATICE KAPLAN CAN, NEVIN TUZCU CUMHURIYETUNIVERSITY, SIVAS, TURKEY HACETTEPE UNIVERSITY, ANKARA, TURKEY Researchers are trying to find ways of improving therapeutic efficacy such as lower cost, biocompatible, multifunctional, fewer side effects, less toxic of traditional lower molecular weight drugs to the polymeric systems by modifying techniques (). Synthetic polymers are known as the most versatile class of biomaterials useful for controlled drug delivery systems, applied in the medical and biotechnologies, as well as in the food and cosmetics industries (). In this study water-soluble poly[maleic anhydride-alt-acrylic acid] (MAAA) copolymer was synthesized by free-radical chain polymerization reaction, in,4-dioxane in the presence of benzoyl peroxide (BPO), 0. %, as the radical initiator at 70 C under a nitrogen atmosphere. The purified copolymer was then modified with an anti-external fungal and anti-cancer active agent, acriflavine (AF). The modification reaction was performed 48 h at 70 C in dimethylformamide (DMF), using triethylamine (TEA) as the catalyst (3). Structural characterization of the copolymer (MAAA), and modified product (MAAA/AF) was carried out by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (H-NMR and 3C-NMR). FTIR, H-NMR, and 3C-NMR spectra confirmed that AF was successfully bound to the MAAA copolymer backbone by ring-opening reaction. A reaction mechanism was then also suggested for the conjugation reaction. Antimicrobial susceptibility of the MAAA, AF, and MAAA/AF was evaluated by Kirby Bauer Disc Diffusion method on Mueller Hinton Agar by using Enterecoccus faecium, Enterohaemorrhagic Escherichia coli (EHEC), Staphylococcus aureus and Listeria monocytogenes. Results obtained indicated that MAAA/AF had antibacterial activity on Enterohaemorrhagic Escherichia coli (EHEC) and Staphylococcus aureus at 50, 40, and 30 µg.. Kadaji VG, V. Betageri G. Water soluble polymers for pharmaceutical applications. Polymers 3. 0; Kenawy ER, Abdel-Hay F, El-Newehy M, Ottenbrite RM. Effect of ph on the drug release rate from a new polymer-drug conjugate system. Polym Int. 008;57: Karakus G, Akin Polat Z, Yenidunya AF, Zengin HB, Karakus CB Synthesis, characterization and cytotoxicity of novel modified poly[(maleic anhydride)-co-(vinyl acetate)]/noradrenaline conjugate. Polym Int. 03;6:

121 PP 05 AN INVESTIGATION OF THE PH EFFECT ON THE STABILITY BEHAVIOR OF POLYMER-DRUG SYSTEM INCLUDING HYDROXYUREA GULDEREN KARAKUS, NUR MELEK CETIN, DOLUNAY SAKAR CUMHURIYET UNIVERSITY, SIAVS, TURKEY YILDIZ TECHNICAL UNIVERSITY, ISTANBUL, TURKEY Polymers have been used as a main tool to control the drug release rate from the formulations (). If a polymeric carrier is to be used, the next step is to design a type of polymeric structure that will permit obtaining the desired release conditions. Therefore, the polymeric structure should be biodegradable, dissemblable, and undissemblable (). Improving delivery techniques that minimize toxicity and improve efficacy offers great potential benefits to patients, and opens up new markets for pharmaceutical and drug delivery companies (3). In this work, poly (maleic anhydrite-co-vinyl acetate) (abbreviated as MAVA) copolymer and Hydroxyurea (HX) is used to treatment types of cancer were used for synthesizing of MAVA-HX bioactive polymeric drug delivery system. At specific intervals, the stability behaviors of MAVA-HX system have been examined by Zeta Potential Analyzer and UV Spectrophotometer at different phs. Zeta potential, mobility, and particle size of prepared polymer-drug system were determined by using the Zeta Potential Analyzer in water with different phs. Absorption and permeability of MAVA/HX, MAVA and HX were also determined by UV Spectrophotometer.. Raizada A, Bandari A, Kumar B. Polymers in Drug Delivery. A Review. 00;79:7-7.. Vilar G, Tulla-Puche J, Albericio F. Curr Drug Deliv. 0;9(4): Kaparissides C, Alexandridou S, Kotti K, Chaitidou S. Recent Advances in Novel Drug Delivery Systems PP 06 STRUCTURAL SIMILARITY AMONG RIBOSWITCHES AND RRNAS: RIBOSWITCHES AS HIGH AFFINITY TARGETS FOR PAROMOMYCIN ELNAZ MEHDIZADEH AGHDAM, ABOLFAZL BARZEGAR, MOHAMMAD SAEID HEJAZI 3 STUDENT S RESEARCH COMMITTEE AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN RESEARCH INSTITUTE FOR FUNDAMENTAL SCIENCES (RIFS), UNIVERSITY OF TABRIZ, TABRIZ, IRAN 3 DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Riboswitches, as cis acting non-coding RNA elements, regulate gene expression via specific binding of various small molecules without proteins interpretation. Some previous studies report possible structural relation between riboswitches and rrnas. In this study we aimed to find out the structural and functional level of similarity among riboswitches and rrna structures including binding of aminoglycosides to aptamer domain of riboswitches through computational tools. For this, paromomycin was chosen as a model. First, the PDB structures of ten classes of riboswitches were selected. Following structure based alignment on selected riboswitches domains, top similar rrnas with high secondary structure identity were selected. Then, multiple, global and local pairwise alignments were conducted on selected rrna sequences. Highly similar rrna motifs with riboswitches (including A site ) were sorted out. At last, the probable functional similarity of riboswitches with A site motif of 6S rrna were studied based on the affinity of paromomycin antibiotic to riboswitches using docking by AutoDock 4.. Statistical analyses on binding energies were performed using one-way analysis of variance (ANOVA). Conserved structural rrna building blocks such as hairpin loop containing UUU, peptidyl transferase center conserved hairpin A loop were detected in different riboswitches. However, no particular sequence based similarity was identified. Interestingly, docking analysis showed significant high binding energies of paromomycin with different riboswitches in comparison to the binding energy of paromomycin with 6S rrna A site (p <0.00). These findings clearly support the evolutionary origin of riboswitches/rrnas and consideration of riboswitches as potential targets for aminoglycosides. -0-

122 PP 07 PREPARATION AND CHARACTERIZATION OF INJECTABLE HYALURONIC ACID DERIVATIVE GELS CONTAINING DICLOFENAC SODIUM SHEIDA SHARBATI MOHAMMAD ERFAN, AFSHIN ZARGHI SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN Hyaluronic Acid (HA) polymers are widely used in osteoarthritis and also in drug delivery. In this study Diclofenac Sodium was used as the model drug. Hyaluronate Sodium, Hyaluronic Acid and Cross-linked Hyaluronate Sodium loaded in each formulation. To measure syringability, viscosity of gels was determined. Drug Release study was carried out using dialysis membrane at ph 7.4. Kinetic studies were subsequently carried out to determine the optimum model as well as mechanism of drug release. The results showed that gels containing HA 4% and NaHA % had the highest and lowest viscosity respectively. Drug release results indicated the the slowest drug release profile is related to the gel containing cross-linked NaHA 4%. Results of kinetic study showed that Higuchi model could predict the process of drug release better than other models employed. Moreover, based on the Peppas index (n), the release seems to follow the non-fickian diffusion process. There was a highly significant (p 0.00) correlation between types of polymers and drug release profile. In conclusion, our results indicate hyaluronate polymers are suitable candidates for sustaining drug release. And may be used as an appropriate drug delivery system. An anti-inflammatory drug loaded in HA polymers could produce a formulation with promising outcomes and could be more effective in osteoarthritis. PP 08 THE EFFECT OF POLOXAMER 88 ON THE PHYSICAL PROPERTIES OF CARVEDILOL BINARY AND TERNARY SOLID DISPERSIONS NAZLI POURMOHAMMAD NOUSHIN BOLOURCHIAN, SIMIN DADASHZADEH SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN,IRAN The solid dispersion (SD) technique provides an efficient method to improve the dissolution rate and solubility of poorly water soluble drugs. Hydrophilic compounds such as poloxamer88 (P88) have been used successfully as a carrier for the preparation of SDs. Carvedilol (CA) used in the treatment of hypertension and congestive heart failure is a poorly soluble drug with lower dissolution rate and bioavailability. The objective of this study was to prepare and evaluate dissolution rate and physicochemical properties of CA from binary and ternary P88-based solid dispersions. Binary and ternary SDs were prepared using CA: P88 and CA: polyethylene glycol 6000 (PEG) with different ratios by solvent evaporation method. The solubility, dissolution rate and efficiency (DE60) dispersions were evaluated. Samples were also characterized using DSC (Differential scanning calorimetry), IR spectroscopy. According to the results, all binary and ternary SDs improved the dissolution rate of CA significantly (p< 0.05). The best results were obtained from CA: P88 and CA: PEG: P88 with the ratios of :7 and : 4: 3, respectively, (DE60= 6% and 84%) compared to the intact drug and (DE60= 3%) related physical mixtures (DE60 =44% and 47%). The solubility of above mentioned samples were also enhanced significantly (p< 0.0). DSC, IR and analysis showed no chemical reaction between ingredients during the preparation method. In conclusion, formulation of P88-based SDs markedly improves carvedilol dissolution characteristics in binary and ternary dispersions. --

123 PP 09 FORMULATION OF METFORMIN HYDROCHLORIDE FLOATING SUSTAINED RELEASE TABLET SAEED SALARI SHAHID BEHESHTI MEDICAL UNIVERCITY, TEHRAN, IRAN The purpose of this study was to develop a gastroretentive formulation of metformin hydrochloride in the form of a floating tablet capable of remaining in the stomach for a reasonable length of time as well as producing sustained drug release over a period of hours.metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type diabetes, in particular, in overweight and obese people and those with normal kidney function. Metformin has an oral bioavailability of 50 60% under fasting conditions, and excretion 0-30% intact in stool. metformin could be used daily up to three times daily, its compliance could be low in the user. An extended release dosage form could help to reduce the frequency of use and improving the pharmacokinetic indices of the drug(such as bioavailability)and the provision of improved drug efficiency. Various amounts of different polymers including HPMC K4M, HPMC K5M, ethyl cellulose, carbomer 934P, Polyethylene Oxide and sodium carboxy methyl cellulose were employed for this study.in order to study the effect of different weight ratio of sodium bicarbonate as the gas generating agent, on the floating properties of the resulting tablets, was investigated.the above excipients were mixed with metformin HCl and were blended with 0.5% magnesium stearate and compressed using a single-punch tablet machine equipped with convex faced mm diameter punches. Overall, 3 formulations were prepared and tested in terms of hardness, thickness, friability, as well as floating lag time and duration of floating. The studies showed that the type and the amount of polymers and the amount of filler and sodium bicarbonate used could influence the floating properties of tablets.next, the formulations that were found acceptable based on physicochemical tests and also had appropriate floating properties were selected for the dissolution studies. Dissolution profile of each formulation was determined for hours using the USP apparatus II (paddle) dissolution tester in ph=3.5 HCl medium at 370C and at a stirring speed of 50 rpm..ultimately, formulations F0 containing 9% HPMC K4M,5% carbomer 934p, 0% sodium bicarbonate; F containing 9% HPMC K4M, 7.5% ethyl cellulose, 7.5% carbomer 934p, 0% sodium bicarbonate bicarbonate were chosen since they had desirable floating properties, appropriate drug release profile, and also complied with the other physicochemical test conducted. Next, complementary studies including the determination of swelling index, kinetics of drug release, the swelling index for selected formulation measurement, assay of active ingredient and weight variation were carried out on the selected formulations.drug release kinetic studies performed on selected formulations showed the higuchi model could forecast the process of drug release from the chosen floating tablet formulations better than the other kinetic models employed. Moreover based on the Peppas index obtained for the release seems to follow the Fickian diffusion process. PP 0 EFFECTS OF ANTIBIOTICS ON POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS, OXIDATIVE STRESS, OXIDANT AND ANTI-OXIDANT ENZYMES IN BRONCHIECTASIS BURÇAK GÜRBÜZ, ÜMRAN SOYOĞUL GÜRER, ÖZGE ÇEVIK, İRFAN YALÇINKAYA 3, GÜLNAZ NURAL BEKIROĞLU 4, ADILE ÇEVIKBAŞ DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, CUMHURIYET UNIVERSITY, SIVAS, TURKEY 3 MINISTRY OF HEALTH, SÜREYYAPAŞA CHEST DISEASES AND THORACIC SURGERY TRAINING AND RESEARCH HOSPITAL, ISTANBUL,TURKEY 4 DEPARTMENT OF BIOSTATISTICS AND MEDICAL INFORMATICS, FACULTY OF MEDICAL, MARMARA UNIVERSITY, İSTANBUL, TURKEY The in vitro effects of colistin (4 µg/ml), tigecycline (0.87 µg/ml), rifampicin (7 µg/ml) and imipenem (30 µg/ml) alone and in combinations at therapeutic concentrations and malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) activities were investigated on polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity) of patients with bronchiectasis. PMNs were isolated from venous blood by Ficoll-hypaque gradient centrifugation method. Phagocytic activity and intracellular killing activities were assayed by modified Alexander s method. MDA level was detected by Beuge s method which is as an indicator of lipid peroxidation. SOD, GSH-Px and MPO activities were assayed by Sun s, Paglia and Valentine s and Hillegas s methods respectively. All results were statistically evaluated. The PMN s phagocytic (p<0.000) and intracellular killing activity (p=0.03, p=0.000, p=0.0056, p=0.003, p=0.0008, p=0.004, p=0.006, p=0.0036, p=0.00) of patients with bronchiectasis significantly increased when compared to control values. Enzyme activities (SOD, GSH-Px and MPO) and MDA levels significantly decreased (p<0.00) in patients with bronchiectasis when compared to control values. --

124 PP FORMULATION AND IN VITRO EVALUATION OF ZOLPIDEM TARTRATE BILAYER TABLETS. AZIN YAGHMAEIAN SCHOOL OF PHARMACY, SHAHEEDBEHESHTI UNIVERSITY OF MEDICAL SCIENCES AND HEALTH SERVICES, TEHRAN, IRAN Zolpidem Tartrate, a non-benzodiazepine agent, is one of the most frequently prescribed hypnotic drugs. Zolpidem was proven as effective as benzodiazepine in the management of short-term insomnia. The purpose of this study was to design bilayer tablet of Zolpidem Tartrate. Bilayer tablets comprised two layers, in which the one layer is formulated to obtain immediate release of the drug, with the aim of reaching a high serum concentration in a short period of time; and The second layer is a controlled release matrix, which is designed to maintain an effective plasma level for a prolonged period of time. The immediate release layer comprised croscarmellose sodium as a super disintegrant and the controlled release layer comprised Hydroxypropyl methylcellulose (HPMC K4M, K5M), ethyl cellulose, Eudragit RLPO as the release retarding polymers. Direct compression method was used for preparation of the bilayer tablets. Tablets were investigated for physicochemical properties and in-vitro performance. In vitro dissolution studies were carried out in a USP apparatus I, using 500mL of 0.0N HCl as dissolution medium. The release profiles of drug from the tablets were analysed by using UV-Visible spectrophotometer at 95 nm. Optimized formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 6 h. Formulation containing 3 mg croscarmellose sodium and 40 mg HPMC K5M was selected as promising formulation among all the developed formulations.the release of Zolpidem Tartrate was found to follow a pattern of Korsmeyer-Peppas, with Quasi-Fickian diffusion. PP METHYLPREDNISOLONE ACETATE EUDRAGIT RS00 ELECTROSPUNS: PREPARATION AND PHYSICOCHEMICAL CHARACTERIZATION AZIN JAHANGIRI, NAZILA JAFARI AGHDAM, SHAHRIAR PAYAB, MOHAMMAD BARZEGAR JALALI, KHOSRO ADIBKIA DRUG APPLIED RESEARCH CENTER AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN The purpose of the present study was to formulate and evaluate the physicochemical characteristics of methylprednisolone acetate -Eudragit RS00 nanofibers (NFs) and nanobeads (NBs). The NFs and NBs of methylprednisolone with eudragit RS00 were prepared using electrospinning technique (). The effect of several process parameters, i.e., drug/polymer ratio and polymer concentration were considered on the size of the nanoformulations. The physicochemical and morphological characteristics of them were evaluated as well. X-Ray crystallography and Differential Scanning Calorimetry studies indicated that the drug crystallinity was notably reduced during the process of electrospinning. FT-IR analysis did not indicate significant interaction between drug and polymer. In vitro drug release studies of prepared electrospuns showed faster drug release pattern compared to the pure drug. The release data were best fitted to the Weibull model and the corresponding shape factor value of the model were less than 0.75, indicating diffusion-controlled drug release. According to this findings, formulation of the methylprednisolone eudragit RS00 NFs and NBs was able to modify the physicochemical characteristics of the drug and may well increase the efficacy of drug. In conclusion, electrospinning could be considered as a simple, surfactant free and cost effective method for fabricating the drug-polymer nanofibers and nanobeads.. Matthews JA, Wnek GE, Simpson DG, Bowlin GL. Electrospinning of collagen nanofibers. Biomacromolecules. 00;3():

125 PP 3 PHYSICOCHEMICAL CHARACTERIZATION OF METHYLPREDNISOLONE ACETATE-PLGA NANOPARTICLES PREPARED VIA ELECTROSPRAYING METHOD AZIN JAHANGIRI, YOUSEF JAVADZADEH, SHAHRIAR PAYAB, POOYA NOORIZADEH, KHOSRO ADIBKIA STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN BIOTECHNOLOGY RESEARCH CENTER AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN The objective of this study was to formulate methylprednisolone acetate - PLGA nanoparticles via electrospraying method (). The electrospuns prepared with different drug: polymer ratios and the various polymer solution concentrations. Physicochemical properties, morphological features and particle size of prepared nanoparticles were evaluated as well. Laser particle size analyzer and scanning electron microscopy was benefited to study particle size and morphology. The drug crystallinity was investigated using X-Ray crystallography and differential scanning calorimetry. Fourier transform infrared spectroscopy was employed to detect any possible interaction between the drug and polymer during the preparation process. The optimum nanobeads with smooth surfaces and particle size of (64 ± 48nm) were prepared using drug: polymer ratio of :5 and the polymer solution concentration of 0%. The drug crystallinity was decreased notabely in the PLGA contained electrospuns and no chemical interaction between the drug and polymer molecules was detected. All the fabricated formulations illustrated sustained drug release profiles compared to the pure drug and physical mixtures. Considering these findings, it was concluded that electrospraying is a simple and cost effective method for preparing the controlled release drug-polymer nano/micro particles.. Bock N, Dargaville TR, Woodruff MA. Electrospraying of polymers with therapeutic molecules: State of the art. Progress in Polymer Science. 0;37():50-5. PP 4 EFFECTIVE FACTORS ON SALT SELECTION IN PHARMACEUTICAL INDUSTRIES AZIN JAHANGIRI, FARNAZ MONAJJEMZADEH STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN DEPARTMENT OF PHARMACEUTICAL AND FOOD CONTROL, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Selection of an appropriate salt is a crucial part of the drug development procedure and can extensively decrease the time need for a drug substance to enter the market. Salt selection studies are typically carried out in early stages of drug development processes. Salts are used to alter the physicochemical, biological and economical properties of a drug substance for different purposes mainly enhancement of solubility. Moreover, they could be used for improving taste, stability, manufacturability and bioavailability of drugs. Salt formation is the most common and effective method of increasing solubility and dissolution rates of acidic and basic drugs. The primary step involves the determination of the ionizable groups in drug structure that can be manipulated under the situation necessary to make salt forms. Salt screening process usually performed based on physicochemical characteristic such as crystallinity, low hygroscopicity, suitable melting point, dissolution rate, solubility, stability and bioavailability. If the proper salt is selected, following development will be facilitated. Here, we are going to discuss importance of salt selection and how it is performed with case studies, also factors that affecting the rational salt selection process for drug candidates. -4-

126 PP 5 FREE RADICAL SCAVENGING, METAL CHELATING ACTIVITIES AND REDUCING POWER OF PLANTAGO LANCEOLATA EXTRACTS SENATOR ABDERRAHMANE, LAOUICHA SALIHA, MESSAOUDI DALILA, KADA SEOUSSEN, BOURICHE HAMAMA LABORATORY OF APPLIED BIOCHEMISTRY, UNIVERSITY SETIF, ALGERIA This study aims to detect the in-vitro antioxidant capacity of the methanolic and aqueous extracts of the aerial part of plantago lanceolata, a plant from the Algerian pharmacopeia, and to estimate its phenolic and flavonoid content. Total phenolic and flavonoid content was estimated by Folin-Ciocalteau s reagent and Aluminium chloride colorimetric method, respectively. The antioxidant activity was determined by using DPPH, metal chelating and reducing power assays. Results showed that methanolic extract contains total polyphenols and flavonoids more than the aqueous extract. Compared to the synthetic antioxidant BHT, used as standard antioxidant, aqueous and methanolic extracts exhibited high antiradical activity against the free radical DPPH, with IC50 of ± 0.83 and ±.04 µg/ml, respectively. This activity was increased with the increasing concentration and became stable when it reached 86% and 80%, respectively. Moreover, the aqueous and methanolic extracts showed a good concentration-dependent chelating activity with IC50 of 53.6 ±.5 mg/ml and ± 4.56 mg/ml, respectively. At the same concentration (00µg/ml), the aqueous extract exerted an important chelating effect (95%), whereas methanolic extract showed only 7%. These values are lower than that of EDTA, used as standard chelator. Both extracts showed a good concentration-dependent reducing power, with IC50 of 5.7 ± 5.64 µg/ml and ± 0.8 µg/ml, respectively. These findings suggest that Plantago lanceolata extracts possess phenolic and flavonoid constituents that are responsible for antioxidant activity and may be exploited as biopreservatives in food applications and in traditional medicinal use. PP 6 ANTIBACTERIAL ACTIVITY OF ALGERIAN PLANTAGO LANCEOLATAL ZERROUG MOHAMED MİHOUB, LAOUİCHA SALİHA, BOURİCHE HAMAMA, SENATOR ABDERRAHAMANE LABORATORY OF APPLİED MİCROBİOLOGY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETİF, ALGERİA LABORATORY OF APPLİED BİOCHEMİSTRY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETİF, ALGERİA The aim of this work is to evaluate the anti-bacterial activity of the extracts of the aerial part of Plantago lanceolata L, known in Algeria under the name of El-Lisan -Haml. This herb is known in traditional medicine for the astringent, healing, antiinflammatory and antitussive. The antibacterial activity of methanol and aqueous extracts of P. lanceolata was evaluated by the agar diffusion disc technique against 6 Gram negative bacterial strains (Pseudomonas aeruginosa ATCC 7853, Escherichia coli ATCC 59, Salmonella typhimurium ATCC 33, Acinetobacter baumannii ATCC 9606, Proteus mirabilis ATCC and Klebsiella pneumoniae ATCC ) and 4 strains Gram positive (Staphylococcus aureus ATCC 593, Bacillus cereus ATCC 0876, Enterococcus faecalis ATCC 4945 and Listeria monocytogenes ATCC 533). Both extracts were used at a concentration of 00 mg/ml. The results of antibacterial activity revealed that the aqueous extract inhibited the growth of four bacterial strains. at has Considerable antibacterial effect was obtained against Proteus vulgaris and Salmonella typhimurium with inhibition zones of 3.±0.38 and 9.78±0.9 mm respectively. Pseudomonas aeruginosa and Bacillus cereus were less sensitive; zones of inhibition were 8.0±0.0, and 7.3±0.58 mm (p<0.05). respectively. The effect of aqueous extract was more important than the amocixilline (Amox), used as reference. The methanol extract inhibited the growth of Salmonella typhimurium with zone of inhibition 6.7±.68, but was less effective against Proteus vulgaris and Listeria monocytogenes which their zones of inhibition were.44±0.0 and 8.0±0.0 (p<0.05) respectively. -5-

127 DESIGN TAYEBEH GHARİ, SEYED ALİREZA MORTAZAVİ, MOHAMMAD REZA KHOSHAYAND, KAMBİZ GİLANİ, FARZAD KOBARFARD SHAHİD BEHESHTİ UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN SHAHİD BEHESHTİ UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN 3 TEHRAN UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN 4 TEHRAN UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN 5 SHAHİD BEHESHTİ UNIVERSITY OF MEDİCAL SCİENCES,TEHRAN, IRAN The aim of this study was the preparation, optimization, and in vitro evaluation of Azithromycin (AZI) encapsulated nanoparticles to overcome the problems associated with the treatment of pneumonia, chronic obstructive pulmonary disease, and cystic fibrosis and to improve the AZI dissolution rate (-). To achieve these goals, AZI-loaded poly(dl-lactide-co-glycolide) (PLGA) nanoparticles were prepared using the nanoprecipitation method and characterized. The Box Behnken design (BBD) was employed to optimize the effects of different variables on particle size and drug encapsulation efficiency of nanoparticles. The results of optimized formulations showed a polydispersity index of 0.06%, an average diameter of 83 ±.8 nm, and encapsulation efficiency of ± 4.8 %. The prepared particles had spherical shape, and the in vitro drug release profile showed a biphasic pattern, showing an initial burst release of 3% in the first h followed by a sustained release for up to 4 h.. Yousef AA, Jaffe A. The Role of Azithromycin in Patients with Cystic Fibrosis. Paediatr Respir Rev. 00;: Sakito O, Kadota J, Kohno S, Abe K, Shirai R, Hara K. Interleukin beta, tumor necrosis factor alpha, and interleukin 8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis: a potential mechanism of macrolide therapy. Respiration. 996;63:4-8. PP 8 AN ETHNOBOTANICAL STUDY OF ANTI-RHEUMATIC PLANTS IN THE REGIONS OF SIDI BEL ABBES, IN THE NORTH OF ALGERIA SELKA MOHAMMED ADIL, ACHOURI MOHAMMED YACINE LABORATORY OF PHARMACOGNOSY, DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE SID BEL ABBES, ALGERIA. LABORATORY OF PHARMACEUTICAL BIOPHYSICS,DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE SID BEL ABBES, ALGERIA Rheumatism is a group of very various diseases that affect the joints and sometimes causes unbearable and disabling pains Non steroidal anti-inflammatory drugs (NSAIDs) and analgesics are their main treatment but they can cause very dangerous side effects like ulcers and gastrointestinal bleeding, however traditional herbal remedies without side effects exist and can treat advantageously these diseases(). This work ames to make an to make an inventory of anti rheumatic plants in the region of Sidi Bel Abbes, in the north of Algeria. Two ethnobotanical studies were conducted, one with Sidi Bel Abbes population ( n = 00) and the other with the herbalists of the same region (n = 6). The results showed that Inula viscosa was the most used plant (35.7%). Followed by Origanum vulgare (9.04%), Anacyclus pyrethrum (4.8%), Eugenia caryophyllata (4.%) and Ortica dioica (4, 0%). Leaves are the most used parts (57.7%), infusion and poultice are the most used modes. As an exemple, Some Magistral Preparations were made from plants found in the studie: nettle tincture of oregano oil, poultice made of clove and Tincture of nettle. This study helped to identify 4 different species of medicinal plants used by the population and the herbalists of Sidi Bel Abbes. The main action of these species being the treatment of rheumatism, for their anti-inflammatory and analgesic effects. The majority of identified plants could be a potential treatment against this disease.. Anton R. Plantes médicinales traditionnelles: suppléments alimentaires et (ou)médicaments. Des sources du savoir aux médicaments du futur. IRD Editions. -6-

128 PP 9 EFFECT OF IONIC SURFACTANTS ON THE ACTIVATED CARBON ADSORPTION OF DRUGS ELIF CALISKAN SALIHI, MEHMET MAHRAMANLIOGLU MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, HAYDARPASA, ISTANBUL, TURKEY ISTANBUL UNIVERSITY, ENGINEERING FACULTY, CHEMISTRY DEPARTMENT, AVCILAR, ISTANBUL, TURKEY The adsorption techniques employing solid sorbents are widely used to remove certain classes of chemical pollutants from waters, especially those that are hardly destroyed in conventional wastewater treatment plants (). Surfactants and other amphiphiles are known to influence the adsorption of many compounds and may be present in the environment from wastewaters or other sources (). The work described here examines the adsorption of three drugs; trimethoprim [TM], carbamazepine [CM], ibuprofen [IBU]; onto activated carbon in aqueous solutions and in the presence of different type of surfactants such as anionic; sodiumdodecyl sulfate and cationic; dodecyltrimethylammonium bromide. The adsorption experiments were carried out as a function of time and initial concentration; and also performed in the presence of surfactants at the concentrations below and above the critical micelle concentrations. The adsorption capacity values found for the adsorption of drugs in aqueous solutions followed the order: TM < CM < IBU. It was observed that the presence of surfactants caused a decrease in adsorption capacities, without affecting the equilibrium time of the adsorption processes for all drugs used.. Janoš P, Šmídová V. Effects of surfactants on the adsorptive removal of basic dyes from water using an organomineral sorbent-iron humate. J Colloid Interf Sci. 005;9:9-7.. Hari A C, Paruchuri R A, Sabatini D A, Kibbey T C G. Effects of ph and cationic and nonionic surfactants on the adsorption of pharmaceuticals to a natural aquifer material. Environ Sci Technol. 005;39(8): PP 0 CHEMICAL REGENERATION OF ACTIVATED CARBON LOADED WITH PHARMACEUTICALS ELIF CALISKAN SALIHI, MEHMET MAHRAMANLIOGLU MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, HAYDARPASA, ISTANBUL, TURKEY ISTANBUL UNIVERSITY, ENGINEERING FACULTY, CHEMISTRY DEPARTMENT, AVCILAR, ISTANBUL, TURKEY The major drawback for wastewater treatment utilization comes from economic consideration. The commercial activated carbons are expensive, rendering its infeasibility for large scale operation (). Regeneration is normally cheaper than replacement and chemical regeneration is attractive because it can be done relatively rapid in situ and no carbon attrition or pore structure degradation occurs compared with other methods (). The aim of this study is to investigate the regeneration of activated carbon (AC) exhausted with promethazine hydrochloride (PM) using alcohols. AC was loaded with the pharmaceutical using an excess of a highly concentrated PM solution, as described in elsewhere (3). Desorption of PM as a function of time was studied with diffrent alcohols and alcohol/water mixtures of several ratios. Maximum desorption was obtained in 4 hours by using the mixture of isopropanol/water. The changes in regeneration efficiencies after successive adsorption-regeneration cycles were also compared.. Putra E K, Pranowo R, Sunarso J, Indraswati N, Ismadji S. Performance of activated carbon and bentonite for adsorption of amoxicillin from wastewater: Mechanisms, isotherms and kinetics. Water Research. 009;43: Lu P J, Lin HC, Yu W T, Chern J M. Chemical regeneration of activated carbon used for dye adsorption. Journal of the Taiwan Institute of Chemical Engineers. 0;4, Caliskan E, Bermudez J M, Parra J B, Menendez J A, Mahramanlioglu M, Ania C O. Low temperature regeneration of activated carbons using microwaves: Revising conventional wisdom. Journal of Environmental Management. 0;0:

129 PP DESIGN AND OPTIMISATION OF TRANSDERMAL FORMULATIONS CONTAINING BETAHISTINE SEVINÇ ŞAHBAZ, BETÜL DORTUNÇ FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, MARMARA UNIVERSITY, HAYDARPAŞA, ISTANBUL, TURKEY Betahistine (BH), used in the treatment of Méniѐre s syndrome, is a good candidate for transdermal delivery because of its low molecular weight (09,), short elimination half life (3-5 hours), low daily dosage range (4-48 mg), frequent dosing regimen (3 times a day) and liquid state. Furthermore the drug is contraindicated in the presence of peptic ulcer (). The aim of this study is to prepare and optimise transdermal formulations of BH. To prepare the formulations, FDA approved polymers, Eudragit RL 00 and Eudragit RS 00, were chosen as matrix forming polymers which are widely used in controlled release dosage forms (). Formulations were prepared using different ratios of these two polymers and as the polymers do not have the elasticity needed, triethyl citrate (TEC), polyethylene glycol (PEG) 400, glycerine, propylene glycol were tested as plasticisers. Acetone and ethanol were preferred as solvents and the drug BH was used in different amounts. All the ingredients were evaluated for their excipient- drug compatibility using Differantial Scanning Calorimetry (DSC) tests (3). Solvent evaporation technique was used for preparing the formulations and they were evaluated for their macroscopic properties (general appearance, transparency, color, softness, homogeneity and flexibility). Results of all these parameters were examined and optimal ratios were determined.. Martindale The Extra Pharmacopoeia. 34th ed. London: The Pharmaceutical Press; Gao Y, Liang J, Liu J, Xiao Y. Double-layer weekly sustained release transdermal patch containing gestodene and ethinylestradiol. Int. J. Pharm. 009; 377 (-): Verma PRP, Chandak AR. Development of matrix controlled transdermal delivery systems of pentazocine: In vitro/in vivo performance. Acta Pharm. 009; 59: PP BIOPHYSICAL STUDIES OF RESPONSIVE DNA BLOCK CO-POLYMER CONJUGATES GÖKÇEN YAŞAYAN, JOHANNES P. MAGNUSSON, STEPHANİE ALLEN, MARTYN C. DAVİES, CAMERON ALEXANDER DEPARTMENT OF PHARMACEUTİCAL TECHNOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY SCHOOL OF PHARMACY, UNIVERSITY OF NOTTİNGHAM, NOTTİNGHAM, UK Nucleic acid nanotechnology offers a range of possibilities for new materials with sophisticated functions. Information encoded into DNA-and RNA-based materials can encompass not only biological signals, but also structural and architectural function. Pioneering work by Seeman and others has shown that synthetic structures of great complexity can be assembled by reprogramming DNA assembly modes. () This study aims to investigate the solution properties of two novel multi-responsive DNA-polymer conjugates. These materials combine smart thermoresponsive tri(ethylene glycol) ethyl ether methacrylate chains and oligomeric nucleic acids with toehold sequences. DNA strand displacement could be modulated by toehold sequences via hybridisation. Toehold sequences, or sticky ends, are short single stranded DNA segments that placed to a DNA strand. (, 3) Characterisation studies of DNA-polymer conjugates were carried mainly by a biophysical technique, AFM, to have information of conjugate properties in solution at the nanoscale. Solution behaviours of the conjugates were probed, including DLS and zeta potential measurements. All these techniques have been used to characterise the changes in conformation of the conjugates as they can be switched by a) temperature changes, b) addition of DNA strands designed to disrupt self-assembly.. Chakraborty B, Sha RJ, Seeman NC. A DNA-based nanomechanical device with three robust states. Proceedings Of The National Academy Of Sciences Of The United States Of America. 008;05(45): Kuzuya A, Komiyama M. DNA origami: Fold, stick, and beyond. Nanoscale. 00;(3): Chakraborty B, Sha R, Seeman NC. A DNA-based nanomechanical device with three robust states. Proceedings of the National Academy of Sciences of the United States of America. 008;05(45):

130 PP 3 ACTIVATION OF AMPK BY A76966 ATTENUATES LPS INDUCED ACTIVATION OF NEUTROPHILS IN LUNG IN RAT MARYAM RAMESHRAD, ALIREZA GARJANI, NASRIN MALEKI-DIZAJI, HAMID SORAYA 3, HALEH VAEZ STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, URMIA UNIVERSITY OF MEDICAL SCIENCES, URMIA, IRAN Activation of AMP-activated protein kinase (AMPK) has been shown to have anti-inflammatory effects. In this study, we determined the effects a direct activator of AMPK, A76966, on LPS induced lung injury. Wistar rats were randomly assigned to one of 3 groups (n=3): normal control was given vehicle, ip; lipolysaccharide (LPS; 0.5 mg/kg), and LPS (0.5 mg/kg) plus A76966 (0 mg/kg). After 9 hours, the heart and lung were removed. Ordinary ANOVA with LSD post-hoc test was used to compare the groups. Compared with control, MPO activity in lung and percentage of neutrophil in peripheral blood markedly were high in LPS group (p<0.00). A76966 significantly decreased both the elevated MPO activity in lung and neutrophil count in peripheral blood (p<0.05 and p<0.0; respectively). Intraperitoneal LPS injection increased the level of MyD88 (p<0.05) in heart but not lung tissue. In comparison to LPS group, administration of A76966 resulted in activation of AMPK (p<0.00) with reduction in MyD88 (p<0.0) level in the heart without any effects on the level of these markers in lung. Totally, LPS in i.p, triggers a signal at systemic or lung level, leading to the accumulation of neutrophils in peripheral and pulmonary vasculature, but failing to induce a full signal at the epithelial level () to increase the MyD88 as LPS receptor, what we see in heart. Activation of AMPK in cardiovascular by A76966 attenuates neutrophil activity and could decrease the severity of LPS lung injury. In this regard, AMPK activation could become a valid therapeutic target in endotoxemia. PP 4 ENDOTOXIN TREATMENT IN ISOLATED RAT HEART: TNF-α RISE DUE TO ACTIVATION OF MYD88 MARYAM RAMESHRAD, ALIREZA GARJANI, NASRIN MALEKI-DIZAJI, HALEH VAEZ, HAMID SORAYA 3, AILAR NAKHLBAND 4 GIFTED AND TALENTED STUDENT SUPPORTING UNIT, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, URMIA UNIVERSITY OF MEDICAL SCIENCES, URMIA, IRAN 4 RESEARCH CENTER FOR PHARMACEUTICAL NANOTECHNOLOGY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Lipopolysaccharide (LPS) Binding Protein (LBP) bound endotoxins are recognized by CD4/ toll-like receptor-4 (TLR4)-MD- complex in innate immune cells which delivers a signal through the plasma membrane and stimulate TNF-α release when the immune system is intact (). This study is designed to answer whether isolated rat heart, which is detached from the immune system, is capable of producing TNF-α through TLR4 activation. Using langendorff method, LPS in 0 ml of the modified Krebs Henseleit-buffer (KHBS) at final concentration of µg/ml was perfused at recycling mood for 0, 80, 40, 300, and 360min in separate groups. In the other protocol to evaluate the effect of LBP and CD4 in presenting LPS to its receptor, KHBS was supplemented with fetal-bovine-serum (FBS) % and method was repeated for 80 min. To assess the TOLR4 activity and TNFα release, ELISA, western blotting, real time-pcr were used. Compared with control, LPS time dependently increased the level of myocardial TLRs adapter-protein, MyD88 (p<0.05) and TNF-α (p<0.05) content of heart tissue during 6 hours. Supplementing with FBS-KHBS had no significant effect on the LPS induced elevation of MyD88 and TNF-α level. The results of this study shows for the first time that myocardial tissue is independently capable of producing TNFα probably through MYD88 activation.. Miyake K. Innate recognition of lipopolysaccharide by CD4 and toll-like receptor 4-MD-: unique roles for MD-. Int Immunopharmacol. 003;3():

131 PP 5 PHYTOCHEMICAL SCREENING AND STUDY OF THE EFFECTS OF ETHANOL EXTRACT OF OCIMUM BASILICUM (BASIL) ON CARRAGEENAN INDUCED PAW EDEMA IN RATS MARYAM RAMESHRAD, RONAK SALEHIAN, NASRIN MALEKI-DIZAJI, FATEMEH FATHIAZAD 3, ALIREZA GARJANI, SANAZ HAMEDEYAZDAN STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN The objectives of the present study were phytochemical screening and study of the effects of ethanol extract of Ocimum basilicum (basil) on carrageenan induced paw edema in rats. The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. The animals received an intraperitoneal (i.p) injection of Ocimum basilicum extracts (.5, 5, 0 mg/kg) hr before subcutaneous (s.c) injection of carrageenan % (w/v) in the left paw were compared with control group. Data were expressed as a percentage of increase in the paw thickness and were compared with those of pre-injection values. Myeloperoxidase (MPO) activity was determined, and a histopathological study was carried out in paw tissue 4 hr after induction of inflammation. Phytochemical screening indicated the presence of phenolic compounds (7.34 %) and flavonoids (.9%). All doses of extract significantly reduced maximum paw thickness after the induction of inflammation (p < 0.00) and inducted a marked reduction in MPO activity (p<0.0, p<0.00, p<0.00: respectively) compare to the control group. Histological examination showed a marked reduction in tissue edema and inhibition leucocyte infiltration in treated rats. The results of the study demonstrate that Ocimum basilicum strongly reduced the inflammation of carrageenan-injection and suggest that the anti-inflammatory effects could be related to inhibition leucocyte infiltration. PP 6 SYNTHESIS, BIOLOGICAL ACTIVITY AND MOLECULAR DOCKING STUDIES OF NOVEL 3-(SUBSTITUTED-BENZYLIDENE)- 5-(4-FLUOROPHENYL)INDOLIN--ONE DERIVATIVES AS INHIBITORS OF C-SRC TYROSINE KINASE ZÜHAL KİLİC-KURT, FİLİZ BAKAR, SÜREYYA ÖLGEN DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY DEPARTMENT OF BİOCHEMİSTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY The c-src is a member of the largest family of nonreceptor protein tyrosine kinase (). c-src plays an important role in the signal transduction pathways that regulates cancer cell proliferation, apoptosis and angiogenesis. Therefore c-src has became potential target for many cancers including colon, breast, lung, ovary, and prostate (). In the present work, we describe the preparation of novel 3-(substituted-benzylidene)-5-(4-fluorophenyl)indolin--one derivatives and their c-src tyrosine kinase inhibitory activity. In addition, the molecular docking study for these compounds carried out by Autodock vina to evaluate the relationships between their structures and binding properties with active site of c-src kinase. For the synthesis of target compounds, 5-iodo indolin- -one were obtained by a Wolff Kishner reduction of 5-iodoisatin. Synthesis of 5-(4-fluorophenyl)indolin--one was achieved by palladium-catalyzed Suzuki cross-coupling reaction of 5-iodo indolin--one with p-fluorophenylboronic acid. Finally, target compounds was obtained by condensation of 5-(4-fluorophenyl)indolin--one with substituted benzaldehydes in ethanol at reflux. The activity results showed that among the synthesized compounds, 3-(4-chloro benzylidene)-5-(4-fluorophenyl) indolin- -one, 5-(4-fluorophenyl)-3-(4-methoxy benzylidene) indolin--one and 3-(4-(dimethylamino) benzylidene)-5-(4-fluorophenyl) indolin--one showed good inhibitory activities with IC50 values of 0.08 µm,.98 µm and.0 µm. According to the docking results, all of compounds located in the active site of c-src kinase. Among the active compounds only the best active compound (3-(4-(dimethylamino) benzylidene)-5-(4-fluorophenyl) indolin--one) created a hydrogen bond between indole nitrogen and carbonyl oxygen of the Met 34. Therefore, this study provides new promising compounds with good enzymatic inhibitory activities for further development of new anticancer drugs targeting c-src tyrosine kinase.. Zhang S, Yu D. Targeting Src family kinases in anti-cancer therapies: turning promise into triumph. Trends in Pharmacological Sciences. 0; 33(3): -8.. Edwards J. Src kinase ınhibitors: an emerging therapeutic treatment option for prostate cancer. Expert Opin. Investig. Drug. 00; 9(5):

132 PP 7 NOVEL INDOLIN--ONE DERIVATIVES AS C-SRC TYROSINE KINASE INHIBITORS: SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY ZÜHAL KILIC-KURT, FILIZ BAKAR, SÜREYYA ÖLGEN DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY Protein kinases are important targets in cancer. c-src kinase is a member of nonreceptor tyrosine kinase, known as the Src family of kinases (SFKs) (). Aberrantly activated c-src lead to development of cancer, including lung, prostate, and breast (). Inhibition of Src and SFKs therefore represents a logical strategy for investigation in the treatment of cancer (3). In this study, synthesis, biological activities and molecular docking studies of novel indolin--one derivatives as inhibitors of c-src are described. Synthesis of the title compounds, firstly, indolin--one was prepared by a Wolff-Kishner reduction of isatine. 5-Nitro indolin--one was synthesized by nitration of indolin--one. Subsequent catalytic hydrogenation led to 5-amino indolin- -one. Reaction of 5-amino indolin--one with ethylisocyanate and benzylisothiocyanate afforded the -ethyl-3-(-oxoindolin- 5-yl)urea and -benzyl-3-(-oxoindolin-5-yl)thiourea. Condensation of these ureidoindolin--ones with various benzaldehyde afforded the target compounds. An array of 6 diversely 3,5-disubstituted indolin--ones was evaluated against c-src. Among the screened compounds, -ethyl-3-(3-(4-fluoro benzylidene)--oxoindolin-5-yl) urea, -benzyl-3-(3-(4-carboxy benzylidene)- -oxoindolin-5-yl) thiourea, -benzyl-3-(3-(4-fluoro benzylidene)--oxoindolin-5-yl) thiourea and -benzyl-3-(3-(,4-difluoro benzylidene)--oxoindolin-5-yl) thiourea showed good inhibition with IC50 values of.06,.0,.38 and.4 µm. Docking simulation was performed to synthesized compounds into the c-src active site to determine the probable binding conformation. By the dock results, it was determined that all compounds located into active site of c-src and exhibited the good binding affinities into c-src with hydrogen bonds. For the best active compound (-benzyl-3-(3-(,4-difluoro benzylidene)--oxoindolin- 5-yl) thiourea), one hydrogen-bond interaction with OH of Thr 338 was found by carbonyl group of indole ring. This study provides insights for further optimizing of indolin--ones for the discovery of the c-src kinase inhibitors.. Lieu C, Kopetz S. The Src Family of protein tyrosine kinases: a new and promising target for colorectal cancer therapy. Clinical Colorectal Cancer. 00; 9: Lee K, Kim J, Jeong K-W, Lee KW, Lee Y, Song JY, Kim MS, Lee GS, Kim Y. Structure-based virtual screening of Src kinase inhibitors. Bioorg. Med. Chem. 009; 7: Saad F, Lipton A. SRC kinase inhibition: Targeting bone metastases and tumor growth in prostate and breast cancer. Cancer Treatment Reviews. 00; 36: PP 8 SYNTHESİS OF PLATINUM(II) COMPLEXES OF -CYCLO-SUBSTITUEBENZİMİDAZOLE AND THEİR CYTOTOXİC EFFECTS AZIME BERNA OZCELIK, FATMA GUMUS, RAHSAN ILIKCI SAGKAN, UGUR MUSABAK GAZI UNIVERSITY, ANKARA, TURKEY UNIVERSITY OF GULHANE MILITARY MEDICINAL ACADEMIA, ISTANBUL, TURKEY In clinical practice, platinum-based complexes are most widely used for the treatment of cancer. Cisplatin, Carboplatin and Oxaliplatin are used for treating various types of cancer, including genitourinary, colorectal and non-small cell lung cancer. However, the clinical success of cisplatin is limited by severe side effect and intrinsic and acquired drug resistance.3 One strategy to overcome cisplatin resistance is to design new platinum complexes that specifically deal with some or even all of the resistance mechanism. In the present study, to investigate the role of the hydrophobic substituents on position of the benzimidazole carrier ligands, cis or trans Pt(II) complexes having -cycloalkylsubstitutedbenzimidazole carrier ligands were synthesized and evaluted for their preliminary in vitro cytotoxic activities against OVCAR-3 and HeLa cell lines. We also report the effect of the most activite compound among the tested compounds on the cell cycle modification and apoptosis.. Rosenberg B, Van Camp L, Trosko JE, Mansour V H. Platinum compounds: a new class of potent antitumour agents. Nature 969;: Jung Y, Lipard SJ. Direct cellular responses to platinum-induced DNA damage. Chem Rev 007; 07: Farrell N, Qu, Y, Hacker, M. P. Cytotoxicity and antitumor activity of bis(platinum) complexes. A novel class of platinum complexes active in cell lines resistant to both cisplatin and,-diaminocyclohexane complexes. J. Med. Chem. 990,33:

133 PP 9 ERLOTINIB LOADED POLYMERIC NANOPARTICLES: SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION LEILA BARGHI, HADI VALIZADEH, DAVOUD ASGARI, JALEH BARAR 3 FACULTY OF PHARMACY AND STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 RESEARCH CENTER FOR PHARMACEUTICAL NANOTECHNOLOGY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Development of polymeric nanoparticles of erlotinib hydrochloride was the main objective of this study. For this purpose poly caprolactone - poly ethylene glycol - poly caprolactone (PCEC) copolymers with different composition were synthesized via ring opening polymerization. Formation of these triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers via solvent displacement method. Physicochemical properties of obtained polymeric nanoparticles depend on composition of used copolymers. Size of particles decreased with decreasing the PCL/PEG molar ratio in used copolymers. Loading efficiency of prepared formulations is declined by decreasing their particle size. The release behavior of erlotinib from the polymeric nanoparticles exhibited a sustained pattern without any burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles decrease with an increase of CL/PEG molar ratio of used block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 7 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be 4.8 μm. From the results obtained, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as novel delivery system for erlotinib. PP 30 ANTIBACTERIAL ACTIVITY OF ALGERIAN PLANTAGO LANCEOLATA L MOHAMED MIHOUB ZERROUG, SALIHA LAOUICHA, ABDERRHAMANE SENATOR, HAMAMA BOURICHE LABORATORY OF APPLIED MICROBIOLOGY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETIF, ALGERIA LABORATORY OF APPLIED BIOCHEMISTRY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETIF, ALGERIA The aim of this work is to evaluate the anti-bacterial activity of the extracts of the aerial part of Plantago lanceolata L, known in Algeria under the name of El-Lisan -Haml. This herb is known in traditional MEDICINE for the astringent, healing, antiinflammatory and antitussive. The antibacterial activity of methanol and aqueous extracts of P. lanceolata was evaluated by the agar diffusion disc technique against 6 Gram negative bacterial strains (Pseudomonas aeruginosa ATCC 7853, Escherichia coli ATCC 59, Salmonella typhimurium ATCC 33, Acinetobacter baumannii ATCC 9606, Proteus mirabilis ATCC and Klebsiella pneumoniae ATCC ) and 4 strains Gram positive (Staphylococcus aureus ATCC 593, Bacillus cereus ATCC 0876, Enterococcus faecalis ATCC 4945 and Listeria monocytogenes ATCC 533). Both extracts were used at a concentration of 00 mg/ml. The results of antibacterial activity revealed that the aqueous extract inhibited the growth of four bacterial strains. at has Considerable antibacterial effect was obtained against Proteus vulgaris and Salmonella typhimurium with inhibition zones of 3.±0.38 and 9.78±0.9 mm respectively. Pseudomonas aeruginosa and Bacillus cereus were less sensitive; zones of inhibition were 8.0±0.0, and 7.3±0.58 mm (p<0.05). respectively. The effect of aqueous extract was more important than the amocixilline (Amox), used as reference. The methanol extract inhibited the growth of Salmonella typhimurium with zone of inhibition 6.7±.68, but was less effective against Proteus vulgaris and Listeria monocytogenes which their zones of inhibition were.44±0.0 and 8.0±0.0 (p<0.05) respectively. -3-

134 PP 3 INFLUENCE OF THE PH AND BUFFER CONCENTRATION ON THE AGGREGATION OF HUMAN ALPHA INTERFERON IN AQUEOUS SOLUTION FARANAK SALMANNEJAD, NASTARAN NAFISSI-VARCHEH, ALIREZA SHAFAATI 3, REZA ABOOFAZELI DEPARTMENT OF PHARMACEUTICS, SCHOOL OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, SCHOOL OF PHARMACY,SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN 3 DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, SCHOOL OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN Stabilization protein molecules in order to achieve an acceptable shelf life is the most challenging obligation in the development of protein formulations (). Protein aggregation is one of the most common and critical manifestations of protein instabilities, encountered in almost all stages of protein drug development (). The aim of this study was to evaluate the effect of buffer conditions on the aggregation propensity of recombinant human interferon alphab (rhifnαb) during thermal stress. The protein was incubated for h at C and for up to 40 h at 50 C and its aggregation tendency was then studied using different analytical methods. The effects of various ph (5, 6 and 7) and buffer concentrations (0, 55 and 00 mm) on the aggregation of the protein following incubation at 50 C for 7 h were also evaluated. The results obtained for samples incubated at 50 C for up to 40 h showed that optical density at 350 nm and the amount of higher molecular weight aggregates increased whereas the monomer content decreased significantly (p<0.05), directly proportional to the incubation time. Data obtained from the incubation of samples at 50 C for 7 h showed that regardless of the buffer concentration, the percentage of monomer at ph 6 was significantly higher than that at ph 7 and ph 5 (p<0.05). At constant ph, although not significant, the same trend was observed when the buffer concentration increased to 00 mm. In conclusion, understanding the effects of such factors would play a key role in rhifnαb stabilization and in turn the development of stable therapeutic formulations.. Wang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. Journal of pharmaceutical sciences. 007;96():-6.. Wang W, Nema S, Teagarden D. Protein aggregation: pathways and influencing factors. International journal of pharmaceutics. 00;390(): PP 3 EFFECT OF METFORMIN ON LPS-INDUCED MYD88 ACTIVATION IN RAT HEARTS HALEH VAEZ, MARYAM RAMESHRAD, ALIREZA GARJANI STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL Metformin has a protective effect in inflammatory processes through activation of AMP-activated protein kinase (AMPK). In the present study, the effect of metformin, on Myeloid differentiation primary response 88 protein (MYD88), a signal transducer in toll-like receptor (TLR4) pathway, and its relation with AMPK phosphorylation level, in Lipopolysaccharide (LPS) induced inflammation is assessed in rat heart. Male Wistar rats were randomly divided in 3 groups (n= 5) and treated intraperitoneally according to this protocol: control group received normal saline (N/S, 0.5 ml), LPS group received LPS (0.5 mg/kg in 0.5 ml N/S) and metformin treated group received metformin (00 mg/kg) + LPS (0.5 mg/kg) in 0.5 ml N/S. Nine hours after injections hearts were removed and the protein content of MYD88 and the ratio of AMPK phosphorylation were evaluated by western blotting. Compared with control, LPS significantly increased MYD88 protein content in the heart (p< 0.05) and a single dose of metformin at 00 mg/kg significantly inhibited the LPS induced MYd88 expression p (p< 0.05). Furthermore, these results were accordance with an increase in the AMPK activation and metformin treatment significantly increased the ratio of phosphorylated AMPK compared to LPS group (p< 0.05). Metformin with inhibitory effect on MYD88 expression can be effective in TLRs pathway induced inflammation. The AMPK activation can be the responsible mechanism for this protective effect of metformin. -33-

135 PP 33 WHAT ARE THE EFFECTS OF HISTONE METHYLATION INHIBITOR AND/OR HISTONE DEACETYLASE INHIBITOR ON HISTONE LYSINE TRIMETHYLATION OR ACETYLATION IN BREAST CANCER CELL LINES? ASLIHAN DAGDEMIR, SEHER KARSLI-CEPPIOGLU, GAëLLE JUDES, MAUREEN ECHEGUT, FRéDéRIQUE PENAULT-LLORCA, ANDRé LEBERT 3, YVES-JEAN BIGNON, DOMİNİQUE BERNARD-GALLON DEPARTMENT OF ONCOGENETICS, CENTRE JEAN PERRIN, CBRV, 8 PLACE HENRI DUNANT, BP 38, 6300 CLERMONT- FERRAND, FRANCE. DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, TIBBIYE CAD. NO: ISTANBUL, TURKEY 3 UNIVERSITY BLAISE PASCAL, INSTITUT PASCAL UMR 660 CNRS/UBP, AUBIèRE, FRANCE The Histone Deacetylase Inhibitors (HDACi) and Histone Methylation Inhibitors (HMTi) were known to interact with epigenetic modifications. We aimed to demonstrate the mechanisms of HDACi and HMTi on modified histones H3K7me3, H3K9ac and H3K4ac in MCF-7 and MDA-MB-3 breast cancer cell lines. Breast cancer cell lines were treated with HMTi 3-Deazaneplanocin A hydrochloride (DZNep) [5µM], HDACi Sodium Butyrate (NaBu) [mm] and Suberoylanilide Hydroxamic acid (SAHA) [μm] for 48 hours. We applied chromatin immunoprecipitation (ChIP) followed by QPCR of 6 selected genes (EZH, BRCA, ERa, ERb, SRC3, P300). Western Blot was performed and mrna levels were analyzed for each cell line. According to our results; SAHA and NaBu increased acetylation at lysine 4 of histone H3 in MCF7 cell line and DZNep decreased methylation on H3K7me3 marks with a slight difference in MDA-MB-3 cell line. We demonstrated that DZNep acted globally and it could inhibit both activating and repressive histone marks, while mrna expression levels, conversely, were increased with the treatments of NaBu and SAHA especially in MCF 7 cell line. These results suggested that HDACi and HMTi have beneficial effects on the genes, which are upregulated in cancer; however they have adverse effects for downregulated genes, so the action did not seem to be specific for genes. Our results add a new outlook of complication to epigenetic dysregulation in cancer and also established histone modifications-mediated silencing or enhancing for up-and-coming therapeutic target. Our data demonstrate that HDACi disposed to modify the transcription into the demethylation and acetylation of the histones in breast cancer cell lines. PP 34 MOLECULAR FARMING OF TRAIL HAMID REZA HEIDARI, BAHRAM KAZEMI, HOSSEIN NADERI-MANESH 3 STUDENT S RESEARCH COMMITTEE AND FACULTY OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN CELLULAR AND MOLECULAR BIOLOGY RESEARCH CENTER, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN 3 DEPARTMENT OF BIOPHYSICS, FACULTY OF BIOLOGICAL SCIENCES, TARBIAT MODARES UNIVERSITY, TEHRAN, IRAN Molecular Farming has been considered as a promising field for production of biopharmaceuticals. In this study, production of TNF related apoptosis inducing ligand (TRAIL) has been tackled in Nicotiana tabacum using Agrobacterium Tumefaciens LBA Initially, the desired coding sequence was obtained using PCR technique on the constructed human cdna library; afterward the other necessary requirements for expression of the product in plant cell system were provided through subcloning into helper and final 079-pGreen expression vectors. The final construct was cloned into A. tumefaciens LBA 4404; subsequently the N. tabacum cells were transformed through co-culture method. The expression of the ligand was confirmed by western blot analysis on the total protein extract from selected N. tabacum cells. The protein of interest was extracted through chromatographic technique and biological activity was evaluated through MTT assay. The results indicated that one gram of N. tabacum cells can successfully produce 5µg recombinant TRAIL. -34-

136 PP 35 PHENOLIC CONTENT OF NEPETA FISSA CA MEYER AND ITS ANTIPROLIFERATIVE ACTIVITY AGAINST HELA CELL LINES FERDA ESER, IBRAHİM DEMIRTAS, SERKAN KOLDAS, LUTFİ BEHCET 3 FACULTY OF PHARMACY GAZIOSMANPASA UNIVERSITY, TOKAT, TURKEY FACULTY OF CANKIRI KARATEKİN UNIVERSITY, CANKIRI, TURKEY 3 FACULTYBINGOL UNIVERSITY, BINGOL, TURKEY The genus Nepeta (Lamiaceae) comprise about 400 species and have been used in folk MEDICINE for centuries due to its antiseptic, astringent, anti-tussive anti-spasmodic, anti-asthmatic, anti-bacterial, antifungal, anti-viral and diuretic properties (). In this study, we aimed to determine the phenolic content of various extracts of N. fissa and the antiproliferative activity of N. fissa against HeLa cell lines. For this purpose, ground and dried parts of N. fissa were boiled with distilled water for h. After filtration, the aqueous extract was extracted with ethyl acetate and the organic layer was dried via CaCl, filtered and evaporated to yield.9 g extract (Fr A). Other parts of the plant material were extracted by maceration with CHCl3/MeOH (:) at room temperature. After filtration, the extract was concentrated to dryness under reduced pressure by rotary evaporation at 60 C to give a mass of g. It was dissolved in methanol and extracted with hexane. This procedure produced hexane fraction (Fr B;.3 g). Methanol phase was evaporated and dissolved with distilled water and then extracted with CHCl to give Fr C (9.7 g). Water phase was extracted with Ethly acetate to yield.7 g crude extract (Fr D). Finally, the water layer was lyophilized at -80 C (Fr E). The content of the each extract was screened by HPLC-TOF and analyzed for antiproliferative activity against HeLa cell lines. The CHCl (Fr C) and Ethly acetate (Fr D) extracts were found more active than the others. PP 36 PHYTOCHEMICAL ANALYSIS AND CYTOTOXIC ACTIVITY OF COLUTEA CILICICA FERDA ESER, AYSE SAHİN YAGLIOGLU, IBRAHIM DEMIRTAS, ADEM ONAL FACULTY OF PHARMACY GAZIOSMANPASA UNIVERSITY, TOKAT, TURKEY FACULTY OF PHARMCY CANKIRI KARATEKIN UNIVERSITY, CANKIRI,TURKEY The genus Colutea comprises about 8 species (Fabaceae), deciduous flowering shrubs peculiar to Southern Europe, North Africa and Southwest Asia. Colutea cilicica Boiss. & Bal., generally known as bladder senna, is native to the Mediterranean, and it is mostly grown for its attractive yellow flowers and fruit. The fruits of the plant play an important role in Turkish folk mediciner because of its antiinflammatory effect and wound healing activity (, ). The decoctions of fruiting branches are generally used for the treatment of abscesses and wounds of kids. In addition, the ash of the plant is used to make ointment in vegetable oil. The wound healing property of the plant is promoted through several of its constituents, such as flavonoids, triterpenes and alkaloids (3). In this study, Colutea cilicica (Fabaceae) was collected from Tokat region. Aerial parts of the plant including flowers, leaves and stem were dried at room temperature (5 C) in the shade and subjected to extraction with methanol:chloroform (:) by maseration method. After filtration and evaporation processes, analysis of the crude extract was performed using HPLC-TOF-MS. According to the results, 4-hydroxybenzoic acid was determined as the main components of the flowers and the stem, as well. The main component of the leaves was identified as rutin. The antiproliferative activities of all extracts were also studied against C6 cells using the BrdU ELISA method. The extracts were shown to have low antiproliferative activity than 5-fluorouracil used as a standard. -35-

137 PP 37 PHYTOCHEMICAL ANALYSIS, DYEING POTENTIAL AND CYTOTOXIC ACTIVITY OF ALKANNA ORIENTALIS (L.) BOISS (BORAGINACEAE) FERDA ESER, AYSE SAHİN YAGLIOGLU, MELDA DOLARSLAN, IBRAHİM DEMIRTAS, EBRU AKTAS, ADEM ONAL FACULTY OF PHARMACY GAZIOSMANPASA UNIVERSITY, TOKAT, TURKEY FACULTY OF PHARMACY CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY Alkanna orientalis L. which belongs to the Boraginaceae family, generally use as spices, is useful for the preparation of dyestuffs. Active agents of the family are mucilage derivatives (arabinose, glucose and galactose), Pyrolizidinalkaloits (Amabilin, Supinidin, Lycopsamin, Intermedin, 7-Asetil-Lycopsamin ve 7-Asetilintermedin). Furthermore, the family contains tannins, saponins, resins, starches, silicic acids, vitamin C and minerals (). The root of the plant contains naphthoquinone derivatives (rate of 5-6%) which is a red dye, mainly Alkannin (). In this study, Alkanna orientalis (Boraginaceae) was collected from Çankırı region. The roots of the plant were dried at room temperature (5 C) in the shade. The extracts of the root were prepared with ethanol and water, respectively, by maseration method. The analysis of ethanol and water extracts was performed by HPLC-TOF/MS. As a result of HPLC-TOF-MS analyzes, ten compounds were determined and, rosmarinic acid and 4-hydroxybenzoic acid were found the main components of the ethanol and water extracts, respectively. The obtained cytotoxic activities of all extracts were determined by LDH assays against C6 cells. The extracts were detected in terms of cytotoxic activities and were found to be less toxic than 5-fluorouracil used as a standard. Dyeing potential of the plant was also studied using different mordanting techniques and fiber types. Best color strength (K/S=8.5) was obtained in the presence of AlK(SO4) mordant, using metamordanting method for cotton fabric. PP 38 FABRICATION OF FULVESTRANT LOADED MODIFIED RELEASED NANOPARTICLES: EFFECT OF COPOLYMER MOLECULAR WEIGHT ON PARTICLE CHARACTERISTICS CANAN HASCICEK, CEYDA TUBA SENGEL-TURK, FILIZ BAKAR, NET DAS-EVCIMEN, MEHMET GUMUSTAS 3, A. SIBEL OZKAN 3, AYHAN SAVASER 4, YALÇIN OZKAN 4 ANKARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ANKARA, TURKEY ANKARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ANKARA, TURKEY 3 ANKARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, ANKARA, TURKEY 4 GULHANE MILITARY MEDICAL ACADEMY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ANKARA, TURKEY Breast cancer treatment has evolved dramatically in the last few years and perhaps the most rapidly developing research area today. Fulvestrant (FLV) is a novel estrogen receptor (ER) antagonist that competitively binds to the ER with a much greater affinity than that of tamoxifen. In our previous study, FLV-loaded PEG-block-PLGA polymeric nanoparticles were successfully prepared by using salting out-emulsion-evaporation technique and various physical characteristics were investigated in terms of the encapsulation efficiency, particle size, surface charge, in-vitro drug release profiles, kinetics and mechanisms (). In this part of our research, the shape of nanoparticles was examined by AFM. The existence of a possible drug-excipient interaction was investigated by using DSC and XRD analyses. The antiproliferative activity of free and nanoparticle conjugated forms of FLV was determined against MCF-7 breast cancer cell line. The colloidal size and the spherical shape of the particles were proved based on the AFM images. The DSC thermograms and the XRD patterns indicated that there was no interaction between FLV and the excipients. The potency of the nanoparticles on the proliferation proficiency of MCF-7 cells was observed for the period of 4 and 48 h. The cell culture studies showed that both of the pure drug and the FLV loaded nanoparticles presented high cytotoxicity in breast cancer cell line.. Hascicek C, Sengel-Turk CT, Bakar F, Das-Evcimen N, Gumustas M, Ozkan AS, Savaser A, Ozkan Y. Fabrication of Fulvestrant Loaded Modified Released Nanoparticles: Comparision of Copolymer Molecular Weight. 3th European Symposium on Controlled Drug Delivery, The Netherlands, April 6-8, 04 :

138 PP 39 COMPLEXATIONS OF L-TYROSINE AND ITS METHYL ESTER WITH CU(II): TEMPERATURE DEPENDENCE OF THE FORMATION CONSTANTS A. SEZA BAŞTUĞ, DENIZ ÇIKLA YILMAZ, MÜRŞID PEKIN DIVISION OF GENERAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, HAYDARPAŞA 34668, İSTANBUL, TÜRKIYE DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, HAYDARPAŞA 34668, İSTANBUL, TÜRKIYE Studies on metal complexes of biologically important substances are very important to provide valuable information on their metabolism. Considerable studies have been carried out on the complexations between metal ions and bioligands [,]. Here, formation constants of Cu(II) with L-tyrosine and its methyl ester and acidity constants of them were determined potentiometrically [3] at 5.0, 0.0 and 35.0 C and I = 0.0 mol/l. ΔG, ΔH and ΔS were determined for protonation of ligands and for complexations of them with Cu(II). The results are tried to explain according to hard and soft acids and bases rule [,,4,5]. Protonation of NH group are found to be endothermic for Cu-Tyr and exothermic for Cu-TyrE systems. Driven force of the latter is both ΔH and ΔS [,]. pk of Tyr and TyrE increase with increasing temperature; driven force is ΔS alone in this protonation. ΔH of Tyr-Cu(II) complexation are found to be positive. Contribution of ΔS to ΔG is 00% [4,5]. Occurring both enthalpic and entropic stabilization together for Cu-TyrE complexations implies that O atom of COO group is participated more effectively in Tyr-Cu(II) complex formation [,4,5]. Cu-TyrE complexation may be included predominantly Cu-N bonds and therefore its formation constant was found smaller than that of Cu-Tyr.. Bastug, etal, J. Coord. Chem., 64(), 8(0). Şişmanoğlu etal, Dyes and Pigments 70(), 4(006) 3. Pekin, etal, Toxicolog. Environ. Chem., 80(3-4), 65(00) 4. Bastug etal, Chim. Acta Turcica, 6, 7(998) 5. Bastug etal, Rev. Inorg. Chem., 7, 53(007) PP 40 CARMINIC ACID: TEXTILE, COSMETIC AND FOOD COLORANT SEVIM KARABULUT, TÜRKAN YURDUN, GÜLBIN ERDOĞAN 3, EMRE DÖLEN 3 DEPARTMENT OF ANALYTICAL CHEMISTRY, INSTITUE OF HEALTH SCIENCE, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY 3 DEPARTMANT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Natural pigments and colorants are widely used in the world in many industries such as textile dyeing, food processing or cosmetic manufacturing. Carminic acid (7-α-D glycopyranosyl-9, 0 dihydro-3,5,6,8-tetrahydroxy--methyl-9,0-dioxo- anthracenecarboxy-lic acid; E-0, color index no ) is a natural dyestuff extracted from dried females of the cochineal insect (Dactylopius coccus Costa). Carmine dyestuff is frequently used in the cosmetic, pharmaceutical, food and textile industries. It is used in cases of severe coughing, the treatment of spasmotic problems and urinary problems as a homeopathic medicine. It was permitted to be used as a food coloring by the European Union in 994 and by the United States in 00. It is a unique natural red dye which is permitted by Food and Drug Administration (FDA) as an eye shadow at cosmetic. Synthetic dyes which are used for coloring have toxic, carcinogenic, allergic effect and their waste cause environmental pollution. Despite the lots of negative qualities of synthetic dyes, natural dyes have the advantages such as minimum environmental pollution and low risk factor to human health. Istanbul Naval Museum is one of the important museums in Istanbul/Turkey, the textiles in this museum have not yet been evaluated through chemical analysis. In this study, the dyestuff components of 90 historical textile samples were identified by high performance liquid chromatography with diode array detector. As a result, carminic acid dyestuff was identified in 3 red-coloured samples. -37-

139 PP 4 APPLICABILITY OF TWO SURFACTANTS IN ENHANCING THE PHYSICOCHEMICAL PROPERTIES AND INTESTINAL ABSORPTION OF SIROLIMUS FROM SELF-NANOEMULSIFYING FORMULATIONS: A COMPARISON ZIBA ESLAMBOULCHILAR, HADI VALIZADEH, PARVIN ZAKERI-MILANI DEPARTMENT OF PHARMACEUTICS, SCHOOL OF PHARMACY, ZANJAN UNIVERSITY OF MEDICAL SCIENCES, ZANJAN, IRAN - STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN DEPARTMENT OF PHARMACEUTICS, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Components of self-nanoemulsifying drug delivery systems (SNEDDS), including surfactants, exhibit solubilizing, emulsifying and bioavailability enhancing properties and control many characteristics of these formulations. This study aimed on investigating and comparing the applicability of two different surfactants (Cremophor RH 40 and Labrasol) in enhancing physicochemical properties, in vitro release and intestinal absorption of sirolimus from SNEDDS formulations. Box Behnken design and desirability function were used to design and optimize SNEDDS formulations. Surface properties of vehicles, formulations and diluted nanoemulsions were investigated. Formulations prepared containing either Cremophor RH 40 or Labrasol and their emulsification efficiency, droplet size, polydispersity index, zeta potential, drug release and intestinal permeability were determined and compared. Formulation containing more Cremophor RH 40, exhibit lowest surface tension. Droplet size of optimized Cremophor-based SNEDDS formulation was nm vs for Labrasol-based one. Formulations revealed significant increase in drug release (more than 85% in 5 min). Intestinal permeability of sirolimus in formulations containing Cremophor RH 40 and different cosurfactants and oils were significantly higher than that of control sirolimus solution. Effective permeability (Peff) value of Cremophor-based formulation was 3.46 times higher than that of sirolimus solution in comparison to.3 times for Labrasol-based formulation. The best physicochemical properties and intestinal permeability enhancement was observed applying Cremophor RH 40 as surfactant with Capryol PGMC and Transcutol as oil and cosurfactant. As a result, incorporating sirolimus in SNEDDS formulations could promisingly enhance its intestinal permeability. Compared to Labrasol, application of Cremophor cause more improvement in physicochemical properties, dissolution and intestinal permeability of sirolimus. PP 4 BINDING PROPERTIES AND INTERACTIONS OF AMPHIPHILIC PHENOTHIAZINE DRUG THIORIDAZINE HYDROCHLORIDE WITH β-cyclodextrin NEŞE ERDINÇ, SINEM GÖKTÜRK MARMARAUNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANAYLITICAL CHEMISTRY MARMARAUNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL BASIC SCIENCES, GENERAL CHEMISTRY Cyclodextrins can increase the apparent solubility and dissolution rate of poorly water soluble drug candidates improving their biopharmaceutical performance. Placing inside the cyclodextrin molecular cavity the substrate can considerably improve physico-chemical and pharmacological properties (solubility, stability, bioactivity, etc.). β-cyclodextrin (β-cd) has an amphiphilic character due to an apolar cavity that shows a certain degree of selectivity in binding organic and inorganic compounds and a hydrophilic annulus consisting of a number of hydroxyl groups [,]. Generally, hydrophobic molecules or those with hydrophobic residues have the highest affinity with the CD cavity in aqueous solution, and it is well established that the ability of β-cyclodextrin to enhance drug stability and solubility depends on formation of inclusion complexes. In the present study Thioridazine hydrochloride (THCl), known as an amphiphilic phenothiazine drug [3], has been chosen a model drug to study the interaction with β-cd in aqueous media. The interaction of THCl with β-cd has been studied by means of UV-vis spectroscopy. Aqueous solutions of THCl containing wide concentration range of β-cd have been prepared and the absorbance spectra recorded. The changes of absorbance were observed as a function of the concentration of β-cd added. A comparison of the binding constants (Kb) and fraction of bound THCl to β-cd were calculated from the Benesi Hildebrand Equation for different concentrations of THCl. Additionally, the effect of β-cd on the CMC of THCl was also studied. The results are discussed in terms of surface activity and binding tendency of THCl to different concentrations of β-cd. References: [] Raoa VM, Nerurkar M, Pinnamaneni S, Rinaldi F, Raghavan K. Int. J. Pharma. 006; [] Göktürk S, Çalışkan E, Talman RY, Var Ü. TheScientificWorldJournal, 0; [3] Erdinc N, Göktürk S, Tunçay M. Colloids and Surfaces B: Biointerfaces 00; 75:

140 PP 43EVALUATION THE ANTICHOLINESTERASE INHIBITORY EFFECTS OF THE ROOT OF VALERIANA ALLIARIFOLIA EXTRACT LAAYA SAADAT, HOSSEIN NAZEMIEH, YADOLLAH AZARMI 3, HALEH VAEZ 4 STUDENT RESEARCH COMMITTEE,TABRIZ UNIVERSITY OF MEDICAL SCIENCE,TABRIZ,IRAN DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,TABRIZ, IRAN 3 3DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 4 DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Valeriana alliarifolia has a wide distribution in Iran,and few studies have been done on this plant.the objectives of the present study were evaluation the anticholinesterase inhibitory effects of methanolic and hexane extract of valeriana alliarifolia. The air-dried underground parts of the plant were extracted,and using TLC and UV spectrophotometry methods to determine valepotriates compound. Biventer cervicis muscle preparation from chickens aged 3-0 days were isolated, and the actions of carbachol and acethylcholine were studied in the presence of the extract on the isolated chicken biventer cervicis muscle.the log dose-response curves for both carbachol and acethylcholine in the presense of methanolic extract(00 / μ ml)did not differ with control dose-response,so methanolic extract was fractionated with ethylacetat, n-butanol and water. The log doseresponse curves for both carbachol and acethylcholine in the presense of water and ethylacetat extract did not differ with control dose-response, but, The log dose-response curves for acethylcholine was moved to up in the presense of n-butanolic extrat (00 μ/ml,p<0.05).the log dose-response curves for both carbachol and acethylcholine were moved to down in the presense of hexane extract.the result of the study suggests that the n-butanolic extract may have anticholinesterase effect. PP 44 STUDY THE EFFECTS OF HESPERIDIN AS A FLAVONOID ON CARDIAC HEMODYNAMIC AND INFARCTED SIZE AND LACTATE CONCENTRATION IN ISCHEMIC-REPERFUSION ISOLATED RAT HEART MAHDIYEH PASHAII, MARYAM RAMESHRAD, HALEH VAEZ 3, NEGISA SEYEDTOUTOUNCHI 4, ALIREZA GARJANI 5, FATEMEH FATHIAZAD 6 STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 4 STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN GIFTED AND TALENTED STUDENT SUPPORTING UNIT, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ 5 DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 6 DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Hesperidin as a flavonoid has been shown to have strong anti-oxidant and anti-inflammatory activities. The aim of the present study is to investigate the effects of Hesperidin on cardiac hemodynamic,size infarct,arrhythmia and lactate concentration. Male Wistar rats were heparinized and anesthetized then harvested heart was cannulated immediately to the langendorff apparatus and prepared for left coronary artery ligation. The control and solvent (DMSO) group received Krebs-Henseleit Buffer Solution (KHBS) during stabilization, ischemia and reperfusion period,while for other groups KHBS with Hesperidin (,.5,5 mcg/ml in separate groups) should be infused 5 minutes before occlusion and during the ischemia and reperfusion period. After reperfusion double staining strategy (Evans blue and TTC) were used. The percentage of infarct size was determined by Image-j software.hemodynamic parameters and arrhythmia in control ver. Hesperidin,.5, 5 mcg/ml were compared too and lactate concentration were measured in three time of this process (end of stab & ischemia and in 60th minute of reperfusion). The results demonstrated that Hesperidin caused a significant reduction in salvose & triplet and total number of arrhythmia(p<.05). The infarct size has been reduced signifacantly by hesperidin(,.5,5mcg/ml,p<.00).lactate concentration has been reduced significantly(,5 mcg/ml,p<.05). The results of the study suggests that Hesperidin has protective effects against I/R injuries in isolated rat heart and it has reduced infarct size dose dependently. -39-

141 PP 45 OPTIMIZATION OF THE EXTRACTION OF PHENOLIC COMPOUNDS FROM BLUEBERRY SERAP AYAZ SEYHAN, CAGLAR DEMIRBAG, GÜLER YALCIN MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF ANALYTICAL CHEMISTRY, ISTANBUL, TURKEY In recent years, berries have gained growing consumers attention due to their potential health benefits. Among berries, blueberries (Vaccinium corymbosum L) have been known for their anticarcinogenic effects due to their ability to reduce oxidative stres. These properties made blueberries popular and many studies were carried out about them. Blueberries (Vaccinium corymbosum L.) contain high amounts of sugars and acids as well as phenolic compounds that display potential health-promoting effects. Furthermore blueberries are grown in large scale in Black Sea Region of Turkey and they are currently being promoted as a rich source of antioxidants (,,3). The extraction condition of the blueberries samples in the peresent study. Extraction was carried out from lyophilized blueberries samples at different temperature, time and solvent. The amount of total phenolics compounds found for each condition and the optimal conditions were determined.. Çelik H. (004). Karadeniz için Yeni Bir Meyve Türü Likapa (Yaban Mersini). Doğa, Çevre ve Kültür Dergisi Ekoloji Magazin Sayı:, Ocak-Mart 004: Rossi M., Giussani E., Morelli R. (003). Effect of fruit blanching on phenolics and radical scavenging activity of highbush blueberry juice. Food Research International 36, Çelik, H., (005). Yaban mersini (Likapa) yetiştiriciliği. HASAD Yay. 8 s PP 46 THE ANALYSIS OF TETRACYCLINES IN FOOD ONUR DEMIRTAS, SERAP AYAZ SEYHAN MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF ANALYTICAL CHEMISTRY, ISTANBUL, TURKEY Tetracyclines are wide spectrum antibiotics. Thereby they have a wide range of usage and by inhibition of protein synthesis they show bacteriostatic effect. They are used in medical science, VETERINARY science, dentistry. The problems which happens when they are taken unboundedly are getting bigger in accordance with this wide range of usage. The most widespread problem is the developing resistence. Developing resistence lay the groundwork for health problems worldwide. One of another fundamental problem is the tatracycline remains in food which appears using it unconsciously in VETERINARY science. Therefore their usage should be kept under control by public outhority. In this study, according to the literature search of in the last decade are given information about the use of tetracyclines and in food analysis. PP 47 APPLICATION OF THE DEVELOPED HPLC-DAD METHOD OF ELLAGIC ACID AND RESVERATROL TO FOUR BLUEBERRY SAMPLES GROWN IN THE TURKEY SULEYMAN SEYHAN, GULER YALCIN MARMARA UNIVERSITY INSTITUTE OF HEALTH SCIENCES,ISTANBUL, TURKEY MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF ANALYTICAL CHEMISTRY, ISTANBUL, TURKEY Many research studies have indicated that fruits and vegetables are contains several components which are recuperative effects for human health. (). As a result of many studies, it has been long known that consumption of fruits and vegetables reduces the risk of cancer and cardiovascular disease. Blueberries has a strong antioxidant property and consequently potential healthpromoting effects. Ellagic acid (phenolic acids group) and resveratrol (stilbenes group) are naturally occurring compounds belonging to one of the group of phenolic compound found in grapes, berries and fruit juise. They are the most explored phenolic compound, which are known to posses a variety of pharmacological and biological activities such as antioxidant, antitumor effects (,,3). In this study, we reported the amount of ellagic acid and resveratrol in four different blueberry varieties, grown in the Black Sea Region of Turkey, (Bluecrop, Brigitta, Darrow and Bluejay) by high performance liquid choromatography and diode array detector. The recovery was % 9.85 for ellagic acid and % for resveratrol. In the four blueberry varieties the amount of ellagic acid was mg/kg and the amount of resveratrol was mg/kg.. Amakura Y., Okada M., Tsuji S., Tonogai Y. (000) High-performance liquid chromatographic determination with photodiode array detection of ellagic acid in fresh and processed fruits. J. Chromatogr A, 896: Soong Y.Y., Barlow J.P. (006). Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chem, 97: Garcıa Moral P., Arın M.J., Resines J.A., Dıez M.T. (007). Determination of ellagic acid in oak leaves and in sheep ruminal fluid by RP-HPLC. J. Chromatogr B, 855:

142 PP 48 OBESITY RELATED ADIPOKINE EXPRESSION AND ION LEVELS IN 3T3-L CELLS UNDER OXIDATIVE STRESS BELGIN SÜSLEYİCİ DUMAN, MELIHA KOLDEMİR GÜNDÜZ, PENBE ÇAĞATAY, NUR BAKIR, ADNAN AYDIN 3 MARMARA UNIVERSITY, FACULTY OF SCIENCE AND ARTS, DEPARTMENT OF MOLECULAR BIOLOGY, İSTANBUL, TURKEY DEPARTMENT OF BIOSTATISTIC AND MEDICAL INFORMATICS, ISTANBUL MEDICAL FACULTY, ISTANBUL UNIVERSITY, İSTANBUL, TURKEY 3 ISTANBUL BILIM UNIVERSITY, SCHOOL OF HEALTH, DEPARTMENT OF NUTRITION AND DIETETICS, ISTANBUL, TURKEY The effects of oxidative stress agents such as saturated fatty acid (stearic acid), non-saturated fatty acid (linoleic acid) and hydrogen peroxide (HO) exposure on fat mass and obesity related (FTO) and CD68 gene expressions and intracellular ion levels in differentiated 3T3-L adipocytes were studied. 3T3-L fibroblasts differentiated into mature adipocytes were real time monitored by using icelligence system. CD68 and FTO gene expression levels were determined with qpcr in nanocycler. Ion levels were measured by using ion selective electrode method. The exposure times of oxidative stressors were determined according to the IC50 values obtained by real time analysis for various concentrations. Stearic acid was found to have no effect on intracellular ion levels whereas decreased gene expression levels of both CD68 and FTO. Linoleic acid application resulted in positive correlation between FTO gene expression and intracellular calcium levels. As a response to 4h and 800µM HO exposure, significant positive correlation was found to exist between intracellular potassium (K) levels and CD68 gene expression. Long time low concentration (4h/600µM) HO administration has been found to correlate negatively for CD68 gene expression and intracellular sodium (Na) levels in 3T3-L cells. Among the studied oxidative stress producing agents; the FTO and CD68 gene expression levels were found to be in positive correlation in response to linoleic acid (4h/480µM) exposure. In conclusion, oxidative stress agents such as HO, stearic and linoleic acid in long term (4h) have reducing effect of gene expression for obesity related gene such as CD68 and FTO. PP 49OBESITY RELATED ADIPOKINE EXPRESSION AND ION LEVELS IN 3T3-L CELLS UNDER OXIDATIVE STRESS BELGIN SÜSLEYİCİ DUMAN, MELIHA KOLDEMİR GÜNDÜZ, PENBE ÇAĞATAY, NUR BAKIR, ADNAN AYDIN 3 MARMARA UNIVERSITY, FACULTY OF SCIENCE AND ARTS, DEPARTMENT OF MOLECULAR BIOLOGY, İSTANBUL, TURKEY DEPARTMENT OF BIOSTATISTIC AND MEDICAL INFORMATICS, ISTANBUL MEDICAL FACULTY, ISTANBUL UNIVERSITY, İSTANBUL, TURKEY 3 ISTANBUL BILIM UNIVERSITY, SCHOOL OF HEALTH, DEPARTMENT OF NUTRITION AND DIETETICS, ISTANBUL, TURKEY The effects of oxidative stress agents such as saturated fatty acid (stearic acid), non-saturated fatty acid (linoleic acid) and hydrogen peroxide (HO) exposure on fat mass and obesity related (FTO) and CD68 gene expressions and intracellular ion levels in differentiated 3T3-L adipocytes were studied. 3T3-L fibroblasts differentiated into mature adipocytes were real time monitored by using icelligence system. CD68 and FTO gene expression levels were determined with qpcr in nanocycler. Ion levels were measured by using ion selective electrode method. The exposure times of oxidative stressors were determined according to the IC50 values obtained by real time analysis for various concentrations. Stearic acid was found to have no effect on intracellular ion levels whereas decreased gene expression levels of both CD68 and FTO. Linoleic acid application resulted in positive correlation between FTO gene expression and intracellular calcium levels. As a response to 4h and 800µM HO exposure, significant positive correlation was found to exist between intracellular potassium (K) levels and CD68 gene expression. Long time low concentration (4h/600µM) HO administration has been found to correlate negatively for CD68 gene expression and intracellular sodium (Na) levels in 3T3-L cells. Among the studied oxidative stress producing agents; the FTO and CD68 gene expression levels were found to be in positive correlation in response to linoleic acid (4h/480µM) exposure. In conclusion, oxidative stress agents such as HO, stearic and linoleic acid in long term (4h) have reducing effect on obesity related gene (CD68 and FTO) expressions. -4-

143 PP 50 CYTOTOXIC AND APOPTOTIC POTENTIAL OF PRIMULA AURICULATA METHANOLIC EXTRACT SAHAR BEHZAD, MAHMOUD MOSADDEGH DEPARTMENT OF PHARMACOGNOSY, SCHOOL OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN Colorectal carcinoma (CRC), one of the most commonly seen cancers globally is the third in men and forth in women highest cancer mortality in Iran(, ). Chemotherapy remains one of the major non-surgical therapeutic approaches for patients with advanced CRC. However, the toxicity of these chemotherapy MEDICINEs to normal tissues and cells has been a major obstacle in successful cancer treatment. Faced with these major problems, the development of novel anticancer agents is urgently required. Primula auriculata is one of the most important local medicinal plants for eye infectious diseases in Hamedan district (locally named Tootia). The aim of this study was to investigate the cytotoxic effect and apoptotic induction of methanolic extract (ME) of Primula auriculata on HT-9 human colon Adenocarcinoma. Cell proliferation was measured by MTT assay and apoptosis induction was analyzed by fluorescence microscopy (annexin V/propidium iodide double staining and TUNEL assay) and Apoptotic index was assessed. The results indicated that ME induced suppression of cell viability in dose dependent manner (IC50= μg/ml). With double staining and TUNEL assay, treated cells exhibited typical characteristics of apoptotic cells, suggesting that ME may be a potent source for the development of novel anticancer agent to treatment of colorectal cancer.. Siegel R, Naishadham D, Jemal A. Cancer statistics, 0. CA Cancer J Clin. 0;6:0-9.. Davoudi Monfared E, Heidarnia MA, Akbari ME, Yavari P, Abadi A. Associations of Demographic and Socioeconomic Factors With Complete Treatment and Follow up of Colon Cancer. Iran J Cancer Prev. 0;5(4):03-9. PP 5 QNAR MODEL FOR THE PREDICTION OF METALOXIDE NANOPARTICLES BIOLOGICAL ACTIVITIES SA. SOLTANI, 3,S. SOLTANI DRUG APPLIED RESEARCH CENTER, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN PHARMACY FACULTY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 3 STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN The role of nanomaterials is rapidly increasing in many aspects of human life. Following the development of new nanomaterials the questions about their possible interaction with biological systems should be answered. In order to save time and resources both design of specific nanomaterials and determination of their biological properties could be done using predictive models prior to lab based experiments. Application of computer based material design methods to nanomaterials have attracted during last decades and among them developing quantitative nanomaterial activity/property relationships (QNA(P)R) was investigated. In this study a number of quantum mechanical descriptors was used to develop a QNAR model for the prediction of toxicity of metal oxide nano particles. LD50 values of MOx nanomaterials on E.Coli were obtained from a Reference []. The 9 different calculated and experimental physicochemical properties were checked using stepwise MLR method to find the significant descriptors. The selected descriptor was used to develop linear and quadratic QNAR models. According to the developed models toxicity of untested nanomaterials could be evaluated theoretically. The best predictors for the studied toxicity was ionic index of metal cation and metal oxide atomization energy. -4-

144 PP 5 SPECTROPHOTOMETRIC DETERMINATION OF FORMOTEROL FUMARATE IN PURE FORM AND PHARMACEUTICAL PREPARATIONS GIZEM CAKIR, DUYGU TASKIN, SIDIKA SUNGUR DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY A simple, accurate, rapid and sensitive method has been developed for the determination of formoterol fumarate in its pure and pharmaceutical dosage forms. The method is based on the formation of a yellow coloured ion-pair, due to reaction of formoterol fumarate and methyl orange which shows maximum absorption at 48 nm after extraction with chloroform. The optimum conditions for ion-pair formation were investigated with the respect to ph of the aqueous solution, extraction solvent and the amount of the reagent. The effect of ph was investigated in the range of.0 to 8.0. Chloroform, toluene, dichlorometane, benzene and carbon tetrachloride were tested as solvents for extraction.maximum absorbance was obtained at ph 4.0 and with chloroform as extraction solvent. The calibration was linear over the concentration range of 4-0 µg/ml. Commercially available pharmaceutical preparations containing formoterol fumarate were assayed using the developed method.the results were statistically compared with those obtained by the reference method in terms of accuracy and precision. PP 53 SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME 4-SUBTITUTED-N -(-(4-MORPHOLINOPHENYL)ETHYLIDENE) BENZOHYDRAZINE DERIVATIVES BEDRIYE SEDA KURŞUN AKTAR, YUSUF SICAK, EMINE ELÇIN ORUÇ EMRE 3, MEHMET ÖZTÜRK, İBRAHIM DEMİRTAŞ 4, AYŞEGÜL KARAKÜÇÜK İYIDOĞAN 3 DEPARTMENT OF PROPERTY PROCTECTİON AND SECURİTY, YAPRAKLI VOCATİONAL SCHOOL, ÇANKIRI KARATEKİN UNIVERSITY, ÇANKIRI, TURKEY DEPARTMENT OF CHEMİSTRY, FACULTY OF SCİENCES, MUĞLA SITKI KOÇMAN UNIVERSITY, MUGLA, TURKEY 3 DEPARTMENT OF CHEMİSTRY, FACULTY OF ARTS AND SCİENCES, GAZİANTEP UNIVERSITY, GAZİANTEP, TURKEY 4 DEPARTMENT OF CHEMİSTRY, FACULTY OF SCİENCES, ÇANKIRI KARATEKİN UNIVERSITY, ÇANKIRI, TURKEY In present research, with the aim of obtaining new antioxidant, anti-alzheimer agents, novel series 4-subtituted-N-(-(4- morpholinophenyl)ethylidene)benzohydrazine derivatives were synthesized. These derivatives have been synthesized by reaction -(4-morpholinophenyl)ethanone with 4-substitutedbenzohydrazide. The antioxidant capacity of hydrazone derivatives was determined as β-carotene-linoleic acid, DPPH radical scavenging, superoxide anion radical scavenging, ABTS cation radical scavenging, and CUPRAC methods (). In vitro inhibitory activity of acetylcholinesterase and butyrylcholinesterase enzymes related with Alzheimers disease was determined using Ellmans method (). Also, to determine the inhibitory activity of urease will be used Mobley method (3).. Öztürk M, Aydoğmuş-Öztürk F, Duru ME, Topçu G. Antioxidant activity of stem and root extracts of Rhubarb (Rheum ribes): An edible medicinal plant. Food Chemistry. 007; 03: Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemistry and Pharmacology and Behaivor. 96; 7: Mobley HLT, Island MD, Hausinger RP. Microbial Ureases-Significance, Regulation, and Molecular Characterization. Microbiological Reviews. 989; 53:

145 PP 54 PLANTS USED AS NATURAL DYE SOURCES IN WESTERN PART OF ALADAGLAR / NIGDE EBRU OZDEMIR NATH, KERIM ALPINAR FACULTY OF PHARMACY YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY KEMERBURGAZ UNIVERSITY, ISTANBUL, TURKEY Some of the chemical dyes were found to be associated with hazards effecting human s health by leading skin diseases and lung problems. Therefore, the scientists started searching the substitutes of synthetic substances and this has led the use natural dyes more. The Aladağ Mountains are the extension of the Taurus Mountains in the west of the Eastern Taurus Mountain Range and harbors the highest peak thereof. The area is usually reached from Niğde side. Its plant diversity is very rich because of its localization where phyto-geographical regions meet (Mediterranean, Irano-Turanian). Yoruks are very familiar in natural dye plants. An ethnobotanical study was conducted between 004 and 005 in order to determine wild plants used in West of Niğde-Aladağlar. During the six field trips held, 4 settlements that are placed in the Western part of Niğde-Aladağlar were visited. During these trips 00 specimens were collected from their natural habitat and information regarding how to use these plants were gathered from the villagers (such as; local names of the plants, local uses, used parts, preparation of natural dye). Collected plant specimens and some parts of the plant samples are kept in ISTE (The Herbarium of the Faculty of Pharmacy in Istanbul UNIVERSITY). Among all collected plants, 9 species have been determined to be natural dye sources. Plants used as natural dye sources in Aladağlar / Niğde are presented as a table. This table comprises various features of these plants (local names, plants parts used in dye, the hazes obtained from dye plants, main coloring component).. Deveoğlu, O., Karadağ, R., Genel Bir Bakış: Doğal Boyarmaddeler, Fen Bilimleri Dergisi, Marmara Üniversitesi, İstanbul, 0; 3: -3.. Karadağ, R. Doğal Boyamacılık, Geleneksel El Sanatları ve Mağazalar İşletme Müdürlüğü Yayınları, Ankara, 007. PP 55 NATURAL DYE PLANTS IN SAVAşTEPE (BALıKESIR) EBRU OZDEMIR NATH, SUKRAN KULTUR FACULTY OF PHARMACY YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY FACULTY OF PHARMACY ISTANBUL UNIVERSITY Natural dyes are recently becoming object of consumer interests because of the harmful effects of the synthetic dyes. The dyeing with natural colourants was one of the oldest techniques practiced by the ancient civilization people. Turkey has a rich potential from the natural dye plants. An ethnobotanical study was conducted between 03 and 04 in order to determine wild plants used in Savaştepe. Savaştepe is a town and district of Balıkesir Province in the Marmara region of Turkey. It has an area of 430 km. Its plant diversity is very rich because of its localization meeting point of phytogeographic regions (Mediterranean, Euro- Siberian). The population is 9.88 (as of 0). Savaştepe has 44 villages. Karakeçili Yoruk communities are living in 5 villages. Specially Yoruks are quite interested in natural dye plants. During the 4 field trip, The villages that are placed in Savaştepe were visited. Local people are interviewed in the area and the plant specimens used as a dye source were collected. The collected specimens were identified and kept in the Herbarium of the Faculty of Pharmacy, Istanbul UNIVERSITY (ISTE). It has been recorded that villagers are using 6 plant species as a natural dye source. Plants used as natural dye sources in Savaştepe are structured as table. This table is based on the various features of these plants (local names, plants parts used for dyeing, the colors obtained from dye plants, main colouring component)..deveoğlu, O., Karadağ, R., Genel Bir Bakış: Doğal Boyarmaddeler, Fen Bilimleri Dergisi, Marmara Üniversitesi, İstanbul, 0; 3 : -3.. Karadağ, R. Doğal Boyamacılık, Geleneksel El Sanatları ve Mağazalar İşletme Müdürlüğü Yayınları, Ankara,

146 PP 56 PROTECTIVE EFFECT OF MORALBOSTEROID ISOLATED FROM MORUS ALBA AGAINST CARBON- TETRACHLORIDE INDUCED HEPATOTOXICITY IN WISTAR RATS GAURAV GUPTA, AFZAL MUHAMMAD, IMRAN KAZMI, FIROZ ANWAR INTERNATIONAL MEDICAL UNIVERSITY, KUALA LUMPUR SIDDHARTHA INSTITUTE OF PHARMACY, DEHRADUN, INDIA The present work presented here evaluates the hepatoprotective potential of moralbosteroid, isolated from Morus alba, against carbon tetrachloride induced hepatotoxicity in Wistar albino rats. Hepatoprotective action was estimated by measuring aspartate amino-transferase (AST), alkaline phosphatase (ALP), serum alanine amino-transferase (ALT), total bilirubin (TB), and total protein (TP), including glutathione transferase (GST), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation (LPO) and superoxide dismutase (SOD). The oral administration of carbon tetrachloride significantly increased the LPO level (3.±.59 μm/mg protein) when compared to control. The levels of antioxidant enzymes including CAT, SOD, GPx and GST were decreased significantly (0.38±0.6 nmol/min/ml, 0.89±0.83 U/ml, 3.90±0.9 μmol and 0.05 ±0.6 U/min/mg proteins in testicular tissue) as compared to control animals. Moralbosteroid significantly prevented the marked escalation of serum markers and inhibited the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and prominently increases the endogenous antioxidant enzyme levels in hepatocellular toxicity induced by carbon tetrachloride. The results obtained in this study suggest the preventive influence of moralbosteroid on liver toxicity in rats induced by carbon tetrachloride comparable with those of Silymarin.. Ahmad A, Gupta G, Afzal M, Kazmi I, Anwar F. Antiulcer and antioxidant activities of a new steroid from Morus alba. Life Sci. 03; 9(3): 0 0. PP 57 VEGF GENE POLYMORPHISMS AND SUSCEPTIBILITY TO COLORECTAL CANCER IN TURKISH POPULATION AYŞE TARBIN JANNUZZI, BUKET ALPERTUNGA, GUL OZHAN DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY According to the International Agency for Research on Cancer (IARC), colorectal cancer is the third most common cancer in the world and its etiology involves the interaction of genetic and environmental factors. New blood vessels form through process called angiogenesis and have essential role in tumour growth, progression and metastasis of malign tumours such as colon cancer. The Vascular Endothelial Growth Factor (VEGF), one of the most important angiogenic factors, is a specific mitogen for vascular endothelial cells. Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation, and they may have a role in an individual s susceptibility to cancer. In the present case-control study, we carried out to evaluate whether VEGF SNPs play a role in modulating susceptibility to colorectal cancer or not. We evaluated VEGF 578 A/C, 460 T/C, and 936 C/T genotypes obtained from 9 patients with colorectal cancer and 03 healthy controls using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated. In conclusion; 578 A/C was significantly associated with colorectal cancer risk (OR=.69; 95% CI= ; P=0.044) while distribution of 460 T/C and 936 C/T genotypes in cases and controls did not significantly differ. These results suggest that the VEGF gene polymorphisms might play a role in the development of colorectal cancer. Therefore, VEGF polymorphisms might be further investigated to use in the determination of risk factors for colorectal cancer and to have predictive value to anti-vegf targeted cancer therapies. -45-

147 PP 58 THE PROTECTIVE EFFECTS OF BUTHANOLIC EXTRACT OF PARONYCHIA ARGENTEA AGAINST PHOSALONE TOXICITY IN PREGNANT WISTAR ALBINO RATS. DJAMILA ZAMA, LEILA BELFARHI, OUAHIBA BENAISSA, FADILA BENAYACHE, SAMIR BENAYACHE UNITé DE RECHERCHE VALORISATION DES RESSOURCES NATURELLES, MOLéCULES BIOACTIVES ET ANALYSES PHYSICOCHIMIQUES ET BIOLOGIQUES (VARENBIOMOL), DéPARTEMENT DE CHIMIE, FACULTé DES SCIENCES EXACTES, UNIVERSITé CONSTANTINE, 5000 CONSTANTINE, ALGéRIE. Polyphenols from plant extracts might play a role in protection against pesticides toxicity. It has been suggested that Reactive Oxygen Species (ROS) are involved in the toxicity of pesticides. The purpose of the current investigation was to study the protective effect of buthanolic extract of Paronychia argentea L against the toxicity induced by an organophosphorus pesticide Chloropyriphos-Ethyl (CE). Pregnant Wistar Albino rats were used in this study, pesticide and plant extract were administered daily by gavages from the 6th to the 5th day of gestation. On day 9, animals were dissected and blood samples were collected and used for the estimation of plasma Malonaldehyde (MDA) as indicator of lipid peroxydation levels (LPO) blood reduced glutathione(gsh) and erythrocyte superoxide dismutase (SOD) activities. In addition, fetuses were counted, weighed and examined for the external congenital malformation; and their LPO levels estimated as was that of their livers. The removed placentas were similarly treated. The data showed a significant increases in the plasma and tissues LPO levels of animals treated with pesticide while it was decreased in the treated with plant extract. Also, CE caused a significant decrease in antioxidant enzymes activities and this decrease was reduced in groups treated with plant extract. Moreover, pesticide induced embryotoxicity as resumption, dead fetus and a reduced of implant number. The present findings establish that (Ph) can cause a strong induction in LPO production in dam and fetus tissues. While treatment by plant extract reduced /or protect Ph toxicity. The decrease in LPO levels and the increase in GSH and SOD enzymes activities revealed the antioxidant property of this extract. PP 59 IN VITRO ANTIOXYDANT ACTIVITY, TOTAL POLYPHENOL AND FLAVONOIDS CONTENT OF ETHANOLIC EXTRACT OF GREEN TEA (CAMELLIA SINENSIS). SOUMIA LASSED, AMEL AMRANI, LEILA BELFARHI, DJAMILA ZAMA, FADILA BENAYACHE, SAMIR BENAYACHE UNITé DE RECHERCHE VALORISATION DES RESSOURCES NATURELLES, MOLéCULES BIOACTIVES ET ANALYSES PHYSICOCHIMIQUES ET BIOLOGIQUES (VARENBIOMOL), DéPARTEMENT DE CHIMIE, FACULTé DES SCIENCES EXACTES, UNIVERSITé CONSTANTINE, 5000 CONSTANTINE, ALGéRIE. Tea is the second most commonly drank liquid on earth after water. Ongoing scientific exploration points that the certain potential health benefits derived from tea have important implications on human health. The American Medical Association shows that green tea can lower cholesterol levels and high blood pressure. The National Cancer Institute reports that because of the highly effective antioxidants in green tea, it can ward off various types of cancer []. The present work aims to assess the total polypfenols and flavonoides content and in vitro antioxidant activity of its ethanolic extract. The antioxidant capacity was evaluated by applying three methods; DPPH (, -diphenyl, -picryl hydrazyl) radical scavenging, inhibition of lipid peroxidation and OH. Scavenging assay. The extract presented high levels of polyphenolic and flavonoides compounds 700 μg of gallic acid equivalents/mg extract and 33.74μg quercetin equivalent/mg extract respectively. Using DPPH free radical scavenging assay, the extract showed remarkable activity; IC50 value 0.95 µg/ml and the highest percentage of the inhibition was 96 % similar to vitamin C in the same concentration (5µg/ml). On the other hand it exhibited the inhibition of lipid peroxidation with an IC50 value µg/ml. The OH. Scavenging assay indicate also that the green tea extract had a significant effect again OH. radical induced in the assay; IC50 value was 3.8µg/ml compared to ascorbic acid (0µg/ml). In the three methods used the effect of the extract was dose dependant. The content of polyphenols and flavonoids especially catechins with meta-5,7-dihydroxyl groups on the A ring, di- or trihydroxyl groups on the B ring and D ring (gallate) allow tea to react with ROS (superoxide radical, singlet oxygen, hydroxyl/peroxyl radical, peroxynitrite) and gave it a maximal of antioxidant activity[,3].the results of this study confirm that the green tea not only a safe beverage but also a potent source of beneficial antioxidants. References - A.B. Sharangi., Medicinal and therapeutic potentialities of tea (Camellia sinensis L.). Food Research International 4: (009). - D. A. Balentine., S. A.Wiseman., and L. C. M. Bouwens., The chemistry of tea flavonoids.critical Reviews in Food Science and Nutrition. 37(8): (997). 3- S. Valcic., J. A. Burr., B. N. Timmermann., and D. C. Liebler., Antioxidant chemistry of green tea catechins. New oxidation products of (-)-epigallocatechin gallate and (-) epigallocatechin from their reactions with peroxyl radicals. Chemical Research in Toxicology. 3(9): (000). -46-

148 PP 60 INTERACTION BETWEEN THE MALE INFERTILITY AND THE GENETIC SUSCEPTIBILITY TO ENDOCRINE DISRUPTORS MERVE ARICI, GUL OZHAN ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY. Reproductive functions are impaired by many environmental, physiologic, and genetic factors. The majority of the environmental factors are xenobiotics and male-factor infertility reportedly accounts for 30 40% of cases of couple infertility. The recent publications related to male infertility have reported that many xenobiotics (phthalates, alkylphenols, heavy metals, bisphenol A etc) being industrially manufactured and occurred by human activity could interfere with human s normal hormone functions and have potentialhazardous effects on male reproductive axis causing infertility (-). These xenobiotics called endocrine disruptors (EDs) are metabolized by the enzymes involved phase I enzymes such as cytochrome P450 familyand phase II enzymes such as N-acetyltransferases (NATs). The activity of these enzymes that are polymorphic may modify the process of activation and/or detoxification of chemicals. Thus, the effects of EDs exposure might vary between individuals. However, to date, the impact of genetic variability in the capacity to metabolize xenobiotics on male reproductive functions has not been studied extensively. In our study, it is aimed to evaluate the interaction between EDs exposure and the metabolizing enzyme polymorphisms in male infertility risk by reviewing data obtained from the previous studies. - Schuppe HC et al. (000). Andrologia3: Pflieger-Bruss S et al. (004). Andrologia36: PP 6 EPIGENETIC MECHANISMS AND ENDOCRINE DISTRUPTING CHEMICALS MINE SENYILDIZ, SIBEL OZDEN ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY Endocrine-disrupting chemicals are synthetic or natural compounds in the environment that can interfere with endocrine functions and result in developmental and reproductive abnormalities. More recently, epigenetic-induced alterations in gene expression, especially in nucleer receptors has emerged as an alternative way in which environmental compounds may exert endocrine effects. Therefore, we aimed to review the role of DNA methylation and histone modification as two major epigenetic mechanisms in the toxicity of endocrine distrupting chemicals. Early exposure to diethylstilbestrol, a nonsteroidal synthetic estrogen, has been reported to cause aberrant CpG methylation and silencing of key uterine cancer (Bromer et al., 009). DNA hypermethylation of the estrogen receptor alfa gene induced by phthalates was also reported (Kang and Lee, 005). Effect of bisphenol A, a high production chemical with estrogenic properties present in many commonly used products such as food and beverage containers, baby bottles and dental components, on the F generation has also been associated with epigenetic mechanisms (Dolinoy, 007). This review will contribute to a better understanding of the key molecular events in the toxicity of endocrine distrupting chemicals for risk assessment process. Bromer JG, Wu J, Zhou Y, Taylor HS. Hypermethylation of homeobox A0 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming. Endocrinology. 009;50: Dolinoy DC, Huang D, Jirtle RL.Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA. 007;04(3): Kang SC, Lee BM.DNA methylation of estrogen receptor alpha gene by phthalates. J Toxicol Environ Health A. 005;68:

149 PP 6 QSAR STUDY OF THIADIAZOLOPIPERAZINYL UREASE INHIBITORS FAAH INHIBITORS PARIZAD GHAREBAGHI FACULTY OF PHARMACY ISFAHAN PAYAME NOOR UNIVERSITY, ESFAHAN, IRAN FAAH is an interacellular serine hydrolase thetcatalyzesthe deactivating hydrolysis of several endogenous lipid amides such as anandamide (AEA).FAAH inhibitors enhance the activation of CB receptors by blocking the degradation of AEA and may have anti -inflammatory effects by suppressing the release of inflammatory chemical mediators by stimulating CB receptors. Quantitative structure-activity relationship of a series of Thiadiazolopiperazinyl urease (TU) inhibitors was studied. This class of inhibitors of FAAH, by increasing the local endocannabinoid, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. 3 TU derivatives along with their experimental data (IC50 values) were obtained from literature and three-dimensional structure of them were constructed using Hyperchem 8. The geometry optimization was carried out using MM+ followed by semi empirical and the resulted molecules were used to calculate the molecular descriptors (QSAR Properties, HOMO-LUMO and Dipole moment). Descriptors selection and model development was done using SPSS software after dividing of the data set to test and train subsets. significant parameters (following equation) was selected by stepwise regression method using training subset. The results showed that the intercept of the model is not significant and we omit it to develop the following model. pic50=0.038 (SAA) (SAG) R²=0.906 R² adjust=0.897 F=0.03 S.E.E=0.79 The prediction error of the model was acceptable according to the experimental RSD values which was reported for the same molecules. PP 63 THE TOXIC POTENTIAL OF MANCOZEB ON ACHE ACTIVITY OF ZEBRAFISH (DANIO RERIO) TISSUES GULLU KAYMAK, HARIKA EYLUL ESMER, FIGEN ESIN KAYHAN, NAZAN DENIZ YON ERTUG, CANSU AKBULUT DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE AND ARTS, UNIVERSITY, SAKARYA, TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCES AND ARTS, UNIVERSITY OF MARMARA, ISTANBUL, TURKEY The wide use of pesticides, particularly dithiocarbamates, in agriculture often leads to contamination of fresh water ecosystems. Mancozeb [ethylenebis (dithiocarbamate)] was registered several times by US EPA (987, 005) and extensively used as an active ingredient of fungicides applied worldwide (,). The present study aimed to evaluate the effects of Mancozeb on zebrafish gills and liver tissues that would have close early contact with the aquatic pollutant. Exposure of zebrafish (Danio rerio) to 5 mgl- and 7,5 mgl- of Mancozeb for 0 hours except the control group. Protein and acetylcholine esterase enzyme activity (AChE) were determined using spectrophotometric methods. The results show that protein level was reduced in all experiments groups when compared to control group. In all groups decreased AChE activity was observed. The intensive use of mancozeb in agriculture is due to its reported low acute toxicity and scarce persistence in the environment. But despite all this, mancozeb is a potentially hazardous compound for aquatic biota, particularly fish..us EPA, 987. Pesticide Fact Sheet Number 5: Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC..US EPA, 005. Reregistration Eligibility Decision for Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC. -48-

150 PP 64 THE TOXIC POTENTIAL OF MANCOZEB ON ACHE ACTIVITY OF ZEBRAFISH (DANIO RERIO) TISSUES GULLU KAYMAK, HARIKA EYLUL ESMER, FIGEN ESIN KAYHAN, NAZAN DENIZ ON ERTUG, CANSU AKBULUT DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE AND ARTS, UNIVERSITY OF SAKARYA,TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCES AND ARTS, UNIVERSITY OF MARMARA, ISTANBUL TURKEY The wide use of pesticides, particularly dithiocarbamates, in agriculture often leads to contamination of fresh water ecosystems. Mancozeb [ethylenebis (dithiocarbamate)] was registered several times by US EPA (987, 005) and extensively used as an active ingredient of fungicides applied worldwide (,). The present study aimed to evaluate the effects of Mancozeb on zebrafish gills and liver tissues that would have close early contact with the aquatic pollutant. Exposure of zebrafish (Danio rerio) to 5 mgl- and 7,5 mgl- of Mancozeb for 0 hours except the control group. Protein and acetylcholine esterase enzyme activity (AChE) were determined using spectrophotometric methods. The results show that protein level was reduced in all experiments groups when compared to control group. In all groups decreased AChE activity was observed. The intensive use of mancozeb in agriculture is due to its reported low acute toxicity and scarce persistence in the environment. But despite all this, mancozeb is a potentially hazardous compound for aquatic biota, particularly fish..us EPA, 987. Pesticide Fact Sheet Number 5: Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC..US EPA, 005. Reregistration Eligibility Decision for Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC. -49-

151 PP 65 SYNTHESIS, IN VITRO CYTOTOXIC ACTIVITY AND DNA INTERACTIONS OF NEW DICARBOXYLATOPLATINUM(II) COMPLEXES WITH -HYDROXYMETHYLBENZIMIDAZOLE AS CARRIER LIGANDS SEMRA UTKU, AZIME BERNA OZCELIK, FATMA GUMUS, SUKRAN YILMAZ 3, TAIBE ARSOY 3, LEYLA ACIK 4, AYTEN CELEBI KESKIN 5 DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, MERSIN UNIVERSITY, MERSIN, TURKEY DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, GAZI UNIVERSITY, ANKARA, TURKEY 3 CELL AND VIRUS BANK DEPARTMENT, FOOT AND MOUTH DISEASE INSTITUTE, ANKARA, TURKEY 4 DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, GAZI UNIVERSITY, ANKARA, TURKEY 5 DEPARTMENT OF BIOLOGY, FACULTY OF ART AND SCIENCE, KIRIKKALE UNIVERSITY, KIRIKKALE, TURKEY Cisplatin is highly effective against testicular, ovarian, and lung cancers but has limited efficacy as monotherapy in breast cancer patients. Breast cancer is the most frequently diagnosed cancer in women and is frequently hormon-dependent. Many breast tumors express high level of estrogen receptor or/and progesterone receptor, and these cancers would be good candidates for cisplatin/carboplatin treatment in conjunction with hormon therapy (). Cisplatin and its analogues bind to various cellular components like DNA, RNA, proteins, and membrane phospholipids. Although targets other than DNA may be also important for these agents, it is generally accepted that DNA is the primary in vivo cytotoxic target of these compounds (). In this study, seven new platinum(ii) complexes having -substituted benzimidazole rings as carrier-ligands and bidentate dicarboxylato groups as leaving-ligands were synthesized and evaluated for their in vitro cytotoxic activities against the human HeLa (ER- ), MCF-7 (ER+) and MDA-MB 3 (ER-) cell lines using MTT assay. The plasmid DNA interactions and inhibition of BamHI and HindIII restriction enzyme activities of the platinum compounds were also investigated using Agarose Gel Electrophoresis method. The growth inhibitory effect results showed that the cytotoxicity of complex which was found to be the most active complex among the synthesized complexes.. He Q, Liang CH, Lippard SJ. Steroid hormons induced HMG overexpression and sensitize breast cancer cells to cisplatin and carboplatin. Proc Natl Acad Sci USA 000;97: Burger H, Loos WJ, Eechoute K, Vermeij J, Mathijssen RHJ, Wiemer EAC. Drug transporter of platinum-based anticancer agents and their clinical significance. Drug Resist Update 0;4:-34. PP 66 PLASMID DNA BINDING OF PLATINUM(II) COMPLEXES CONTAINING IMIDAZOLE AND -PHENYLIMIDAZOLE LIGANDS CAGLA BOGATARKAN, SEMRA UTKU, LEYLA ACIK DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, MERSIN UNIVERSITY, MERSIN, TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, GAZI UNIVERSITY, ANKARA, TURKEY Since the discovery that cisplatin (cis-diamminedichloroplatinum(ii)) promotes cancer cell death by binding to DNA, thousands of platinum complexes have been synthesized and screened in the last 30 years. Among these complexes, only carboplatin and oxaliplatin have received worldwide approval so far, nedaplatin, loboplatin and heptaplatin have gained regionally limited approval (). It is well established that cisplatin binds to DNA through covalent bonding, known as platinum-dna adducts such as guanine N7 and forms mostly,-intrastrand cross-link, which deforms the DNA structure, preventing DNA replication and transcription, activate the apoptotic pathway, resulting in cell death. The replacement of ammine groups can result in different structural and formational alterations in target DNA, which may affect the character of biological effects of the anologues. It has been shown that increasing cytotoxicity of cisplatin analogues, in which NH3 groups were replaced by more hydrophobic amine ligands, correlated with growing hydrophobicity of these analogues. One noteworthy approach in the design of new platinum anticancer drugs is to use physiologically active compounds as ligands. The imidazole ring is a physiologically active ligand, as a histidine moiety, function as ligands toward transition metal ions in a variety of biologically important molecules including iron-heme systems, vitamin B and its derivatives and several metalloproteins. It also serves as a good ligand in various transition metal complexes (). In the present paper, four platinum(ii) complexes with the structures cis-[ptlcl] and cis-[ptli] (L=imidazole or -phenylimidazole as non-leaving groups) which were synthesized by us (3) determined by their ability to modify the electrophoretic mobility of the form I and II bands of pbr3 plasmid DNA.. Wexselblatt E, Yavin E, Gibson D. Cellular interactions of platinum drugs. Inorg Chim Acta 0;393: Zivkovic MD, Rajkovic S, Djuran MI. Reaction of [Pt(Gly-Gly-N,N`,O)I]- with the N-acetylate dipeptide L-methionyl-L-histidine: selective platination of the histidine side chain by intramolecular migration of the platinum (II) complex. Bioorg Chem. 008; 36: Utku S, Boğatarkan Ç, Gümüş F. Synthesis and Characterization of Platinum(II) Complexes with Imidazole and -Phenylimidazole Ligands. International Symposium on Drug Research & Development From Chemistry to MEDICINE, P-085 (40), Antalya, Turkey, 7-9 May

152 PP 67 EVALUATION OF NOVEL EXCIPIENTS FOR ENHANCEMENT THE RELEASE OF EZETIMIBE MAI KHANFAR, MUTAZ SHEIKH SALEM, SANDRA HABABEH JORDAN UNIVERSITY OF SCIENCE AND TECHNOLOGY-IRBID- JORDAN Liquisolid technique is a powdered solution technology used to convert a liquid medicament into an acceptably flowing and compressible powder by physical blending with selected excipients. In this study the Ezetimibe will be used with new coprocessed excipients (compacted Chitin Magnesium silicate and/or Mannitol & their physical mixtures) & compared to Avicel PH0 & Aerosil 00 that were used in the original mathematical method of Spireas et.al (998) with the aim of having a novel multifunctional excipient that act as carrier, coating, disintegrant at the same time, thus reducing cost & drug excipient interactions. Compacted powder blends containing different ratios of Chitin, Magnesium silicate & /or Mannitol were prepared using roller compacter and tested for their surface area, particle size & flowability to be compared with Avicel and then liquisolid compacts were prepared according to Spireas. For all prepared liquisolid formulation, interactions between the drug & selected excipients had been detected by a lot of techniques. Co- processing of excipients using roll compactor has a remarkable improve in the flowability, and compressibility of the powder. The best dissolution profile was achieved by using the compacted Chitin: Mannitol (0:80) PP 68 PHARMACODYNAMICAL EVALUATION OF MATRIX TYPE TRANSDERMAL THERAPEUTIC SYSTEMS CONTAINING CAPTOPRIL OYA KERIMOGLU, SEVINC SAHBAZ, OZER SEHIRLI, ZARIFE NIGAR OZDEMIR 3, SULE ÇETINEL 4, BETUL DORTUNC, GOKSEL SENER FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY MARMARA UNIVERSITY, HAYDARPAŞA, ISTANBUL, TURKEY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY MARMARA UNIVERSITY, HAYDARPAŞA, ISTANBUL, TURKEY 3 FACULTY OF MEDICINE, DEPARTMENT OF PHYSIOLOGY MARMARA UNIVERSITY, ISTANBUL, TURKEY 4 FACULTY OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY MARMARA UNIVERSITY, ISTANBUL, TURKEY The objective of this study was to evaluate the pharmacodynamical properties of transdermal therapeutic systems (TTS) containing captopril together with synthetic and ph independent polymers, Eudragit RL 00 and RS 00 (). Control group, hypertension group (HT) and TTS containing captopril hypertension group (HT-CAP) were assessed for the pharmacodynamic activity of the study. Pharmacodynamic activity of transdermal patches containing captopril was evaluated in rats by the measurement of systolic blood pressure for 4 hours with the use of the tail cuff method (). Blood pressure, heart rate, body and heart weight, heart and body weight ratio were determined. Lactate dehydrogenase (LDH), creatinin phosphocinase (CPK), glutation (GSH), malondialdehyde (MDA), myeloperoxidase (MPO) and Na+, K+-ATPase were measured in serum of the rats. Histopathological evaluation of the heart tissue was conducted in order to determine any tissue damage. Blood pressure values of the TTS containing captopril hypertension group were decreased significantly and became almost similar with the blood pressure values of the control group. These results indicated that TTS containing captopril prepared with synthetic and ph independent polymers, Eudragit RL 00 and RS 00, can be considered as a transdermal therapeutic system for chronical treatment of hypertension and congestive heart failure. However further in vivo pharmacokinetic studies should be performed in order to determine the blood level of the drug. Kerimoğlu O, Keskin E, Dortunç B, Anah Ş. Matrix type transdermal therapeutic system containing captopril: formulation optimization, in Vitro and Ex Vivo Characterization. Acta Pol. Pharm. 03; 70 (): ) Laffan RJ, Peterson A, Hitch SW, Jeunelot C. A technique for prolonged, continuous recording on blood pressure of unrestrained rats. Cardiovasc. Res. 97; 6:

153 PP 69 ANTIOXIDANT ACTIVITY OF FERULAGO HUMULIS BOISS. GROWING IN TURKEY SEVDA SUZGEC-SELCUK, NURTEN OZSOY, EMINE AKALIN URUSAK 3 DEPARMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY, ISTANBUL, TURKEY 3 DEPARTMENT OF PHARMACEUTICAL BOTANY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY,ISTANBUL, TURKEY The genus Ferulago W.Koch. (Apiaceae) is represented by 34 species of which 8 are endemic in Turkey. Turkey is a major centre of diversity for Ferulago genus when the endemism rate is considered (). Ferulago species are known as çakşırotu, kişniş, asaotu, kuzubaşı ve kuzukemirdi in different regions of Turkey. Since Dioscoride s times, Ferulago species have been used in folk MEDICINE as sedative, tonic, digestive, carminative, aphrodisiac as well as in the treatment of intestinal worms and hemorrhoids (). This study was conducted to evaluate polyphenolic contents and antioxidant activities of methanol extracts from aerial parts and rhizomes of Ferulago humulis Boiss. measuring their ability of inhibiting lipid peroxidation induced by Fe3+-ascorbate, DPPH and ABTS + scavenging activities, and ferric reducing antioxidant power (FRAP value) (3,4). It was concluded that methanol extract from the aerial parts of the plant, containing the highest amount of total phenolics and flavonoids, has the antioxidative potential for chain-breaking inhibition of lipid peroxidation and shows the strongest hydrogen and a single electron donor activities, thus could serves as free radical scavenger, acts as reductant and provide protection against oxidative stress. Although the methanol extract from rhizomes did not show any inhibitory effect on lipid peroxidation, it may also be expected to protect against oxidative damage by scavenging free radicals and acting as reductant. The results demonsrated the health promoting potential of rhizomes and aerial parts from F. humulis. References. Akalın Uruşak E, Kızılarslan Ç. Fruit anatomy of some Ferulago (Apiaceae) species in Turkey. Turk J Bot. 03; 37: Baytop T. Türkiye de Bitkilerle Tedavi (Therapy with Medicinal Plants in Turkey, past and present).baskı. İstanbul: Nobel Tıp Kitapevi; 999. p Eroğlu Özkan E, Özsoy N, Özhan G, Özbek Çelik B, Mat A. Chemical composition and biological activities of Hypericum pamphylicum. Ind Crop Prod. 03; 50: Ozsoy N, Kultur S, Melikoglu G, Can A. Screening of the antioxidant potential of the leaves and flowers from Rosa horrida Fischer. J Med Plants Res. 03; 7: PP 70 THE PREPARATION AND IN VITRO CHARACTERIZATION OF METFORMIN HCL-LOADED ALGINATE BEADS BEHZAD MOKHTARE, RUKIYE SEVINC OZAKAR, MELTEM CETIN DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY Metformin is hypoglycemic agent widely used for management of Type diabetes (). It is primarily absorbed from the small intestine and it has a relatively low (50 60%) bioavailability. The extent of metformin absorption is improved when the gastrointestinal motility is slowed (). The objective of our study was to prepare and characterize metformin HCl-loaded alginate beads. Alginate beads were obtained by ionotropic gelation process based on the interaction between sodium alginate and calcium chloride as a crosslinking agent. The metformin-loading capacity and encapsulation efficiency were.98±0.08% and 33.58±.56%, respectively. The drug-loaded beads have a mean diameter of.85±0.0 mm, a narrow size distribution. For in vitro release study, beads were incubated in phosphate buffer (ph 6.8) under sink conditions. Approximately 98% of the encapsulated metformin HCl was released at 9 days. The in vitro release profile showed a sustained release of metformin from the beads. This study was supported by Ataturk UNIVERSITY Research Foundation (project number: 03/057).. Shamsa A., Vivian F. Overview of metformin: special focus on metformin extended release. Expert Opin. Pharmacother. 0;3(): Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl-β-cyclodextrin. Eur J Pharm Biopharm. 008;68:

154 PP 7 CHITOSAN MICROPARTICLES CONTAINING METFORMIN HCL: PREPARATION AND IN VITRO CHARACTERIZATION BEHZAD MOKHTARE, RUKIYE SEVINÇ ÖZAKAR, MELTEM CETIN DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY Metformin in the biguanide class has antihyperglycemic effect (). It is primarily absorbed from the small intestine and it has a relatively low (50 60%) bioavailability. The extent of metformin absorption is improved when the gastrointestinal motility is slowed (). The aim of this study was to formulate and characterize chitosan microparticles containing metformin HCl. These microparticles were evaluated for particle size and size distribution, encapsulation efficiency and in vitro drug release in ph 6.8. Chitosan microparticles were prepared by the emulsion-crosslinking method. The average particle size of the prepared microparticles was 9.08±.6 μm. The drug loading and encapsulation efficiency were about.44±0.47% and 0.05±6.9%, respectively. Approximately 98% of the drug was released from chitosan microparticles in 4 days. These data demonstrated the efficacy of these microparticles in sustaining the metformin HCL release profile. This study was supported by Ataturk University Research Foundation (project number: 03/057).. Cetin M, Atila A, Sahin S, Vural I. Preparation and characterization of metformin hydrochloride loaded-eudragit RSPO and Eudragit RSPO/PLGA nanoparticles. Pharm Dev Technol. 03;8(3): Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl-β-cyclodextrin. Eur J Pharm Biopharm. 008;68: PP 7 NIFEDIPINE-LOADED PLGA NANOPARTICLES: THE PREPARATION AND IN VITRO CHARACTERIZATION EMRAH OZAKAR, MELTEM CETIN, ORHAN ATES, AHMET HACIMUFTUOGLU 3 DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY DEPARTMENT OF OPHTHALMOLOGY, FACULTY OF MEDICINE, ATATURK UNIVERSITY, ERZURUM, TURKEY 3 DEPARTMENT OF PHARMACOLOGY, FACULTY OF MEDICINE, ATATURK UNIVERSITY, ERZURUM, TURKEY In this study, the preparation and in vitro characterization of nifedipine-loaded PLGA nanoparticles (NPs) were aimed. Nifedipin is a dihydropyridine calcium-channel blocker and rapidly and almost completely absorbed from the gastrointestinal tract, but undergoes extensive hepatic first-pass metabolism. Thus, it has exhibited low drug bioavailability (). PLGA NPs were prepared using nanoprecipitation method. The average size and the zeta potential of nifedipine-loaded nanoparticles was 45±4.96 nm and 0.47±0.9 mv, respectively. The nanoparticles showed the encapsulation efficiency and drug loading values of 3.03±.8% and.98±0.3%. Nanoparticles showed highly reproducible drug release profile. Approximately 98% of the loaded drug was released at 38 days in a phosphate buffer (ph 7.4). These data demonstrated the efficacy of these nanoparticles in sustaining the nifedipine release profile. This study was supported by Ataturk University Research Foundation (project number: 03/0).. Sweetman SC (Ed.). Martindale: The Complete Drug Reference. London: Pharmaceutical Press, Electronic version PP 73 DETERMINATION OF NIFEDIPINE IN PHARMACEUTICAL PREPARATIONS BY LINEAR SWEEP VOLTAMMETRY METHOD BILAL YILMAZ, EMRAH ÖZAKAR, SELÇUK KABAN, RUKIYE SEVINÇ ÖZAKAR, BILGE KAAN AKÇAY, MELTEM CETIN DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY Nifedipine is a dihydropyridine calcium channel antagonist widely used in the treatment of angina pectoris, hypertension and other vascular disorders such as Raynaud s phenomenon (). The goal of this work was the development of new linear sweep voltammetry (LSV) method for the direct determination of nifedipine in pharmaceutical preparations without any time-consuming. This paper describes fully validated simple, rapid, selective and sensitive procedure for the determination of nifedipine employing LSV method. To determine the linearity of LSV method, standard solutions of nifedipine were prepared in acetonitrile solution containing 0. M LiCIO4. The linear range was found to be 5-50 µg/ml. The regression equation obtained by least square regression was y=34.884x (y and x are mean peak current and concentration, respectively, r =0.999). The limits of quantitation (LOQ) and detection (LOD) were 4.8 µg/ml and.6 µg/ml, respectively. Intra- and inter-day precision, expressed as the relative standard deviation (RSD) was less than 4.78 %, and accuracy (relative error) was better than.85 %. The developed method was applied to the analysis of the pharmaceutical preparations. The percent analytical recovery values were found to be 00.7 % (Adalat Crono tablet; 30 mg/tablet) and 98.8 % (Adalat Crono tablet; 60 mg/tablet), respectively. No interference was found from two tablet excipients at the selected assay conditions. Developed method in this study is accurate, precise and can be easily applied to Adalat Crono tablets as pharmaceutical preparation.. Henry PD. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 980; 46:

155 PP 74 DEVELOPMENT AND VALIDATION OF SQUARE WAVE VOLTAMMETRY METHOD FOR DETERMINATION OF NIFEDIPINE IN PHARMACEUTICAL PREPARATIONS BILAL YILMAZ, EMRAH OZAKAR, SELCUK KABAN, RUKIYE SEVINC OZAKAR, BILGE KAAN AKCAY, MELTEM CETIN DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY Nifedipine, a lipid soluble drug, is rapidly and completely absorbed from the gastrointestinal tract after oral administration. The systematic bioavailability of nifedipine is 50-70% due to extensive first-pass metabolism. The elimination half-life of nifedipine is approximately -5 h (). The goal of this work was the development of new square wave voltammetry method (SWV) for the direct determination of nifedipine in pharmaceutical preparations. Besides, the method was successfully applied for the quality control of two commercial nifedipine tablets form to quantify the drug and to check the formulation content uniformity. The linear range was found to be 5-50 µg/ml. The regression equation obtained by least square regression was y=3.44x (y and x are mean peak current and concentration, respectively, r =0.999). The limits of quantitation (LOQ) and detection (LOD) were.7 µg/ml and 0.9 µg/ml, respectively. Intra- and inter-day precision as the relative standard deviation (RSD) was less than 3.96 %, and accuracy (relative error) was better than.55 %. The percent analytical recovery values were found to be 98.7 % (Adalat Crono tablet; 30 mg/tablet) and 0.8 % (Adalat Crono tablet; 60 mg/tablet), respectively. The method has been effectively and efficiently used to analyze nifedipine pharmaceutical tablets without any interference from the pharmaceutical excipients. The voltammetric run time of min allows the analysis of a large number of samples in a short period of time. Therefore, the method can be used effectively without separation for routine analysis of nifedipine in pure form and its formulations.. Henry PD. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 980; 46: PP 77 THE EFFECT OF MONTELUKAST ON 3-NITROPROPIONIC ACID INDUCED EXPERIMENTAL HUNTINGTON S DISEASE MODEL MERAL YUKSEL, SEZGIN AYDEMIR, HULYA SAHIN, NAZIYE OZKAN, NUSRET ERDOGAN DEPARTMENT OF MEDICAL LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA UNIVERSITY, HAYDARPASA-ISTANBUL, TURKEY DEPARTMENT OF PATHOLOGY LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA UNIVERSITY, HAYDARPASA-ISTANBUL, TURKEY Huntington s disease is an autosomal dominant inherited disease, which is associated with cognitive deficits and striatal neudegeneration. 3-nitropropionic acid (3-NP), is a fungal toxin, inhibits succinate dehydrogenase in Krebs cycle and electron transport chain. Systemic administration of 3-NP to rats cause neuronal degeneration in striatum and cognitive deficits, like Huntington s disease. Montelukast (ML) is a cysteinyl-leukotriene receptor antagonist, which has a reducing effect of inflammation in various diseases. The aim of this study was to investigate the putative neuroprotective effect of ML against 3-NP induced rat model. Female Sprague-Dawley rats were included in the study. Rats were divided into four groups; 3-NP group (0 mg/kg/ day), ML group (0 mg/kg/day), 3-NP-ML group and control group (SF). After 0 days, rats were decapitated and brains were removed. We measure luminol and lucigenin enhanced chemiluminescence (CL) for free radical release, malondialdehyde (lipid peroxidation) and glutathione levels (an antioxidant) for oxidative stress determination and histopathological observations. Luminol enhanced CL measurements were increased in 3-NP group with respect to controls (5.3±. vs..8±,6 rlu/mg; p<0.05). ML treatment reduced the release of OH, HO and HOCl- radicals, significantly (.0±. rlu/mg; p<0.0). Superoxide radical generation via lucigenin CL was significantly higher in 3-NP group, with respect to control group, which was reduced with ML treatment (5.6±.4 vs. 8.±. vs. 9.9±. rlu/mg; p<0.00). MDA levels were higher and GSH levels were lower in 3-NP group. ML treatment ameliorates the effects, significantly. Histopathologic observations show that striatal lesions after 3-NP induction are reduced with ML treatment. In conclusion, ML treatment reduces free radical induced oxidative stress lesions in 3-NP induced experimental Huntington s disease model. -54-

156 PP 76 INVESTIGATING PROTEIN BINDING INTERACTIONS OF SIROLIMUS AND MACROLIDE ANTIBIOTICS HADI VALIZADEH, SAYEH MOSTAFIDI, PARVIN ZAKERI-MILANI FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN Binding of drugs to plasma and tissue proteins significantly affects the pharmacokinetic and pharmacodynamic behaviors of drugs. Protein-binding displacement interactions become an important consideration for the patient when multiple drugs are prescribed. The aim of this project was investigating plasma protein binding of sirolimus and protein binding interaction of sirolimus with macrolide antibiotics, erythromycin, clarithromycin, and azithromycin. Aqueous solutions containing, 4, 6, 8, 0 µg/ml of sirolimus and 0.04 g/ml of human serum albumin were prepared. Ultrafiltration method was used for protein binding determination. The same process was performed in the presence of macrolide antibiotics. Free sirolimus concentration in the resulted ultrafiltrate was measured by RP-HPLC. Binding data were analyzed by means of Klotz and Scatchard graphical procedures. The obtained data showed that the presence of macrolide antibiotics, decreased the protein binding percentage of sirolimus from % to 40-6% for erythromycin, 38-70% for clarithromycin and 6.-73% for azithromycin. Decreasing the protein binding of sirolimus in the presence of macrolide antibiotics was significant (p<0.05). Furthermore the number of binding sites was decreased while the binding affinity of sirolimus to albumin was increased. According to the results it is recommended to monitor the plasma concentration of sirolimus in concurrent use of these drugs, and adjusting the dose of sirolimus, if it is necessary. PP 77 PATIENT SATISFACTION AND PHARMACY MANAGEMENT ASLI CULDUZ, ADİLE SERKİ, NAZLI SENCAN DEPARTMENT OF PHARMACY MANAGEMENT AND SOCIAL PHARMACY, FACULTY OF PHARMACY, YEDITEPE UNIVERSITY YEDİTEPE UNIVERSITY Patient satisfaction is an individual s cognitive evaluation of, his or her health-care experience. It has become an important factor of the quality of healthcare services and could be a predictor of health related behavior. Patient satisfaction has been used for the purpose of performance assessment, reimbursement and quality management of health service delivery. Pharmacies are the first step access to health services. Pharmacists, who are in constant contact with the patient can be considered as a single drug advisor. Pharmaceutical care needs more informal and comprehensive relationship between the pharmacist and patient than basic pharmaceutical dispensing and patient satisfaction measurements evaluates the needs fulfillment. In this study, it is aimed to discuss the context of patient satisfaction and to describe contemporary worldwide developments regarding the promotion of the matter. Researches conducted in USA, Canada, Australia and European countries have been reviewed as patient satisfaction measurements have been developed increasingly in these countries. Patient satisfaction which is an input and outcome as a performance indicator of pharmacy management, will be considered more in the future. PP 78 COMPARATIVE STUDY OF ANTIOXIDANT PROPERTIES OF FOUR UMBELLIFERAE SPECIES WILDLY GROWING IN TURKEY LEYLA BITIS, TURGUT TASKIN, ALI SEN, GIZEM BULUT, ERTAN TUZLACI DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF PHARMACEUTICAL BOTANY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY The fresh young leaves and shoots of Ammi visnaga, Daucus carota, Foeniculum vulgare, Oenanthe pimpinelloides,belong to the Umbelliferae family are traditionally used as vegetable and MEDICINE by local people in Turkey.The aim of this study is to reveal antioxidant properties of methanol extracts from these plants which were prepared using Soxhlet apparatus and by maceration, and to determine their relationship with the phenolic contents.the antioxidant capacity of these species were assayed with various methods, DPPH free radical scavenging, metal chelating and ABTS radical cation scavenging capacity, including total phenolics contents by Folin Ciocalteu reagent.the obtained results were compared with standard antioxidants such as Ascorbic acid, BHT and EDTA.The methanol extract of Daucus carota, prepared by maceration exhibited stronger DPPH free radical-scavenging (IC50: 0.30±0.0 mg/ml) and ABTS radical cation scavenging activity (IC50:.307± 0.mg/mL) than other extracts. The positive correlation was observed between the total phenolic contents and the DPPH free radical, ABTS radical cation scavening activity; indicating that phenolic compunds are mainly responsible for the antioxidant power of this extract.the methanol extract of Oenanthe pimpinelloides, prepared using Soxhlet apparatus exhibited stronger DPPH free radical (IC50: 3.±0.04 mg/ml) and ABTS radical cation scavenging activity (IC50: 5.± 0.03 mg/ml) than the others. The positive correlation was observed between the total phenolic contents and, the DPPH,ABTS methods, indicating that phenolic compunds are mainly responsible for the antioxidant power of this extract.cold extracts showed higher DPPH radical and ABTS radical cation scavenging activity than hot ones. It was shown, extraction method has an effect on antioxidant capacity. Acknowledgment : This work was supported by Scientific Research Projects Committee of the UNIVERSITY of Marmara(BAPKO, project number SAG-B ) -55-

157 PP 79 TWO FLAVONES FROM SAMBUCUS EBULUS L. LEAVES ZEHRA ILKE MERIC, LEYLA BITIS DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, YENI YÜZYIL UNIVERSITY, 3400,ISTANBUL, TURKEY DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, 34668, ISTANBUL, TURKEY The aim of this study was to isolate of flavonoids from fractionated extracts of Sambucus ebulus L. leaves. Leaves, flowers and fruits of Sambucus species (Caprifoliaceae) have been used to treat various disorders in Turkish folk MEDICINE. There are two Sambucus species in Turkey, Sambucus ebulus L. and Sambucus nigra L. Pharmacological effects have been reported for Sambucus species as antiviral, antibacterial, anti Helicobacter pylori, antioxidant and wound healing activity. The ethanol extracts of Sambucus ebulus (leaf, fruit and flower) which was collected from Çatalca in İstanbul at September 009, have been evaluated their total phenolic content, antioxidant and anticarcinogenic activities. Leave extract showed the highest activity as antioxidant, anticarcinogenic and total phenolic content. Therefore, leave extract was chosen for isolation. Plant material was extracted using Soxhlet apparatus with petroleum ether and ethanol respectively. In addition, toluene, chloroform, ethyl acetate and aqueous fractions were obtained from diluted ethanol extract by means of liquid-liquid extraciton methods, respectively. Chloroform extract was chromatographed on a silica-gel column and one flavonol glucoside was isolated. UV, NMR spectra and TLC comparisons with authentic samples were used for the structure elucidation of the purified compound. Finally; The compound was determined as Quercetine-3-O-β-galactoside. Also, Kaempferol-3-O-glucoside and Quercetine-3-O-galactoside from ethyl acetate extract were detected chromatographycally by TLC in comparison with authentic sample. PP 80 EFFICACY ENHANCEMENT OF HYDROPHOBIC ANTIBIOTICS EMPLOYING RHAMNOLIPID AS BIOSURFACTANT ABDURRAHIM ELOUZI FACULTY OF PHARMACY, TRIPOLI UNIVERSITY,LIBRA Antibiotic resistance has become a global public-health problem, thus it is imperative that new antibiotics continue to be developed. Major problems are being experienced in human MEDICINE from antibiotic resistant bacteria. Moreover, no new chemical class of antibiotics has been introduced into MEDICINE in the past two decades. The aim of the current study presents experimental results that evaluate the capability of biosurfactant rhamnolipid on enhancing the efficacy of hydrophobic antibiotics. Serial dilutions of azithromycin and clarithromycin were prepared. A bacterial suspension (approximately 5X05 CFU) from an overnight culture in MSM was inoculated into 0ml sterile test tube each containing a serial 0-fold dilution of the test antibiotic(s) in broth with or without 00mg/L rhamnolipid. The tubes were incubated for 4 h with vigorous shaking at 37 C. Antimicrobial activity in multiple antibiotic-resistant gram-negative bacteria pathogens and gram-positive bacteria were assessed using optical density technique. The results clearly demonstrated that the presence of rhamnolipid significantly improved the efficiency of both antibiotics. We hypothesized that the addition of rhamnolipid at low concentration, causes release of LPS which results in an increase in cell surface hydrophobicity. This allows increased association of cells with hydrophobic antibiotics resulting in increased cytotoxicity rates. -56-

158 PP 8 ASSESSMENT OF AND INTERVENTIONS TO SOLVE DRUG RELATED PROBLEMS IN PATIENTS WıTH ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) THAT IS NOT FULLY CONTROLLED GOZDE YESILYAPRAK, SULE APIKOGLU-RABUS, FIKRET VEHBI IZZETTIN ENDOTEK SAGLIK GERECLERI, IZMIR, TURKEY MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT, ISTANBUL, TURKEY The aim of this study is to assess drug related problems in patients with asthma and chronic obstructive pulmonary disease (COPD) that is not fully controlled and to make interventions to solve the problems. The control states were assessed by asthma control test (ACT) or clinical COPD questionnaire (CCQ). Asthma and COPD patients older than 8 years old who visited the community pharmacy (Hastaneler Eczanesi, Sivas, Turkey) during a six-month period were randomly selected. The patients whose disease control states were found to be not fully controlled were included in our study for further steps. On the first interview, present and potential drug related problems were assessed, interventions were made, patient satisfaction questionnaires were administered. For the assessment of the drug-related problems, Turkish translation of the PCNE-DRP Classification (V6.) was used. Follow-up interviews were held one month and two months later than the first interview date. During the interviews, patients reported data was recorded. For the 44 asthma patients, 59 drug related problems and 34 causes for these problems were determined. Eighty-four interventions were made to solve the problems. As a consequence of interventions, 54.% of the problems were solved and 0.% of the problems were partially solved. For the 37 COPD patients, 60 drug related problems and 8 causes for these problems were determined. Ninety-five interventions were made to solve the problems. As a consequence of interventions, 63.3% of the problems were solved and 6.7% of the problems were partially solved. As a conclusion, we can suggest that when pharmacists take part in therapy and management of asthma and COPD, this could lead patients to be more educated about their disease and medications and enhance their adherence to therapy, pharmacists could significantly help taking the disease under control and achieving better therapy outcomes. PP 8 ASSESSMENT OF THE EFFECTS OF QUINCE SEED MUCILAGE AND WHEAT GERM OIL ON WOUND HEALING IN RATS CANAN ATALAY, SULE APIKOGLU-RABUS, FIKRET VEHBI İZZETTIN MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT In our study we aimed to investigate the effects of wheat germ oil and quince seed mucilage on cutaneous wound healing in rats. The study was conducted on three groups of animals, which received topical wheat germ oil and topical quince seed mucilage as the therapy groups; and usual wound care as the control group. Wound healing was assessed by planimetric measurements of the contracting wound and the full epithelialization time. The findings yielded that when compared with the control rats, rats receiving topical wheat germ oil displayed lower wound closure rates in the first four days, while this rate was significantly higher in the 8., 0. and. days. The median duration of complete epithelialization was days for the wheat germ oil group and 3 days for the control group. Compared with the control group, the topical application of wheat germ oil accelerated wound healing by reducing the time required for complete epithelialization. On the other hand, the wound closure rates of the rats receiving quince seed mucilage were not different from those of the control rats different. In conclusion, the application of wheat germ oil was observed to accelerate wound healing. This finding could suggest an alternative or complementary approach to wound treatment. On the other hand, we think that the effect of the quince seed mucilage on wound healing should be assessed using higher concentrations of the preparation at further studies. -57-

159 PP 83 CLASSIFICATION FOR DRUG-RELATED PROBLEMS: TURKISH TRANSLATION AND ADAPTATION OF THE PCNE-DRP CLASSIFICATION (V6.) SULE APIKOGLU-RABUS, GOZDE YESILYAPRAK MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT ENDOTEK SAGLIK GERECLERI, IZMIR, TURKEY A drug-related problem is an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes. Drugs-related problem classification systems have been developed for the determination and characterization of drugs-related problems, to propose solutions, conduct follow up and document all these activities. One of these systems is the drug-related problems classification scheme [PCNA-DRP (Drug Related Problems) Classification] developed by the Pharmaceutical Care Network Europe (PCNE). This classification scheme has been designed to be used in the investigation of the nature and incidence of the drug-related problems; as a process indicator of the quality of the pharmaceutical care provided; and as an aid in documentation of the drug-related problems identified during the pharmaceutical care process. The classification system is validated and adapted regularly. The current version is V6.. As there is no classification system for the drug-related problems in Turkish, we aimed to translate and adapt the PCNE-DRP Classification (V6.). As the adaptation process, the PCNE-DRP Classification was first forward translated in Turkish, then reviewed by an expert panel and then backward translated by a native English speaker. Pre-testing was done on 0 pharmacists. Pre-testers were asked to comment on wording of the classification (they were asked about any word they did not understand or they found unacceptable and make alternative suggestions for it). Each pre-tester was interviewed in-depth one by one. The final version of the instrument was structured by the expert panel taking into consideration of these comments. PP 84 A MODEL PROGRAM FOR OBESITY PREVENTION AND CONTROL IN COMMUNITY PHARMACY SULE APIKOGLU-RABUS, GOKCEHAN GULTEKIN, FIKRET VEHBI IZZETTIN MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT, ISTANBUL, TURKEY SAGLIK ECZANESI, ISTANBUL, TURKEY The studies show that the worlds population is increasingly getting fat. This uncontrolled weight increase with its problems arising suggests that measures from all aspects should be taken in order to prevent weight gain. Today, pharmacists have a role in raising public awareness about obesity in countries such as USA, UK, Denmark, Australia, Germany, Switzerland and Scotland. The reason for this expanding role is that patients often primarily visit the pharmacies for weight loss or control; pharmacists can be easily reached without an appointment; and people trust the pharmacists and are able to speak with them comfortably. Despite this, the majority of the patients report that they would first admit to a doctor or a dietitian for weight loss or control. Patients concerns on this issue rise on the basis of their thoughts regarding the lack of pharmacists knowledge on the subject and concerns about the protection of privacy. Patients also think that the workload of the pharmacists will not let them counsel on weight loss efficiently and there is a bias that the pharmacists would be trying to market weight loss products. In this study, a model program for Obesity Prevention and Control in Community Pharmacy which aims helping to prevent and treat the increasing obesity cases; informing the patients about the role of the pharmacist in obesity prevention and control; raise awareness about obesity in general, its harms and the treatment approaches; and teaching healthy life-style, will be introduced. -58-

160 PP 85 DEVELOPMENT AND VALIDATION OF THE TURKISH DIABETES-SPECIFIC QUALITY OF LIFE SCALE SULE APIKOGLU-RABUS, DILEK YAZICI, MEHMET HURSITOGLU 3, FATIH METE 4, AKIN DAYAN 5, REFIK DEMIRTUNC 5, FIKRET VEHBI IZZETTIN MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT MARMARA UNIVERSITY MEDICAL SCHOOL; DEPARTMENT OF ENDOCRINOLOGY AND METABOLISM 3 KANUNI SULTAN SULEYMAN TRAINING AND RESEARCH HOSPITAL; DEPARTMENT OF INTERNAL MEDICINE 4 KANUNI SULTAN SULEYMAN TRAINING AND RESEARCH HOSPITAL; DEPARTMENT OF PEDIATRICS 5 HAYDARPASA NUMUNE TRAINING AND RESEARCH HOSPITAL; DEPARTMENT OF INTERNAL MEDICINE One of the primary goals in the treatment of diabetes is to improve patients quality of life. To our knowledge, the only available diabetes-specific quality of life scale in our country is the Turkish version of the Diabetes Quality of Life Measure. The scale consists of 46 questions in which the response options are graded using a 5-point Likerts scale. In our study we aimed to develop the Turkish Diabetes-Specific Quality of Life Scale to measure diabetes-specific quality of life in patients with diabetes as a shorter and easy to answer alternative. The newly developed quality of life scale was administered to 80 patients with type diabetes, together with the Nottingham Health Profile for validation studies. Internal consistency was assessed by Cronbachs alpha, test-retest reliability was evaluated by intra-class correlations, and validity was assessed by principal component analysis. The Cronbachs alpha value of the newly developed 4-item scale was The test retest reliability was Principal component analysis demonstrated three components, which explained 35.0 percent, 0.8 percent and 8.6 percent of the variation. The inter-item correlations were smaller than 0.6 in 98.9 percent of the cases. All domains of the Nottingham Health Profile showed a significant correlation with the new scale, except for the sleep domain. These findings revealed that the Turkish Diabetes- Specific Quality of Life Scale is a valid and reliable tool for measuring quality of life in patients with diabetes. PP 86 INFORMATION OF PUBLIC PHARMACISTS IN GIVEN DISTRICTS OF ISTANBUL ABOUT NEW STRUCTURING OF DRUG SAFETY AND EVALUATION OF THEIR APPROACH TO PHARMACOVIGILANCE GUNSELI CANSU ASKIN, GULDEN ZEHRA OMURTAG, SEMRA SARDAS MARMARA UNIVERSITY DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY This study was carried out as a face to face questionnary with pharmacists in Istanbul city in between , with the support of Istanbul Pharmacists Chamber. Aim of the study is by using the questionnaire, to survey information and awareness level of the pharmacists in given districts about the new structuring of drug safety and to increase the awareness level, contribute to increment and improving of adverse effect notice of pharmacists The questionnaire was carried out with two group of pharmacists who are graduated before and after year 005. The questionnaire was applied to 78 community pharmacists and the pharmacies were located in the neighborhood of Istanbul. The most frequently reported drug classes are, anti-depressants, non-steroidal anti inflamation drugs, antibiotics, oral contraceptives, anti-obezite drugs. When pharmacists are being asked about how to find the adverse drug reporting form, it is observed that 59% of pharmacists do not know, 4% of parmacists know how to find reporting forms. There is no statistical difference according to the year of graduation. Past and future professional educations which are followed by pharmacists are improving the steps of drug safety Pharmacists are being asked about the reasons for not-transmitting the adverse drug reaction. Primary reasons are lack of time and information about how to report the reaction. Pharmacists mostly rely on pharmacy faculties for the better education of adverse drug reaction and reporting. Pharmacists are informed about adverse drug reaction, reporting forms and pharmacovigilance. For the pharmacists who are graduated after 005, it is observed that information and the awareness of basic terms about drug safety is improved more than the other group. With implemention of pharmacovigilance education into faculty programme, the information about drug safety improvement and awareness to basic terms of drug safety has increased. There is a huge need for more education, information, studies and programmes about pharmacovigilance for well-informed healthcare professionals. -59-

161 PP 87 EFFECT OF ANTIBIOTICS ON POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS AND MYELOPEROXIDASE ACTIVITY, GLUTATHIONE AND MALONDIALDEHYDE LEVELS IN ALLERGIC ASTHMA PERVIN RAYAMAN, ERKAN RAYAMAN, ADILE CEVIKBAS, REFIK DEMIRTUNC, AHMET OZER SEHIRLI 3, SEYDA GUL ALAGOZ 4, UMRAN SOYOGUL GURER DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY DEPARTMENT OF INTERNAL MEDICINE, HAYDARPAŞA NUMUNE TRAINING AND RESEARCH HOSPITAL, İSTANBUL, TURKEY 3 DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY 4 DEPARTMENT OF PNEUMONOLOGY, HAYDARPAŞA NUMUNE TRAINING AND RESEARCH HOSPITAL İSTANBUL, TURKEY Oxidative stress may play a critical role in the pathogenesis of inflammatory diseases such as allergic asthma. Our objective was to compare polymorphonuclear leukocytes (PMN) functions to myeloperoxidase (MPO)activity, glutathione (GSH) and malondialdehyde (MDA) levels in PMN and determine the relationship between PMN functions and MPO activity, GSH and MDA levels in allergic asthma patients and healthy volunteers. Also we investigated the effect of rifampicine and doxycycline on PMN functions and MPO activity, GSH and MDA levels. PMNs were isolated from venous blood of allergic asthma patients and healthy volunteers with ficoll-hypaque gradient centrifugation method. MPO activity was assayed with modified o-dianisidine method. GSH levels were determined by Ellman s and MDA levels by Beuge s method. PMN s phagocytic(p<0.0) and intracellular killing activity(p<0.00) and MDA levels (p<0.00) of patients significantly decreased when compared to healthy volunteers. Rifampicine and doxycycline have decreased both PMN functions of healthy volunteers (p< 0.05, p<0.05 respectively). Rifampicine has increased MDA levels (p<0.0) of healthy volunteers, but doxycycline has decreased MDA levels (p<0.05) of allergic asthma patients. In conclusion, the relationship between MDA levels and PMN functions was shown. In relationship with the disease and therapy of these patients, the decrease of PMN s GSH levels, might bring up the usage of new pharmacaeutical preparations which increase the MPO activity and GSH levels and decrease MDA levels in neutrophils of these patients. PP 88 SYNTHESIS, EVALUATION OF THE ANTIOXIDANTACTIVITY OF NEW ONO DONOR HETEROCYCLIC SCHIFF BASE AND ITS NOVEL CU(II) COMPLEX MEHMET EMİN HACIYUSUFOĞLU, MEHMET SÖNMEZ, İSMET BERBER 3, ZÜLBİYE ÖNAL 4 DEPARTMENT OF FOOD TECHNOLOGY, AKÇAKOCA VOCATIONAL SCHOOL, UNIVERSITY OF DÜZCE, DÜZCE,TURKEY DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND ARTS, GAZIANTEP UNIVERSITY, GAZIANTEP,TURKEY 3 DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND ARTS, SINOP UNIVERSITY,SINOP,TURKEY 4 DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, ERCIYES UNIVERSITY, KAYSERI,TURKEY N donor bases known as pyrimidines and purines are two of the basic building elements of DNA; they are necessary elements in cell programming. Also they accomplish a variety of functions in the metabolism of the cell, and without them, many cellular functions would not be accomplished (). These rings are known to take important role in biological systems. Therefore, pyrimidine derived Schiff base ligands and their complexes have been extensively investigated for biological activities, including antimalarial, antibacterial, antitumor, antiviral activities etc. in recent years (). N donor containing Schiff bases form complexes with metal ions by strong binding, thus these complexes have high stability. The metal(ii) complexes of polydentate Schiff base ligands of the N-aminopyrimidine type have impressive electrochemical properties and structural richness, in addition to their potential use as a model for a number of important biological systems (3).In the study, A new heterocyclic Schiff base ligand and its transition metal complex of the type ML, where M= Cu(II) has been synthesized the ligand (HL) and its metal complex we was evaluated for in vitro the antioxidant activity using DPPH activity assay. Chang YT, Gray NS, Rosania GR, Sutherlin DP, Kwon S, Norman TC, Sarohia R, Leost M, Meijer L, Schultz PG (999) Synthesis and application of functionally diverse,6,9-trisubstituted purine libraries as CDK inhibitors. Chemistry and Biology 6: Saha N, Kar SK (977) Chelating behavior of a new pyridylpyrazole: tris-complexes of Cu(II), Ni(II) and Co(II) perchlorates and fluoborates with 3,5-dimethyl--( -pyridyl) pyrazole. J Inorg Nucl Chem 39: Gülcan M, Sönmez M, Berber I (0) Synthesis, characterization, and antimicrobial activity of a new pyrimidine Schiff base and its Cu(II), Ni(II), Co(II), Pt(II), and Pd(II) complexes. Turk J Chem 36:

162 PP 89 SYNTHESIS AND STRUCTURE ELUCIDATION OF SOME NOVEL CHIRAL,,4-TRIAZOLE-3-THIONES EYUP BASARAN, AYSEGUL KARAKUCUK-IYIDOGAN, EMINE ELCIN ORUC-EMRE DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY Nitrogen based heterocyclic compounds are very important in the field of medicinal chemistry.,,4-triazole nucleus is associated with diverse biological activities such as antinflammatory, antiviral, antifungal and cytotoxicity activities etc. (-3). Taking these observations into account in the present study, some novel chiral,,4-triazoles were synthesized. Firstly, D-phenylalanine methylester/l-phenylalanine ethylester were converted to the sulfonamide derivatives with arylsulfonyl chlorides in the presence of triethylamine. These sulfonamides were reacted with hydrazine monohydrate to give hydrazide derivatives. Then, hydrazide derivatives were treated with various substituted isothiocyanates to obtain new chrial thiosemicarbazide derivatives. Finally, enantiomerically pure new chiral,,4-triazole-3-thiones were prepared by cyclization of chrial thiosemicarbazides in basic medium. The structures of all the synthesized compounds were confirmed by elemental analyses (CHNS), IR, UV-Vis, HNMR, 3C NMR and MS spectra. In the future, in vitro cytotoxic and antiviral activity of all compounds will be screened.. Mathew V, Keshavayya J, Vaidya VP, Giles D. Studies on Synthesis and Pharmacological Activities of 3,6-disubstituted-,,4- triazolo [3,4-b]-,3,4-thiadiazoles and Their Dihydro Analogues. Eur J Med Chem. 007;4: Kritsanida M, Mouroutsou A, Marakos P, Pouli N, Papakonstantinou-Garoufalias S, Pannecouque C, Witvouw M, De Clercq E. Synthesis and Antiviral Activity Evaluation of Some New 6-substituted 3-(-adamantyl)-,,4-triazolo[3,4-b][,3,4]thiadiazoles Il Farmaco. 00;57: Lesyk R, Vladzimirska O, Holota S, Zaprutko L, Gzella A. New 5-substituted thiazolo [3,-b][,,4]triazol-6-ones: Synthesis and Anticancer evaluation. Eur J Med Chem. 007;4: PP 90 ENANTIOPURE AMIDES: SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY CANER CEVIK, EYUP BASARAN, AYSEGUL KARAKUCUK-IYIDOGAN, EMINE ELCIN ORUC-EMRE DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY The synthesis of chiral drugs in enantiopure form is very important in synthetic organic chemistry, medicinal chemistry, natural product chemistry and the pharmaceutical industry. Approximately half of the drugs currently in use are chiral compounds, and about 88% of these chiral synthetic drugs are used therapeutically as racemates. Unfortunately, there are many racemic drugs where the stereospecificity of the metabolism and/or the pharmacodynamic effects of the enantiomers is not known. Therefore, development of new effective and selective techniques are required for the manufacture of chiral drugs. Chiral building blocks have an important place for the production of modern pharmaceutical drugs. Chiral amines have some advantages for drug R&D such as a highly versatile, cheap and having attractive group of chiral building blocks [-]. In present work, we synthesized twelwe chiral amide derivatives in high yields by the reaction of (R)-(-)-,,3,4-tetrahydro--methylamine/ (S)-(+)-,,3,4-tetrahydro--methylamine with various 4-substitutedbenzoyl chlorides in diethylether at room temperature. The chemical structure of new compounds were characterized by IR, H NMR, 3C NMR data and elemental analysis. In future, the in vitro cytotoxic and antiviral activity of all chiral amides will be evaluated. [] Laumen K, Brunella A, Graf M, Kittelmann M, Walser P, Ghisalba O. New biocatalytic approaches for the synthesis of chiraldrugs, intermediates, and substrates, Pharmacochemistry library, 998; 9: 7-8. [] Nguyen L, A, He H, Pham-Huy C. Chiraldrugs: An Overwiev, Int J Biomed Sci. Jun, 006; ():

163 PP 9 SYNTHESIS OF NOVEL CHALCONE DERIVATIVES AND INVESTIGATION OF THEIR BIOLOGICAL ACTIVITY ZEKERIYA TURGAY SELEN, EMINE ELCIN ORUC-EMRE, EYUP BASARAN, AYSEGUL KARAKUCUK-IYIDOGAN, AYSE KARADUMAN, IBRAHIM HALIL KILIC, MEHMET OZASLAN DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY DEPARTMENT OF BIOLOGY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY Chalcones, the member of α,β-unsaturated ketone, have attracted a great deal of interest due to their applications as antibacterial, antifungal, anti-inflammatory, antitubeculosis and anticancer pharmacological agents (-3). We synthesized different substituted chalcone compounds, N-(4[3-(4-substitutedphenyl)prop--enoil]phenyl)-4-fluoro/trifluoromethylbenzamide, by using N-(4- acetylphenyl)-4-fluoro/trifluoromethylbenzamide as a starting compound. The structures of these compounds were elucidated by spectroscopic method such as UV, IR, ¹H NMR, mass and elemental analysis. In addition to that, antibacterial activity of synthesized chalcones were investigated against 9 different bacteries (Staphylococcus aureus ATCC 593, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 7853, Klebsiella pneumoniae ATCC , Staphylococcus aureus ATCC 93, Escherichia coli ATCC 53, Escherichia coli ATCC 358, Escherichia coli ATCC 0799, Escherichia coli ATCC 8739).. Mishra N, Arora P, Kumar B, Virendra K. Synthesis of novel,3-diaryl propenone derivatives and theri antimalarial activity in vitro. Eur. J. Med. Chem. 008; 43: Jin C, Liang Y, He H, Fu L. Synthesis of novel chalcone derivatives. Biomed. Pharmacotherapy 03; 67: Yaylı N, Mısır G, Yaşar A, Demir E, Demirdağ Z. Synthesis and antimicrobial activity of N-alkyl substituted p-methyl (E)-3- and 4-azachalconium bromides. Turk J. Chem. 00; 34: 9-8 PP 9 THE SYNTHESIS OF NEW HYDRAZONE DERIVATIVES FROM 4-FLUOROBENZOHYDRAZIDE NAZIRE MERVE KARTAL, EMINE ELÇIN ORUC-EMRE, EYUP BASARAN, AYSEGUL KARAKUCUK-IYIDOGAN, SEVIM ROLLAS, BEDIA KOCYIGIT-KAYMAKCIOGLU DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Hydrazone is a special member of Schiff base which contents the azomethine group and it is an important organic compound that has RC=NNH general formula. Hydrazide-hydrazone derivatives exhibited broad spectrum of biological activities such as anticonvulsant, antidepressant, antimicrobial, antitumoral, analgesic, anti-inflammatory and antitubercular activities. In our previous work, we synthesized some hydrazide-hydrazone derivatives which were shown to exhibit high antituberculosis activity (). Some of these compounds showed interesting in vitro activity against Mycobacterium tuberculosis H37Rv; especially 4-fluorobenzoic acid [((5-nitro)thiophen--yl)methylene]hydrazide, which showed the highest inhibitory (99% inhibition, MIC value 3.3 µg/ml) activity. In this study, 4-fluorobenzohydrazide has been synthesized by the reaction of phenyl 4-fluorobenzoate with hydrazine monohydrate (). This compound reacted with 4-(4-substituted phenoxy)benzaldehyde in the presence of methanol to form N-{[4-(4-substituted phenoxy)phenyl]methylidene}-4-fluorobenzohydrazide (). The structure of new compounds was confirmed using IR, NMR, mass and elemental analysis. These derivatives have been screened for anti- Alzheimer activity.. Koçyiğit-Kaymakçıoğlu B, Oruç EE, Unsalan S, Kandemirli F, Shvets N, Rollas S, Dimoglo A. Synthesis and characterization of novel hydrazide-hydrazones and the study of their structure antituberculosis activity. Eur J Med Chem. 006; 4(): Koçyiğit-Kaymakçıoğlu B, Oruç EE, Unsalan S, Rollas S. Antituberculosis Activity of hydrazones derived from 4-fluorobenzoic acid hydrazide. Med Chem Res. 009;8:

164 PP 93 SYNTHESIS AND CHARACTERIZATION OF NEW THIOSEMICARBAZONE DERIVATIVES DERIVED FROM 4-(DIETHOXYMETHYL)BENZALDEHYDE MUHAMMET IBRAHIM OZSOY, EYUP BAŞARAN, AYSEGUL KARAKUCUK-IYIDOGAN, EMINE ELCIN ORUC-EMRE DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY Thiosemicarbazones are thiourea derivatives and analogues of semicarbazones which contains a sulfur atom in place of the oxygen atom. The biological properties of thiosemicarbazone derivatives such as antibacterial, antifungal, antimalarial, anticancer, anti-inflammatory, anticonvulsant, antioxidant, antiviral, activities have been extensively studied over the last 50 years (). Generally thiosemicarbazone derivatives are synthesized by condensation of the corresponding thiosemicarbazides with aldehydes or ketones. Therefore, their biological activities depend on the parent aldehyde and ketone (,3). In view of the above mentioned findings, we synthesized some new thiosemicarbazone derivatives derived from 4-(diethoxymethyl) benzaldehyde in good yields and high purity The structure of the new synthesized,3-thiazoline derivatives were characterizated by using UV, IR, H NMR, MS spectroscopy and elemental analysis.. Karaküçük-İyidoğan A, Mercan Z, Oruç-Emre EE, Taşdemir D, İşler D, Kılıç İH, Özaslan M. Synthesis, Characterization, and Biological Evaluation of Some Novel Thiosemicarbazones as Possible Antibacterial and Antioxidant agents. Phosphorus, Sulfur, and Silicon, 04;89: Karaküçük-İyidoğan A, Taşdemir D, Oruç-Emre EE, Balzarini J. Novel Platinum(II) and Palladium(II) Complexes of Thiosemicarbazones Derived from 5-Substitutedthiophene--carboxaldehydes and Their Antiviral and Cytotoxic Activities. Eur J Med Chem 0;46(): Beraldo H, Gambino D. The wide pharmacological versatility of semicarbazones, thiosemicarba-zones and their metal complexes. Mini Rev Med Chem 004;4: PP 94 SYNTHESIS OF NEW 4-THIAZOLIDINONES INCORPORATED IMIDAZO[,-B]THIAZOLE MOIETY AS ANTIVIRAL AGENTS ERKAN PEHLIVAN, NURAY ULUSOY GUZELDEMIRCI DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, İSTANBUL UNIVERSITY A series of 3-alkyl/aryl--[[[6-(phenyl/4-chlorophenyl)imidazo[,-b]thiazol-3-yl]acetyl]hydrazono]-5-nonsubstituted/methyl- 4-thiazolidinones (5a-l) was synthesized by cyclization of 4-alkyl/aryl--[[6-(phenyl/4-chlorophenyl)imidazo[,-b]thiazol-3-yl] acetyl]-3-thiosemicarbazides (4a-j) with ethyl bromoacetate or ethyl -bromopropionate (). Their structures were elucidated by elemental analyses and UV, IR, H-NMR, 3C-NMR (APT), 3C-NMR (DEPT), HSQC and ESI-MS data. The new compounds were evaluated against some DNA and RNA viruses in CRFK, VERO, HEL and HeLa cell cultures.. Habib NS, Fahmy S, El-Khawass SM, Abdel Aziem T. Novel thiazolinyl, thiazolidinoyl, thiadiazolyl and oxadiazolylbenzotriazole derivatives with potential antiinflammatory activity and minimum ulcerogenic effect. Pharmazie 000; 55:

165 PP 95 INVESTIGATION OF INHIBITORY EFFECTS OF 3- AND 4- ARYL COUMARIN DERIVATIVES ON ACETYLCHOLINESTERASE ACTIVITY MERT GURCAN KARALI, OZKAN DANIS, MUSTAFA MUHLIS ALPARSLAN, CIHAN GUNDUZ, AYSE OGAN DEPARTMENT OF CHEMISTRY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF MEDICAL BIOCHEMISTRY, FACULTY OF MEDICINE, ÇUKUROVA UNIVERSITY, ADANA, TURKEY Alzheimers disease (AD) is a progressive, chronic, neurodegenerative disorder that is characterized by a loss of memory and cognition, decline in language, and severe behavioral abnormalities. It is the most common form of dementia among the elderly and it is the fourth leading cause of death in developed countries. Neuropathological evidence has shown that the decreased levels of acetylcholine, β- amyloid senile plaques and neurofibrillary tangles formation within the brain play a crucial role in the pathogenesis of Alzheimers disease. Accordingly, the most promising approach for the symptomatic treatment of AD is to increase the synaptic levels of ACh in the brain by inhibiting the acetylcholinesterase (AChE) enzyme, which is primarily responsible for its hydrolysis and termination of action. Therefore, AChE inhibitors such as galanthamine, donepezil, and tacrine are the main drugs for the clinical management of AD. These compounds have shown to induce a modest improvement in memory and cognitive functions. However, they don t appear to prevent or slow down the progressive neurodegeneration. Coumarins are naturally occurring phytochemicals in many plant species with a wide range of biological activities such as antiinflammatory, antitumor, antiviral, antimicrobial, antioxidant, antidepressant, anticancer and anticoagulant effects. The studies have shown that naturally occurring and chemically synthesized coumarin analogs exhibit potent AChE inhibitory activity. In this study, in order to evaluate potential AChE inhibitors, forty coumarin derivatives bearing different functionalities such as amino, hydroxy, methoxy and acetoxy have been synthesized and confirmed on the basis of their spectral data. They were examined for the first time for their inhibitory effect on Electrophorus electricus AChE by using acetylthiocholine iodide as substrate. Our studies showed that 4-aryl coumarins were found to possess the highest inhibitory activity among the tested substances. PP 96 SYNTHESIS AND STRUCTURAL ELUCIDATION OF SOME AMIDE DERIVATIVES SEYMA ECE, EMİNE ELCIN ORUC-EMRE, EYUP BASARAN, AYSEGUL KARAKUCUK-IYIDOGAN DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY Amide derivatives have been associated with various types of biological properties such as antitumor, anticonvulsant, antimicrobial, analgesic and anti-inflamatory activities (-3). In this research, -chloro-n-[4-(morpholin-4-yl)phenyl]acetamide (I) was prepared by reaction of aniline with chloro acetylchloride in dioxane. This compound (I) was treated with different aromatic or alicyclic amines such as aniline, 4-trifluoromethylaniline, morpholine to obtain N-[4-(morpholin-4-yl)phenyl]--substituted acetamide. Synthesis of the final compounds has been caried out for the first time in this study. Physical and chemical properties of these compounds have been confirmed by using their melting points, IR, NMR and elemental analysis results.. Zhang S, Zhao Y, Liu Y, Chen D, Lan W, Zhao Q, Dong C, Xia L, Gong P. Synthesis and antitumor activities of novel,4-disubstituted phthalazine derivatives. Eur J Med Chem. 00;45: Khanna S, Madan M, Vangoori A, Banerjee R, Thaimattam R, Ramesh M, Casturib SR, Pala M. Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase- (COX-) inhibitors. Bioorg Med Chem 006;4: Ding L, Zhu J, Zheng C, Sheng C, Qi J, Liu X, Han G, Zhao J, Lv J, Zhou Y. Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives. Bioorg Med Chem Lett. 0;: PP 97 SYNTHESIS AND CHARACTERIZATION OF NEW SULFONYLHYDRAZONE DERIVATIVES MEVLUDE BETUL KOSELI, EMİNE ELCIN ORUC-EMRE, EYUP BASARAN, AYSEGUYL KARAKUCUK-IYIDOGAN DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY It is well known that compounds containing sulfonylhydrazone group have been reported to possess antibacterial, antifungal, antitumor and antidepressant activities (,). New sulfonylhydrazone derivatives bearing electron donating or electron withdrawing substitutions were designed and synthesized from 4-fluorobenzenesulfonohydrazide. N -[[4-(4-substitutedphenoxy)phenyl] methylidene]-4-fluorobenzohydrazides were obtained by reaction of 4-fluorobenzenesulfonohydrazide with different aldehydes in methanol. The structure of the new compounds have been established by elemental analysis and IR, H-NMR and mass spectra.. Hafez HN, El-Gazzar ABA. Synthesis and antitumor activity of substituted triazolo[4,3-a]pyrimidin-6-sulfonamide with an incorporated thiazolidinone moiety. Bioorg. Med. Chem. Lett. 009; 9: Navakoski de Oliveira K, Costa P, Santin JR, Mazzambani L, Bürger C, Mora C, Nunes RJ, Souza MM. Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones Bioorg. Med. Chem. 0; 9:

166 PP 98 EFFECTS OF METHANOL EXTRACT OF MARRUBIUM CRASSIDENS BOISS ON ISCHEMIA/REPERFUSION INDUCED ARRHYTHMIAS AND INFARCT SIZE IN THE ISOLATED RAT HEART SEYEDEHNEGISA SEYEDTOUTOUNCHI 4, MARYAM RAMESHRAD, HALEH VAEZ, SANAZ HAMEDEYAZDAN, MAHDIYEH PASHAII 3, ALIREZA GARJANI, FATEMEH FATHIAZAD DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES 3 STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY,TABRIZ UNIVERSITY OF MEDICAL SCIENCES 4 STUDENT RESEARCH COMMITTEE, GIFTED AND TALENTED STUDENT SUPPORTING UNIT, TABRIZ UNIVERSITY OF MEDICAL SCIENCES The objectives of present study were phytochemical screening and study of the cardioprotective effects of the methanol extract of Marrubium crassidens on Ischemia/Reperfusion (I/R) injuries in isolated rat heart. The leaves of plant were extracted with methanol by maceration and subjected to colorimetry to determine its compounds. The isolated hearts were mounted on a Langendorff apparatus then perfused during 30 min regional ischemia and 0 min reperfusion, either by modified Krebs- Henseleit solution (KHBS) in control group or enriched KHBS with the extract (0, 50, and 00 µg/ml) in treatment groups. After reperfusion, the hearts stained by Evans blue solution then incubated by triphenyltetrazolium chloride. The percentage of infarct size was determined by Image-j software. Phytochemical screening indicated the presence of phenolic compounds and flavonoids. The results demonstrated that the extract caused a significant reduction in the number of total ventricular ectopic beats (00 µg/ml, p<0.05) during ischemia and reperfusion. It also significantly reduced the ventricular tachycardia (VT) number (0µg/ml, p<0.05and 00 µg/ml, p<0.00) and duration (0 µg/ml, p<0.05) during ischemia. The VT incidence was reduced from 00% in the control group to 0% in the treated-group with 00 µg/ml (p<0.0). The infarct size was reduced from 70.74±0.35% in the control group to 9.±6.6 (p<0.00) and 5.7±3.89% (P<0.0) in groups treated by 0 and 50 µg/ml of extract, respectively. The results of the study suggest that the extract has protective effects against I/R injuries in isolated rat heart which could be related to antioxidative activities of its phenolic and flavonoids compounds. PP 99 SUPRESSION OF DIABETIC RETINOPATHY FORMATION VIA ALPHA-AMYLASE AND GLUCOSIDASE INHIBITION POTENTIAL OF RUMEX ACETOSELLA NADIRE OZENVER, L. OMUR DEMIREZER HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOGNOSY ANKARA, TURKEY Diabetic retinopathy (DR) is the main cause of blindness in industrialised countries. The most effective medical treatment to slow the progression of DR is glycemic control. Therefore to decrease hyperglycemia is a very significant therapeutic approach for treating diabetes. This can be achieved through the inhibition of carbohydrate hydrolyzing enzymes such as alpha glucosidase and alpha amylase. Alpha amylase and alpha glucosidase inhibitors can be an important strategy in the development of compounds in the management of hyperglycemia linked to type II diabetes (). Rumex acetosella L. (Polygonaceae) has been commonly used for diabetes, stomach and heart diseases in traditional MEDICINE. The phytochemical studies have shown the presence of anthraquinones, naphthalens, tannins in Rumex acetosella. The frequently occurring anthraquinone derivatives of Rumex species are aloe-emodin, chrysophanol, emodin, physcion, rhein and their glycosides. In this study nonpolar extract of Rumex acetosella roots were characterized with HPLC-DAD. Due to the main anthraquinone aglycones have significant interactions with alpha amylase as a result of in silico docking study, crude standardised extract from Rumex acetosella were validated for alpha amylase and alpha glucosidase inhibition potential. This study has provided a basis for future research about whether R. acetosella and including compounds will have a potential to treat diabetes or not in traditional uses.. Kwon YI, Apostolidis E, Shetty K. In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type diabetes and hypertension. Bioresource Technology. 008; 99:

167 PP 00 BIOLOGICAL ACTIVITY OF SOME CHALCONE DERIVATIVES YUSUF SICAK, BEDRIYE SEDA KURŞUN AKTAR, EMINE ELCIN ORUC EMRE 3, MEHMET OZTURK, IBRAHIM DEMIRTAS, AYSEGUL KARAKUÇUK IYIDOĞAN 3 FACULTY OF PHARMACY MUGLA SITKI KOCMAN UNIVERSITY, MUGLA, TURKEY FACULTY OF PHARMACY CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY 3 FACULTY OF PHARMACY GAZIANTEP UNIVERSTY, GAZIANTEP, TURKEY This work is a research on antioxidant, anti-alzheimer and urease enzyme activities of chalcones derivated from 4-morpholinoacetophenone. These derivatives have been synthesized by Claisen-Schmidt condensation of substitutedaldehyde with 4-morpholinoacetophenone (). The antioxidant activity of chalcone derivatives was determined as β-carotene-linoleic acid, DPPH radical scavenging, superoxide anion radical scavenging, ABTS cation radical scavenging, and CUPRAC methods. In vitro inhibitory activity of acetylcholinesterase and butyrylcholinesterase enzymes related with Alzheimers disease was determined using Ellmans method (). Also, to determine the inhibitory activity of urease was used Mobley method (3).. Kurşun BS. The synthesis and characterization of novel chalcone derivated from 4morfolinoacetophenone and anticancer activity. Yüksek Lisans Tezi. 0.. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemistry and Pharmacology and Behaivor. 96; 7: Mobley HLT, Island MD, Hausinger RP. Microbial Ureases-Significance, Regulation, and Molecular Characterization. Microbiological Reviews. 989; 53: PP 0 SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY OF NOVEL THIOUREAS DERIVATED FROM 4-(4-FLUOROPHENOXY)ANILINE INCI NEJLA YILDIZ, YUSUF SICAK, EMINE ELÇIN ORUÇ EMRE, MEHMET OZTURK, AYSEGUL KARAKUCUK IYIDOGAN FACULTY OF PHARMACY GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY FACULTY OF PHARMACY MUGLA SITKI KOCMAN UNIVERSITY, MUGLA, TURKEY Thioureas used in pharmaceutical research are an important class of compounds nitrogen and sulphur-containing. During recent years, thiourea compounds have known many biological properties such as anti-hiv, antitubercular, analgesic, anticancer activities (-3). In this research; a new series of thiourea derivatives were obtained by the reaction of 4-(4-flourophenoxy) aniline with the different isothiocyanates (3). The purity were controlled by TLC and the chemical structures of the synthesized compounds were elucidated using UV, IR, H-NMR, 3C-NMR, mass spectroscopy and elemental analysis. The biological activities of synthesized thiourea derivatives have been screened as antioxidant, anti-alzheimer activity and urease enzyme activity.. Küçükgüzel I, Tatar E, Küçükgüzel ŞG, Rollas S, De Clercq. Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-,4-d,hydro-3H-,,4-triazole-3-thiones and evaluation as antiviral/anti-hiv and antituberculosis agents. Eur. J. Med. Chem. 008; 43(): Mahajan A, Yeh S, Nell M, van Rensburg CJ, Chibale K. Synthesis of new 7- chloroquinolinyl thioureas and their biological investigation as potential antimalarial and anticancer agents. Bioorg. Med. Chem. 007; 7: Kaymakçıoğlu, B.K, Rollas, S, Körceğez, E, Arıcıoğlu, F. Synthesis and biological evaluation of new N substitued-n -(3,5-di/,3,5-trimethylpyrazole-4-yl) thiourea/urea derivatives. Eur. J. Pharm. Sci. 005; 6 :

168 PP 0 SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME NOVEL -(4-MORPHOLINOPHENYL)-3-(4-(4-SUBTITUTEDPHENOXY) PHENYL)PROP--EN--ONE DERIVATIVES YUSUF SICAK, MEHMET OZTURK, B. SEDA KURSUN AKTAR, IBRAHIM DEMIRTAS, E. ELCIN EMRE 3, AYSEGUL KARAKUCUK IYIDOGAN 3 DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCES, MUGLA SITKI KOÇMAN UNIVERSITY, MUGLA, TURKEY DEPARTMENT OF PROPERTY PROCTECTION AND SECURITY, YAPRAKLI VOCATIONAL SCHOOL, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY 3 DEPARTMENT OF CHEMISTRY, FACULTY OF ARTS AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY Searching for the therapeutic agents, novel series of -(4-morpholinophenyl)-3-(4-(4-subtıtutedphenoxy)phenyl)prop-- en--one derivatives were synthesized by using Claisen-Schmidt condensation with -(4-morpholinophenyl)ethanone and 4-(4-substitutedphenoxy)benzaldehyde. The in vitro antioxidant, anticholinesterase and urease inhibitory activities of newly isolated chalcones derivatives were carried out. The antioxidant activity was determined by five complimentary assays; namely, β-carotene-linoleic acid, DPPH radical scavenging, superoxide anion radical scavenging, ABTS cation radical scavenging, and CUPRAC methods ().The anticholinesterase activity was determined by using Ellmans method against acetylcholinesterase and butyrylcholinesterase which were the chief enzymes of Alzheimers disease (). In order to determine the urease enzyme inhibitory activity, however, Mobley method was used (3).. Oztürk M, Aydoğmuş-Oztürk F, Duru ME, Topçu G. Antioxidant activity of stem and root extracts of Rhubarb (Rheum ribes): An edible medicinal plant. Food Chemistry. 007; 03: Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemistry and Pharmacology and Behaivor. 96; 7: Mobley HLT, Island MD, Hausinger RP. Microbial Ureases-Significance, Regulation, and Molecular Characterization. Microbiological Reviews. 989; 53: PP 04 EFFECTS OF BENTAZONE ON LIPID PEROXIDATION AND ANTIOXIDANT SYSTEMS IN HUMAN ERYTHROCYTES IN VITRO MAHMOUD ABUDAYYAK, SIBEL OZDEN, BUKET ALPERTUNGA, GUL OZHAN DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY Bentazone, a benzothiadiazole herbicide, is widely used for a variety of crops including cereals, maize, peas, rice and soy beans. The concern for human health is stil very high because bentazone is continuously monitored in environment and several studies to evaluate its potential carcinogenic effects when chronic and high doses were administered to animals. We aimed to investigate the possible effects of bentazone on lipid peroxidation, levels of glutathione and activities of antioxidant enzymes in human erythrocytes in vitro. For that, erythrocyte were incubated with bentazone in different concentrations (0 50 nm) at 37 C for hr. Bentazone showed significant increase in the levels of malondialdehyde (MDA) at the highest concentration in erythrocytes as an index of lipid peroxidation. Besides, alterations in the levels of reduced glutathione (GSH) and activities of glutathione peroxidase (GSH-Px) were observed while the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH-Rd) were unchanged. In conclusion, findings from this study indicate that in vitro toxicity of bentazone may be associated with oxidative stress and this work warrants further in vivo investigations. PP 04 RESEARCHİNG OF TOCILIZUMAB EFFECT S IN EXPERİMENTAL ALZHEIMER MODEL ERSIN ASLAN, HATICE KUBRA ELCIOGLU, LEVENT KABASAKAL MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer s Disease (AD). It was suggested that IL-6 shows overespression and pleiotropic activity in AD s brain. Tocilizumab (TCZ) that is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody, inhibits IL-6 signal transduction. The aim of our study is to learn that the effect of Tocilizumab on AD cognitive deficits caused by intracerebroventricular (i.c.v.) injection of streptozotocin (STZ). Male Sprague-Dawley rats were divided into three different groups: control, STZ and TCZ+STZ. Rats that are in STZ and STZ+TCZ groups, were injected single dosed bilaterally i.c.v STZ (3mg/kg) stereotaxically to induce experimental Alzheimer s disease. We used single dose of i.c.v. TCZ beginning h prior to injection of STZ for days. Behavioral parameters were evaluated between 5st-st days, and the rats were sacrificed on day st to examine histopathological changes. Histopathological changes were examined using hematoxylin-eosin. Tocilizumab treatment attenuated significantly STZ induced cognitive impairment and histopathological changes. Further studies are warranted to investigate more protective effect about Tocilizumab on AD. STZ injection caused a significant decrease in the mean escape latency in passive avoidance and decreased improvement of performance in morris water maze tests. Brain sections of TCZ treated rats showed decreased Aβ and IL-6 levels in the neurons and glial cells of cortical area compared to STZ. -67-

169 PP 05 PHYTOCHEMICAL ANALYSIS AND SOIL PROPERTIES OF CERINTHE GLABRA MILLER (BORAGINACEAE) EBRU GUL, AYSE SAHIN YAGLIOGLU, MELDA DOLARSLAN 3, HASAN SOYLEMEZ, IBRAHIM DEMIRTAS DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 800, CANKIRI, TURKEY DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY 3 DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 800 CANKIRI, TURKEY Cerinthe glabra Miller belongs to the family Boraginaceae, the plants of family use decorative plants, spices, and useful for the preparation of dyestuffs. Active agents of the family are mucilage derivatives (arabinose, glucose and galactose), Pyrolizidinalkaloits (Amabilin, Supinidin, Lycopsamin, Intermedin, 7-Asetil-Lycopsamin ve 7-Asetilintermedin). Also, The family contains tannins, saponins, resins, starches, silicic acids, vitamin C and minerals (). C. glabra Miller is a perennial herb. However, this plant grow Central and Southern Europe, the Balkans and the Caucasus in the World; the North and East Anatolian (Çankırı, Kastamonu, Bitlis, Ağrı, Artvin, Tunceli and Van) in Turkey (). In this study, C. glabra Miller (Boraginaceae) were collected from Çankırı. Physical and chemical soil properties of collected area are moderately alkaline ( ph), sandy clay loam-clay loam texture and unsalted soil. Species identification of the collected materials were performed. This plant were separated as leaves, stems and roots and dried at room temperature (5 C) in the shade. The extracts of these materials which were acetone, chloroform, ethyl acetate and ethanol extracts were prepared, respectively. The fatty acides of acetone and chloroform extracts by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by the HPLC-TOF/MS were performed. As a result of GC-MS analyzes were detected 9 fatty acid, palmitic acid, linolenic acid and linoeic acid as the main component. The 6 different phenolic compounds were determined from HPLC-TOF-MS and were obtained vanillic acid, 4-hydroxybenzoic acid and cicoric acid as the main components.. Baytop, T Türkiye de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul.. Davis, P. H., , Flora of Turkey and the East Aegean Islands, vol. -9, Edinburgh: Edinburgh UNIVERSITY Pres. PP 06 THE PHYTOCHEMICAL ANALYSIS, ANTIPROLIFERATIVE AND CYTOTOXIC EFFECTS OF RHYTIDIADELPHUS TRIQUETRUS (HEDW.) WARNST. MOSS EXTRACTS MUHAMMET SAMIL YAGLIOGLU, GOKHAN ABAY, IBRAHIM DEMIRTAS, AYSE SAHIN YAGLIOGLU DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY Bryophyt species have been used as medicinal plant from the more than 400 years (,). Bryophyt species have some biological activity such as, the antidote, antipyretic, diuretic, hair extenders, burns, jaundice, hemostasis, epilepsy, lowering blood pressure, soothing, antimicrobial, antifungal (3). In this study, Rhytidiadelphus triquetrus moss material was collected in forest area from Çankırı. Species identification of the collected material was performed. This moss dried at room temperature in the shade. The extracts of the materials which were hexane, chloroform, ethyl acetate, methanol, water, water / ethyl acetate and water / n-butanol, were prepared respectively. The fatty acids of hexane extracts by GC-MS and other phenolic compounds in extracts by the HPLC-TOF-MS were performed. As a result of GC-MS analyzes were detected 8 compounds and arachidic acid (% 5.39), linolenic acid (% 0.70), arachidonic acid (% 7.60), 4,7,7-trimethylbicyclo[3.3.0]octan--one (% 4,67) and palmitic acid (% 3,5) as the main components. As a result of HPLC-TOF-MS analyzes were determined, salicilic acid from the choloroform extract; 4-hydroxybenzoic acid from the ethyl acetate and methanol extractc; gallic acid from water extract; quercetin and gentisic acid from the water-ethyl acetate; gentisic acid and 4-hydroxybenzoic acid from the water-n-buthanol extract as the main components. The obtained antiproliferative activity of all extracts were determined by BrdU ELISA method against HeLa and C6 cells. The hexane, chloroform, ethyl acetate extracts have high antiproliferative activity. Thus, the extracts were detected cytotoxic activities and was found to be less toxic than 5-fluorouracil used as a standard.. Asakawa, Y. 990a. in eds.: R.N. Chopra and S.C. Bhatla, Biologically Active Substance from Bryophytes, Bryophyte Development: Physiology and Biochemistry, Boston: CRC Press.. Asakawa, Y., Ludwiczuk, A., Nagashima, F. 03. Phytochemical and biological studies of bryophytes. Phytochemistry, 9; Ding, H., 98. Zhong guo Yao Yun Bao zi Zhi Wu. Kexue Jishu Chuban She. Shanghai, 409 p. -68-

170 PP 07 THE PHYTOCHEMICAL ANALYSIS, ANTIPROLIFERATIVE AND CYTOTOXIC EFFECTS OF TORTELLA TORTUOSA (HEDW.) LIMPR. MOSS EXTRACTS MUHAMMET SAMIL YAGLIOGLU, GOKHAN ABAY, IBRAHIM DEMIRTAS, AYSE SAHIN YAGLIOGLU DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY Some bryophyt species have biological activities such as anticancer (), antimicrobial and antifungal (), insecticidal activity (3). In this study, the moss Tortella tortuosa (Hedw.) Limpr. was collected in forest area from Çankırı. Species identification of the collected material was performed. This moss dried at room temperature in the shade. The extracts of the material, hexane, chloroform, ethyl acetate, methanol, water, water / ethyl acetate and water -n-butanol were prepared respectively. The fatty acids of hexane extracts by GC-MS and other phenolic compounds in extracts by the HPLC-TOF-MS were performed. As a result of GC-MS analyzes 5 compounds and Linolenic acid, methyl ester (% 5,97), Linoleic acid (% 8,53) and Palmitic acid (% 5,5) were detected as the main components. As a result of HPLC-TOF-MS analyzes, caffeic acid from the chloroform extract; 4-hydroxybenzoic acid from the ethyl acetate extract; gentisic acid and 4-hydroxybenzoic acid from methanol and water-ethyl acetate extracts; gallic acid from water extract; gentisic acid from the water-n-buthanol extract were determined as the main components. The antiproliferative activity of all extracts was determined by the BrdU ELISA method against HeLa and C6 cells. The hexane, chloroform, ethyl acetate and water-ethyl acetate extracts were shown to have high antiproliferative activity. Thus, the extracts (exceptional water-ethyl acetate extract) were found to be less toxic than 5-fluorouracil used as a standard.. Oztopcu Vatan, P., Kabadere, S., Uyar, R., Savaroglu, F., Kus, G. 0. Time dependent cytotoxic role of Homalothecium sericeum extracts on glioma. Biological Diversity and Conservation, 5(); -4.. Savaroglu, F., Ilhan, S., Filik-Iscen, C. 0. An evaluation of the antimicrobial activity of some Turkish mosses, Journal of Medicinal Plants Research, 5 (4); Abay, G., Karakoç, Ö. C., Tüfekçi, A. R., Koldaş, S., Demirtaş, İ. 0. Insecticidal activity of Hypnum cupressiforme (Bryophyta) aganist Sitophilus granarius (Coleoptera: Curculionidae), Journal of Stored Products Research, 5; 6-0. PP 08 MITRAL RING ANNULOPLASTY IN A PATIENT WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA SUCCESSFULLY MANAGED WITH CORTICOSTEROIDS MURAT BULENT RABUS, SULE APIKOGLU-RABUS, MURAT SONGUR, ONUR YERLIKHAN, RAHMI ZEYBEK KARTAL KOSUYOLU TRAINING AND RESEARCH HOSPITAL; CARDIOVASCULAR SURGERY DEPARTMENT MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT A 38 years old woman admitted to our hospital with the complaints of increasing dyspnea, ortopnea and pretibial edema. She had been diagnosed with rheumatoid mitral regurgitation for 0 years and with idiopathic thrombocytopenic purpura for 8 years. On admittance, her platelet count was 39000/mm3. Intravenous metilprednisolon treatment was started three days before the operation. The platelet count reached 8000/mm3 on the day of operation. She underwent a successful surgery. The postoperative course was uneventful. The patient received postoperative thrombocyte suspension and intravenous methylprednisolon on the postoperative first and second days. Oral prednisolon was administered as the maintenance therapy. Platelet counts were stable throughout the preoperative, operative and early-postoperative periods. Mitral ring annuloplasty was safely performed with no postoperative complications in a patient with idiopathic thrombocytopenic purpura, by administration of preoperative and postoperative intravenous methylprednisolone and platelet transfusion at early-postoperative period. -69-

171 PP 09 PROTECTIVE EFFECT OF CHARD EXTRACT ON GLYCOPROTEIN COMPONENTS AND HYDROXYPROLINE LEVELS IN DIABETIC LUNG TISSUE OZLEM SACAN, ONUR ERTIK, YESIM IPCI, LEVENT KABASAKAL, GOKSEL SENER, REFIYE YANARDAG ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY-3430 AVCILAR/ISTANBUL/TURKEY MARMARA UNIVERSITY, SCHOOL OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, HAYDARPASA, ISTANBUL/ TURKEY Chard (Beta vulgaris L. var cicla) is a popular vegetable, known for a long time for its beneficial health effects. Various reports have demonstrated that chard has antioxidant, antiacetylcholinesterase, antidiabetic and hepatoprotective effects. Moreover, chard exhibits mineralizing, antiseptic and choleretic activities as well as it contributes to the reinforcement of the gastric mucosa. In the present study, the protective effect of chard on glycoprotein and hydroxyproline levels in the lung tissue of streptozotocin (STZ) induced diabetic rats was examined. Male, Sprague Dawley rats were used in the study. Rats were randomly divided into three groups.group I; Control animals given citrate buffer,group II; Diabetic animals treated with STZ, Group III; STZ-diabetic animals given chard extract. The chard extract was administrated by gavage technique to rats at a dose of g/kg/day for 45 days, 5 days after animals were made diabetic. Hyperglycemia was induced by as a single dose STZ (60 mg/kg), intraperitoneally. On day 60, lungs were removed from rats and used for the analysis of glycoprotein and hydroxyproline levels. Glycoprotein components such as hexose, hexosamine, fucose and sialic acid, and hydroxyproline levels significantly increased in lung tissues of diabetic rats. Administration of chard significantly decreased glycoprotein components and hydroxyproline levels in the diabetic group, indicating that chard possess a significant beneficial effect on glycoprotein components and hydroxyproline levels. These results suggested that chard might have a significant role in alleviating lung damage in STZ diabetic rats. PP 0 INHIBITION OF NEURAMINIDASE BY SOME CHEMICAL COMPOUNDS AND SOME PLANT EXTRACTS ONUR ERTIK, REFIYE YANARDAG ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY, 3430-AVCILAR, ISTANBUL/TURKEY Neuraminidase (Sialidase, EC:3...8, NA) belongs to a class of glycosyl hydrolases that release terminal N-acetyl neuraminic acid residues from glycoproteins, glycolipids and polysaccharides. It is known to play an important role in pathogenesis, bacterial nutrition and cellular interaction. Neuraminidase is especially believed to play at least two critical roles in influenza viral life cycle; the facilitation of virion progeny release; and general mobility of the virus in the respiratory tract.in order to develop new agents to treat viral disease, significant attention has been devoted to compounds that inhibit viral adsorption to epithelial cells, viral intrusion into cells, transcription and replication of viral genomes, viral protein expression and progeny virus release from cells. In this study, neuraminidase inhibitory activities of some chemical compounds and some plant extracts were investigated. Neuraminidase activity was determined using the method of Myers et al. with some modification. All plant extracts and chemical compounds have good antineuraminidase activities. The enzyme inhibitory activity was found to increase dose dependently. We can conclude that the examined plant extract and chemical drugs can be used in pharmaceutical industry due to their excellent antineuraminidase activities. PP EFFECTS OF COMBINATION TREATMENT WITH AMIODARONE AND WHITE CABBAGE EXTRACT ON RAT GINGIVA AND SALIVARY GLAND BURCIN ALEV, ISMET BURCU TURKYILMAZ, SARP KAYA 3, SERAP AKYUZ 3, REFIYE YANARDAG, AYSEN YARAT MARMARA UNIVERSITY, FACULTY OF DENSITY, DEPARTMENT OF BASIC MEDICAL SCIENCES, ISTANBUL,TURKEY ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMİSTRY, ISTANBUL,TURKEY 3 MARMARA UNIVERSITY, FACULTY OF DENSITY, DEPARTMENT OF CLINICAL SCIENCES, ISTANBUL,TURKEY Cabbage (Brassica oleracea L. var. capitata) is one of the most important vegetables grown worldwide. It provides significant amounts of vitamins (A, C, E, K) and other photochemicals, such as glucosinates and other sulfur containing compounds which are beneficial for human health. Numerous studies report protective effects of cabbage against many chronic diseases, several cancer types, cardiovascular, cerebrovascular, ocular and many neurological diseases and peptic ulcers. It may protect from the side effects of amiodarone which is used for the treatment of arrhythmias. In the literature there is no study which focuses on the effects of these substances on oral tissues. Female Sprague-Dawley rats were randomly divided into four groups as follows; control group receiving corn oil; cabbage extract (500 mg/kg/day) given group; amiodarone (00 mg/kg/day) given group; amiodarone + cabbage extract (in same dose) given group. Cabbage extract and amiodarone were given by gavage to rats for 7 days. Amiodarone was given to the animals one hour after cabbage extract administration during the experimental period. All animals were fasted overnight and on the 8th day they were sacrificed under anesthesia. Gingiva and salivary gland samples were taken from animals and homogenized in saline. Oxidant-antioxidant biochemical parameters were determined in homogenized samples. Results were evaluated statistically and discussed. -70-

172 PP EFFECTS OF EXERCISE AND CALORIC RESTRICTION ON METABOLIC SYNDROME INDUCED INTESTINAL OXIDATIVE INJURY IN RATS HAZAL IPEKCİ, REYHAN OZCELIK, BURCIN ALEV, UNSAL VELI USTUNDAG, OZAN OZCAN, TUGBA TUNALI-AKBAY, EBRU EMEKLI-ALTURFAN, GOKSEL SENER, AYSEN YARAT MARMARA UNIVERSITY FACULTY OF DENTISTRY, DEPARTMENT OF BASIC MEDICAL SCIENCES, ISTANBUL TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY In the pathogenesis of the metabolic syndrome, an increase of oxidative stress may play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of this study was to assess the effects of exercises and caloric restriction on some small intestine oxidative stress parameters in rat with metabolic syndrome. Fifty-six male Sprague-Dawley rats, weighing g, were divided into five groups: control, metabolic syndrome, metabolic syndrome with exercise, metabolic syndrome with caloric restriction and metabolic syndrome with exercise and caloric restriction. To induce metabolic syndrome 0 % fructose solution was given to rats in their drinking water for 3 months. Exercise and caloric restriction were applied to the related groups for 3 weeks after the induction of metabolic syndrome. At the end of the experiment all animals were fasted overnight. They were sacrificed under anesthesia. Small intestine samples were taken from animals and homogenized in saline. Oxidant-antioxidant biochemical parameters were determined in homogenized intestine samples. Results were evaluated statistically and discussed. PP 3 EFFECTS OF EXERCISE AND CALORIC RESTRICTION ON AGING INDUCED INTESTINAL OXIDATIVE INJURY IN RATS UNSAL VELI USTUNDAG, CAGLAR MACIT, BURCIN ALEV, HAZAL IPEKCI, HAZAL HAZINECI, EBRU EMEKLI-ALTURFAN, TUGBA TUNALI-AKBAY, GOKSEL SENER 3, AYSEN YARAT MARMARA UNIVERSITY FACULTY OF DENTISTRY, DEPARTMENT OF BASIC MEDICAL SCIENCES, ISTANBUL, TURKEY YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY 3 MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY Aging is related with increased intestinal inflammation and elevated risk of chronic diseases such as inflammatory bowel diseases and colon cancer. Accordingly reduced risk of these diseases has been shown in many epidemiologic studies by regular exercise. Physical activity including regular and repetitive exercise has been shown to decrease the incidence of age-related diseases. In this study, male 5 months old Sprague-Dawley rats, weighing g, were divided into four groups: aging, aging with caloric restriction, aging with exercise, aging with exercise and caloric restriction. Young animals (3 months old) were used as control group. Exercise and caloric restriction were applied to the related groups for 6 weeks.at the end of the experiment all animals which were fasted overnight,were sacrificed under anesthesia. Small intestine samples were taken from animals and homogenized in saline. Oxidant-antioxidant biochemical parameters were determined in homogenized intestine samples. Results were evaluated statistically and discussed. PP 4 SYNTHESIS AND CHARACTERIZATION OF NEW 4-SUBSTITUTED-N -(PIPERIDIN-4-YLIDENE) BENZENESULFONOHYDRAZIDES NURCAN KARAMAN, EMINE ELCIN EMRE, AYSEGUL IYIDOGAN FACULTY OF PHARMACY GAZIANTEP UNIVERSITY, ANKARA, TURKET Sulfonylhydrazone type of compounds have been reported that they have good level of antimicrobial, anticancer and antidepressant activity (,). On the basis of this knowledge, in this study a series of sulfonylhydrazones of piperidin-4-one derivatives were synthesized. In order to obtain these compounds, sulfonyl hydrazides were reacted with ethyl 4-oxopiperidine -carboxylate and,6-diphenylpiperidin- 4-one to afford sulfonylhydrazones. Physical and chemical properties of synthesized compounds have been characterized by utilizing their melting point, elemental analysis, IR, H-NMR and mass spectra results. Acknowledgement: This study was supported by the Research Foundation of Gaziantep UNIVERSITY (Project no: FEF..03 ). Navakoski K., Costa P., Santin J.R., Mazzambani L., Bürger C., Mora C., Nunes R.J., Souza M.M. Synthesis and antidepressantlike activity evaluation of sulphonamides and sulphonyl-hydrazones. Bioorganic & Medicinal Chemistry. 0; 9; Zhang L., Yang F., Shi W., Zhang P., Li Y., Yin S. Synthesis and antigastric ulcer activity of novel 5-isoproyl-3,8-dimethylazulene derivatives. Bioorganic & Medicinal Chemistry Letters. 0;,

173 PP 5 DRUG-INDUCED LIVER INJURY GIZEM KAYA, SIBEL OZDEN ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY Drug induced liver injury Gizem Kaya, Sibel Ozden Istanbul UNIVERSITY, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Beyazit, 346, Istanbul-TURKEY. Drug-induced liver injury (DILI) is increasingly being recognised as a significant cause of both acute and chronic liver disease. The most commonly implicated agents are paracetamol, antimicrobials, non-steroidal antiinflammatory drugs, statins and isoniazid. It is seen herbal and dietary supplements cause to DILI. Drug induced-liver injury is generally divided into intrinsic and idiosyncratic reactions. The idiosyncratic nature and poor diagnosis of DILI make this type of reaction as major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The formation of reactive metabolites during drug metabolism can lead to oxidative stress and mitochondrial damage. The mitochondrial alterations are able to induce mild to fulminant hepatic cytolysis and steatosis. Numerous investigations have also suggested a role for the host immune response. DILI depends on environmental, chemical, pharmacological and genetic factors. This review manifests the potential role of reactive metabolites, mitochondrial toxicity, host immune-response pathways and biliary transporters in the pathogenesis of DILI and also indicates risk factors for DILI. PP 6 DETERMINATION OF ANTIOXIDANT ACTIVITY OF ASPLENIUM CETERACH SUBSP. ASPLENIUM CENGIZ SARIKURKCU, SILA GULBAG, BASAK GOKCE FACULTY OF PHARMACY,SULEYMAN DEMIREL UNIVERSITY, ISPARTA, TURKEY In this study, the antioxidant activity of ethanol and water extracts from Asplenium ceterach subsp. asplenium was studied. The antioxidant properties of both extracts from A. ceterach subsp. asplenium were evaluated by using different antioxidant tests; ferric reducing power, free radical scavenging effect on,-diphenyl--picrylhydrazyl (DPPH) and metal chelating activity on ferrous ions ().Total flavonoid content in the both extracts was also determined as quercetin (QEs) equivalents (). In the radical scavenging effect and reducing power assays, it was observed that both extracts from A. ceterach subsp. asplenium increased with increasing concentration of the extracts and that the water extracts showed stronger DPPH scavenging activity and reducing power rather than those of the ethanol extracts. It was found that the total flavonoid content in the ethanol and water extracts were 5.3 and.34 QEs/g extract, respectively. On the basis of the results of this study, it is clear that both extracts have powerful antioxidant activity against various antioxidant systems in vitro, moreover, this plant can be used as easily accessible source of natural antioxidants and as a possible food supplement or in pharmaceutical applications.. Zengin G, Sarikurkcu C, Aktumsek A, Ceylan R, Ceylan O. A comprehensive study on phytochemical characterization of Haplophyllum myrtifolium Boiss. endemic to Turkey and its inhibitory potential against key enzymes involved in Alzheimer, skin diseases and type II diabetes. Ind. Crop Prod. 04; 53:

174 PP 7 THE STUDY ON THE FREQUENCY OF XENOBIOTIC-METABOLIZING ENZYME GENE POLYMORPHISMS CYPC9 IN A TURKISH POPULATION SERRA VILDAN AKGUL, TUGCE YESIL, OSMAN EKINCI 3, BERNA TERZIOGLU, GULDEN Z. OMURTAG, SEMRA ŞARDAŞ,I.OMER BARLAS 4 DEPARTMENTS OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, DR. SIYAMI ERSEK GOGUS KALP VE DAMAR CERRAHISI EGITIM VE ARASTIRMA HASTANESI 3 DEPARTMENTS OF ANAESTHESIOLOGY AND REANIMATION, HAYDARPASA NUMUNE TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY 4 MEDICINAL AND GENETICS, FACULTY OF MEDICINE, MERSIN UNIVERSITY, MERSIN, TURKEY The inter-patient differences in drug response are documented to be attributable to heritable genetic variations in the nucleotide sequence of drug-metabolizing enzymes. The identification of variant allele frequencies in specific ethnic groups is important to individualize drug dosing and improve the therapeutics which refers to the term called pharmacogenomics. Pharmacogenomics as a science aims at individualizing the treatment- based on the genetic makeup, to mitigate the chances of adverse drug events and/ or to maximize the efficacy in sub-population. With clarification of exposure-response relationship, it makes it possible to make dosing recommendations in special populations leading to approval doses/dosing regimen that were not studied in registration trials. This study aims to detect single nucleotide polymorphism (SNP) in CYPC9 in Turkish population. CYPC9 metabolizes approximately 0% of clinically used drugs, including the narrow therapeutic window drugs such as warfarin, phenytoin, etc. Extensively studied alleles are CYPC9 and CYPC93. However, in addition to these two alleles, other genetic factors and an individual biological characteristics contribute to the overall drug phenotype. A major bottleneck for CYPC9 pharmacogenomics in clinical field applications is the lack of knowledge regarding the numerous genetic polymorphisms and their molecular functionalities. In this study, subjects were studied for CYPC9 SNP using PCR-RFLP followed by agarose gel electrophoresis. 6 of these subjects were detected as heterozygous type while no homozygous polymorphisms have been detected yet. In order to report the frequency of CYPC9 polymorphism in the Turkish population, the study will be continuing by increasing number of subjects. PP 8 SAFETY CONCERNS OF BIOSIMILARS IN TURKEY SERRA VILDAN AKGUL, SEVCAN GUL AKGUN, GULDEN Z. OMURTAG, SEMRA ŞARDAŞ DEPARTMENTS OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Biotechnological drugs also called biopharmaceuticals can be defined as drugs can be produced either in living organism or by biological processes. Biosimilar medicinal products needed to be regulated by guideline. In Turkey the guideline for these kinds of products have been prepared and released in August 008. It was aimed to define number and status of biosimilar products in this study. There are 67 authorised biotechnological drugs are available in Turkey. Derivative blood products have higher ratio in therapeutic index classes of biosimilars, approximately as 7%. Antineoplastics and immunomodulating agents follow them with 5% share. Clinical safety of biosimilar medicinal products must be monitored closely on an ongoing basis during the post approval phase including continuing risk-benefit assessment. The biosimilar applicant must provide the Ministry of Health Drug and Medical Device Agency of Turkey with a risk management and pharmacovigilance programme with its application. The most critical safety concern about biopharmaceuticals (also biosimilars) is immunogenicity. In this poster, the pharmacovigilance risk minimization activities required by the Ministry of Health Drug and Medical Devices of Turkey will be introduced and discussed with the reqıirements of the health authorities.. Leyre Zuniga, Begona Calvo. Biosimilars: pharmacovigilance and risk management. Pharmacoepidemiology and Drug Safety. 00;b9: Kresse G. Biosimilars. Science, status, and strategic perspective. Eur J Pharm Biopharm. 009; 7:

175 PP 9 COMPARATIVE IN-VITRO EFFICACIES OF VARIOUS ANTIPSEUDOMONAL ANTIBIOTICS BASED CATHETER LOCK SOLUTIONS ON ERADICATION OF PSEUDOMONAS AERUGINOSA BIOFILMS BERNA OZBEK CELIK, EMEL MATARACI KARA ISTANBUL UNIVERSITY FACULTY OF PHARMACY DEPT. OF PHARMACEUTICAL MICROBIOLOGY Antibiotic lock technique (ALT) may be an adjunct therapy in treating catheter-related infections. The aim of this study was to determine the in-vitro stability and efficacy of colistin, meropenem and levofloxacin alone or in combination with clarithromycin or heparin lock solutions against biofilm embedded Pseudomonas aeruginosa strains. The efficacy of antibiotic lock solutions was tested in an in- vitro catheter biofilm model against P. aeruginosa isolated from catheter-related bacteremia. We observed that the use of meropenem, levofloxacin or colistin as a lock solution had potent bactericidal effects and could be prevented bacterial regrowth at 96 or 7h, respectively. When the tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and rapid in eliminating P. aeruginosa colonization in biofilm than each of the antibiotics were used alone. Moreover, tested antibiotics in combination with heparin were not significantly different for killing effect against PA- and PA-7853 compared with that of each antibiotics alone. Tested catheter lock solutions may have promising adjuvants for treating infections caused by P. aeruginosa. PP 0 INHIBITION OF ALDOSE REDUCTASE AND MONOAMINE OXIDASE BY SOME PLANT EXTRACTS BEYHAN KARA KISLA, REFIYE YANARDAG ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY, ISTANBUL/ TURKEY Aldose reductase (ALR) belongs to aldo-keto reductases super family. It is the first and the rate limiting enzyme in the polyol pathway where it reduces glucose to sorbitol utilizing NADPH as a cofactor. Accumulation of sorbitol leads to osmotic swelling, changes in membrane permeability and also oxidative stress, culminating tissue injury. Experimental animal models suggest that the inhibition of ALR could be effective in prevention of certain diabetic complications. Monoamine oxidases (MAO) are mitochondrial bound enzymes which metabolize neurotransmitter and dietary amines in the brain and peripheral tissues.the monoamine oxidase inhibitors are used primarily to treat neuropsychiatric syndromes. In this study ALR and MAO inhibitory activities of some plant extracts were investigated. All plant extracts have good ALR and MAO inhibitory activities. Enzyme inhibitory activities were found to increase dose dependently. It may be concluded that examined plant extracts are promising leads for the therapy of diabetes mellitus and neurological disease. PP LITHIUM INCORPORATION INTO PLGA FILMS BY THE EMULSION TECHNIQUE BEYZA BETUL KOCAK, ANNA BERGSTRAND, ANETTE LARSSON DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY CHEMICAL AND BIOLOGICAL ENGINEERING, PHARMACEUTICAL TECHNOLOGY, CHALMERS UNIVERSITY OF TECHNOLOGY, GOTHENBURG, SWEDEN Drug-loaded biodegradable film coating for implantable medical devices may provide a better treatment by combination of several functions within the same device which offers both a mechanical support and drug targetting at the same time (). Poly (lactide-co-glycolide) (PLGA) is one of the most popular biodegradable polymers which is important for pharmaceutical applications (). The aim of this project was to develop adequately stable emulsion formulations and produce PLGA films with incorporated lithium salt for coating orthopedic implants that could provide controlled drug release in the human body. The films were produced by a solvent casting method and the w/o emulsion technique was employed for drug incorporation. A Layer by layer coating was applied on metallic screws by a spray coating method. The external and internal morphology of the produced films was analyzed by a scanning electron microscope (SEM) and the release properties of Li+ were monitored by an atomic absorption spectroscopy with flame emission. The emulsion stability was affected by the homogenization conditions and by the amount of PLGA used in the formulations. Increasing homogenization rate led to more stable emulsions. Likewise an increase in the polymer content resulted in more stable emulsions with more viscous external phase. The desired PLGA films were only produced when the emulsions were dried under the conditions without any lid. Li+ release from PLGA films showed clear variation depending on the molecular weight (Mw) of the PLGA that was used. The films made of PLGA with low Mw exhibited a controlled release profile which was relatively slow and linear. However a more burst-like release profile was yielded by the ones made of PLGA with high Mw.. Schmidmaier G, Wildemann B, Stemberger A, Haas NP, Raschke M. Biodegradable poly(d,l-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res. 00;58(4): Lakshmi SN, Cato T Laurencin. Biodegradable polymers as biomaterials. Prog Polym Sci. 007;3:

176 PP ANTIOXIDANT CAPACITY OF METHANOL EXTRACT FROM ORIGANUM HYPERICIFOLIUM AERIAL PARTS AYGUL KOSEOGLU, TURGUT TASKIN, NARIN SADIKOGLU, LEYLA BITIS DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, İNÖNÜ UNIVERSITY, MALATYA, TURKEY The genus Origanum (Lamiaceae) is represented throughout the world by 50 species and in Turkey by species or 3 taxa, being endemic to Turkey []. Origanum species have traditionally been used as a spicy additive for food instead of thyme. This genus is rich in essential oils. The species of Origanum genus are known in Anatolia as Yalancı kekik, Kekik, Istanbul kekiği and Keklik otu. Origanum species are used as sedative, diuretic, sweater and antiseptic and also in the treatment of gastrointestinal diseases and constipation []. Origanum hypericifolium O. Schwartz & P.H. Davis is an endemic species with limited distribution and is included in the lower risk and conservation-dependent category in the red data book of Turkey [3]. The aim of this study is to reveal antioxidant capacity of extract, which is prepared by maceration in methanol from Origanum hypericifolium aerial parts. The antioxidant capacity of methanol extract were assayed with various methods, DPPH free radical scavenging activity, metal chelating capacity and ABTS radical cation scavenging, including total phenolic compound contents by Folin Ciocalteu reagent (FCR). The obtained results were compared with standard antioxidants such as Ascorbic acid, BHT and EDTA. The methanol extract of Origanum hypericifolium aerial parts exhibited stronger DPPH free radical-scavenging (IC50: 0.47±0.03) and ABTS radical cation scavenging activity (0.56±0.07) than BHT (0.3±0.03;.03±0.5, respectively). It was concluded that aerial parts of Origanum hypericifolium are beneficial to consume as spice. References []. Askun, T., Tumen, G., Satil, F., Ates, M., Food Chemistry, 009, 6 (009), []. Kordali, S., Cakir, A., Ozer, H., Cakmakci, R., Kesdek, M., Mete, E., Bioresource Technology, 008, 99 (008), [3]. Celik, A., Herken, EN,, Arslan, İ,Donmez, Özel, MZ, Mercan N, Natural Product Research, 004, 4(6), PP 3 SAFETY EVALUATION OF ORAL CONTRACEPTIVES AHMET KOC, HANDE SIPAHI, BANU UNAL, AHMET AYDIN YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF TOXICOLOGY, ISTANBUL, TURKEY BAYER TURK KIMYA SAN. LTD. STI., ISTANBUL, TURKEY In recent years, unintended pregnancy rate primarily result from the lack of, incongruous or incorrect use of effective contraceptives methods has been significantly increased. In order to reduce the risk of unintended pregnancy, appropriate contraceptive method should be selected. Oral contraceptive pills are the most selected contraception method among women. During the past years a huge amount of research has been undertaken to assess both risk of oral contraceptives and the medical benefits. Use of oral contraceptives has long been known to be associated with a highly increased risk of venous thromboembolism (VTE) that one of the more important side effect. Certain studies have shown that compared with no oral contraceptive using, use of second generation oral contraceptives has been associated with the lower increase in VTE risk(). Nevertheless, massive evidence documenting various non-contraceptive health benefits of oral contraceptives has been accumulating for many years. Many studies have been indicated that oral contraceptives are showing the reduced risk/effective treatment maintained with low estrogens-dose formulations such as endometrial cancer, ovarian cancer and dysmenorrhea(). Furthermore, there are a growing body of evidence supporting reduced risk/effective treatment such as endometriosis and benign ovarian tumors(3). Bioavailability of oral contraceptives is another important subject that interaction should be considered because of at risk of contraceptive failure or other adverse effects. Selection of rational oral contraceptives should be evaluated based upon women s medical background (such as age, overweight, smoking and family history). Advantages and disadvantages also should be taken into consideration before selection of contraceptive methods. References:. Manzoli L, De Vito C, Marzuillo C, Boccia A, Villari P. Oral contraceptives and venous thromboembolism: a systematic review and meta-analysis. Drug Saf [Internet]. 0 Mar ;35(3):9 05. Available from: pubmed/ Kaunitz AM. Noncontraceptive health benefits of oral contraceptives. Rev Endocr Metab Disord [Internet]. 00 Sep;3 (3): Available from: 3. Sherif K. Benefits and risks of oral contraceptives. Am J Obstet Gynecol [Internet]. 999 Jun;80(6 Pt ):S Available from:http://www.ncbi.nlm.nih.gov/pubmed/

177 PP 4 CURRENT APPROACHES IN CALCULATION OF ROYALTY RATES FOR PHARMACEUTICAL INDUSTRY SALIH GUMRU DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Royalty payments can be defined as a profit sharing mechanism, in which technology licensor becomes shares from profit generated by licensee s efforts in commercializing the patented technology. In many deals, royalty rates are seen as a percentage of sales or a payment per unit. However, the profitability of the products or services that incorporate the patented technology plays a dominant role in royalty determination. Much upward pressure on royalty rates has been felt over the last two decades in pharmaceutical industry, since it is becoming harder to discover effective and marketable new drugs and biotechnologies. Several million dollars are discarded, in addition to endless pressure and length of more than 0 years for development of a single product. These characteristics of pharmaceutical and biotechnological products have created a need for the effective royalty rates concept to analyze and explain various deal scenarios. New approaches, such as Analytical Approach, Comparable License Transactions Analysis and Investment Rate of Return Analysis have succeeded old royalty assumptions, such as 5% of Sales Method and Profit Split Rule of Thumb. In this study, by reviewing many theoretical approaches and latest royalty calculation strategies of different companies for their brand new products, it is aimed to provide those working on it some tools for creating a clear path through royalty rate jungle. PP 5 A LITERATURE REVIEW: COMPARATIVE ANALYSIS OF KNOWLEDGE, ATTITUDE AND PRACTICES OF HEALTH PROFESSIONALS TOWARDS PHARMACOVIGILANCE IN DIFFERENT COUNTRIES OGUZHAN AYDEMIR, SALIH GUMRU DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Although pharmacovigilance has gained attention in the last two decades, there are differences in perception about practices in different countries. Developed countries have already solved problems about this vital health problem and created their well-grounded pharmacovigilance systems. On the other hand, despite an increase in access to MEDICINEs, fully functional pharmacovigilance and regulatory systems are not yet in place in low- and middle-income countries. In this study, we performed a systematic and detailed literature review to be able to compare pharmacovigilance perception of healthcare professionals in different countries. A better understanding of the existing regulatory and pharmacovigilance systems not only in developed countries, but also in developing and undeveloped countries can help guide every national government and international donors towards effective and viable pharmacovigilance systems. As a result of this awareness, US Agency for International Development (USAID) and the US Food and Drug Administration (FDA) funded the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program through an interagency agreement to assess pharmacovigilance systems in five Asian countries: Bangladesh, Cambodia, Nepal, the Philippines, and Thailand. These efforts are only for assisting countries to protect the public from poor quality and unsafe medicines. For this purpose, we have focused on many different countries from every corner of the globe, including Iran, Malaysia, Nepal, Nigeria, Norway, Kingdom of Saudi Arabia, Turkey and United States of America. As a result of elaborative studies on the subject, pioneering districts on Earth may be defined to enhance pharmacovigilance systems in developing and non-developed countries. PP 6 EFFECTS OF DIRECT-TO-COMSUMER ADVERTISEMENT IN DRUG INDUSTRY: DEVELOPED COUNTRIES COMPARED WITH TURKEY SALIH GUMRU, OGUZHAN AYDEMIR DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY Direct-to-consumer pharmaceutical advertising (DTCPA) can be defined as an effort, especially by using popular media, made by a pharmaceutical company to promote its prescription products directly to patients. USA and New Zealand are only two countries allowing DTCPA that includes product claims. However, other countries don t allow DTCPA at all. Canada appears to be the third country, allowing ads that mention either the product or the indication, but not both. Efforts of pharmaceutical industry and lobby groups have been useless to overturn bans against DTCPA in Canada and regions, such as in the European Union (EU). Despite all of these efforts, in 008, of the 7 EU member states voted against possible legislation that would have allowed even limited information to patients to be provided. While developed countries approach DTCPA applications with hesitation, the use of a similar strategy for non-prescribed drugs has come into use in developing countries. It is accepted that DTCA would affect health services and economy negatively in these countries. In this study, we discuss the current situation of this marketing strategy that prevents underuse of pharmaceuticals in developed countries, but also leads to potential overuse. The fine tune is always tried to be caught. We also criticize the applicability of this marketing strategy in Turkey, considered as a developing country, compared with the situation in developed countries. -76-

178 PP 7 COMPASSIONATE USE OF MEDICINAL PRODUCTS IN DIFFERENT EUROPEAN COUNTRIES: CURRENT STATUS AND PERSPECTIVES SALIH GUMRU, ZEHRA CETIN, MUGE SIRVANCI YALABIK DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY DEPARTMENT OF MEDICAL PHARMACOLOGY, FACULTY OF MEDICINE, MARMARA UNIVERSITY, ISTANBUL, TURKEY Compassionate use refers to the use of an investigational drug outside of a clinical trial by patients with unmet medical needs who do not meet the inclusion criteria for ongoing clinical progress. If a company decides to distribute its drug via compassionate use program in Europe, it has to be in compliance with a patchwork of national regulations. The Regulation of European Commission draws a frame for using these types of drugs. However, national authorities might take differential views on compassionate use programs, especially when there is an unmet medical condition. Currently, compassionate use programs in three major European markets (France, Germany and Spain) are subject to tight supervisory control, while regulations are upcoming in two additional major markets (Italy and United Kingdom). Compassionate use programs in accordance with respective national European rules not only provide companies the chance to meet ethical obligations towards patients they suffer from an unmet medical need, but also offer the possibility of gaining access to patients before becoming marketing authorization. In addition, companies have the opportunity to obtain clinical experience with drugs outside the controlled environment of ongoing clinical trials. In this study, we discuss different compassionate use regulations in different European countries. In Turkey, there is also a similar procedure, which will be explained in detail. PP 8 ALZHEIMER AND CHEMICALS GULSAH ARAMAN, SIBEL OZDEN ISTANBUL UNIVERSITY FACULTY OF PHARMACY PHARMACEUTICAL TOXICOLOGY Alzheimer is a progressive neurodegenerative disease. Its patogenesis has two neuropathological markers including senile (amyloid) plaques and neurofibrillary tangles. Based on molecular studies it is known that the main component of senile plaques and neurofibrillary tangles are consecutively; amyloid beta (β) and tau protein. These components form various agregates, therefore lead to a neurodegeneration. These neurodegenerations are affected by some protective/risk factors which are genetic factors, chemicals (heavy metals, pesticides, organochlorinated substances, medication) nutrition, age, psychosocial situation, vascular pathways, smoking, alcohol consumption and others (such as inflammation, oxydative stress and free radical formation etc). One particular factor is much more detailed in this review; chemical substances. The aim of this review have provide a comprehensive overview on the medical importance of the positive (the ones who could prevent or stop the neurodegeneration such as caffeine or ginkgo biloba extract) and the negative (the one who could accelerate the neurodegeneration such as local anesthetics, isoflurane) relationships between some chemical substances and Alzheimer. It is important to see how chemicals affect human on a daily basis and how people can avoid Alzheimer by taking or not these chemicals. -77-

179 PP 9 ANTIMICROBIAL ACTIVITIES OF SOME NOVEL SYNTHESIZED IMINOTHIAZOLIDINON DERIVATIVES F. TULAY TUGCU, BERNA OZBEK CELIK, YIGIT SABRI UNLU, GÜL CEVAHIR OZ FACULTY OF PHARMACY YILDIZ TECHNICAL UNIVERSITY FACULTY OF PHARMACY ISTANBUL UNIVERSITY Iminothiazolidinones and derivatives have an important place in the area of heterocyclic compounds because of their presence in the structures of macrocyclic complex drugs, their applications in industry and usage in pharmaceutical researches due to their biological properties (). These heterocycles display diverse biological activities such as herbicidal, fungicidal, bactericidal and pesticidal (). In this study, the new synthesis iminotiyazolidinon derivatives (compounds -6) against six species of bacteria and the yeast C. albicans were conducted to assess the antimicrobial activity. Disk diffussion method was used for antimicrobial activity (3). All of the synthesized compounds were tested for antimicrobial activity using Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 8, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 435, Pseudomonas aeruginosa ATCC 539, Proteus mirabilis ATCC 453 and Candida albicans ATCC 03. Among the synthesized compounds -[(6-methylpyridin--yl)imino]-5-[(3-methylthiophen--yl)methylidene]-3-phenyl-,3-thiazolidin-4-one (compound 5) was found the most active derivative at an MIC value of mg/l against C. albicans ATCC 03. The obtained data reported that compounds (-4 and 6) were able to inhibit the growth of the selected micro-organisms in vitro showing MIC values between mg/l. None of the compounds exhibited any activity against Klebsiella pneumoniae while all the compounds showed microbial effect against Staphylococcus aureus ATCC Bonde C.G., Gaikwad N.J. Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents. Bioorg. Med. Chem. 004; :5-6. Singh S.P, Parmar S.S, Raman K, Stenberg V.I. Chemistry and biological activity of thiazolidinones. Chem. Rev. 98; 8: Koca M, Servi S, Kirilmis C, Ahmedzade M, Kazaz C, Özbek B, Ötük G. Synthesis and antimicrobial activity of some novel derivatives of benzofuran: part. Synthesis and antimicrobial activity of benzofuran--yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives. European J. Of Med. Chem. 005; 40: PP 30 EVALUATION OF CYTOTOXIC AND GENOTOXIC EFFECTS OF SOME NOVEL SYNTHESIZED IMINOTHIAZOLIDINON DERIVATIVES ON HELA CELL LINE (CCL) F. TULAY TUGCU, MEHMET RIFKI TOPÇUL, IDIL CETIN, YIGIT SABRI UNLU, YUSUF CAN GERCEK, GUL CEVAHIR OZ FACULTY OF PHARMACY YILDIZ TECHNICAL UNIVERSITY FACULTY OF PHARMACY ISTANBUL UNIVERSITY The thizolidinones are useful scaffold in medicinal chemistry: it can be found as a pharmacophore in a wide variety of biologically active compounds, such as antitumorals, antibacterials, antivirals, anti-convulsant, anti-inflammatory, anti-diabetic, anti-hiv and many other therapeutic agents (,). In this study, we investigated the cytotoxic and gynotoxic effects of some novel synthesized iminothiazolidinone derivates on HeLa (3) cell line (CCL) that originated from human cervical carcinoma. In this direction, cell kinetics parameters of proliferation rate, mitotic index and the labeling index was used., 5, 0 µm doses were applied for 7 hours to determine the optimum dose for all compounds and was interpreted by proliferation rate analysis. The obtained results have shown a 0 µm dose the optimum doses for all compounds. Parameters of mitotic index and labeling were observed by during the 0-7 hours using by optimum dose. The results from all parameters have shown that used compounds causes a significant decrease in the proliferation of HeLa cell cultures.. Edwards P J. Thiazolidinone derivatives targeting drug-resistant lung cancer cells. Drug Discovery Today. 008; 3: Singh S.P, Parmar S.S, Raman K, Stenberg V.I. Chemistry and biological activity of thiazolidinones. Chem. Rev. 98; 8: Özcan Arıcan G, Soy N. N. Effects of epirubicin and daunorubicin on cell proliferation and cell death in HeLa cells. Journal of Cell and Molecular Biology, 005; 4:

180 PP 3 CENTRALLY AND PERIPHERALLY MEDIATED ANTINOCICEPTIVE ACTIVITIES OF SOME,3,5-TRIARYL-4,5-DIHYDRO-H- PYRAZOLE DERIVATIVES HARIKA AYDIN, UMUT IRFAN UÇEL, UMIDE DEMIR OZKAY, OZGUR DEVRIM CAN ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY Some new,3,5-triaryl-4,5-dihydro-h-pyrazole derivatives were synthesized via the treatment of,3-diaryl--propen-- ones with phenylhydrazine hydrochloride derivatives in hot acetic acid. The antinociceptive properties of the compounds were evaluated by hot-plate, tail-clip and acetic acid induced writhing tests in mice. Motor coordination of the animals was evaluated in a Rota-rod model. Morphine sulphate used as a reference drug in all nociceptive tests. Statistical evaluation of the obtained data indicated that compounds c, e, g, h, j, l, and m, when administrated at 00 mg/kg, increased the reaction time of animals both in hot plate and tail clip tests. Additionally, the same compounds reduced the number of acetic acid induced writhing behaviors. Obtained data exhibited antinociceptive effect of these compounds on supraspinal, spinal and peripheral nociceptive pathways. Besides, in the Rota-rod tests, c, e, g, h, j, l, and m did not cause any change in the motor coordination of mice, indicating that the observed antinociceptive effect is specific. These results supported the previous papers reporting the antinociceptive potential of various pyrazoline derivative compounds. PP 3 ANTIDEPRESSANT-LIKE ACTIVITY OF SOME AROYL PROPIONIC ACID-HYDRAZONE DERIVATIVES FEYZA ALYU, HARIKA AYDIN, OZGUR DEVRIM CAN, YUSUF OZTURK, GULHAN TURAN-ZITOUNI ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY The aim of the present study was examining the effect of some 4-[4-[-(-(4-substituted benzylidene)hydrazinyl)--oxoethoxy] phenyl]-4-oxobutanoic acid derivatives on depression, anxiety and spontaneous locomotor activity parameters of mice. In tail suspension tests, when administrated at 50 mg/kg dose, compounds a, b, d, e, f, g and i in the series, caused significant reduction in the immobility time of mice. Additionally, in modified forced swimming tests, the same compounds decreased the immobility and increased the swimming times of mice without any change in climbing durations. Data obtain from these two tests clearly pointed out the antidepressant-like effects of the aforementioned compounds. Exact mechanism of the antidepressant action exhibited in the present study need to be clarified with further detailed investigations. On the other hand, none of the compounds changed the exploratory parameters in hole-board tests or total numbers of spontaneous locomotor activities in activity cage measurements at the applied dose. In other words, neither anxiolytic nor sedative effects induced by the test compounds. PP 33 ANTIHYPERALGESIC AND ANTIALLODYNIC EFFECT OF MIANSERIN ON DIABETIC NEUROPATHIC PAIN IN RATS UMUT IRFAN UCEL, OZGUR DEVRIM CAN, UMIDE DEMIR OZKAY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY In this study, effects of subacute administration of mianserin on diabetic hyperalgesia and allodynia, which developed 4 weeks after streptozotocin injection, were investigated using several experimental pain-induction methods in rats with diabetes. Mianserin administered at 30 and 45 mg/kg doses during 7 and 4 days not only showed opioid-mediated acute anti-nociceptive activity but also effectively improved mechanical and thermal hyperalgesia caused by diabetic neuropathy. In addition to having an anti-hyperalgesic effect, mianserin attenuated diabetes-related mechanical and thermal allodynia. To the best of our knowledge, this is the first study to show that the anti-hyperalgesic and anti-allodynic effects of mianserin, an atypical anti-depressant, in the experimental diabetes model were comparable to those of the reference drug pregabalin (dose, 0 mg/kg). However, the pharmacological mechanisms underlying these anti-hyperalgesic, and anti-allodynic effects of mianserin remain to be elucidated. The results of this study will provide a pre-clinical basis for new approaches of proper drug selection for the treatment of neuropathic pain, which has a high incidence among diabetes patients. Nevertheless, for mianserin to be considered an effective alternative drug for the treatment of diabetic neuropathy, it is necessary to confirm the results of this pre-clinical study in clinical studies. -79-

181 PP 3 34 CENTRALLY ANXIOLYTIC AND ACTIVITIES PERIPHERALLY OF SOME MEDIATED PYRAZOLE ANTINOCICEPTIVE DERIVATIVES ACTIVITIES OF SOME,3,5-TRIARYL-4,5-DIHYDRO-H- NAZLI TURAN, FEYZA ALYU, UMUT IRFAN UÇEL, HARIKA AYDIN, UMIDE DEMIR OZKAY, YUSUF OZTURK ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY ESKISEHIR, TURKEY In this study, the putative effect of some pyrazole derivatives on anxiety parameters of mice was investigated using plus-maze and hole-board methods. In plus-maze tests, the percentage of open arm entries (POAE) and the percentage of time spent on the open arms (PTOA) were calculated for each animal. Furthermore, in hole-board test, latencies to the first head-dips, total numbers of head-dips and holes explored were measured as criterion of anxiety. Diazepam ( mg/kg) was used as a reference drug for the behavioral tests. Among the tested 8 compounds g, h, k, and s significantly increased the POAE and PTOA values in the plus maze tests. The same compounds significantly decreased the latency to the first head-dip, whereas increased the total numbers of head-dips and holes explored. Further g, h, k, and s induce alteration neither total spontaneous locomotor activities recorded in the activity cage, nor falling latencies measured in the Rota-Rod. Obtained data from all of these tests pointed out the anxiolytic-like effect of these aforementioned pyrazole derivatives. The exact mechanism of action underlying this anxiolytic-like effect should be clarified with further detailed studies. PP 35 ANTIFUNGAL AND ACETYLCHOLINESTERASE INHIBITORY EFFECTS OF SOME TRIAZOLE DERIVATIVES ULVIYE ACAR, UMIDE DEMIR OZKAY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY Triazole and its derivatives are interesting class of compounds, which were reported for their extensive biological effects as antibacterial, antifungal, antitubercular, antidepressant, anti-inflammatory, anticancer, analgesic, anticonvulsant, and insecticidal (). It has been reported that,,4-triazole based antifungal drug tebuconazole causes significant inhibition on acetylcholine esterase level (). In the present study some new triazole compounds were synthesized in order to investigate their anticandidal and anticholinesterase activities. Structures of the synthesized compounds were elucidated by spectral data and elemental analyses. Anticandidal activity tests were performed against four different fungal strains. Some of the compounds exhibited equal anticandidal activity to reference drug fluconazole. Anticholinesterase activity of the synthesized compounds against acetylcholinesterase (AChE) was also studied. However, enzyme inhibitory effects of the tested compounds were evaluated as insignificant. Reference. Sahin D, Bayrak H, Demirbaş A, Demirbaş N, Alpay-Karaoğlu Ş, Design and synthesis of new,,4-triazole derivatives containing morpholine moiety as antimicrobial agents. 0;36: Kolesarova V, Sinko G, Sivikova K, Dianovsky J, In vitro inhibition of blood cholinesterase activities from cattle by triazole fungicides, Caryologia 03;66: PP 36 DESIGN, SYNTHESIS AND BIOLOGICVAL EVALUATION OF SOME PIPERAZINEDITHIOCARBAMATE DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS ULVIYE ACAR, UMIDE DEMIR OZKAY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY Carbamate derivatives are inhibitors of acetylcholinesterase through carbamoylation of the esteratic site of the enzyme.they are subsequently reversed upon decarbamoylation (). The compounds which bear dithiocarbamate moiety, considered as bioisoster of carbamate, may be shown as potential anticholinesterases. Thus, in this study we designed and synthesized new piperazine based dithiocarbamate derivatives to investigate their inhibitory profile on acetylcholinesterase and butrylcholinesterase enzymes. Structures of the final compounds were confirmed by H-NMR, IR, MS spectroscopic methods and elemental analyses. In the series, the compound f was found as the most active derivative against both of the cholinesterases.. Becker RE, Moriearty P, Unni L. The second generation of cholinesterase inhibitors: Clinical and pharmacological effects. In Becker, Giacobini E,editors. Cholinergic basis for Alzheimer s therapy. Boston: Birkhauser, 99:

182 PP 37 SYNTHESIS OF SOME NOVEL DITHIOCARBAMATE DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS BEGUM NURPELIN SAGLIK, UMIDE DEMIR OZKAY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKIŞEHIR, TURKEY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY,ESKIŞEHIR, TURKEY Carbamates as pyridostigmine, rivastigmine, and physostigmine constitue a class of ChE inhibitors. However, carbamates have a relatively short duration of action and limited penetration to blood brain barrier (). Therefore, bioisosteric replacement of carbamate moiety with dithiocarbamate moiety may be rational to gain new anticholinesterases. Prompted from these observations, some new dithiocarbamate derivatives were synthesized in the present study. Structures of the target compounds were elucidated by spectroscopic methods. Tested compounds showed enzyme inhibitory effects to different extents. Especially, activity of the piperidine containing compounds was better than other derivatives in the series.. Lieske CN, Gepp, RT, Clark JH, Meyer HG, Blumbergs P, Tseng CC. Anticholinesterase activity of potential therapeutic 5-(,3,3-trimethylindolinyl) carbamates. J Enzyme Inhib. 99;5:5-3. PP 38 SYNTHESIS OF SOME 6-NITROBENZOTHIAZOLE DERIVATIVES AND INVESTIGATION OF THEIR INHIBITORY ACTIVITY ON MAO ENZMES BEGUM NURPELIN SAGLIK, YUSUF OZKAY, UMIDE DEMIR OZKAY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKIŞEHIR, TURKEY ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKIŞEHIR, TURKEY Monoamine oxidases are important drug targets for the treatment of some neurological disorders. 6-Nitrobenzothiazole derivatives were reported as MAO-B inhibitors in recent study (). Hence, in this study we synthesized some novel 6-nitrobenzothiazole derivatives to investigate their potency on MAO-A and MAO-B enzymes. Structures of the synthesized compounds were confirmed by NMR, MS and IR spectral data. Inhibitory, activity of the synthesized compounds against MAO-A and MAO-B enzymes were investigated by an in vitro flurometric method (). Compound 3e showed significant MAO-B inhibitory activity. Some of the compound also displayed good inhibition profile to MAO-A enzyme.. Tripathi RK, Goshain O, Ayyannan SR. Design, synthesis, in vitro MAO-B inhibitory evaluation, and computational studies of some 6-nitrobenzothiazole-derived semicarbazones. ChemMedChem. 03;8(3): Matsumoto T, Suzuki O, Furuta T, Asai M, Kurokawa Y, Nimura Y, Katsumata Y, Takahashi I. A sensitive fluorometric assay for serum monoamine oxidase with kynuramine as substrate. Clin. Biochem. 985;8():

183 PP 39 DESIGN, SYNTHESIS AND MOLECULAR MODELING STUDIES ON NOVEL FLUOROQUINOLONES AS POTENTIAL DNA GYRASE INHIBITORS NECLA KULABAS, ASLI DEMIRCI, ILKAY KUCUKGUZEL MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY DNA Gyrase is an essential enzyme that maintains the supercoils in DNA and has become an important drug target for antibacterial and anticancer chemotherapy. DNA Gyrase, which is a subtype of Topoisomerase enzyme family, is composed of two heterodimeric subunits, GyrA and GyrB. While GyrA helps in DNA binding, GyrB is responsible for ATPase activity. Fluoroquinolones (FQs), possessing DNA Gyrase inhibition, have been used as antibacterial agents since 960s. These agents specifically bind GyrA domain of DNA Gyrase [-3]. For this purpose, substituted aryl/heteroaryl/alkyl amines as starting compounds were converted to -chloro-n-(aryl/heteroaryl/alkyl)acetamide derivatives by using α-chloroacetyl chloride. Equimolar amounts of -chloro-n-(aryl/heteroaryl/alkyl)acetamide derivatives and selected FQ containing antibacterial agents were reacted to yield the target compounds. Following the isolation process, the crude products were crystallized from appropriate solvents. Purity of the synthesized compounds was checked by HPLC and their structures were confirmed by IR, H-NMR, 3C-NMR and mass spectral data besides elemental analysis. Molecular docking studies concerning the synthesized compounds were performed to simulate potential inhibition of DNA Gyrase. Studies on calculation of binding energy (Ebind=kcal/mol) between Staphylococcus aureus DNA Gyrase as receptor (PDB code: XCT) and synthesized compounds as ligands. DSV, Chimera and MGLTools were used to prepare data before docking. Gasteiger charges were assigned to the substrate and the ligands. Receptor-ligand docking was performed using AutoDock Vina [4]. References [] Shen LL, Mitscher LA, Sharma PN, ODonnel TJ, Chu DWT, Cooper CS, Rosen T, Pernett AG. Mechanism of inhibition of DNA Gyrase by quinolone antibacterials: A cooperative drug-dna binding model. Biochem. 8, , 989. [] Khodursky AB, Nicholas R. The Mechanism of inhibition of Topoisomerase IV by quinolone antibacterials. J. Biol. Chem. 73, , 998. [3] Ostrov D, Hernández Prada J, Corsino PE, Finton KA, Le N, Rowe TC. Discovery of novel DNA gyrase inhibitors by highthroughput virtual screening. ACC. 5, 0, , 007. [4] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem. 30, 3(), , 00. PP 40 SYNTHESIS AND ANTITUBERCULOSIS EVALUATION OF,,4-TRIAZOLE DERIVATIVES CARRYING THIOACETIC AMIDE STRUCTURE NECLA KULABAS, ESRA TATAR, ILKAY KUÇUKGUZEL, SINEM OKTEM OKULLU, NIHAN UNUBOL, TANIL KOCAGOZ MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY ACIBADEM UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL MICROBIOLOGY Tuberculosis (TB) is still a very serious chronic infection disease, which caused by several species of mycobacteria. Although tuberculosis is not a serious cause of death in countries where the disease control efforts, especially with the spread of AIDS, is an increase in the incidence of tuberculosis.the need for novel, more effective drugs to improve TB control is evident. Treatment of active disease needs to be shortened, simplified, and should not interfere with the administration of antiretroviral agents. Among azoles,,,4-triazoles nucleus that is one of the active components present in many standard drugs, is known to increase the pharmacological activity of the molecules and have been reported to exhibit antibacterial, antifungal, antiviral, antiinflammatory and antituberculosis activities. In addition to compounds possessing a thioacetic ester or amide function displayed significant activity against M. Tuberculosis [-5]. According to our synthesis procedure ring cyclization of the thiosemicarbazides led to the corresponding triazoles and the linkers were obtained by condensing appropriate anilines with chloroacetyl chloride; then these two fragments were reacted in DMF in the presence of KCO3 in order to gain the desired target compounds with potential antitubercular activities. Structures and purity of the synthesized target compounds were confirmed by the use of their IR, H-/3C-NMR and mass spectral data; besides TLC, HPLC-UV/DAD and elemental analysis. Antituberculosis activity has been viewed by broth dilution method for Minimum Inhibitory Concentration (MIC). [] Küçükgüzel İ, Tatar E, Küçükgüzel ŞG, Rollas S, De Clercq E. Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-,4-dihydro-3H-,,4-triazole-3-thiones and evaluation as antiviral/anti-hiv and antituberculosis agents. Eur J Med Chem. 008; 43(): [ -Küçükgüzel İ, Küçükgüzel ŞG, Rollas S, Kiraz M. Some 3-thioxo/alkylthio-,,4-triazoles with a substituted thiourea moiety as possible antimycobacterials. Bioorg Med Chem Lett. 00; (3): [3] Ananthan S, Faaleolea ER, Goldman RC, Hobrath JV, Kwong CD, Laughon BE, Maddry J, Mehta -8-

184 A, Rasmussen L, Reynolds RC, Secrist J, Shindo N, Showe DN, Sosa MI, Suling WJ, White EL. High-Throughput Screening for Inhibitors of Mycobacterium Tuberculosis H37Rv. Tuberculosis. 009; 89(5): Demirbas A, Şahin D, Demirbas N, Alpay Karaoglu Ş. Synthesis of some new,3,4-thiadiazol--ylmethyl-,,4-triazole derivatives and investigation of their antimicrobial activities. Eur J Med Chem.009;44(7): Kravchenko MA, Verbitskiy EV, Medvinskiy ID, Rusinov GL, Charushin VN. Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and SN reactions. Bioorg Med Chem Lett.04;4: PP 4 PROTECTIVE EFFECT OF CARNITINE AGAINST ACRYLAMIDE-INDUCED TOXICITY IN RATS HULYA SAHIN, SEZGIN AYDEMIR, MERAL YUKSEL, NAZIYE OZKAN 3, NUSRET ERDOGAN 3, GULDEN Z. OMURTAG DEPARTMENT OF TOXICOLOGY, SCHOOL OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY DEPARTMENT OF MEDICAL LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA UNIVERSITY, İSTANBUL, TURKEY 3 DEPARTMENT OF PATHOLOGY LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA UNIVERSITY, İSTANBUL, TURKEY Acrylamide (ACR) is a high-production vinyl compound whose polymeric form is used in oil industry, paper, plastics and textiles. The same compound is generated in many common foods during cooking at high temperatures. Carnitine, plays an important role in the transport of long-chain fatty acids through the mitochondrial membrane for their beta-oxidation, and in ATP production in peripheral tissues. The purpose of the study is conducted for determine the effect of carnitine on acrylamide induced tissue injury in rats. Sprague-Dawley rats were included in the study. ACR was given i.p. at a dose of 40 mg/kg/day and carnitine for a dose of 00 mg/kg/day, for 0 days. Control group received SF injection. After the time rats were sacrified and brain, liver and lung tissues were removed. For free radical determination luminol (selective for hydroxyl radical, hydrogen peroxide and hypochlorous acid) and lucigenin (selective for superoxide radical) enhanced chemiluminescence (CL) measurements were used. Histopathological examination, malondialdehyde (MDA; a lipid peroxidation product) and glutathione (GSH) levels were examined. In ACR group luminol enhanced CL results were higher in liver tissues; lucigenin enhanced CL measurements were increased in liver, lung and brain tissues, with respect to their control groups. Carnitine treatments reduce ACR induced free radical release in all tissue groups, significantly. MDA levels confirmed the increased lipid peroxidation in ACR induced groups, with respect to controls. Whereas carnitine treatment, reduces MDA levels, and increases GSH formation, which is decreased with ACR toxicity. In conclusion, treatment with carnitine of ACR induced toxicity has been found to reverse some oxidative stress parameters in brain, liver and lung tissues. PP 4 THE EFFECT OF PELARGONIUM SIDOISES EXTRACT (UMCA ) ON ACRYLAMIDE INDUCED TOXICITY IN RATS SEZGIN AYDEMIR, HULYA SAHIN, NAZIYE OZKAN, MERAL YUKSEL 3, NUSRET ERDOGAN, GULDEN Z. OMURTAG DEPARTMENT OF TOXICOLOGY, SCHOOL OF PHARMACY, MARMARA UNIVERSITY, HAYDARPAŞA-İSTANBUL, TURKEY DEPARTMENT OF PATHOLOGY LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA UNIVERSITY, HAYDARPAŞA-İSTANBUL, TURKEY 3 DEPARTMENT OF MEDICAL LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA UNIVERSITY, HAYDARPAŞA-İSTANBUL, TURKEY Acrylamide (ACR) is a water-soluble, vinyl monomer used in preparing polymers and copolymers containing polar functional groups. Exposure to monomeric ACR has the potential for cytotoxic and genotoxic effects by decreasing oxidative defense system. Pelargonium sidoises extract, (UMCA ), is available for treatment of upper respiratory tract infections. The aim of this study is to determine the effects on oxidative stress parameters of Pelargonium sidoises extract on acrylamide-induced liver, lung and kidney injury. Female Sprague-Dawley rats were included in the study. ACR was given at a dose of 40 mg/kg/ day. ACR-UMCA group received additionally 00 mg/kg/day UMCA. Controls were injected saline at the same dose. After 0 days their liver, lung and kidney tissues were removed and the degree of oxidative stress was measured by glutathione (GSH), malondialdehyde (MDA), luminol and lucigenin enhanced chemiluminescence (CL) methods. Additionally histopathological observations were analyzed. Liver, lung and kidney MDA levels in ACR induced group are significantly higher than control group. Because, GSH levels are significantly lower in ACR induced liver and kidney tissues, with respect to control tissues. But GSH levels in lung tissues were not changed. UMCA treatment reduces MDA levels and increased GSH levels, significantly. Additionally, luminol (which is specific for.oh, HO, HOCl) enhanced CL levels were significantly increased in ACR induced liver tissues with respect to control (5.8±4. vs. 6.3±.5 rlu; p<0.00), and treatment with UMCA reduced the free radical release, significantly (9.4±.9 rlu; p<0.0). Lucigenin enhanced CL measurements, which is selective for superoxide radical, were increased in ACR induced lung and kidney tissues, which is reversed by UMCA treatment, significantly. Histopathological observations show cellular degeneration in tissues of ACR group. UMCA treatment reduced the degeneration, slightly. In conclusion, ACR induced toxicity in rats increases oxidative stress which results with increased MDA, reduced antioxidative capacity, and increased free radical release in liver, lung and kidney. UMCA treatment was protective against oxidative stress in tissues after ACR toxicity. -83-

185 PP 43 CONTROLLED PORE GLASS BASED IMMUNOSORBENT SURFACE FACILITATES THE THEOPHYLLINE MEASUREMENT TUGBA TUNALI-AKBAY, HAZAL IPEKCI, AYSEN YARAT MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY Theophylline, also known as,3-dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases. In determining theophylline toxicity or in monitoring the treatment of theophylline, theophylline determination is made by expensive methods. The aim of this study is to facilitate the measurement of low concentrations of theophylline in cow s milk. Determination of theophylline in biological media such as milk, in order to avoid background interference, the extraction step should be added. In the present study, an immunosorbent surface which facilitates the theophylline measurement without extraction step has been developed. For this purpose protein-a controlled pore glass (CPG) matrix was used. Theophylline antibody was immobilized to the protein A-controlled pore glass matrix for generating an immunosorbent surface. This step helps to concentrate theophylline in the solution for the theophylline determination by colorimetric method. All results were evaluated statistically and discussed. This study was supported by a grant from Scientific Research Project Department of Marmara UNIVERSITY (Projects No: SAG-B-305-0). PP 44 IMMUNOSORBENT SURFACE REMOVES COTININE FROM MILK TUGBA TUNALI-AKBAY, MEHMET V. KAHRAMAN, NILHAN APOHAN, HAZAL IPEKCI, BURCU OKTAY MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF ORGANIC CHEMISTRY, İSTANBUL, TURKEY Breastfeeding is the best way of food intake in the early child hood. The adverse effects of maternal cigarette smoking on postnatal development of infant have been well documented. Cotinine is an alkaloid found in tobacco and is also a metabolite of nicotine. It is used as a biomarker for exposure to tobacco smoke. Similarly to nicotine, cotinine binds to, activates, and desensitizes neuronal nicotinic acetylcholine receptors, though at much lower potency in comparison. Nicotine itself in tobacco smoke truly exits body in a matter of hours ahead of breast feeding; cotinine delays much further. Therefore, the aim of this study is to remove cotinine from milk by using an immunosorbent featured surface. For this purpose cotinine antibody was immobilized to the nanofiber surface and immunosorbent surface was developed. A total of 0 fresh cow s milk samples were used. Cotinine was added to cow s milk in different concentrations. Binding efficiency of cotinine to immunosorbent surface was measured by using ELISA method. Binding percentages were evaluated statistically and discussed. This study was supported by TUBITAK with the project numbered SBAGS38. PP 45 REMOVAL OF FLUOXETINE FROM MILK BY USING IMMUNOSORBENT FEATURED SURFACE TUGBA TUNALI-AKBAY, MEHMET V. KAHRAMAN, NILHAN APOHAN, BURCU OKTAY, HAZAL IPEKCI MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF ORGANIC CHEMISTRY, İSTANBUL, TURKEY Fluoxetine is one of the most used drug for reducing the postpartum depression either doctor s advice or previous experiences of mother s. Maternal fluoxetine usage adversely affect the infant s health. It increases crying, vomiting, diarrhea, colic and decreases sleep of infants. Women who are maintained on therapeutic doses of fluoxetine are recommended to discontinue breast-feeding their infants if they wish to breast-feed. Maternal fluoxetine therapy carries risks for nursing infants, but untreated depression is also risky for mothers and infants. The aim of this study is to remove fluoxetine from milk by using an immunosorbent featured surface. For this purpose fluoxetine antibody was immobilized to the nanofiber surface and immunosorbent surface was developed. A total of 0 fresh cow s milk samples were used. Fluoxetine was added to cow s milk in different concentrations. Binding efficiencies of fluoxetine to immunosorbent surface was measured by using ELISA method. Binding percentages were evaluated statistically and discussed. This study was supported by TUBITAK with the project numbered SBAGS

186 PP 46 OPTIMIZATION AND EVALUATION OF CLARITHROMYCIN FLOATING TABLETS USING EXPERIMENTAL MIXTURE DESING TIMUCIN UGURLU, UGUR KARACICEK, ERKAN RAYAMAN MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ISTANBUL, TURKEY The purpose of the study was to prepare and evaluate clarithromycin (CLA) floating tablets using experimental mixture design for treatment of Helicobacter pylori provided by prolonged gastric residence time and controlled plasma level. Ten different formulations were generated based on different molecular weight of hypromellose (HPMC K00, K4M, K5M) by using simplex lattice design (a sub-class of mixture design) with Minitab 6 software. Sodium bicarbonate and anhydrous citric acid were used as gas generating agents. Tablets were prepared by wet granulation technique. All of the process variables were fixed. Results of cumulative drug release at 8th h (CDR 8th) were statistically analyzed to get optimized formulation (OF). Optimized formulation, which gave floating lag time lower than 5 s and total floating time more than 0 h, was analyzed and compared with target for CDR 8th (80%). A good agreement was shown between predicted and actual values of CDR 8 th with a variation lower than %. The activity of clarithromycin contained optimized formula against H. pylori were quantified using well diffusion agar assay. Diameters of inhibition zones vs. log0 clarithromycin concentrations were plotted in order to obtain a standard curve and clarithromycin activity. PP 47 THE IMPACT OF PLATELET FUNCTIONS AND INFLAMMATORY STATUS ON THE SEVERITY OF PREECLAMPSIA SADIK SAHIN, OZLEM BINGOL OZAKPINAR, MUSTAFA EROGLU, AYSIN TULUNAY 3, ENVER CIRACI, FIKRIYE URAS, SERMIN TETIK DEPARTMENT OF BIOCHEMİSTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY ZEYNEP KAMIL WOMEN AND CHILDREN DISEASES TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY. 3 DEPARTMENT OF IMMUNOLOGY, FACULTY OF MEDICINE, MARMARA UNIVERSITY, ISTANBUL, TURKEY. To find out whether there is a correlation between the extent of platelet activation and inflammation and the severity of preeclampsia in the third trimester of pregnancy. Forty-one women with preeclampsia (n=3 severe, n=8 mild) and 80 normotensive pregnant women were included in the study. Their blood samples were obtained and IL-8 and IL-0 levels measured by an enzyme-linked immunosorbent assay. Basal CD6 and CD6P expressions on CD4 positive platelets were analyzed with the use of flow-cytometry. Platelet aggregation was induced by adenosine diphosphate and determined by aggregometry. CD6P expression was increased in severely preeclamptic women and the platelet aggregation was decreased in both mildly and severely preeclamptic women in comparison with normotensive pregnant women. However, CD6 expression was similar among the groups. An enhanced inflammatory response was seen in severely preeclamptic women demonstrated by increased levels of IL-8 and decreased levels of IL-0. However, the intensity of platelet activation did not correlate directly with the change in plasma levels of IL-8 and IL-0 in preeclamptic women. Platelets may have a role in the inflammatory response in preeclampsia. However, the severity of inflammation is found to be independent from the intensity of platelet activation in preeclamptic women. This seems to be related to mechanisms causing alterations of cytokine levels such as IL-8 and IL-0, rather than platelet activation. -85-

187 PP 48 GG POLYMORPHISM OF PLATELET GLYCOPROTEIN IIB ITGAB GENE INCREASES THE MAGNITUDE OF INTERLEUKIN-6 RELEASE AFTER CARDIOPULMONARY BYPASS KORAY AK, SAMET ERGUN, HILAL ALTINOZ 4, ENVER CIRACI, OYA UYGUNER 5, SELIM ISBIR, SINAN ARSAN, SERMIN TETIK MARMARA UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF CARDIOVASCULAR SURGERY MARMARA UNIVERSITY, HEALTH SCIENCES INSTITUTE DEPARTMENT OF BIOCHEMISTRY 3 TAKSIM EDUCATION AND RESEARCH HOSPITAL PATHOLOGY DIVISION 4 ISTANBUL SÜREYYAPASA THORACIC DISEASE AND THORACIC SURGERY EDUCATION AND RESEARCH HOSPITAL 5 ISTANBUL UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICAL GENETICS 6 CYPRUS INTERNATIONAL UNIVERSITY, LEFKOSA, CYPRUS Cardiopulmonary bypass induces a systemic inflammatory response which is thought to be a significant cause of postoperative organ dysfunction and mortality. In this study we aimed to investigate the effect of glycoprotein IIb ITGAB gene polymorphism on the magnitude of the inflammatory response after cardiac surgery. Twenty patients (study group, n=0) undergoing coronary artery bypass grafting were included. Blood samples were taken at the three different times for analyses of Interleukin 6, Interleukin 0 and Nuclear Factor Kappa B by ELISA (t: before operation, t:0 minutes after removal of aortic cross clamping and t3: 4 hours after operation. Glycoprotein IIb ITGAB receptor polymorphism was studied in patients and 7 healthy volunteers by polymerase chain reaction. Perioperative organ dysfunction was evaluated by cardiac surgery scorring (CASUS) system. There was no perioperative mortality. The mean ages of the patients and controls were 67.45±.30 and 5,38±7,03 years old. In the study group, 35% (n=7) revealed TT, 45% (n=9) TG and 0% (n=4) GG polymorphism of Glycoprotein IIb. The allele frequencies of the study group were similar to the controls (33,3%, n=9 revealed TT, 55,5 %, n=5 TG and,3%, n=3 GG). There was no significant difference in terms of genetic polymorphism (p>0.05). Postoperative day and day CASUS scores were similar among the three polymorphisms. In the study group, patients with GG allele had significantly higher interleukin 6 levels 4 hours after operation than the others (for TT allele 36,4±, 0 pg/ml, TG allele 38, ±4,50pg/ml and GG 338,4±.0pg/ml) (p<0.05). Our results reveal that GG allele of Glycoprotein IIb ITGAB gene has a significant role in the magnitude of the inflammatory response seen after cardiac surgery with cardiopulmonary bypass. PP 49 BIOLOGICAL ACTIVITIES OF AERIAL PARTS OF CENTAUREA SALICIFOLIA ALI SEN, BURCAK GURBUZ, OZLEM BINGOL OZAKPINAR 3, SUKRAN KULTUR 4, UMRAN SOYOGUL GURER, FIKRIYE URAS 3, LEYLA BITIS MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOGNOSY, ISTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, ISTANBUL, TURKEY 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY 4 ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACETICAL BOTANY, ISTANBUL, TURKEY In this study, we reported, for the first time to our knowledge, biological activities of hexane, chloroform and aqueous methanol fractions of methanol extract obtained from the aerial parts of Centaurea salicifolia Bieb. ex Willd. Antibacterial activity was assessed by agar well diffusion and microdilution methods while antiproliferative activity was measured against five human cancer cell lines (A549: lung adenocarcinoma, Hela; cervix adenocarcinoma, HT-9: colon adenocarcinoma, MCF- 7; breast adenocarcinoma, PC-3; prostate adenocarcinoma) using MTT assay (,). Aqueous methanol extract exhibited weak antimicrobial activity with MIC of µg/ml, µg/ml, µg/ml against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. Hexane and chloroform extracts showed antimicrobial activity in the range of µg/ml against Staphylococcus aureus and Staphylococcus epidermidis. Antiproliferative activity indicates that chloroform extract exhibited strong activity with IC50 values of,66; 5,89 and 6,9 µg/ml against HT-9, MCF-7 and PC-3, respectively. The same extract showed good antiproliferative activity with IC50 values of 70,03 and 76,73 µg/ml against A549 and HeLa, respectively. The results show that active extracts are good candidates for further activity-guided fractionation in the search for new active antimicrobial and antitumor compounds. References. Sen A, Gurbuz B, Gurer US, Bulut G, Bitis L. Flavonoids and Biological Activities of Centaurea stenolepis. Chemistry of Natural Compounds, 04; 50(): Csapi B, Hajdú Z, Zupkó I, Berenyi A, Forgo P, Szabo P, Hohmann J. Bioactivity-guided isolation of antiproliferative compounds from Centaurea arenaria, Phytotherapy Research, 00; 4:

188 PP 50 AN ASSESSMENT OF ANTIPROLIFERATIVE AND CYTOTOXIC ACTIVITY OF ESSENTIAL OIL OF CHAEROPHYLLUM AROMATICUM AGAINST NORMAL AND TUMOR CELL LINES ALI SEN, OZLEM BINGOL OZAKPINAR, AHMET DOGAN 3, FIKRIYE URAS, LEYLA BITIS MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOGNOSY, ISTANBUL, TURKEY MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY 3 MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY Chaerophyllum aromaticum L. (Syn. C. byzantinum Boiss.) is one of the 6 species of the genus Chaerophyllum (Apiaceae) growing wild in Turkey. This species, which is known as Mendek in Giresun province, is used as digestive by people in cooked food. In this study, the antiproliferative and cytotoxic activities of essential oil of Chaerophyllum aromaticum on normal (NIH) and cancer (K56, PC-3, MCF-7, HeLa, A549, HT-9) cell lines have been investigated for the first time by the MTT method. In a previous study ıt was revealed that major components in essential oil of aerial parts of Chaerophyllum aromaticum collected in Greece were cis-ocimene (3.98 %) and α-terpinolene (.8 %). In an another study although it was reported that α-terpinolene has antiproliferative activity against brain tumour cells, there isn t any study about effect of cytotoxic or antiproliferative of Ocimene. The current study we have found that essential oil of Chaerophyllum aromaticum does not exhibit any cytotoxic and antiproliferative activity at 00 µg/ml concentration against all the human cell lines. This result is similar to the work of Lone et al. (04) who reported essential oil of leaves of Senecio graciliflorus, the main compound were identified as cis-ocimene (4.4 %), had no cytotoxic activity on A-549, PC-3 cancer cell lines. However, to definitely decide activity essential oil of Chaerophyllum aromaticum, the composition and activity on different cell lines of essential oil of this plant originated in Turkey is to be also planned to investigate in our further studies. When considered ethnobotanical use of this plant, It would safely consume by people because this plant had no cytotoxic effect on normal cell line. PP 5 CHITOSAN HYDROGEL FOR DERMAL GENE DELIVERY SUNA OZBAS-TURAN, JULIDE AKBUGA MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTİCAL BİOTECHNOLOGY, HAYDARPAŞA- İSTANBUL, TURKEY The skin is an attractive and the largest organ for local and systemic drug applications. Skin gene therapy is a new approach with great potential because the accessibility and the possibility to the modified area. In present study, chitosan hydrogels were investigated for nucleic acid delivery into the skin. In our study, chitosan hydrogel was prepared for dermal gene delivery and physico-chemical properties and in vitro/in vivo transfection characteristics of hydrogel formulations were investigated. Chitosan could form ph-sensitive hydrogels by addition of PEG 400. The highest swelling values were obtained at ph 3.5 buffer. The concentrations of chitosan, PEG 400 and glutaraldehyde affected the water uptake and swelling of chitosan:peg hydrogels (p<0.05). The release of pdna from hydrogels was monitored over 40 hours. Mouse fibroblastic NIH 3T3 cell line and primary human dermal fibroblasts were used for in vitro transfection studies. Transfection efficiency of formulation was monitored by measuring of β-galactosidase activity expressed by β-gal reporter plasmid. In vitro b-gal production was obtained with the chitosan-peg 400 (:0.5) hydrogels. Baby and adult Sprague Dawley rats were used for in vivo transfection studies. By using enzyme assays and histological techniques, it was shown that the reporter gene expression in dermis and hypodermis layers of skin sustained for 7 days. Highest b-gal amount was measured at 3. days after transfection. As a result, high b-gal expression was obtained with DNA-chitosan hydrogels in the in vitro and in vivo studies. Chitosan-based delivery systems including hydrogels, can be efficiently used for DNA transfer through the skin. -87-

189 PP 5 ILLNESS PERCEPTION AND DIABETES SELF CARE ACTIVITIES IN PATIENTS WITH TYPE II DIABETES MELLITUS AT COMMUNITY PHARMACY SETTING HARUN DOGRUSEVER, BETUL OKUYAN, MESUT SANCAR, H. KUBRA ELCIOGLU DEPARTMENT OF PHARMACOLOGY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the study is to determine illness perception and diabetes self care activities in patients with type II diabetes mellitus at community pharmacy setting. This study was conducted at two community pharmacies located in Istanbul and Sakarya. The patients were eligible if they came to community pharmacy with any reason, accepted to participate after informed about study, were 8 years old or older, and diagnosed with type diabetes mellitus. The self care activities of patients with type diabetes mellitus were measured by The Summary of Diabetes Self-Care Activities (), was scored between 0-7 according to how many times patients performed diabetes self-care activities (diet, exercise, blood glucose testing, foot care, and medication utilisation) over the past 7 days. The illness perception of patients was assessed by Brief Illness Perception Questinnaire (), was scored between 0-80 and a higher score represented a more threatening point of view for the illness. Eighty patients (mean of age: 56.0±8.67 years old; male/female 35/45) were included the present study. When evaluating patients recent haemoglobin AC level, which was gathered in sixty-three patients, only twenty- three patients haemoglobin AC levels were equal and less than 6.50%. Of them, 7.50% used alone metformin, 6.5% used sulfonylurea plus metformin combination, and 6.5% used metformin and insulin combination for management of diabetes. The median scores (interquartile 5-75) of the self care activities in the patients were calculated as 7 (7-7) for general diet, 7 (6-7) for specific diet, 5 (3-6) for exercises, 4 (3-6) for blood glucose testing, 3 (-5) for foot care and 7 (6-7) for medication utilization. The median overall scores for brief illness perceptions questionnaire was 4 (36-48). According to patients belief, the most common factors that caused their illness were hereditary, diet or eating habits, and stress, respectively. As a conclusion, the diabetic patients illness perception and self-care activities should be also assessed to improve diabetic patients therapeutic outcomes.. Kav S, Akman A, Dogan N, Tarakci Z, Bulut Y, Hanoglu Z. Turkish validity and reliability of the summary of diabetes self-care activities measure for patients with type- diabetes mellitus. J Clin Nurs. 00;9(9-0) Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 006 Jun;60(6):

190 PP 53 DETERMINANTION OF MEDICATION UTILIZATION AND ILLNESS PERCEPTION AMONG PATIENTS WITH II DIABATES MELLITUS H.KUBRA ELCIOGLU, BETUL ÇAGLAYAN, ALI CAGRI DEMIREL, OGUZHAN DEYNELI, MESUT SANCAR 3, BETUL OKUYAN 3 DEPARTMENT OF PHARMACOLOGY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY DIVISION OF ENDOCRINOLOGY AND METABOLISM, MARMARA UNIVERSITY, FACULTY OF MEDICINE, ISTANBUL, TURKEY 3 DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY The aim of the study is to determine medication utilization and illness perception among patients with type II diabetes mellitus. This cross sectional study was conducted in outpatient clinic of a research and training hospital between April 0 and April 30, 03. Patients type diabetes mellitus admitted to outpatient clinic with any reason during the present study were eligible if they were 8 years or older, utilized at least one medication for treatment of diabetes during at least 4 weeks, and accepted to participate to the present study. Medication utilization was assessed by medication taking self care component of The Summary of Diabetes Self-Care Activities (), was scored between 0-7 according to how many times patients took their medication recommended for diabetes over the past 7 days. The illness perception of patients was assessed by Brief Illness Perception Questionnaire (), was consist of eight dimension scored between 0-0. A hundred and four patients (mean of age: 55.7±.7 years old; male/female 40/64) were included the present study. When evaluating patients recent haemoglobin AC level, haemoglobin AC levels were equal and less than 6.5% in 33.7% of them. Duration of diabetes was more than five years in 55.6% of them. The common utilized medications for treatment of diabetes were metformin (6.5%), insulin (5.9%), and sulfonylurea (4.0%). Besides medication for treatment of diabetes; it was also observed that statin (5.0%), aspirin (.%), and angiotensin II receptor blockers (8.3%) were also prescribed among study patients. Of them, 7.7% was utilized dietary supplements. Medication taking self-care activities in the patients were calculated as 7 (7-7). When assessed illness perception; the median scores (interquartile 5-75) of each dimensions of illness perception were 7 (5-8) for consequences, 0 (0-0) for timeline, 6 (3-8) for personal control, 8 (5.-0) treatment control, 7 (4-8) for identity, 6 (.-8) for illness concern, 0 (8-0) for coherence, 7 (4-9) for emotional representation. According to patients belief, the most common factors that caused their illness were hereditary, stress and ageing, respectively. Although the moderate illness perception and high medication adherence determined among patients with type II diabetes mellitus in the present study, poor therapeutic outcomes have been observed according to their haemoglobin AC levels.. Kav S, Akman A, Dogan N, Tarakci Z, Bulut Y, Hanoglu Z. Turkish validity and reliability of the summary of diabetes self-care activities measure for patients with type- diabetes mellitus. J Clin Nurs. 00;9(9-0) Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 006 Jun;60(6):

191 PP 54 TISSUE FACTOR EXPRESSION OF ADIPOSE TISSUE IN OBESITY USTUNDAG, EMEKLI-ALTURFAN, KESKIN, SUTCU, YIGITBASI 3, EMEKLI 3 MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY MEDIPOL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY MEDIPOL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF PLASTIC SURGERY 3 MEDIPOL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF BIOCHEMISTRY Tissue factor (TF) has both procoagulant signaling activities. TF has been associated with many biochemical events including haemostasis, thrombosis, inflammation, angiogenesis and cancer. Recently the expression of TF has been demonstrated in adipose tissue of leptin-deficient (ob/ob) mice. In obese patients altered expression of some haemostatic parameters such as fibrinogen and Factor VII have been shown. This may contribute to the coronary artery disease or other metabolic diseases such as diabetes. The aim of this study is to investigate the expression of TF in the adipose tissue of a patient with obesity. TF expression was determined immunohistochemically on formalin fixed paraffin-embedded adipose tissues that were obtained during the liposuction procedure. The images were then obtained with the microscope fitted with a digital camera and TF expression was evaluated and discussed. PP 55 NEW DIFLUNISAL HYDRAZONES AND THIAZOLIDINONES AS ANTI-HCV AND ANTIMICROBIAL AGENTS SEVIL SENKARDES, SINEM OKTEM OKULLU, TANIL KOCAGOZ, NEERJA KAUSHIK-BASU 3, DINESH MANVAR 3, AMARTYA BASU 3 S.GUNIZ KUCUKGUZEL MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPASA ISTANBUL, TURKEY ACIBADEM UNIVERSITY, FACULTY OF MEDICINE,DEPARTMENT OF MEDICAL MICROBIOLOGY, ISTANBUL, TURKEY 3 RUTGERS-NEW JERSEY MEDICAL SCHOOL, DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BİOLOGY NEWARK, NEW JER- SEY, USA Hydrazide-hydrazones have been demonstrated to possess biological activities (,). 4-Thiazolidinone derivatives are known to possess biological activities (3). In addition,,4 -difluoro-4-hydroxybiphenyl-3-carboxylic acid [-(-fluorophenyl)- 4-thiazolidinone-3-yl]amide exhibited an IC 50 value of 48 mm against HCV NS5B RdRp (4). These observations led us to synthesize novel diflunisal hydrazide-hydrazones and 4-thiazolidinones and to investigate their possible antimicrobial and anti- HCV activities (5,6). Thus, these derivatives showed moderate antimicrobial activity and excellent anti-hcv activity. References: () Rollas S, Küçükgüzel ŞG. Biological activities of hydrazone derivatives. Molecules. 007; : () Aydın S, Kaushik-Basu N, Arora P, Basu A, Nichols DB, Talele TT, Akkurt M, Çelik İ, Büyükgüngor O, Küçükgüzel ŞG. Microwave assisted synthesis of some novel flurbiprofen hydrazidehydrazones as anti-hcv NS5B and anticancer agents. Marmara Pharm J. 03; 7: (3) Tripathi AC, Gupta SJ, Fatima GN, Sonar PK, Verma A, Saraf SK. 4-Thiazolidinones: the advances continue Eur J Med Chem. 04; 7: (4) Kaushik-Basu N, Bopda-Waffo A, Talele TT, Basu A, Chen Y, Küçükgüzel ŞG. 4-Thiazolidinones: A novel class of hepatitis C virus NS5B polymerase inhibitors. Front Biosci. 008; 3: (5) Aydın S, Bingöl Özakpınar Ö, Özsavcı D, Çevik Ö, Şener A, Şahin F, Küçükgüzel Ş.G. Synthesis and Anticancer Activity Of Diflunisal Hydrazide-Hydrazones As Apoptosis Inducing Agents International Symposium on Drug Research&Development, 03, Antalya. P-45. (6) Aydın S, Bingöl Özakpınar Ö, Özsavcı D, Çevik Ö, Şener A, Küçükgüzel Ş.G. Synthesis Of New Diflunisal Thiazolidinones As Potential Pro-Apoptosis and Anticancer Effects 50th International Conference on Medicinal Chemistry, 04, Rouen, FRANCE. Acknowledgments: This research was supported by TUBITAK, Project Number: S03. The authors are grateful to Dr. Jürgen Gross for obtaining HR-EI/FAB mass spectra of the compounds. -90-

192 PP-57 SYNTHESIS AND CYTOTOXIC EVALUATION OF SUBSTITUTED UREA DERIPVATIVES DERIVATED FROM GABAPENTIN SEVDA TURK, FATIH TOK, SEVGI KARAKUS, BEDIA KOCYIGIT-KAYMAKCIOGLU, SUNA OZBAS-TURAN, JULIDE AKBUGA, SEVIM ROLLAS DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, MARMARA UNIVERSITY FACULTY OF PHARMACY, HAYDARPASA ISTANBUL, TURKEY DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, MARMARA UNIVERSITY, FACULTY OF PHARMACY HAYDARPASA,ISTANBUL, TURKEY Within the past ten years, a huge volume of research on the synthesis, structure-activity relationships (SAR), and anticancer activities of the urea derivatives was reported. Many aromatic urea derivatives such as N-phenyl-N'-(- chloroethyl)ureas (CEUs) and benzoylureas (BUs) show good anticancer activity, and these compounds have mainly been proved to be tubulin ligands that inhibit the polymerization of tubulin. Heterocyclic urea derivatives play an important role in anticancer agents because of their good inhibitory activity against receptor tyrosine kinases (RTKs), raf kinases, protein tyrosine kinases (PTKs), and NADH oxidase, which play critical roles in many aspects of tumorigenesis (- 3). All of these data made it exciting to study for novel urea derivatives as possible anticancer agents. In the present study, new urea derivatives are synthesized by reacting the gabapentine with substituted isocyanates. All new compounds are characterized by elemental analysis and various spectroscopic methods (IR, H-NMR, MS). The newly synthesized compounds have been tested for their possible cytotoxic activity by using MTT test. References:. Li H.Q., Lv P.C., Yan T., Zhu H.L. Urea derivatives as anticancer agents. Anticancer Agents Med Chem. 009, 9(4): Mounetou E., Legault J., Lacroix J., C-Gaudreault R. Antimitotic antitumor agents: synthesis, structure-activity relationships, and biological characterization of N-aryl-N'-(-chloroethyl)ureas as new selective alkylating agents. J Med Chem. 00, 44(5): Cao P., Huang X.F., Ding H., Ge H.M., Li H.Q., Ruan B.F., Zhu H.L.Synthesis and cytotoxic evaluation of substituted urea derivatives as inhibitors of human-leukemia K56 cells. Chem Biodivers. 007, 4(5):

193 PP56 THERAPEUTIC DRUG MONITORING IN PEDIATRIC PATIENTS TREATED WITH ANTI-TUBERCULOSIS MEDICATIONS: PRELIMINARY STUDY BETUL OKUYAN, MESUT SANCAR, NAZAN DALGIC, SEVGI KARAKUS 3, ERKAN CAKIR 4, LEVENT MIDYAT 5, UFUK ERENBERK 4, FIKRET VEHBI IZZETTIN, SEVIM ROLLAS 3, BEDIA KAYMAKCIOGLU 3 CLINICAL PHARMACY DEPARTMENT, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY DIVISION OF PEDIATRIC INFECTIOUS DISEASES, SISLI ETFAL TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY 3 PHARMACEUTICAL CHEMISTRY DEPARTMENT, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY 4 DEPARTMENT OF PEDIATRIC PULMONOLOGY, BEZMIALEM VAKIF UNIVERSITY, ISTANBUL, TURKEY 5 DEPARTMENT OF PEDIATRIC PULMONOLOGY, SUREYYAPASA CHEST DISEASES AND THORACIC SURGERY TRAINING AND INVESTIGATION HOSPITAL, ISTANBUL, TURKEY There is a growing concern according to results of a few recently published data about a low therapeutic serum concentration of anti-tuberculosis medications in pediatric patients with tuberculosis when compared with adult patients with tuberculosis, which resulted in poor therapeutic outcomes in pediatric patients. The aim of the study is to determine therapeutic serum concentration of isoniazid, rifampicin and pyrazinamide in pediatric patients treated with standard primary anti-tuberculosis medications (the combination of isoniazid, rifampicin, ethambutol, and pyrazinamide) by using a high performance liquid chromatography (HPLC) in different periods during treatment and to investigate association between therapeutic outcome such as medication adherence and therapeutic serum concentration of medications. Patients were eligible for the present study; if they were 4 years old or younger, diagnosed with pulmonary and extra pulmonary tuberculosis and started treatment with standard primary anti- tuberculosis medications and provided consent form from their parents. The serum sample has been collected at baseline (0 h) and.5, 3, 4.5 and 6 hours after giving the first dose of anti-tuberculosis drugs on the first day. The serum sample has been also taken before and 3 hours after anti-tuberculosis therapy on the fourth day and fourth months of treatment to determine medication adherence during management of tuberculosis. Therapeutic serum concentrations of isoniazid, rifampicin and pyrazinamide have been assayed by previously described HPLC method (). The appropriateness of HPLC method that previously developed in adult patients with tuberculosis () has been also established for the pediatric patients according the results thus far obtained. It has been still continued to determine serum concentration of medications in pediatric patients.. Unsalan S, Sancar M, Bekce B, Clark P, Karagoz T, Izzettin FV, Rollas S. Therapeutic Isoniazid, Pyrazinamide and Rifampicin Monitoring Using High Performance Liquid Chromatography in Tuberculosis Patients. Chromotographia. 005; 6:

194 04 IMPPS-4 International Congress Sponsors -9-

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