DIAGNOSTIC CATALOG PART 1: RIA

Transcription

1 DIAGNOSTIC CATALOG PART 1: RIA Auto-Immunity, Biogenic Amines, Bone Metabolism, Cancer Markers, Cardiovascular & Salt Balance, Diabetes & Metabolism, Fertility, Growth Factors, Immunology Markers, Thyroid Function

2 TO CONTACT US Our people, Our professional and experienced Customer Service and Technical Support teams are dedicated to ensuring complete customer satisfaction. We take pride in providing helpful and accurate information in a 24-hour turnaround time. Ordering: please see below and consult the How to order section for your local contact. CEO Dr. Jozef Vangenechten Tel: +32 (0) Fax: +32 (0) jef.vangenechten@diasource.be CUSTOMER SERVICE - ORDERING Tel: +32 (0) Fax: +32 (0) Belgium Free Phone: France Free Phone: France Free Fax: customer.service@diasource.be Customer & Supplier Manager Nathalie Dierickx Tel: +32 (0) Fax: +32 (0) nathalie.dierickx@diasource.be Business Development Manager FraBeLux & Marketing Manager Juan Puigdevall Tel: +32 (0) Mobile: +32 (0) Fax: +32 (0) juan.puigdevall@diasource.be Sales Director for Spain & Export Manager LatAm Alberto Rosell Mobile SP: Fax SP: alberto.rosell@diasource.be Product Manager & Principal Scientist Vitamin D Product Manager Nicolas Heureux Tel: +32 (0) Fax: +32 (0) nicolas.heureux@diasource.be David Degels Tel: +32 (0) Fax: +32 (0) david.degels@diasource.be Customer Service Manager Muriel Hirsoux Customer Service Representatives Sabrina Baio Isabelle Rosman Hélène Lempereur - Fanny Gruloos SALES & MARKETING International Sales Director & Business Segment Manager RIA Peter Kerckx Mobile: +32 (0) Fax: +32 (0) peter.kerckx@diasource.be Business Segment Manager ELISA & Instrumentation (a.i.) & Product Manager Eric Maes Mobile: +32 (0) Fax: +32 (0) eric.maes@diasource.be Sales Manager France & District Manager Wallonia Philippe Oliva Mobile BE: Fax BE: +32 (0) Mobile FR: Free Fax FR: philippe.oliva@diasource.be Sales Executive Flanders Jan Wauters Tel/Fax: +32 (0) Mobile: +32 (0) jan.wauters@diasource.be Sales Manager Latinoamerica Delegado Comercial Olga Lucia Guayacan Mobile: olga.guayacan@diasource.be Willy Joe Natera Mobile: Fax: willy.natera@diasource.be TECHNICAL SUPPORT SPECIALIST Valérie Preud Homme Tel: +32 (0) Fax: +32 (0) valerie.preudhomme@diasource.be SHIPPING SURPERVISOR Luciana Frasson Tel: +32 (0) Fax: +32 (0) luciana.frasson@diasource.be PRODUCT DEVELOPMENT, QUALITY & REGULATORY AFFAIRS MANAGER Isabelle Dehart Tel: +32 (0) Fax: +32 (0) isabelle.dehart@diasource.be FINANCE & ADMINISTRATION DIRECTOR David Georges Tel: +32 (0) Fax: +32 (0) david.georges@diasource.be

3 Table of Content Our Company 30 years of experience in IVD 2 Mission 2 Product range 2 Commitment to quality 2 Branch and International Distributors by country To order from your country 3-10 Products Auto-Immunity Biogenic Amines Bone Metabolism Cancer Markers Cardiovascular & Salt balance Diabetes & Metabolism Fertility Growth Factors Miscellaneous Thyroid Function Custom Diagnostic Laboratory services & Sales Conditions 39 Index by Catalog # & Product Name 40 Table of Content 1

4 Our Company 30 years of experience in IVD (kits and instrumentation) DIAsource ImmunoAssays (formerly BioSource) an international diagnostics company (Belgium), develops, manufactures and markets clinical diagnostic products in the field of endocrinology and infectious diseases. Core products are RIA and ELISA technology and reagents for open ELISA automated analyzers as well as antibodies for use in in-vitro diagnostic assays with specific development and manufacturing programs for Vitamin D, Renin, Calcitonin and many others. We also provide selected instrumentation : we offer Elisa reader, washer and shaker, along with open and closed fully automated Elisa platforms helping our customers to automate their tests. It is our ambition to use our 30 years of expertise in Antibody and Assay development to become a well-known company of diagnostic immunoassays and instrumentation for the IVD market. Mission Our mission is to develop, manufacture and market a complete panel of quality immunoassays and instrumentation as accurate, reliable, diagnostic tools to detect and monitor endocrine disorders and infectious diseases. We are dedicated to provide highly reliable quality assays and instrumentation to deliver uncompromising support to our customers. We strive for meeting our customers needs through a long-term professional relationship and by representing a real added value. Our company is driven by commitment to quality of products and services. Product range During the last 30 years, we have developed manual ELISA and RIA immunoassays for the diagnosis and monitoring of a wide variety of endocrine disorders. We constantly reworked and developed specific antibodies for use in our diagnostic assays and we offer these antibodies also to other diagnostic companies. Constantly looking for new technologies and applications, we put our expertise in the development of new antibodies (patent pending) and assays to measure 25 OH Total Vitamin D (D2+D3). We are strengthening our position in the diagnostic market by validating our ELISA assays on our open and closed automates. This innovation marks a turning point for our company, and makes of DIAsource, already renowned in the RIA market, a complete diagnostic provider. The interest in Vitamin D is rising rapidly. Since more than 10 years DIAsource manufactures immunoassays for 25 OH Vitamin D3 and 1,25 (OH) 2 Vitamin D. In our assay development program we are focusing specifically on new Vitamin D assays. We introduced a new Total Vitamin D (D2 + D3) Ria and Elisa assay, together with a Rat 25 OH Vit D Elisa kit for clinical research studies. A 1,25 (OH) 2 Vit D Elisa kit will complete our panel soon. The ELISA versions will also be made on our instruments. Commitment to quality We believe that the quality of products and services finds its origin in scientific expertise, a good organization of all operational activities and in well-structured decision processes. These principles are laid out in our ISO 13485:2003 quality manual. Through an integration of product quality in our development and manufacturing processes and a specific customeroriented approach we have directed our quality system to comply with the harmonized standard for quality systems within the context of the European Directive for In Vitro Diagnostics. Our internal quality management system is designed to pursue a continuous improvement of our customer service, our product quality and the efficiency of our operations. All our kits and instruments for in-vitro diagnostics (IVD) carry the CE mark and comply with IVD Directive requirements. Peter Kerckx International Sales & Marketing Director DIAsource ImmunoAssays S.A. Dr. Jozef Vangenechten CEO DIAsource ImmunoAssays S.A. 2 Our Company

5 To order from your country Branch and International Distributors by country Australia c Chile 4 China c Czech Republic 5 Denmark c Hungary 6 India c Latvia 7 Lebanon c Pakistan 8 Peru c South Africa 9 South Korea c Uruguay 10 To order from your country 3

6 To order from your country Australia Taylor Bio-Medical Pty Ltd 5 Taringa Street 2131 Ashfield NSW Tel: Fax: office@taylorbiomedical.com.au Bangladesh SMT International 14, Purana Palton (7th Floor) 1000 Dhaka Tel: smtbd@inbox.com smtbd@inbox.com Canada Inter-Medico 50 Valleywood Dr. Unit 1 L3R 6E9 Markham Ontario Tel toll free (EN): Tel (local): Tel toll free (FR): Fax: info@inter-medico.com Argentina Diagnos Med S.R.L. Conesa Buenos Aires Tel: Fax: info@diagnosmed.com Brazil Genese Produtos Diagnosticos Ltda Rua Diogo Vaz, 291 / Cambuci CEP Sao Paulo Tel: Fax: Mr Ricardo Di Dio ricardo.didio@gen.com.br Chile Gold Support Avda. Andrés Bello, 1051 Loc. 57 Providencia Santiago Tel: Mr Jose Francisco Vergara jfvergara@globalsupport.cl Austria Dia-Chrom Handelsges mbh Trazerberggasse Wien Tel: Fax: office@dia-chrom.at Bulgaria Electroncommerce Ltd Samokovsko Shose Sofia Tel: Fax: electron@techno-link.com Chile Laboratorio Livio Barnafi SA Avda. Andres Bello, 1195 Providencia Santiago Tel: Fax: Mr Esteban Barnafi ebarnafi@bklab.cl 4

7 To order from your country China Beijing North Institute of Biotech (BNIBT) Pan Jiamiao A20, Fengtai District Beijing Tel: Fax: jiazhengqian@sina.com Costa Rica Siemens Healthcare Diagnostics SA 200 este Plaza de Deportes La Uruca, Apdo San José Tel: Fax: Mr Ruben Alvarado ruben.alvarado@siemens.com Cyprus C & V Kriticos Suppliers Ltd 28 b,c,d Kalypsus Street P.O. Box Nicosia Tel: Fax: Mr Constantinos Kriticos constantinos@kriticos.com.cy China Union Medical & Pharmaceutical 238 Baidi Road, Nankai District Tianjin / Kun Yu Tel: Fax: info@union-med.com Croatia Jasika d.o.o. Remetinečka cesta Zagreb Tel: Fax: Mrs Ivana Tomicic ivana.tomicic@jasika.hr Czech Republic Eurorad Ltd Radiova Prague 10 Tel: Fax: euroradltd@seznam.cz Colombia Annar Diagnóstica Import SAS Calle 49 N Bogota Tel: Fax: info@annardx.com Cuba C.P.M. Scientifica Cuba 5ta Avenida y 80 Edificio Raffaelo Ciudad de La Habana Tel: Fax: cpm@cpmsas.it Czech Republic Lacomed Ltd Husinec Rez Tel: Fax: lacomed@lacomed.cz 5

8 To order from your country Denmark Biotech-IgG A/S Østerbrogade Copenhagen Tel: Fax: info@biotech-igg.com Finland Electra-Box Diagnostica Oy Lyhtytie Helsinki Tel: Fax: jussi.kontturi@electrabox.com Guatemala PCT Diagnostica Km 19.4 Carretera a El Salvador Villas del Pinar N 58 Fraijanes Tel: Fax: pctdiagnostica@gmail.com Denmark Electra-Box Diagnostica ApS Hvidsværmervej RØDOVRE Tel: Fax: berit.nielsen@electrabox.com Germany IBL International GmbH Flughafenstrasse 52a Hamburg Tel: Fax: ibl@ibl-international.com Honduras Prodylab Edificio Plaza San José Boulevard Suyapa Frente a Hospital Escuela Tegucigalpa Tel: eortezbprodylab@gmail.com Egypt Root Diagnostic Co. 3G/4 El Shekh El Shaarawy St. From El Laselky St. El Maadi Cairo Tel: Fax: Mr Abd El-Menem Nabih Mr Kamal El-Masry info@rootdiagnostic.com Greece Diachel S.A. 1 Alkimachou & 78 Sp. Merkouri street Athens Tel: Fax: info@diachel.gr Hungary Izinta Trading, Co. Ltd Konkoly Thege Miklos street Budapest Tel: Fax: info@izinta.hu 6

9 To order from your country India Immunoshop India Private Ltd 309, Raheja Arcade, Sector 11, CBD Belapur New Bombay Tel: Fax: Israel Medison Pharma Ltd 10 Hashiloach Street P.O. Box Petach-Tikva Tel: Mr Doron Belleli doronb@medison.co.il Jordan Al-Wafi Group P.O. Box Amman Tel: Fax: Mr Hamdallah hamdallah@al-wafigroup.com Iran Aria Pharmed N 41 Sayeh Street North Africa Boulevard Teheran Tel: Fax: ariadiagnostics@yahoo.com Italy Pantec Corso Svizzera, Torino Tel: Fax: info@pantec.it Kosovo Eramed Street Vasil Andoni, N Pristina Tel: info@era-med.com Ireland Cruinn Diagnostics Ltd 5b/6b Hume Centre Parkwest Industrial Estate Nangor Road Dublin 12 Tel: Fax: info@cruin.ie Japan Sceti K.K. DF Kasumigaseki Place Kasumigaseki, Chiyoda-Ku Tokyo Tel: Fax: Mr Atsushi Takiguchi atsushi.takiguchi@scetimedilabo.co.jp Latvia Interlux, SIA Jaunbumani. 2. korpuss Dreilini LV-2130 Stopuni Novads Tel: Fax: info@interlux.lv 7

10 To order from your country Lebanon Meato SARL BP Gouraud Street Zeeneh bldg. 5th Floor Beirut Tel: Fax: info@meato.net Moldova Global Biomarketing Group Tighina street 65 Office Chisinau Tel: Fax: gbg@mcc.md New Zealand Taylor Bio-Medical Pty Ltd 5 Taringa Street 2131 Ashfield NSW Tel: Fax: office@taylorbiomedical.com.au Lebanon Numelab SARL Le 457 New Naccache P.O. Box Antelias Tel: Fax: purchase@numelab.com Morocco Cnesten BP 1382 RP Rabat Tel: Fax: Lalaoui Khalid lalaoui@cnesten.org.ma Norway Biotech-IgG A/S Østerbrogade Copenhagen Tel: Fax: info@biotech-igg.com Moldova DAC-SpectroMed srl 5/1 Cuza-Voda street MD 2060 Chisinau Tel: Fax: office@dascpectromed.com Netherlands MT-Diagnostics Netherlands BV Graafschap BX Etten-Leur Tel: Fax: info@mt-diagnostics.nl Pakistan Med Lab Services Flat N 1, ABC Plaza Commercial Center Satellite Town Rawalpindi Tel: Fax: hipropk@gmail.com 8

11 To order from your country Peru Genia Tech SAC Av. Castilla La Nueva F-20 La Molina Lima Tel: Fax: ventas@genia-tech.com Poland Lencomm Trade International, SJ Wolczynska P.O. Box Warszawa Tel: Fax: office@lencomm.pl Slovakia Bio Spectrum plus s.r.o. V Zahradach street Bratislava Tel: Fax: info@bio-spectrum.sk Tel: Fax: info@bio-spectrum.sk Philippines Global Medical Solutions 3/F, 14 Economia Street Bgy. Bagumbayan 1110 Quezon City Tel: (52-53) Fax: gms@info.com.ph Portugal Meditecno Praceta de Portugal N 63B Quinta de Sao Goncalo Carcavelos Tel: Fax: info@meditecno.pt Slovenia Karanta Ljubljana d.o.o. Poljanski nasip Ljubljana Tel: Fax: karanta.medicals@siol.net Poland Institut of Atomic Energy (Polatom) ul. Andrzeja Soltana Otwock-Swierk Tel: (57) Fax: Mrs Malgorzata Kozielska m.kozielska@polatom.pl Singapore Dyamed Biotech Pte Ltd 10 Ubi Crescent, Lobby C Ubi Techpark Singapore Tel: Fax: Mrs Rose Tan rosetan@dyamed.com South Africa Laboratories Specialities (Pty) Ltd P.O Box Randburg Tel: Fax: Mr Christiaan Johannes Stoltz johannes.christiaan.stoltz@thermofisher.com 9

12 To order from your country South Korea Kwang Won Trading 3F, 12, Teheran-ro 19-gil Ganam-Gu Seoul Tel: Fax: kwtc@kwtc.kr Syria Biomedical Technologies Center Baghdad Street-Salim Abdoon Avenue P.O. Box 5660 Damascus Tel: (9) Fax btclab@btclab.com United Kingdom Oxford Biosystems 40 Church Road, Wheatley OX33 1NB Oxford Tel: Fax: sales@oxfordbiosystems.com Spain DIASource Iberia S.L. Avinguda Josep Tarradellas, 38, Despacho Barcelona Tel: Tel: Mr Alberto Rosell alberto.rosell@diasource.be Taiwan Taiwan Life Support Systems, Inc. 15F N 81, Chen-Teh Road, Sec Taipei Tel: Fax: info@tlss.com.tw United States of America Gold Standard Diagnostics 2851 Spafford Street, Suite A CA Davis Tel: Fax: info@gsdx.us Sweden Electra-Box Diagnostica AB Solkraftsvägen 18B Stockholm Tel: Fax: Mrs Annika Karlen annika.karlen@electrabox.com Turkey Algen Diagnostik Laboratuvar N 30/3 Varlik Mahallesi Yenikapi Sokak Yenimahalle / Ankara Tel: (29) Fax: info@alpingen.com United States of America IBL America 8201 Central Ave NE, Suite P MN Minneapolis Tel: Fax: info@ibl-america.com Switzerland Dispolab AG Altmoosstrasse Dielsdorf Tel: Fax: dispolab@bluewin.ch United Arab Emirates SCINTILLA For Lab & M. Equipment. Butina, Sharq Street, Helal Bldg. F.N. 204 P.O. Box Sharjah Tel: Fax: Mr Saffouh Appesh appesh@emirates.net.ae Uruguay ENOL I. Raffo Arrosa 971 Montevideo Tel: Fax: enol@netgate.com.uy 10

13 Auto-Immunity Introduction 12 Acethylcholine Receptor (AChR) 12 Anti-Insulin Antibodies (AIA) 12 Anti-Thyroglobulin AutoAntibodies (Tg Ab) 12 Anti-Thyroperoxidase AutoAntibodies (TPO Ab) 12 Anti-TSH Receptors AutoAntibodies (TSH-R Ab) 12 Anti-ds DNA 12 Auto-Immunity 11

14 Auto-Immunity Introduction Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease. Prominent examples include Coeliac disease, diabetes mellitus type 1 (IDDM), systemic lupus erythematosus (SLE), Sjögren's syndrome, Churg-Strauss Syndrome, multiple sclerosis (MS), Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, and rheumatoid arthritis (RA). Hashimoto s Thyroiditis The body normally produces antibodies to foreign substances such as bacteria; however, some people are found to have antibodies against their own thyroid tissue. A condition known as Hashimoto's Thyroiditis is associated with a high level of these thyroid antibodies in the blood. Whether the antibodies cause the disease or whether the disease causes the antibodies is not known; however, the fin- ding of a high level of thyroid antibodies is strong evidence of this disease. Occasionally, low levels of thyroid antibodies are found with other types of thyroid disease. When Hashimoto's thyroiditis presents as a thyroid nodule rather than a diffuse goiter, the thyroid antibodies may not be present. Myasthenia gravis (MG) is a skeletal muscle disorder characterized by muscular weakness. In such cases, muscular weakness is due to anti-acetylcholine receptor (AChR) antibodies. Anti-AChR antibodies are present in approximately 90% of patients with MG. Anti-AChR antibodies could be: binding antibodies (multitudes of wide populations of antibodies directed to hydrophilic domains of receptors), blocking antibodies (preventing binding of acetylcholine to receptors) and modulating antibodies (accelerating endocytosis resulting in loss of receptors). Thyroid Antibody Acronym Present in: Thyroid peroxidase antibody TPOAb Hashimoto s thyroiditis; Graves disease Thyroglobulin antibody TgAb Thyroid cancer; Hashimoto s thyroiditis FORMAT CAT# LABEL SIZE Acethylcholine Receptor (AChR) SAMPLE TYPE SAMPLE SIZE (µl) CONTROL LEVELS RANGE SENSITIVITY INCUBATION (HOURS) RIA KIPIB21021 I 100 T S, P ,2-8,0 nmol/l 0,01 nmol/l 3 11 Anti-Insulin Antibodies (AIA) RIA KIP0091 I 100 T S, P % <8,2% 2,25 8 Anti-Thyroglobulin AutoAntibodies (Tg Ab) RIA CT RVR-CI-100** I 100 T S IU/mL 6 IU/mL 1,5 8 Anti-Thyroperoxidase AutoAntibodies (TPO Ab) RIA CT RVR-CO-100** I 100 T S U/mL 1,3 U/mL 1,5 8 Anti-TSH Receptors AutoAntibodies (TSH-R Ab) RIA CT RVR-CT-100** I 100 T S U/mL 0,8 U/mL 2,5 5,5 Anti-ds DNA RIA KIPIB19011 I 100 T S IU/ml 2.5 IU/ml MAX SHELF LIFE (WEEKS) REMARKS not distributed in Austria, Germany & Netherlands not distributed in Belgium, and Germany not distributed in Belgium, and Germany not distributed in Belgium, and Germany 12 Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates

15 Biogenic Amines Introduction 14 2 CAT (Adrenaline and Noradrenaline) 15 3 CAT (Adrenaline, Noradrenaline and Dopamine) 15 Adrenaline (Epinephrine) 15 Dopamine 15 Melatonin 15 Melatonin (Saliva) 15 Metanephrine 15 Nephrines 15 Noradrenaline (Norepinephrine) 15 Normetanephrine 15 Serotonin 15 Biogenic Amines 13

16 Biogenic Amines Introduction Biogenic amine is a chemically imprecise term, which, by convention, includes the catecholamines: Epinephrine (or adrenaline), Norepinephrine (or Noradrenaline) and Dopamine, the indoleamine Serotonin, the imidazolamine Histamine and compounds closely related to each of these. They are produced by decarboxylation of amino acids. These biogenic amines play key roles in neurotransmission and other signalling functions. IgE receptor Granula with mediators Sensitised mast cell with IgE Catecholamines The principal catecholamines are norepinephrine (noradrenaline), epinephrine (adrenaline) and dopamine. These compounds are formed from phenylalanine and tyrosine. Tyrosine is produced in the liver from phenylalanine through the action of phenylalanine hydroxylase. The tyrosine is then transported to catecholamine-secreting neurons where a series of reactions convert it to dopamine, to norepinephrine and finally to epinephrine. The measurement of catecholamines in biological luids ( biogenic amines ) is routinely performed for the diagnosis of biogenic amine-secreting tumours (i.e., pheochromocytoma, neuroblastoma). Pheochromocytoma, a tumour of the chromain tissue, is associated with the presence of greatly increased plasma and urinary catecholamine concentrations. Elevated catecholamines have also been found in patients with other tumours of neural tube origin, such as neuroblastomas and ganglioneuroblastomas. Assessment of Biogenic Amines Antigen (Allergen) Histamine Antigens binding to IgE receptor release of mediators Histamine is the most important mediator in human and is mostly found in the initial phase of anaphylaxis ( immediate type allergy). Histamine acts predominantly on smooth muscle and blood vessels. Major effects include widespread arteriolar dilation, local increased capillary permeability by contracting endothelial cells, contraction of nonvascular smooth muscle, bronchoconstriction, chemotaxis for eosinophils, blocking T lymphocyte function and gastric acid secretion. Melatonin The major hormone secreted by the pineal gland - is a key modulator of annual and circadian biorhythms. Its circadian profile in body fluids is an excellent marker for the setting of the endogenous clock. Daytime plasma Melatonin levels are low and rise in the evening (onset). Night-time levels peak at around hrs. (acrophase) in most healthy humans. As a general modulator of human biorhythm, Melatonin is involved in the timing of functions such as sleep, mood, reproduction and immune system activity. Nephrines Normetanephrine and metanephrine are physiologically formed from the catecholamines noradrenaline and adrenaline by the enzyme catechol-o-methyltransferase (COMT). Increased levels of normetanephrine und metanephrine can be found in patients suffering from pheochromocytoma, ganglio - neuroma and other neurogenic tumors. Serotonin is well established as a neurotransmitter in the central nervous system. Altered concentrations of circulating serotonin have been implicated in several pathologic conditions including chronic tension migraine, schizophrenia, hypertension, Huntington s disease, Duchenne s muscular dystrophy and early acute appendicitis. The determination of serum serotonin levels is of high clinical significance for diagnostic assessment of carcinoid syndrome. The concentrations of catecholamines may be determined in serum, plasma, urine, other body fluids and even cell culture supernatants. The most commonly used methodology is HPLC combined with electrochemical detection.however this methodology is subject to analytical error, when synthetic sympatho-mimetic therapeutic agents, in comparatively high concentrations present, interfere with the quantitative determination of endogenous catecholamines. Peaks arriving from these synthetic agents will mask the biogenic amine peaks, making exact determinations almost impossible. An alternative and more specific method for the determination of biogenic amines in any type of sample is immuno-assay, whether as radioimmunoassay (RIA) or enzyme immunoassay (ELISA) These immunoassays correlate very well with the standard HPLC methodology, but have additional advantages: No predilution of the sample Short assay time Easy automation for high sample throughput, esp. ELISA No interference from therapeutic drugs and their metabolites High specificity : the only compound measured is the biologically active L-isomer Superior sensitivity, even in combination with small sample volume 14 Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates

17 Biogenic Amines FORMAT CAT# LABEL SIZE SAMPLE TYPE 2 CAT (Adrenaline and Noradrenaline) SAMPLE SIZE (µl) CONTROL LEVELS RANGE SENSITIVITY INCUBATION (HOURS) MAX SHELF LIFE (WEEKS) RIA KIPL1500 I 2 x 96 T U,EP 10/300 2 see Adrenaline RIA and Noradrenaline RIA 3 CAT (Adrenaline, Noradrenaline and Dopamine) RIA KIPL1600 I 3 x 96 T U,EP 15/600 2 see Adrenaline RIA, Noradrenaline RIA and Dopamine RIA Adrenaline (Epinephrine) RIA KIPL0100 I 96 T U,EP 10/ ,9-90 ng/ml 300/10 pg/ml 4 or ON 14 Dopamine RIA KIPL0300 I 96 T U,EP 15/ ng/ml 800/20 pg/ml 4 or ON 14 Melatonin RIA (direct) KIPL3300 I 100 T EP, S pg/ml 2 pg/ml ON 14 Melatonin (Saliva) RIA (direct) KIPL3400 I 100 T Sa pg/ml 1,4 pg/ml ON 14 Metanephrine RIA (Plasma) KIPL0700 EP pg/ml 5 pg/ml ON I 50 T RIA (Urine) KIPL0500 U ng/ml 5 pg/ml 3 Nephrines RIA (Plasma) KIPL1400 I 14 REMARKS 2 x 48 T EP see Metanephrine Plasma RIA and Normetanephrine Plasma RIA RIA (Urine) KIPL x 48 T U 25 2 see Metanephrine Urine RIA and Normetanephrine Urine RIA Noradrenaline (Norepinephrine) RIA KIPL0200 I 96 T EP, U 10/ ,9-90 ng/ml 1500/50 4 or ON 14 Normetanephrine RIA (Plasma) KIPL0600 EP pg/ml 10 pg/ml ON I 50 T 2 RIA (Urine) KIPL0400 U ng/ml 13 ng/ml 3 Serotonin RIA KIPL0900 I 100 T S/P/U/Pl/ CSF ng/ml 0,33 to 6,7 ng/ml 2, *=For Research Use Only Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates 15

18 Bone Metabolism Introduction 17 Osteocalcin 18 Intact ParaThyroid Hormone (PTH) 18 1,25 (OH) 2 Vitamin D OH Vitamin D OH Vitamin D Total Bone Metabolism

19 Bone Metabolism Introduction Bones are continuously undergoing a dynamic process of resorption and absorption known as bone metabolism. Signaling pathways on which bone metabolism rely include the action of several hormones, including Osteocalcin, parathyroid hormone (PTH) and Vitamin D. As Osteocalcin, the major non-collagenous protein of the bone matrix, is manufactured by osteoblasts, it is often used as a biochemical marker, for the bone formation process. A large number of studies indicate that serum-osteocalcin levels reflect very well the rate of bone formation. The determination of blood levels of Osteocalcin is valuable for The identification of women at risk of developing osteoporosis Monitoring bone metabolism in several clinical conditions: during peri- and post menopause during Hormone Replacement Therapy patients with GH deficiency, Renal osteodystrophy Vitamin D plays an important role in the maintenance of major organ systems: Vitamin D regulates the calcium and phosphorus levels in the blood and inhibits parathyroid hormone secretion from the parathyroid gland. Vitamin D deficiency can result from inadequate intake coupled with inadequate sunlight exposure, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders, or, rarely, by a number of hereditary disorders. Deficiency results in impaired bone mineralization, and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis. Research has also indicated that vitamin D deficiency is linked to colon cancer and more recently, to breast cancer. Conflicting evidence links vitamin D deficiency to other forms of cancer. The major form of Vitamin D, 25 OH Vitamin D, has a limited biological activity and is converted in the kidney to 1,25 (OH)2 Vitamin D3 a more active derivate; The blood levels of 1,25 (OH)2 D3 being 100 to 1000 less than 25OH D it requires extraction and separation steps prior to measurement. Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids and is the major physiological regulator of phosphocalcic metabolism. It acts to increase the concentration of calcium (Ca2+) in the blood. Measurements of PTH is used in: Diagnose hyperparathyroidism (elevated levels of intact PTD Differentiation between hypoparathyroidism and hypercalcemia It allows documenting the occurrence of secondary hyperparathyroidism in patients with Vitamin D deficiency, intestinal malabsorption, or renal failure. In this last situation the absence interference with the inactive carboxyl-terminal fragments is especially valuable. Aggrecan (PG) is the predominant proteoglycan species in articular cartilage. The loss of PG and other matrix components from the cartilage leads to destruction of the tissue, causing complete deterioration of the articular surface. PG and PG fragments released in synovial fluid and serum during this degradation process might serve as markers of the metabolic changes in diseased cartilage. The DIAsource Aggrecan EASIA assay provides and easy, non-invasive methodology for the quantification of cartilage turnover. It can also be used for the monitoring of the effect of drugs on the cartilage turnover. Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates 17

20 Bone Metabolism UVB Dietary sources of Vitamin D2 and D3 skin 7-dehydrocholesterol pre Vitamin D3 Heat Vitamin D lipoprotein Vitamin D3 DBp Vitamin D Vitamin D 25-ohase DBp CIrCUlATIoN 25(oh)D - Vitamin D Urine Calcitroic acid 24-ohase 1,25(oh)2D + 1-ohase 1-ohase p, Ca2+, & other factors 1,25(oh)2D preosteoclast rankl pth ng/ml of 25(oh) Vit D* VITAMIN D related DIseAses: Vit D Deficiency <10 Rickets in Children Vit D Insufficiency Osteoporosis, Osteomalacia patient status Vit D Sufficiency > Risk for Toxicity >100 osteoblast pth Calcium & phosphorus Ca2+AND hpo42absorption Cancer Bone mineralization Peripheral Artery Disease on a vast majority of clinical studies to define normal circulating 25 OH VIT D levels e.g. US National health and Nutrition Examination Survey (US NHANES-study) Auto Immune Diseases Ca2+AND hpo42- release Mature osteoclast Blood Type II Diabetes *Based rank Metabolic functions Neuromuscular functions Parkinson s disease DIAsource ImmunoAssays S.A., Belgium Vitamin D2-D3-Shéma3-ssfond.indd 1 19/10/ :53:54 FORMAT CAT# LABEL KIP1381 SIZE SAMPLE TYPE SAMPLE SIZE (µl) CONTROL 96 T S, P 50 MAX SHELF RANGE SENSITIVITY INCUBATION (HOURS) 2 1,9-69 ng/ml 0,22 ng/ml 2 7 LEVELS LIFE (WEEKS) REMARKS Osteocalcin IRMA I Intact ParaThyroid Hormone (PTH) IRMA KIP1491 I 96 T S, P ,4-973 pg/ml 4,1 pg/ml 2 7 I 48 T S, P pg/ml 1,4 pg/ml ON 10 1,25(OH)2 Vitamin D KIP1929 RIA CT set including solvents for 5 kits of 1,25(OH)2 Vitamin D shaker for extraction (IKA Vibrax 1200 RPM) support rack for tubes (to be used with shaker) extra cartridges for extraction (1 bag of 20 cartridges) 25OH Vitamin D3 RIA CT KIP1961 I 96 T S, HP ng/ml 1,2 ng/ml T S ng/ml 1.5 ng /ml OH Vitamin D Total RIA CT 18 KIP1971 I Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates

21 Cancer Markers Introduction 20 Alpha-Fetoprotein (AFP) 21 CA 21 CA CA Calcitonin Ultra Sensitive (CT US) 21 Carcino Embryonic Antigen (CEA) 21 Chromogranin A (CgA) 21 Gastrin 21 b-hcg Free 21 Neuron Specific Enolase (NSE) 21 Prostate Specific Antigen (PSA) 21 Free Prostate Specific Antigen (Free PSA) 21 Thyroglobulin (Tg S) 21 Cancer Markers 19

22 Cancer Markers Introduction Serum tumor markers is a term commonly used to refer to molecules that can be detected in a blood sample by immunochemical methods. Tumor markers are produced either by the tumor (cancer) itself or by the body in response to the presence of cancer or certain non-cancerous ( benign ) conditions. Measurements of tumor marker levels by serum markers can be useful in following clinical settings: 1. Diagnosis Serum tumor markers can, when used along with X-rays or other tests, aid in diagnosis of some types of cancer. They also can aid in locating the source of cancers that have metastasized. 2. Monitoring for recurrence of tumor After successful treatment of a cancer patient, tumor marker(s) are regularly tested to indicate whether there is a recurrence of the cancer. 3. Prognosis and staging Serum tumor markers can be used as aid in the tumor volume estimation, as a helpful tool to indicate tumor progression, or as indicator of metastasis involvement. 4. Detection of residual disease After surgery of a specific cancer, serum tumor markers can be used to indicate whether the entire tumor burden has been successfully removed. 5. Monitoring treatment Serum tumor markers can be used as tool to assess the outcome of treatment by monito ring a patient s response to a specific or various treatment regimens. In general serum marker levels will drop if treatment is beneficial and will remain e-levated or increase when treatment is not effective. Currently, the main use of tumor markers is to assess a cancer s response to treatment and to check for recurrence. Carcinoid Tumor Tumor secretes CgA into the blood Blood Test CgA Cancer marker Clinical use AFP (Alpha-Fetoprotein) CA CA 15-3 CA 19-9 Testicular Cancer, Ovarian cancer, Malignant teratoma Ovarian cancer, Endometrial cancer Breast cancer Pancreatic cancer, Colorectal CEA (Carcino Embryonic Antigen) Colorectal, lung and breast cancers CgA (Chromogranin A) CT us (Calcitonin Ultra sensitive) Gastrin Beta-hCG( Free beta human Chorionic Gonadotropin) NSE (Neuron Specific Enolase) Tg-S (Thyroglobuline) Small - Cell Lung Carcinoma (SCLC) Tumors of neuroendocrine origin Medullary Thyroid carcinoma (MTC) Gastrin producing tumors Throphoblastic and testicular cancers Medullary thyroid carcinoma Pancreatic islet cell cancer Small Cell Lung Cancer (SCLC) Thyroid cancer 20 Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates

23 Cancer Markers FORMAT CAT# LABEL SIZE Alpha-Fetoprotein (AFP) SAMPLE TYPE SAMPLE SIZE (µl) CONTROL LEVELS RANGE SENSITIVITY INCUBATION (HOURS) IRMA KIPB1441 I 96 T S IU/mL 0,2 IU/mL <1 10 CA IRMA KIP0301 I 96T S ,8-786 U/mL 0,7 U/mL 3 11 CA 15-3 IRMA KIP0321 I 96 T S , U/mL 0,33 U/mL 3 11 CA 19-9 IRMA KIP0311 I 96 T S ,8-1061U/mL 0,7 U/mL 1,5 11 Calcitonin Ultra Sensitive (CT US) IRMA KIP0429 I 96 T S pg/ml 0,9 pg/ml ON 5 Carcino Embryonic Antigen (CEA) IRMA KIP0331 I 96 T S ng/ml 0,17 ng/l 2 9 Chromogranin A (CgA) RIA KIPERB321 I 100 T S, P ,156-5 nmol/l 0,04 nmol/l ON 12 Gastrin RIA KIPEMD302 I 100 T S ,6-500 pmol/l 5 pmol/l 1,75 11 b-hcg Free IRMA KIP1001 I 96 T S ,29-93 miu/ml 0,03 miu/ml 1 9 Neuron Specific Enolase (NSE) IRMA KIP2471 I 96 T S ,5-270 ng/ml 0,19 ng/ml 2 11 Prostate Specific Antigen (PSA) IRMA RVRK-10CT I 100 T S ,1-80 ng/ml 0,004 ng/ml 2 8 Free Prostate Specific Antigen (Free PSA) IRMA RVRK-85CT I 100 T S ,1-100 ng/ml 0,047 ng/ml 2 8 Thyroglobulin (Tg S) MAX SHELF LIFE (WEEKS) REMARKS 1 IU= 1IU 1st IRP 72/225 1pg= 0,19µIU 2nd IS 89/620 1 IU= 1IU st IRP 73/601 1 miu=1miu 3rd IRP 75/551 IRMA Normal 50 1,5-600 ng/ml 0,3 ng/ml 8 not distributed RVR-CM-100 I 100 T S, P in Belgium IRMA Sensitive 100 0, ng/ml 0,10 ng/ml 8 and Germany Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates 21

24 Cardiovascular & Salt Balance Introduction 23 Adrenocorticotropic Hormone (ACTH) 24 Aldosterone 24 Angiotensin II 24 Corticosteroid Binding Globulin (CBG) 24 Cortisol Desoxycortisol 24 Renin (Active) 24 Renin Plasma Activity 24 Vasopressin Cardiovascular & Salt Balance

25 Cardiovascular & Salt Balance Introduction The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance. Renin activates the renin-angiotensin system by cleaving angiotensinogen, produced by the liver, to yield angiotensin I, which is further converted into Angiotensin II by ACE (Angiotension Converting Enzyme). Most important site for Renin release is the kidney. Angiotensin also stimulates the secretion of the hormone Aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body, which also increases blood pressure.if the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. Angiotensin II also stimulates the release of vasopressin (antidiuretic hormone, ADH) from the pituitary which acts upon the kidneys to increase fluid retention Vasopressin (ADH) also known as Arginine vasopressin (AVP), vasopressin, argipressin or antidiuretic hormone (ADH), is a cyclic nanopeptide with a molecular weight of 1083 Dalton. Most of it is stored in the posterior pituitary to be released into the blood stream; however, some of it is also released directly into the brain. One of the most important roles of Vasopressin is to regulate the body's retention of water: when the body is dehydrated. Vasopressin is released causing the kidneys to conserve water, thus concentrating the urine, and reducing urine volume. It also involved in the blood circulation because it increases the resistance of the peripheral vessels and thus increases arterial blood pressure. Vasopressin released within the brain has many actions It is suggested that ADH has been implicated in memory formation, including delayed reflexes, image, short- and long-term memory. Adrenocorticotropic Hormone (ACTH) is released intermittently from the anterior pituitary (adenohypophysis). ACTH circulates in plasma without any obvious binding to transporting peptide and, like other small protein hormones, disappears rapidly from blood with a half-life of 5 to 10 minutes in vivo. The production of ACTH by the pituitary is primarily under the influence of three factors: the level of cortisol-like steroids, a biologic clock, and stress. When the cortisol level increases, the production of ACTH decreases, due to a negative feed-back control. Associated medical conditions are: Addison s disease, Cushing s syndrome, Congenital Adrenal hyperplasia. Cortisol Binding Globulin (CBG) or Transcortin a plasma α1-glycoprotein with a molecular weight of approximately Dalton. Since the plasma concentration of transcortin varies between 0.4 and M, the major fraction of cortisol in plasma is bound to this protein. This transcortinbound cortisol is considered to be biologically inactive, whereas the unbound cortisol constitutes the active form of cortisol. Transcortin is produced by the liver and is regulated by estrogens. Therefore, plasma transcortin levels increase during pregnancy, and are decreased in cirrhosis. 4 Angiotensin II 3 Angiotensin converting enzime Fetuin, a glycoprotein present in the circulation, is synthesized by hepatocytes. It is the most important and major calcification regulating protein in the circulation. Fetuins are blood proteins, which are made in the liver and secreted into the blood stream. They belong to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the blood stream (e.g. Serum Albumin) The function of inhibiting soft tissue calcification is achieved by forming a soluble colloidal microsphere of fetuin-calcium-phosphate complex in the bloodstream. 11-Deoxycortisol (or cortodoxone) is a steroid, and an immediate precursor to the production of cortisol. It can be synthesized from 17-hydroxyprogesterone. Used clinically in a) the diagnosis of, and monitoring therapeutic response in, congenital adrenal hyperplasia due to 11b-hydroxylase deficiency b) the Assessment of adrenal response in the metyrapone test. Blood pressure rises 5 Aldosterone Salt retention Angiotensin I 2 Renin 1 Angiotensinogen Blood pressure falls Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates 23

26 Cardiovascular & Salt Balance Paraventricular nucleus Supraoptic nucleus ADH and oxytocin produced here Anterior pituitary Anterior pituitary ADH and oxytocin released FORMAT CAT# LABEL SIZE SAMPLE TYPE Adrenocorticotropic Hormone (ACTH) SAMPLE SIZE (µl) CTRLS RANGE SENSITIVITY INCUBATION (HOURS) IRMA KIP0061 I 96 T EP , pg/ml 1,16 pg/ml 3 7 Aldosterone RIA CT RVR-CW-100 I 100 T S, U 200, pg/ml 1,4 pg/ml ON or 3 8 Angiotensin I RIA KIPB3518 I 100 T P , ng/ml 0,07 ng/ml 2 8 Angiotensin II MAX SHELF LIFE (WEEKS) REMARKS 1pg=1pg of NIBSC 74/555 not distributed in Belgium, and Germany, RIA KIPERB320 I 100 T P ,7-150 pmol/l 2 pmol/l ON 11 Corticosteroid Binding Globulin (CBG) RIA CT KIP1809 I 96 T S ,44-8 µg/ml 0,26 µg/ml 2,5 7 Cortisol** S, P, U: 25 µl S, P, U: µg/l S, P, U: 0,9 µg/l S, P, U: 0,75 RIA CT KIPI28000 I 96 T S, P, U, Sa 2 8 Sa: 200 µl Sa: µg/l Sa 0.53 µg/l Sa: 2 11-Desoxycortisol RIA CT KIPI20000 I 96 T S ,3-65 ng/ml 0,04 ng/ml 2,5 12 Renin (Active) IRMA KIP1531 I 96 T EP pg/ml 0,78 pg/ml 3 6 Renin Plasma Activity RIA RVR-EX- I T EP ,2-25 ng/ml 0,033 ng/ml ON 7 Vasopressin RIA KIPERB319 I 100 T P, U ,9-60 pmol/l 0,5 pmol/l *=For Research Use Only * This product can be sold in Canada not distributed in Belgium and Germany 24 Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates

27 Diabetes & Metabolism Introduction 26 Anti GAD Anti IA2 27 Anti Insulin Antibodies (AIA) 27 C-Peptide (C-PEP) 27 Ghrelin 27 Glucagon 27 Insulin (INS) 27 Leptin 27 Diabetes & Metabolism 25

28 Diabetes & Metabolism Introduction Diabetes mellitus is a disorder of carbohydrate metabolism. It is a disease characterized by persistent hyper-glycemia (high blood sugar levels). It is a metabolic disease that requires medical diagnosis, treatment and lifestyle changes. There are three main forms of diabetes: type 1, type 2 and gestational diabetes (or type 3, occurring during pregnancy), although these three types of diabetes are more accurately considered patterns of pancreatic failure rather than single diseases. Type 1 is due to autoimmune destruction of the insulin-producing cells Type 2 and gestational diabetes are due to insulin resistance by tissues Type 2 may progress to destruction of the insulin producing cells of the pancreas, but is still considered Type 2, even though insulin administration may be required. Since insulin is the principal hormone that regulates uptake of glucose into most cells from the blood (primarily muscle and fat cells, but not central nervous system cells), defciency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus. Diabetes is a chronic disease, and emphasis is on managing short-term as well as longterm diabetes-related problems. There is an important role for patient education, nutritional support, self glucose monitoring, as well as long-term glycemic control. Obesity is a condition in which the natural e-nergy reserve, stored in the fatty tissue of humans and mammals, is increased to a point where it is a risk factor for certain health conditions or increased mortality. Obesity develops from the interaction of individual biology and the environment. Excessive body weight has been shown to correlate with various diseases, particularly cardiovascular disease, diabetes mellitus type 2, sleep apnea, and osteoarthritis. Obesity is both an individual clinical condition and is increasingly viewed as a serious public health problem. 26 Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates

29 Diabetes & Metabolism FORMAT CAT# LABEL SIZE Anti GAD 65 SAMPLE TYPE SAMPLE SIZE (µl) CONTROL LEVELS RANGE SENSITIVITY INCUBATION (HOURS) RIA RVRIA2057 I 100 T S µ/ml 0,6 U/mL 3,33 8 Anti IA2 RIA RVRIA5226 I 100 T S, ,75-50 U/mL 0,19 U/mL 19 5 Anti Insulin Antibodies (AIA) RIA KIP0091 I 100 T S, P % <8,2% 2,25 8 C-Peptide (C-PEP) RIA CT KIP0409 I 96 T S ,09-9,94pmol/mL 0,04 pmol/ml 3 8 Ghrelin RIA KIPMR90* I 100 T E P pg/ml 40 pg/ml ON 10 Glucagon RIA RV I T P pg/ml 14,5 pg/ml ON 5 Insulin (INS) IRMA Leptin KIP1** KIP4 I 96 T 384T MAX SHELF LIFE (WEEKS) S, P ,7-440 µiu/ml 1 µiu/ml 2 7 RIA CT KIPMR44 I T S, P ng/ml 0,1 ng/ml REMARKS Incubation at 2-8 C 1ng= 1ng of the NIBSC 84/510 1 µiu= 1µIU 2nd IRP 66/304 *=For Research Use Only * *This product can be sold in Canada Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates 27

30 Fertility Introduction 29 Androstane Diol Glucuronide RIA CT 30 Androstenedione 30 Dehydroepiandrosterone- Sulfate (DHEA-S) 30 Dehydroepiandrosterone (DHEA) 30 Estradiol, 17b (E2) 30 Estrone (E1) 30 Total Estrogens 30 Follicle Stimulating Hormone (FSH) 30 Chorionic Gonadotropin + b (hcg+b) 30 Luteinizing Hormone (LH) 30 Progesterone (PROG) 30 Progesterone, 17 a Hydroxy- (17aOH-PROG) 30 Prolactin (PRL) 30 Sex Hormone Binding Globulin (SHBG) 30 Testosterone 30 Testosterone, Free 30 Testosterone, 5 a Dihydro (DHT) Fertility

31 Fertility Introduction In order to understand the causes of infertility and the role modern infertility treatment plays in assisting conception, it is useful to look at the natural process - a woman's ovulatory cycle and the production of sperm in the male - and the hormones that play a major role in those processes. The gonadotropins are hormones that primarily affect the ovaries and the testes. They regulate the development and hormone-secreting functions of these organs and contribute to the production of sperm in the male and to the development and maturation of eggs (oocytes) in the female. Three gonadotropins are essential to reproduction: human follicle stimulating hormone (hfsh), human luteinizing hormone (hlh) and human chorionic gonadotropin (hcg). FSH and LH are secreted by the pituitary gland situated beneath the brain. Their secretion is controlled by another hormone, the gonadotropin-releasing hormone (GnRH) produced by the hypothalamus. hcg is primarily produced by the placenta following successful implantation, and plays a role in maintaining pregnancy. Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and development of male secondary sex characteristics. Androgens, which were first discovered in 1936, are also called androgenic hormones or testoids. Androgens are also the original anabolic steroids. They are also the precursor of all estrogens, the female sex hormones. The primary and most well-known androgen is testosterone. A subset of androgens, adrenal androgens, includes any of the 19-carbon steroids synthesized by the adrenal cortex, the outer portion of the adrenal gland (zonula reticularis - innermost region of the adrenal cortex), that function as weak steroids or steroid precursors, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione. Besides testosterone, other androgens include: Dehydroepiandrosterone (DHEA): a steroid hormone produced in the adrenal cortex from cholesterol. It is the primary precursor of natural estrogens. Androstenedione (Andro): an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenediones are converted metabolically to testosterone and other androgens, they are also the parent structure of estrone. Androstenediolandandrostanediolglucuronide: steroid metabolites that is thought to act as the main regulator of gonadotropin secretion Androsterone: a chemical by-product created during the breakdown of androgens, or derived from progesterone, that also exerts minor masculinising effects, but with one-seventh the intensity of testosterone. It is found in approximately equal amounts in the plasma and urine of both males and females. Dihydrotestosterone (DHT): a metabolites of testosterone, and a more potent androgens than testosterone in that it binds more strongly to androgen receptors. It is produced in the adrenal cortex. Legend: AF=Amiotic Fluid CP=Citrate Plasma CSF=Cerebrospinal Fluid EP=EDTA Plasma F=Feces HP=Heparin Plasma HS=High Sensitive IVD=In Vitro Diagnostics ON=Over night P=Plasma Pl=Platelets S=Serum Sa=Saliva SF=Synovial Fluid SP=Seminal Plasma TH=Tissue Homogenate U=Urine UD=Ultra-dialysates 29