Officiai Journal of International Society of Cosmetic Dermatology

Transcription

1 : 1 o y e a. r s Officiai Journal of International Society of Cosmetic Dermatology INTERNATIONAL EDIEMME Volume 10 - Number 4 October/December 1992 ISSN Sped. abb. post. IV 0 70

2 MAVI IN GINECOLOGlfl LA GIUSTA SOLUZIONE,,. l.,. "... 8.i'Ef:NO INTIMO E»6EID.~ INTIMO ttf1 mav1 GYNECOlOGY la ricerca scientifica nella dermocosmesi Per Campioni Medici e Documentazione Scientifica scrivere a: MAVI SUD s.r.l. - Direzione Propaganda Medica Viale dell'industria, Aprilia (LT)

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5 DERMATOLOGIA COSMETOLOGICA A cura di P. Morganti e L. Muscardin Ed. International Ediemme Indice 1 Volume Sezione I Considerazioni Generali 1 Cenni storici 2 La bellezza della figura umana Sezione II Fisiologia e Biologia della cute 3 Sviluppo della pelle 4 La struttura della cute 5 Biochimica e Fisiologia dell'epidermide 6 Biologia del tessuto connettivo 7 Sistema Vascolare ed innervazione de11a cute Sezione III La Cute come organo di assorbimento 8 Nozioni basilari sulla permeabilità e sull'assorbimento 9 Membrane e assorbimento 10 Metabolismo della cute e degli annessi cutanei Sezione IV Chimica e Chimico-Fisica dei preparati topici 11 Materie prime e principi attivi di uso cosmetologico 12 Emulsioni cd emu1sionanti 13 Tensioattivi di uso cosmetico 14 Gli antiossidanti e i fenomeni ossidativi dei grassi 15 Antimicrobici e preservanti cutanei 16 La profumazione dei cosmetici 17 Chimica e tossicologia dei coloranti 18 Prodotti cosmetici in aerosol Indice 2 Volume Sezion e V Trattamenti dermocosmetici del viso e del corpo 19 Detersione, protezione e normalizzazione della pelle 20 La cosmesi per l'uomo 21 Cosmetici per bambini 22 Preparati per il bagno 23 Maschere e peeling 24 I Depilanti Sezione VI La cute senile 25 Invecchiamento cutaneo 26 Il trattamento della cute senile Sezione VII Cosmetici e Psiche 27 Aspetti psicosomatici e somatopsichici in dermatologia cosmetologica Sezione VIII I danni cutanei 28 Patologia cutanea da cosmetici su base immunologica 29 Danni da cosmetici Sezione IX Annessi cutanei e dermocosmesi 30 Ghiandole sudoripare e sebacee 31 Deodoranti e antisudore 32 Struttura e proprietà dei capelli 33 [!etersione, protezione e normalizzazione dei capelli e del cuoio capelluto 34 Cosmetici decorativi ad effetto duraturo 35 Le unghie 36 Prodotti decorativi ad effetto temporaneo superficiale Indice 3 Volume Sezione X Seborrea e dermocosmesi 37 Caratteristiche chimico-fisiche e funzioni fisiologiche del sebo 38 Produzione e modificazioni del sebo nel sano e nel seborroico 39 Influenza dei trattamenti cosmetologici sui lipidi di superfice del viso e del capillizio 40 Attività ormonale e ghiandole sebacee 41 Il problema terapeutico dell'acne 42 Possibilità terapeutiche nella seborrea Sezione XI M~lanogenesi e dermocosmesi 43 Il sistema pigmentario 44 Filtri solari, pigmentanti diretti e depigmentanti Sezione XII Mucose orali e dermocosmesi 45 La salute della bocca e dei denti 46 Profilassi ed igiene dei denti e della bocca 47 Preparazioni cosmetiche per Ja cavità orale Sezione XIII Prodotti speciali 48 Omeopatia e cosmetici 49 Sollizioni per lenti a contatto 50 Cosmetici ipoallergenici 51 Cosmesi su basi naturali Sezione XIV Trattamenti estetici correttivi 52 Interventi correttivi di chirurgia plastica 53 Laserterapia 54 Crioterapia 55 Principi di mesoterapia 56 Ionoforesi 57 Interventi correttivi di camoufdage Sezione XV Controlli dermotossicologici 58 Valutazione delle materie prime e dei cosmetici finiti 59 Controlli tossicologici delle materie prime e del prodotto finito 60 Cosmetognosia. Funzionalità ed efficacia dei prodotti cosmetici Sezione XVI Problemi normativi e di Marketing 61 Nozioni di marketing e di pubblicità 62 Grafica pubblicitaria: implicazioni psicologiche 63 Normative di legge sui cosmetici nei vari paes i del mondo 64 La responsabilità civile dei trattamenti cosme tici 65 Giudizio medico-legale del danno estetico INFORMAZIONI PER L'ACQUISTO Il pagamento di Lit (Centoventimila) per l'acquisto del 1 volume di Dermatologia Coometologica può essere effettuato mediante assegni di conto corrente o per contanti indirizzandoli a: O Prenoto fin da ora i volumi 2 e 3 Con la presente richiedo: Copie n... del Volume n. 1 INTERNATIONAL EDIEMME Via Innocenzo XI, ROMA e/e bancario n Banco di Santo Spirito Ag. 23, ROMA O Invio in contrassegno O Accludo assegno n... (a pagamento quale anticipo di prenotazione) SpecificarecondizionidipagamentoefomireN Codice Fiscale se è r ichiesta fattura. TIMBRO E F1RMA

6 MAVIGEN. SHAMPOO EXTRA DELICATO AL COLLAGENE --

7 DALLA RICERCA MAVI GLI IDRATANTI A PERMEABILITA' SELETTIVA IDRATANTE PERLA CUTE SEBORROICA IDRATANTE DOPO TRATTAMENTO CON FARMACI IDRATANTE MONODOSE privo di conservanti NELLE XEROSI PRONUNCIATE L'IDRATAZIONE E L'ASSORBIMENTO PROGRAMMATI CON PRECISI INDICI NUMERICI LU1 ma VI La ricerca scientifica nella dermocosmesi. Mavi Sud S.r.l. - Viale dell'industria, Aprilia (L T). "' E ff.

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9 Cosmetic Dermatology Series Editor: P. Morganti Volume 2 Every day Problems in Dermatology: The Cosmetic Connection Editors: P. Morganti, F.J.G. Ebling Every day Problems in Dermatology: The Cosmetic Connection is the second addition to the Cosmetic Dermatology Series This book is comprised of 41 previously unpublished papers dealing with research in various fields of cosmetic dermatology. The main themes covered are: inter-relationship between drugs and cosmetic in the skin; the efficacy of, and the raction to, cosmetics; cosmetics in sports and work; cosmetics in relation to sexuality and pregnancy; and finally, the interconnection existing between cosmetics and diet. By so comprehensively covering the science of cosmetics, this text is indispensable to those involved in research and development for the cosmetics, toiletries and pharmaceutical industries. It will also be a great benefit to university and hospital pharmacists and health care professionals entrusted with any aspect of skin care. CONTENTS (Main Chapters) Psycological aspects of every day cosmetic dermatology (E. Panconesi) Cosmetic, drugs and common skin disorder (W. Raab) Percutaneous absorption and lipids of the elderly skin (J. Wepierre) Mechanism of solar erythema (E. Quencez, P. Agache) The skin plasticisation effect of a medium chain alpha-hydroxy acid and the use of potentiators (J.C. Hill, R.J. White, M.D. Ba1nt, E. Mignini) Analytical problems of cosmetic evaluation resulting from EEC ltalian regulato1y procedures (L. Gagliardi, A. Amato) Kathon C.G.: risk of sensitization (A.C. De Groot) Methods for evaluating initant - e1ythematogenic activity in:cosmetics (A. Se1toli, S. Gio1gini, C. Mrutinelli, M.C. Melli) Socia! problems related to perspiration: the cosmetic connection (C. Jacobson) Barriers creams (L.C. Parish) Evaluation of a new skin baitier providing water and solvent protection (P. Morganti, S.D. Randazzo) Cosmetology and sexuality in the hi story of gynaecology (G. Forleo, M. Fraticelli) Metabolism of steroids in human skin (A. Lanzone, A.M. Fulghesu, F.P. Bellante, A. Caruso, S. Mancuso) T he stucture and permeability of the ora! mucosa (A. Jarret) Ora! mucosa and dental care problems (E. Benagian) Vitarnins and minerai nutrition in the skin (B. Berra, S. Zoppi, S. Rapelli) Good manufacturing and quality contro! practices in the cosmetic industry (F. Pocchiari) Cosmetology and public health (L.Toti) 400 pages about - Hard-bound Price: U.S. $ I in ltaly L

10 International Society of Cosmetic Dermatology PRESIDENT HONORARY PRESIDENT VICE-PRESIDENTS SECRETARY-GENERAL PROGRAM DIRECTOR BOARO OF TRUSTEES ADVISORY BOARD Colernan Jacobson (USA) William Montagna (USA) Emiliano Panconesi (ltaly) Rodolfo Paoleui (ltaly) Pierfrancesco Morganti (llaly) M. Brodie James (USA) Pierre Agache (France) Fritz Kernper (Germany) Lawrence Parish (USA) W.E. Parish (England) Wol fgang Raab (Austria) Salvatore Randazzo (llaly) Hans Schaefer (France) William Abramovitz (Venezuela) Mohamed Arner (Egypt) Rubem David Azulay (Brasi I) Claude Benezra (France) LA. Bernstein (USA) O. Binet (France) Otto Braun- Falco (Germany) Peter Fritsch (Austria) J. Morton Gillespie (Australia) Marwall Harahap (Indonesia) Vaino Hopsy- Havu (Finland) Stephanie Jablonska (Poland) A. Jarret (England) Jon Kabara (USA) F. Kardel Vegas (Venezuela) Ch.M. Lapiere (Belgium) Juhlin Lennan (Swedén) R.S. Lester (Canada) Howard Maibach (USA) Ronald Marks (Wales) Jose Mascara (Spain) J.P. Ortonne (France) G.E. Pierard (Belgium) Jaime Rubin (Argentina) Wolfgang Rupilius (Germany) Raul Vignate (Uruguay) Jacques Wepierre (France) Chu-Kwan Wong (Taiwan)

11 Trimestrale di Dermatologia Cosmetologica Quarterly Review of Cosmetic Dermatology EDITO R ASSOCI AT E EDITOR ASSISTANT ED ITOR SECRETA RY EDITOR I'. ~ IORGANTI PhD. SECRETARY GENERAL INT ERNATIONAL SOCIETYof COSMETIC DERMATOLOGY Via lnnoccnlo X l Roma. (ltnly). Fax 06/ S.D. RANDAZZO ~ I.O. Prorc.-or or EXPERl~ I ENTA L DER~ 1ATOLOGY UNIVERSITY OF CATANIA Via laco1rn i Catania ( llaly) - F:1~ ' ~I.Il JAMCS ~l.d. l'rogram DIRECTOR INTERNATIONAL SOCIETY ofcosmetic DERMATOLOGY JAMES CLINIC Sui1c 1076 Tanncry Lmc Camllcn. Mai ne o.is.ij USA - Fax M.C. PROIETTI Vi;:1 l nnoccn10 Xl Roma ( h ;1ly) EDITORIA!. A DVISORY lloard I~ AGACHE G. ll ELLO~IONTE W.F. BERGFELD Il. BlòRRA R.CAPUTO O. CA RLES1~10 D.CERIMEL E E. ClllACClllERINI J. COTTE M.A. DINA G. FABRIZI A. FIDANZA D. GRAFNETl'ER J.1\. GRAI IA~I L. GAGLIARDI B. GUARNIERI A.J.JOUllA R F. 11. KEMPER A.M. KLIGMAN N. LOPRIENO S. M ADDIN G. MAZZONE C.L. MENEGHINI W. MONTAGNA L. MUSCARDIN N. ORENTREICH E. PANCONESI R. PAOLETr! IV.E. PARISH L. l'uglisi IV. RAAB G. RABBIOSI A. REBORA V. RIZZA G. SALVATORE A. SANNA P. SANTOIANNI H. SCHAEFER F. SERR I A. SERTOLI A. STMl~ 1 ATI l.ta DDEI H. TRONNIER V. VALKOVIC ~ I D. Prof. ol IXrm:u. Cenare liosp. Rcgion:il dc Bc~rnçon <F) CChcm. Prof. of Chcm.. Food Dep:ut Sup. Sanità - Rom::i. (I) ~ I D. FACI' Clc,clan<l Cl ime Ohio (USA) DSc. Prof. of B1ol. Chcm. Uni\. of Mihmo Cl) 1'10. Prof. and Chairman. Dcpart of Derma!. Uni\. of Miiano (I) f\id.. Prof. ;ind Chainn<.m Dcpart. of Dcrmal. Um\'. of Romc (I) MD. Prof. and Chairman. Dcpan. of Dcrm:it. Ca1holic Unh. of Romc (I) CChcrn. Prof. and Chairman. Dcpart. Tcdrn. of Conuncrcc Uni v. of Romc (I) DSc. Prof. or Co,rnct.!PIL Lyon {F) MD. Prof. :md Chairm:rn. D\:p::i.rl. of Phatol. ;\n:n. C:uho l1c. Univ. of Romc (I) MD. A :}". Prof. of Pacdri:1tic Denn:1tologi..,1. C:.uholic Uni,cr,i1y of Romc (I) DSc. Prof. and Ch<.1irm;m. Depart. of Ph}siol. Uni\. of Romc {I) PhD. 1n,1. for Clinica! and Exp. ~ledic i ne Pragu~ <CS) B.Sc. PhD. Dcpt. Dcrma1olog} Uni\. of Pcn ll"-) h :mia (USA) Chairman. Dcpan. of Pham1. Chcm. b1. Sup. Sani1à Roma (I) MD. Prof. :md Chainnan. Dcpan. of Derma1. Unh. of ~ lc..,ina ( I) ~ 1. 8.MRSC llcacon,ficld (GB) MD. Prof. and Ch;:iirman. Dcpan. of Pharm;:icol. and Tm.. Uni\. Mun<;;ter (0 ) MD. PhD. Pro f. of Dcrmatol. Uni\. of Pcnn,}l'ania Philaddphia ( USA) OSc. Prof. of Gcnc1ica Univ. of Pisa (I)!\ ID. ERCP Clin. Pro f. Dcrrnatol. Di v. Derma!. Univ. BR. Columbia. Vancouver (C) MD. Prof. :md Chairni:rn. Dcpart. of Ph:1rmacol. and Tox. Univ. ofc.uaniil (I) MD. Prof. ;.m<l Ch:1irm:111. Dcpart. of Derm a!. Uni\. of 13:1ri (I) OSc. Prof. or Ocrmat. Oregon Hcalt Scicm. c Uni,cr,il) (USA) ~10. Emcritu' Prof. of Dcrma1. Ccntre H o~p. Rcgional IDI Rome (i) MD. Clin. Prof. of Dcrm<n. Ne\\ York (USA) MD. Prof. and Chairman. Dcpan. of Dcnnat. Unh. of Fi n.~ n 1c (I) ~ I D. Prof. ijnd Chainn:m. Dep:ln. of Pharmacol. an<l Tox. Um\. of k'\lilano ( I) ~ I A. PhD. BVSc. Heild of Em ironmcnta.i Safet} Di' h1on. Unilc,cr Rcsearch Schiln brooj.. (GBJ DSc. Prof. of Pharmacogno') Uni,. of Mil:mo (I) MD. Prof. ijnd Chairman. Depart. of Dcrmat. Uni,, of \Vien (A) f\ 10. Prof. and Chnirm:rn. Dcpiln. of Dcnnat. Uni \, of f>a, ia (I) MD. Prof. ;ind Chairman. Dcpar1. of Dcrm.il. Uni,, of Gcnm a ( I) Ph.0. Prof, o!' Bio l. Chcm. Unìv. of Ca1ania (I) CChcm. Dt.:p:lrl. oftoxìc:ol. ls1. Sup. Sani1ù Roma (I) MO. Prof. and Chairman. Dcpart. of Microbio!. Catho lic. Uni\. of Roma (I) MD. Prof. and Chairman. Depart. of Dcrmat. Uni,. o f Napoli (I) ~10. PhD. Prof. and Chairmiln. Depa.n. of Pharrnacol. CIRO Sophia-Anlipolis Valbonc (F) MD. Prof.. Dcpan. of Dcrrna1. Catholic. Uni\. of Roma (I) ~10. A.;o;.oc. Prof. of Allergie md Occupational Dem1:u. Uni\. of Firenze (I) DSC. Depart. oftoxicol. lst. Sup. Sani1à of Roma Cl) B.Sc.. Prof. and Chairm.:in. Depan. of Phannacol. Scicncc Unh. of Siena (I) MD. Prof. and Cha1m1an. Dcpan. of Dcrmatol. S1ad1ischcn Klinikcn of Dortmund CD) CCht!m. Prof. of Pti)sic Rudcr Bo.-.kovic ln!-1. of Z.1grcb (Y)

12 GENERAL INFORMATION The JOURNAL OF APPLIED COSMETOLOGY is an international journal devoted to publisching o riginai papers, reviews and other materiai which represent a useful contributi on to research on the skin and on cosmetics. It is aimed at cosmetic chemists, dermatologists, microbiologists, pharmacists, experimental biologists, toxicologists, plastic surgeons, and ali other scientists working on products which will come into contact with the skin and its appendages. The Journal is publisched quarterly in English. It is distributed to cosmetic chemists, dermatologists, plastic surgeons, medicai and pharmaceutical schools, medicai li braries, selected hospitals and research institutions throught the world, and by subscription to any other interested individuals or organizations. Statements and opini o ns expressed are pe rsona! to the respective contributo rs and are not necessarily e ndorsed by the Editor(s), Advisers, Publishers of Distributors of this Journal. COPYRIGHT S ubmitted materiai must be the originai work of the autor(s) and must not have been submitted for publication elsewhere. By submitting a manuscript, the authors agree that the copyright for their articles is transferred to the publisher if and when the article is accepted for publication. None of the content of this publication may be reproduced in whole or in pan, translated, stored in a retrieval system, or transmitted or distributed in any fonn or by any means (electronic, mechanical, photocopy, recording or othe rwise) without the prior written permission of the Publishers. Sections of J ournal The following sections will be features of the Journal: Originai Laboratory Studies: descriptions of originai in vesti gative laboratory research in cosmetics and related areas. Special Reports: Items of special interest to the readers, including reports on meetings, societies, legislation, etc. Generai Articles: scientific articles of generai interest to our readers will be considered for publicati on. These artic les should be concerned with newer developments in such relateci fields as dennatology, biology, toxicology, etc. Short Communicatio11s: the lenght should not exceed 5 typewritten pages with not mo re than 3 figures included. Headings ("Materials", "Discussion", etc.) as well as Summaries are to be omitted. If accepted, these submission will appear in print in a very short time. Letter to the Editor: comments on Journal articles are invited as well as brief contri butions on any aspects of cosmetic science. Letters may include figures, and/or references, but brevity is necessary. Guest Editorials: concise, authoritative, substantiated commentary on specific topics of contemporary interest. Book Reviews: book and monographs (domestic and foreign) will be reviewed depending on their interest and value to subscribers. Send materiai for review to the Editor, D r. P. Morganti. No such materiai will be returned. Address: ali papers should be submitted to: Dr. P. Morganti INTERNATIO NAL EDIEMME Via Innocenzo XI, 4 t Rome - I tal y Te!. 06/

13 INFORMATION FOR AUTHORS Papers 111ust be sub111itted in English. Authors whose 111other tongue is not English should arrange for their 111anuscripts to be written in proper English prior to sub111ission. Procedure of Submission of Ma1111scripts: sub111it three copies of both the manuscript and ali illustrati ve materiai to the above address. Orga11izatio 11 of tlze Manuscript: investigative studies should be organized as follow: title, abstract page. introduction, materiai and methods, results, discussion, acknowledgments. references, legend for figures. tables. Ali pages should be numered consecutively starting with the abstract. The entire manuscript is to be typewrinen, double-spacecl, ancl with 3 cm margins. Trade names must be capitalized: the common na111e for compounds may be used i f the formai chemical name as established by international convention is given after the first use. Any abbreviations other than those which are general ly accepted must be defined. In the text. references to dual authors will use both surnames throughout. For multiple authors. use the surnames of ali authors al the first reference and only the first author followed by "et al." thereafter. Please mark in the margin of the manuscript the desired position of the figures and tables. To allow faster publication only set of proofs will be furnisched to the author including the figures and tables in their final position. Tille page: list the title, name(s) ancl degree(s) of author(s), department(s) and institution(s) at which the work was done, city, state, and postai code. Any preliminary report or abstract of the work shoulcl be referred lo as a footnote to the title. Summary: each paper must be headed by an English language tille of not over 70 characters (including spaces) suitable for use as a running head and must also be proceded by an English summary not exceeding 300 worcls typed double-spaced. The summary will include statements of the problem, method of study, results, and conclusions. Since this summary will be used by astracting journals, il musi be self- explanatory a'nd should inlcude abbreviations, footnotes, and references. Footnotes: should be listed consecuti vely at the bottom of the page on which they fall, designateci by the following symbols in order *, +, +.. IT, **,etc. Key Words: key words for computerised storage and retrieval of information should be incorporated in the summary. References: the references have to be abbreviateci as listed in the l ndex Medicus. The style of the references must conform to the examples given below: I) Robbins CR, Kellych ( 1970) Aminoacid composition of h.uman hair. Text Res J 40: ) Strehler BL ( J 977) Time, cells and aging 2nd edn. A cademic Press, New York 3) Ebling FJ, Rook ( 1972) Ci clic activity of the follicle. In : Textbook of dermatology 11, Blackwell. Oxford, p l/lustratio11s: figures should be numbered consecutively using Arabic numerals Tables should be m1111bered consecutively. using Roman numerals. Ali photographs should be black and white. glossy and unmounted. The number and size of illustration should be restricted to the minimum needed to clarify the text. Authors requiring extra space for illustrations will be charge accordingly. This is also the case for color illustrations. Ali figures, photographs, graphs. or diagrams should be submitted on separate sheets. Animai Experiments: descriptions of animai experiments should include full details of the types of animai used (inbred, etc.) and the conditions under which they were kept (standard diet. etc.) Trade Names: ali common cosmetic ingredients should be referred to by their generic names, as indicateci in the latest edition of CTFA Cosmetic Ingredient Dictionary, and the European Pharmacopeia. If a materials is not listed, then the trademarked name can be used, with the chemical composition given in footnotes.

14 INFORMAZIONI PER L'ABBONAMENTO L"abbonamento annuale comprende quattro numeri. È possibile ottenere abbonamenti a prezzo ridotto da parte dei ricercatori che lavorano presso Istituti che abbiano sottoscritto almeno un abbonamento a prezzo normale. L' Editore potrà fornire a richiesta notizie più dettagliate. Le sottoscri zioni di abbonamento possono essere effettuate mediante assegni postali, bancari, di conto corrente o per contanti ind irizzandoli a: L' IVA è a carico dell'editore, non detraibile dall'abbonato a norma a1t. 74 lett. C DPR 633/72 INTERNATIONAL EDIEMME - Via Innocenzo XI, 41, ROMA (c/c bancario n /37 Banca di Roma Ag. 123 (653) Piazza Pio XI Roma) SOTTOSCRIZIONI ANNUALI ftalia L Altre Nazioni $ 60 Numero singolo L Numero arretrato L SUBSCRIPTION INFORMATION Subscriptions are entered on a calendar years basis only and include four regular quarterly issues. Half-price subscriptions are available to research scientists whose institutions already subscribe at full rate. Details on application from publishe r. Payment muse be made in U.S. dollars us ing bank draft, international postai money o rder onl y. ltalian residents only may pay by persona! check: INTERNATIONAL EDIEMME - Via Innocenzo XI, 41, ROMA (c/c bancario n /37 Banca di Roma Ag. 123 (653) Piazza Pio XI Roma) ANNUAL SUBSCRIPTION RATE: ftaly, Lit Other Countries, $ 60 Additional Air Mail postage rate: $ l S Statements and opinions expressed in the articles and communications herein are those of the author(s) and not necessaril y those of the Editor(s), or publisher. The Editor(s) and publisher, disclaim any responsability or liability for such mate1ial and do not guarantee, warrant, or endorse any produce or service adverised in this publicatio n nor do guarantee any claim made by the manufacturer of such product or service

15 Quarterly Review of Cosmetological Dermatology IN FOR~\IA Z IO N I PER L'ABBO AMENTO L"abbonamcnto annuale comprende quallro numeri. È possibile ouenerc abbonamenti a prcno ridouo da pan e dci ricerca1o ri che Ja, orano presso ls1imti che abbiano souoscri110 almeno un o.ibbonamenlo a prezzo normale. L'Editore polrà fornire a richic.:;1a noti1ie più dcuagliatc. Le solloscrizioni di abbonamento poswno c~scrc cffcuuatc mediarne assegni postali. bancari. di conio corrcn1c o per con1a111i indiriu.andoli a: INTERNATI ON/\ I, EO I E~IM E - Via Innocenzo Xl, ~I Roma dc b::incario n /37 Uanca di n.oma Ag. 123 (653). PiàZZ4t Pio X l Roma ABBONAMENTO J OURNAL OF APPLIED COSMETOLOGY Italia L Altre Nazioni $ 60 lstru~io11 i per l 'abbo11ato: O desidero abbo1wr111i t1 questa rivista per l'a11110 i11 corso O ri1111ovo auto111atica111e111e il mio abbo11ame1110 per gli m111if11111ri (questa forma di abbo11a111e1110 può essere co111u11q11e disdeua i11 og11i e11to ). O desidero ricevere le 11or111e editoriali per eve11111ali collabom~io11 i. (Scrivere in sw111pa1el/o) Nome ~ Indirizzo Città CAP Nazione ~~ ~Y Quarterly Review of Cosmetological Dermatology SUIJSCIU PTION INFORMAT IO N Subscriptions are cntcrcd on a cnlcnd:ir yc;1r bà.'!ìs only and include four rcgular qu;:1ncrl y is~ u cs. H:tl f- pricc ~ubsc riptio n s are availablc 10 rcsearch scicn1ist whosc ins litutions alrcndy subsribc m fu ll r;uc. Dc1;:1il ~ on ;ipplic;nion from publishcr. Paymc nt nrnst be made in U.S. dolh1rs using b::mk draft, intemational postai moncy ordcr onl y. lrnli;m rc!'lidcnts only may pay by pcrson<il check: e/e bancario /37 1Janc;1 di Roma Ag. 123 (653). Piana Pio Xl - OOJ65 Roma ORDER FORM JOURNAL OF APPLIED COSMETOLOGY A 1111ual s11bscrip1io11 rate: Jtaly, Lit Other Countries S 60 Addilional Air Mail post.age rate: Africa and Middle East S 12. North. Centrai ami South Arncric:.i $ l.t. Fa r East $ 15. Oceania $ Please Check O I year subscription O Rem!n "'.".mfjsrriptimr araommically i11/11111re yet1rs (tl1is co111itmt11io11 order i s i11s1e11dedfor subscriber 's l'0111"t!11ie11ce 011/y tmd my be ctmcelled ar a11y lime). O Senti me a copy of i11forma1io11for Awhor.f. O Pleose cjwrge 111is ordl'r 10 my credil carri (Ali order subje110 credit llfjprom/). Dclclc as ncccssary: O AMERJCAN EXPRESS O DINERS CL UB - Card Numbcr Expiration d:uc.... (Piea se Prim) Narne Address City Postal Code Country~~~~~~~~~~~~~---~---~~~~~~~~~--

16 We wish to dedicate this Journal of Applied Cosmetology, to the memory of the well-known italian dermatologist, professor LUCIANO MUSCARDIN. lt is with sorrow thai we report the unexpected and untùnely death of our dear.fi iend and colleague Professor Luciano Muscardin. We ali knew Di: Muscardin far his outstanding professional and human credentials. He was a very known dermatologist in the specific fiels of Cosmetic Dermatology, and an expert member of many scientific and legai committees for italian and european government authorities. He has written extensively on Cosmetology editing one book and many scientific papers. However, this does not measure the man, and this is ùnportant, because, above all D1: Muscardin was a warm, caring, and happy human. His high professional standing was a small part of his presence. Of greater importance were his companionship with those near to hùn, his ready smile, his warmth, his dependable faith in his fellow man. Luciano Muscardin 's qualities were those which earn the title "Physician ". He was loved by his patients and respected by his peers. Our society is priveleged to have many great names on its rosters. Perhaps, because of this, we find the loss of any member to be noteworthy. The loss of Dr. Muscardin is deeply felt by usali. Our sympathy is sent to ali who share in the sorrow.

17 Trimestrale di Dermatologia Cosmetologica Quarterly Review of Cosmetic Dermatology Contents Generai Articles 81 Role of lipids in cellular membranes and skin biology B. Berra, S. Rapelli 91 Advances in percutaneous absorption W. Schalla 1 O 1 Activity of vehicles and diffusion through the horny layer W. Schalla XIX Announcements 5'h World Congress of the lnternational Society of Cosmetic Dermatology "Progress in Cosmetic Dermatology: Basic Science and Technology New York City- U.S.A. October 7-9, 1993

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19 J. Appl. Cosmetol. 10, 87-89(0ctober-December 1992) ROLE OF LIPIDS IN CELLULAR MEMBRANES ANO SKIN BIOLOGY. B. Berra, S. Rapelli lnstitute of Generai Physiology and Biochemistry, School of Pharmacy, University of Milano, ltaly. Received: October 30, Presented at the IV lnternational Congress on Cosmetlc Dermatology "Progress in Cosmetic Dermatology: Science and Safety" Roma (ltaly) October November 2, Key words: Membrane Fluidity: Cellular Membrane: Biologica/ Membrone: G/ycoproteins: Glycolipids; Phospholipid Bilayer; G/ycoshingolipids: Liposomes; Lipidbilayers: Stratum Corneum Lipids. Synopsis A barrier that separates cellular contents from the environment is an absolute condition for li fe. This separation is provided by the plasma membrane also called the celi membrane. Ali biologica! membranes. whether from eucaryotic or procaryotic cells, have the same classes of chemical components. a similarity in struclural organ ization and a number of properties in common. Biologica! membrane consist of a con tinuous double layer of lipid molecules in which proteins are embedded. This lipid bilayer is flu id, with individuai lipid molecu les able to diffuse rapidly within their own monolayer but usually not from on monolayer to the other. The three major I i pid components of membranes are phosphoglycerides, sph ingoi i pids and cholesterol; their percentage varies significantly in the different membranes and is related to the specific roles of the individuai membranes. A lthough lipid molecu les display considerable structural diversity. ali of them share one important structural property: they are amphipatic, so they can assemble spontaneously into bilayer when placed in water, forming sealed compartments that reseal if torn. The functional significance of the lipid compositions of different membranes will be discussed and focused mainly on the lipid lamellar struclure of stratum corneum. La barriera che separa dall'ambiente il contenuto delle cellule rappresenta la condizione indispen sabile per la vita. Questa separazione è mantenuta dalla membrana plasmatica chiamata anche membrana cellulare. Tutte le membrane biologiche sia che provengano da cellule eucariotiche che precariotiche, sono formate dagli stessi componenti chimici e posseggono una uguale struttura organizzata. La membrana biologica è formata da un doppio strato continuo di molecole lipidiche attraversate da qualche molecola proteica. Il doppio strato lipidico è fluido e permette soltanto l' interscambio tra i diversi l ipidi di uno stesso trato. I tre principali componen ti delle membrane sono i fosfogliceridi, gli sfingolipidi ed il colesterolo. La loro percentuale varia in un modo significativo tra le diverse membrane ed è legato al loro specifico ruolo. Anche se i diversi lipidi posseggono considerevoli diversità 81

20 Raie of lipids in ce/lular membranes and skin biology strutturali. sono tutte molecole anfi patiche che formano spontaneamente strati bimolecolari se inserite in un ambiente acquoso. li significato funzionale della composizione lipidica delle diverse membrane verrà di cu so in modo da mettere a fuoco soprattutto la struttura lamellare lipidica dello strato corneo. 82

21 B. Berra, S. Rape/li Basic structural features of cellular membranes. Biologica! membranes, both from eucaryotic and procaryotic cells are built up from the same classes of che mical compounds - lipids, proteins and in smalle r quantity, carbohydrates. however there are important qual itati ve and quantitative di f ferences within any g iven class of compounds. Biologica! membranes divide the intracellular milieu from the exte rnal environment. In contrast to the procaryotes, eucaryotic cells have a well defined me mbrane surrounding a centrai nucleus and a vari ety of intracellular structures and organe lles. The intracellular membranous syste m establishes a number of distinct subcellula r specializalion. By means of this compartmentalization of the celi, diffe re nt che mical reactions, requiring different e nvironments, can occur simultaneously. As it w ill be discussed late r in more detail, membranes are lipid in na ture and many substances that are soluble in a hydrophobic environme nt wi ll concentrate in cellu lar membranes, w here ma ny specific bioche mical reacti ons can occur; the extensive me mbrane syste m of eucaryoti c cell s c reate an additional e nvironment that the celi can use for its di ffere nt functions. The mean thickness of a typical plasma membrane is À, but this value is lower for intracellular membra nes. A li of the m, however, constitute a dynamic struc ture in which lipids a re present in a fluid state and make up a non a queous compartme nt where the differe nt compounds can move and possibly interact. Biologica! me mbranes, and particularly the plasma membranes. share unique properties: they are impermeable to a great varie ty o f substances and within the membranes itself there are selecti ve transport systems th at a llow strict contro! of the flux of substrates, cofactors and ions from one compartment to the others. In th is way the concentrati on of the di ffere nt substances and conseque ntl y the different metabolic pathways can be modulated. The plasma membrane of e ucaryotic cells also plays an important role in celi-celi recognition and interaction and represents the target of many hormones and metabolic regulatory factors which are important for the signal transmission and transduction to intracell ular mediators. As already mentio ned, lipids and proteins are the main components of biologica) membranes; their amount varies cons idera bly in different membranes according to the type and the fun cti on of a given celi. A smaller amount of carbohydrates is also present, not in free fo rm, but linked to glycoproteins a nd glycolipids. Based on evidence from physicochemical, biochemical and electro n mi c roscope investigatio ns knowledge of the structure o f biologica! me mbranes has evolved. Prote ins can be divided, roughly, into two main categories on the basis of their extractibility from the membrane: I - peripheral (or extrins ic) localized on the membra ne s urface, to w hich they are loo e ly bound and from where they can be easily removed. T hey account fo r approximately 30% o f the tota! and in many instance have e nzymatic acti vity. 2 - integrai (or intrinsic) which span the phospholipid bil ayer (see a lso be low), with portio ns protruding on each side. Hydrophobic interactions be tween the lipids and the hydrophobic domains of these integrai proteins prevent the m fro m be ing readily re moved, and their e xtractio n leads to di sruptio n of the membrane. In generai me mbrane prote ins play di versified roles and are involved in many functions: transport of small molecul es; recogni tion and adhesion phenomena; transduction of signals from e x te rnai ligands; they can act as enzymes and receptors. besides their struc tural role. Me mbrane lipids belong to three ma in classes: phospholipids, sphingoglycolipids and chole terol. Their pe rcentage in d iffere nt membranes varies significantly and it is quite clearly re lated to the celi and/or organe lle functions. The phospholipids (or g lycerophospholipids) a re polar, ionie lipids composed of 1,2 diacylglycerol with a phosphodiester bridge that links the 83

22 Rote of lipids in cellular membranes and skin biology glycerol backbone to a specific base, usually a nitrogenous one, such as choline. serine, ethanolamine. Phosphatidylcholine (PC) contains mostly palmi tic (C 16:0) in rhe sn- 1 position of glycerol and primarily the unsaturated 18-carbon fatty acids - oleic, linoleic or linolenic - in the sn-2 position. Phosphatidy lethanolamine (PE) has the same saturateci fatty acids as PC at the sn- J pos ition bu t contains more of the longchain polyunsatured fatty acids, namely 18:2, 20:4, 22:6 - at the sn-2 position. PC, PE and phosph atidylserine (PS) are the most abundant phospholipids in human tissue. At ph ysiological ph PC and PE have no net charge and exist as a dipolar zwitterions, whereas PS has a net charge of - 1, i.e. it is an acid phospholipid. There are two other compounds with this characteristic: phosphatidy l inositol and phosphatidylglycerol; the first one occurs in mammalian membranes and it i rather unusual because it o ften contains almost exclusively stearic acid at the sn- 1 position and arachidonic acid (C20:4) at the sn-2 hydroxygroup. Phosphatidylglycerol occurs in relati vely large amount in mitochondrial membranes and it is a precursor of cardi o Jipin. M ost phospholipids contain more than one kind 01 fatty acids per molecule, so that a given class of these compounds actually represents a family of different molecular species. Sphingolipids are complex lipids whose core structure is provided by the long-chain aminoalcohol sphingosine. There is a close similarity between carbons 1,2 and 3 of sphingosine and glycerol mainly because both of them have nucleophilic groups, hydroxyl or amino, at these carbon atoms. Sphingosine as such with its free amino group does not occur naturally. The fundamental building block or core structure of natural phingolipids is ceramide, the long-chain fatty acid amide derivative of sphingosine. Therefore there are two long-chain hydrocarbon domains in the ceramide molecule and these hydrophobic regions are responsible for the lipoidal character of sphingolipids. Free ceramide is not a component of membrane lipid but rather it is an intermediate in the bioynthesi and catabolism of glycosphingolipids and sphingomyelin. In sphingomyelin the primary alcohol group at C- 1 of sphingosine is esterified to cho line through a phosphodiester bridge of the kind that occurs in the acyl glycero-phospholipid; the amino group of sphingosine is attached to a longchain fatly ac id by means of an amide bond. Sphingosine is therefore a ceramide phosphocholine. lt contains one negati ve and one positive charge so that it is neutra! at physiological ph. As indicateci above. in plasma membranes there are also carbohydrate-conlaining sphingolipids. which include cerebrosides, sulfatides, globosides and gangliosides. In this compounds the polar head group is attached to sphingosine via the glycosidic linkage of a sugar molecule rather than a pho. phate ester bond, as in the case of the phospholipids. In other words the glycosphingolipids do not contain phosphate and have a sugar attached by a B-glycosidic linkage to the 1-hydroxyl group of the sphingosine in a ceramide. One subgroup is the cerebrosides, which contain either a glucose or a galactose attached to ceramide and are referred to as glucocerebrosides or galactocerebrosides, respectively. Cerebrosides are neutra! compounds. Galactocerebrosides are found predominantly in brain and nervous tissues. whe- reas the small quantities of cerebrosides in nonneutral tissues usually contain glucose. Galactocerebrosides may contain a sul fate group esterifi ed on the 3 position of the sugar. T hey are called sulfatides. Cerebrosides and sulfatides u sually contain very long-chain fatty acids with 22 to 26 carbon atoms. In piace of one monosaccharide, neutra! glycosphi ngolipids often bave 2 (dihexosides), 3 (trihexosides), 4 (tetrahexosides) sugar residues attached to the 1-hydroxyl group of sphingos ine. 0 -g lucose, d-galactose, N-acety lglucosamine, and N-acetylgalactosamine are the usual sugars. The most complex group of glycosphi ngolipids 84

23 B. Berra, S. Rape/li is represented by gangliosides, which contain o ligosaccharide head groups with one or more residues of sialic acid; these are amphipathic compounds with a negative charge at ph 7.0. Specific gangliosides and glycolipids are found in the skin either in normai or pathological conditions. The third major lipid present in membranes is cholesterol that contains four fused rings - which makes it a planar structure - a palar hydroxyl group at carbon-3, and an eight-member branched hydrocarbon chain attached to the D ring at position 17. Cholesterol is a compact hydrophobic molecule; however the hydroxyl group, that can be esterified, g ives, when it is free, a little hydrophilia to the molecule. In a given membrane cholesterol is located between the phospholipid molecules, orienced in a way which allows it to internet with the other lipid components, rnodulating the fluidity and, consequently, the permeability of the membrane itself. Micelles, lipid bilayers and liposomes The physicochemical properties of the lipid components just described dictate the bas ic structural characteristic of their organization in living cell s. Ali amphipathic compounds, with a hydrophilic head and a hydrophobic tail, react in a unique fashion in an aqueous system because o f their low solubility in water. Under proper conditions, these lipid molecules will come together to form spheres, termed micelles, with the hydrophobic tails interacting to exclude water and wi th the charged polar head groups on the outside. Micelles with a single lipid or a mixture of lipids can be made. The formation of the micelle depends also on the temperature of the system and, if a mixture of lipids is used, on the ratio of concentrations of the different lipids in the mjxture. The micelle structure is very stable because of the hydrophobic interaction of the hydrocarbon chains and the attraction of the palar groups to water. Depending upon the condi- tion, amphipathic lipids will interact to fonn a bimolecular leaf structure with two layers of lipid in which the polar head groups are at the interface between the aqueous medium and the lipid while the hydrophobic tails internet in a second way to form an environment that excludes water. This bilayer conformation is the basic lipid structure of ali biologica) membranes as described later in more detail. Lipid bilayers are extremely stable structures held together by noncovalent interactions of the hydrocarbon chains of the acyl groups and the ionie interactions of the charged groups w ith water. Hydrophobic interactions of the hydrocarbon chains lead to the srnallest possible area for water to be in contact with the chains, and water is essentially excluded from the interior of the bilayer. A lipid bilayer may close in on itself, forming a spherical vesicle separating the external space from an internal compartment. These vesicles a re termed liposomes. Individuai phospholipid molecules can readily exchange piace with the neighbouring molecules, which leads to rapid lateral diffusion in the piane of the membrane. In addition, the fatty a cyl chains can rotate around the carbon-carbon bonds; in fact there is a greater degree of rotation nearer the methyl end, leading to greater motion at the center of the lipid bilayer. Individuai lipid molecules cannot migrate readily from one monolayer to the other, a process termed flip-flop. Thus the lipid bilayer has not only an inherent stability but also a flu idity in which individuai molecules can move rapidly in their own monolayer but do not exchange with the adjoining monolayer. Artificial membrane systems have been studied extensively as a mean to determine the properties of biologica! membranes. A variety o f techniques are available to prepare liposomes, u sing synthetic phospholipids and lipids extracted from natural membranes. Depending on the procedure, unilamellar vesicles and multilarnellar vesicles (vesicles within vesicles) of various 85

24 Raie of lipids in ce/lular membranes and skin biology size (20nm- l µm in diameter) can be prepared. The interioi of the vesicle is an aqueous environment, and it is possible to prepare liposomes with different substances entrapped. Thus the e xternal and internal environments of the liposome can be manipulated. Biologica/ membranes T he basic structure is a bimolecular leaf arrangement of lipids in which phosphoglycerides, sphingolipids, and cholesterol are oriented so that the hydrophobic portions of the molecules interact to minimize their interactions with water or other polar groups. The polar head groups of the amphipathic compounds are at the interface with the aq ueous environment. A number of models for the structure of biologica! membranes have been suggested dating back to one by H. Davson and J. Danielli in 1935, whi ch was refined in later years by J.D. Robertson. In early 1970s, G.L. Nicolson and S.J. Singer proposed the mosa ic model for membranes in which it was suggested that proteins are on the surface as well as in the lipid bilayer. Some proteins could span the lipid bilayer wi th their polar groups in contaci with the aqueous surroundings on both sides and the hydrophobic portions interacting with the lipids in the interior of the membrane. This model has been extensively retìned and now is referred to as the fluid mosaic model to indicate the movement of both lipids and proteins in the membrane. The proposed structure accounts for many properties of mammalian membranes, but it continues to undergo modifications and refinements. These properties, including fluidity, flexibility, which allow changes of shape and form, selfsealing features and impermeability for many substances are mainl y related to the physicochemical characteristics of the lipid bilayer. Jr is now recognized that the membrane lipids may nor be randomly distributed in the monolayers, but that there are islands of lipids associated together or in contact with a specific protein. The indivi- dual lipids are not, however, immobilized in the e islands but rapidly exchange with molecules in the suitounding area of the membrane. A n importane difference between the Nicolson Singer model and earlier models is that the lipid bilayer is discontinuous, with proteins embedded in the hydrophobic portion of the bilayer. M any membrane proteins span the bilayer, with portions protruding on each side. Hydrophobic interaction between the lipid and the hydrophobic domains of these integrai proteins prevents these proteins from being readily removed, and their extraction leads to disruption of the membrane. Protein can al so be loosely bound to the membrane by interaction between charges on the protein and these peripheral proteins are easily removed by mild treatment with little damage to the membrane. Even though the model would suggest that proteins are randomly distributed throughout and on the membrane, evidence from a variety of sources supporrs a high degree of functional organi zation with definite restriction on the loca lization of some proteins. M embrane proteins also have a defini te orientation within and across the membrane. Integrai proteins with enzymatic acti vity may bave their catalytic site on either the inner or outer surface. This orientation is e stablished during the biosynthesis of the membrane and remains unchanged. A nother restriction is th at spec i fic peripheral proteins are bound to only one side. Asymmetry of the Membrane In contrast 10 the random distribution of lipids between the outer and inner lipid monolayer of liposomes, there is an asymmetric distribution of lipid components across biologica! membranes. Each layer of the bilayer has a different composition with respect to individuai phosphoglyceri des and sphingolipids. Sphingomyelin and phosphatidylcholine are predominantly in the outer layer, whereas phosphatidy leth anolamine, phosphatidylserine and 86

25 B. Berra. S. Rape/li phosphoinositides are predominantly in the inner lipid layer. In contrast. cholesterol is equally distributed on both sides of the membrane. Membrane fluidity The interaction among the different lipids and between lipids and proteins are complex and dynamic. There is a fluidity in the lipid portion of the membrane in which both the lipids ancl proteins move. The clegree of fluiclity is dependent on the temperature ancl the composition of the membane. A t low temperature the lipids are in a gel-crystalline state, with the lipicls restrictecl in their mobility. As the temperature is increasecl, therc is a phase transition into a liquid-crystalline state. with an increase in fluiclity. With liposomes prepared from a single pure phospholipid, the phase transition temperature, Tm, is rath er precise; but with liposomes prepared from a mixt ure of lipids. the Tm becomes less precise because individuai clusters of lipids may be in either the gel-crystalline or the liquicl-crystalline state. The Tm is not precise for biologica! membranes because of their heterogeneous chemical composition. lnteractions between speci fic lipids and between lipids and proteins also leacl to variations in the gel-liquid state throughout the membrane ancl 10 clifferences in the fluiclity of cli fferent areas of the membrane. The specific composition of the individuai biologica! membranes leads to differences in fluiclity. Phosphoglycerides containing short-chain fatty acids will increase the fluidi ty as does an increase in unsaturation of the fatty acyl groups. The cis double bond in an unsaturated fatty acid of phospholipid leacls to a kink in the hyclrocarbon chain. preventing the tight packing of the chains, and creates pockets in the hydrophobic areas. lt is assumecl that these spaces, which will also be mobile due to the mobility of the hyclrocarbon chains, are filled with water molecules and small ions. Cholesterol with its flat stiff ring structure reduces the coiling of the fatty acicl chains and decreases fluidity. Ca2+ dire- ctly clecreases the fluidity of a number of membranes because of its interaction with the negati vely chargecl phospholipicls, which. in turn, recluces repul sion between the polar groups and increases the packing of lipicl molecu les. Ca2+ causes aggregation of lipids into clusters. which also reduces membrane fluidity. Fluidity at different levels within the membrane also varies. The hydrocarbon chains of the lipicls bave a motion, which procluces a fluidity in the hydrophobic core. The centrai area of the bilayer is occupiecl by the encl s of th e hydrocarbon chains ancl is more fluid than the areas closer to the l wo surfaces, where th ere are more constraints due to the sti ffer portions of the hyclrocarbon chains. Cholestcrol makes the membrane more rigicl towarcl the periphery because it does not reach into the centrai core of the membrane. Individuai lipids and proteins can move rapiclly in a lateral motion along th e surface of the membrane. However. electrostatic interacti ons of polar beaci groups. hydrophobic interactions of cholesterol w ith selected phospholipids or glycolipids, and protei n- lipid interactions ali lead to constraints on the movement. Thus there may be lipid domains in which lipicls move together. such as islancls floating in a sea of lipicls. Integrai membrane proteins also move in the lipid environment, even if their movements are slower than that of lipicls. There is very little transverse motion of proteins in membranes. Movement of membrane proteins may be restrictecl by other membrane proteins, matri x proteins, or cellular structural elements such as mi crotubules or microfilaments to which they may be attachecl. Evidence is accumulating th at the fluiclity of cellular membranes can change in response to changes in diet or physiological state. Their contene of fatty acid and cholesterol is modified by a variety of factors. In addition, pharmacological agents may bave a direct effect on membrane fluidity (e.g. anaesthetics). Thus cellular membranes are in a constantly changing state, with not only movement of pro- 87

26 Rote of lipids in cettutar membranes and skin biotogy teins and lipids laterally on che membrane but with molecules moving into and out of the membrane. A variety of forces. including hydrophobic and electrostatic interactions are involved in maintaining the basic structural characceri stics. Stratum corneum lipids as bound-water modulators and their importance tor water uptake In the kin or ali vertebrates a membrane is present to function as a homeostatic barrier which regulates water diffusion throughout the skin itself: this membrane is constilllted by the horny layer of which the main components - proteins. lipids. water - are assembled in a very ordered struclllre. Lipids derive from desquamated keratinocytes and from the sebaceous secretion. In the horny layer the intercellular spaces include a super imposed lamel lar structure. derived by exocytosis from granules localized in the lower granular layer. The basic unit o f lamellar structures that are fou nd in the end-phase of keratinocytes differentiation consists of a lipid bilayer similar to that found in myelin and rods of the retina. In common with other biologica! membranes the lipid distribution shows asymmeu-y: however a characteristic feature is that this asymmetry is not due to phospholipids butto glucosylceramides and ceramides. Altogether these compounds are prevalently localized in the external leaflet. The less potar species have an unusual structure in which the fatty acid linked lo sphingosine is represented by a long chain alpha-hydroxyacid esterified in turn main ly with linoleic acid. In some glyco ylceramides thi s last one esterifies the glucose moiety in the 3' position. Thus glycolipids have the fu nction of a " reservoir" of essential fatty acids normally accomplished in biologica! membranes by phospholipids. These last molecules are present only in the living cells of the basai and spi nous layer and are rapidly degraded when keratinogenesis starts. The hydrolyzed fatty acids from phosphol ipids contribute to che pool of free acyls present in the horny layer together with those derived from sebaceous secretion: the sphingosine moiety is recycled for the synthesis of glucosylceram icles or ceramides. The remainder of the lipid component of the horny layer is represented by free cholesterol (20%), and free fatty acids. Lamellar granules. in which the bilayer is organizecl in a disk-shape configuration, assemble to give the fi nal structure of the layer under the influence of: I - acylglucosylceramides which during the.. dispersion of lamellar disks undergo a deglycosilation process: 2- lysophospholipids formation. catalyzed by a Ca-dependent phospholipase that acts on phospholipids of the granular layer: 3- the parallel increase of free fatty acids in the arca between the granular and horny layers. A ro te which is not on ly structural but also functional is played by the cholesterol esters localized in the stratum corneum: th e exfoliation or horny layer cells, which constitutes the last stage of epiclermal di fferentiation, is accompl ishccl by the hydrolysis of cholesterylsulfate. In conclusion, stratum corneum lipids that form the lamellar structure serve as a water modu lator. This water-holding function of the stratum corneum is thought to be completely distinct from the water permeability barrier, although the same intercellular lipids play a crucial role and pa th ological (delipidated) skin generally suffer a defect in both functions. Recent data from the literalllre suggest that although ceramides are the main determinane of both functions, ceramides with relati vely short. non-branched, and satu rateci alkyl chain lengths are mainly associateci with the water-holding function, whereas acylceramides with linoleic acid or ceramides with long alkyl chain lengths serve as a permeability barrier. 88