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Objective: In venous leg ulcer (VLU), the impaired healing has been shown to be associated with excessive levels of protease activities such as matrix metalloproteinases (MMPs) and elastases found in exudates. The present study focused on exudates absorption and proteases trapping capacity of a new generation of polyacrylate superabsorbent, Tegaderm superabsorber (TS), compared with a traditional dressing such as Zetuvit. Method: We studied the proteases implicated in VLU (MMP-1, MMP-2, MMP-9 and PMN elastase). Absorption was tested using an artificial exudate like fluid, over 30 minutes. The protein trapping ability was obtained using ELISA assays (enzyme-linked immunosorbent assay) to determine the amount retained by the dressings from spiked fluid samples. Results: TS had a higher exudate absorption capacity (72.8±1.7%) compared with the standard dressing (36.5±1.6%), and was also able to trap and retain proteases while the standard dressing released them. The difference was shown to be much larger for MMP-2 and PMN elastase. Conclusion: In our knowledge, this is the first comparative in vitro study evaluating absorption capacity as well as protease trapping capacity of a polyacrylate dressing for the four most implicated proteases in VLU. TS could be an appropriate alternative to improve the management of VLU by trapping MMPs and PMN elastse with a particularly high affinity for MMP-2 and PMN elastase.

Prevalence of leg ulcer in general population is important and new efficient treatments are now needed, especially for chronic leg ulcers. Human amniotic membrane (HAM) can be used as an alternative treatment for recalcitrant leg ulcers. The aim of this study is to investigate the effects of a HAM extract on normal fibroblasts (NF) and ulcer fibroblasts (UF). NF and UF were obtained from biopsies by explants technique. HAM extract was used at 10 μg of total proteins per ml. Single patient-matched NF and UF were compared, without or with HAM extract. Studied parameters were proliferation rate, retraction of free-floating lattices, alpha smooth muscle actin expression by flow cytometry, and synthesis of elastin, glycosaminoglycans (GAGs), pro-collagen I, MMP-1 and TIMP-1. Our results show that UF had a specific phenotype compared to NF: low proliferation, high expression of alpha-SM actin and high synthesis of MMP-1, TIMP-1 and elastin. HAM extract significantly increased the synthesis of GAGs, pro-collagen I and MMP-1 in NF and decreased retraction of free lattices. HAM extract transiently increased UF proliferation, slowed down lattices retraction and decreased elastin synthesis. In conclusion, HAM extract has little effect on UF for the parameters studied and NF are more responsive than UF. However, clinical beneficial effect of HAM application on leg ulcers was previously observed and might rather be related to an action on keratinocytes and/or a modulation of the highly inflammatory environment of these chronic wounds.

Objective: To describe an in vitro fibrin clot model that could reliably assess the fibrinolytic activity of enzymatic debriding agents for wound care application. Method: A model of a fibrin clot was reconstructed in vitro by mixture of human fibrinogen and a-thrombin supplemented with factor XIII. These clots were then treated with enzymatic ointments. Fibrinolytic activity was investigated by measuring D-dimer levels, using an automated immunoturbidimetric Liatest D-dimer assay. Results: Collagenase and papain-urea ointments demonstrated fibrinolytic activity which was macroscopically visible. Their effect was identical on the in vitro reconstructed fibrin clot and ex vivo collected wound fibrin clot; collagenase and papain-urea both induced a complete degradation and dissolution of both fibrin clots after 24 hours of treatment. This was associated with an increase in D-dimer concentration. Conclusion: This reconstructed fibrin clot in vitro model has the potential to predict the efficacy of fibrinolytic agents and therefore appears to be a suitable model for in vitro assays. Declaration of interest: This study was supported by a grant from URGO Laboratory.

Gli apparecchi fotografici digitali (AFD), compatti, bridge o reflex, ubbidiscono agli stessi principi ottici delle macchine fotografiche a pellicola del passato. La sola cosa che conta sempre, alla fine, e lasciare entrare la giusta quantita di luce, ne piu ne meno. Tutte le regolazioni ottiche consistono nel trovare un compromesso in questo equilibrio, controllando il piu precisamente possibile tale ingresso di luce e tenendo conto al tempo stesso delle condizioni variabili e spesso imprevedibili di cattura dell’immagine. Questa padronanza dell’esposizione passa anche attraverso la conoscenza dei sistemi di flash e di illuminazione disponibili, ma anche attraverso la conoscenza di strumenti piu specifici, quali i filtri polarizzanti concepiti per isolare la componente speculare della cute e la luce ultravioletta (UV) riflessa, che permette di rappresentare il fotoinvecchiamento. Si notera anche l’esistenza da alcuni anni di apparecchi integrati che costituiscono un insieme completo di cattura delle immagini standardizzata. La fotografia digitale presuppone una gestione informatica delle immagini, sia dal punto di vista dell’hardware che del software. Il dermatologo deve, quindi, in una certa misura, essere anche un po’ informatico, e conoscere il suo materiale digitale, ma anche i suoi programmi di ritocco e di classificazione. In effetti, la fotografia digitale e raramente utilizzabile direttamente, senza il trasferimento su un computer, senza la visualizzazione su uno schermo, senza ritocchi e manipolazioni, allo scopo di ridimensionarla, di commentarla o di archiviarla. I concetti di formati di immagine, di compressione, di risoluzione e di definizione sono critici da questo punto di vista, poiche, se mal compresi, essi possono provocare un deterioramento rapido e irreversibile dell’immagine. Questa gestione software dell’immagine e spesso sottovalutata dal medico, che la giudica troppo complessa, per mancanza di informazione. Esistono, tuttavia, una vasta libreria software disponibile su questo soggetto e dei programmi gratuiti, semplici e user-friendly, che offrono una liberta di lavoro praticamente senza limiti. Noi riteniamo che la costituzione e la padronanza di questa «scatola di attrezzi» sia indispensabile quanto la padronanza dell’apparecchio fotografico propriamente detto. Per il dermatologo, lo scopo della fotografia digitale e di tendere a divenire una fotografia scientifica, vale a dire una fotografia standardizzata, ripetibile e riproducibile. Lo scopo non e tanto quello di ottenere una bella fotografia, quanto di ottenere una fotografia realistica e fedele dell’oggetto di studio. Un’attenzione del tutto particolare deve, quindi, essere prestata agli aspetti pratici della cattura dell’immagine, ma anche all’aspetto del paziente e, in particolare, alla sua neutralita al momento della cattura dell’immagine. Questa volonta di standardizzazione richiede di prevedere e di organizzare uno spazio fotografico dedicato, in maniera da renderlo il piu pratico e immutabile possibile.

Currently, numerous patients who receive targeted chemotherapy for cancer suffer from disabling skin reactions due to cutaneous toxicity, which is a significant problem for an increasing number of patients and their treating physicians. In addition, using inappropriate personal hygiene products often worsens these otherwise manageable side-effects. Cosmetic products for personal hygiene and lesion camouflage are part of a patients' well-being and an increasing number of physicians feel that they do not have adequate information to provide effective advice on concomitant cosmetic therapy. Although ample information is available in the literature on pharmaceutical treatment for cutaneous side-effects of chemotherapy, little is available for the concomitant use of dermatological skin-care products with medical treatments. The objective of this consensus study is to provide an algorithm for the appropriate use of dermatological cosmetics in the management of cutaneous toxicities associated with targeted chemotherapy such as epidermal growth factor receptor inhibitors and other monoclonal antibodies. These guidelines were developed by a French and German expert group of dermatologists and an oncologist for oncologists and primary care physicians who manage oncology patients. The information in this report is based on published data and the expert group's opinion. Due to the current lack of clinical evidence, only a review of published recommendations including suggestions for concomitant cosmetic use was conducted.

Resume But L’objectif de l’etude etait de determiner le niveau de contamination bacterienne de l’environnement lors de la refection des pansements de plaies chroniques. Methodes Des prelevements de plaies chroniques et d’environnement (air et surfaces) ont ete realises lors des refections de pansements de plaies chroniques. Une serie de prelevements etait definie comme l’ensemble des prelevements realises un jour donne autour d’un patient donne. Cinq prelevements sequentiels d’air et six de surface etaient effectues pour chaque serie. Les bacteries cibles recherchees etaient Staphylococcus aureus , Pseudomonas aeruginosa et les enterobacteries. Resultats Trente series de prelevements ont ete realisees chez 26 patients differents. Vingt-sept des 30 plaies etaient colonisees par une (ou deux) des bacteries cibles. Pour 13 series de prelevements d’environnement (13/27, soit 48,1 %), l’espece bacterienne trouvee dans la plaie etait retrouvee dans les prelevements d’environnement. Les deux especes trouvees dans l’environnement etaient S. aureus et P. aeruginosa . Aucune des six enterobacteries isolees des plaies n’etait detectee dans l’environnement. Les prelevements d’air etaient plus frequemment positifs que les prelevements de surface. Conclusion Les resultats observes attestent d’une contamination frequente de l’environnement par les bacteries des plaies chroniques lors des refections de pansements. Ils soulignent l’importance du port de masque par les soignants pour la realisation des soins de plaies et de la desinfection des mains apres contact avec l’environnement du patient.

Resume Introduction La place de la maladie du Morbihan dans la nosographie est incertaine. Tantot denommee « œdeme facial persistant solide », tantot « rosacee lymphœdemateuse », elle pourrait correspondre a une forme clinicopathologique particuliere de lymphœdeme ou de rosacee. Elle est peu frequente et pose un veritable probleme de prise en charge chronique au long cours. Nous rapportons, pour la premiere fois dans la litterature francaise, un effet favorable du traitement par diuretiques dans trois cas de maladie du Morbihan. Observations Trois hommes âges de 38, 66 et 76 ans, suivis pour une maladie du Morbihan invalidante evoluant respectivement depuis deux, cinq et huit ans, presentaient un œdeme de la face predominant sur les paupieres. Le diagnostic etait retenu selon des criteres cliniques et paracliniques, apres exclusion d’un certain nombre d’affections (lupus cutane chronique, sarcoidose, causes infectieuses, notamment demodecie faciale, et enfin rosacee granulomateuse). Apres plusieurs echecs therapeutiques (cyclines, antipaludeens de synthese, danazol, corticoides et isotretinoine), ces patients ont recu un traitement par diuretiques : furosemide a la dose de 60 mg/j chez deux d’entre eux et spironolactone chez le troisieme, a raison de 75 mg deux fois par jour. Resultats Nous avons constate une regression quasi-totale, voire totale, de l’œdeme avec un recul allant d’un a 16 ans. Aucun effet secondaire n’a ete rapporte. Discussion La prise en charge de la maladie du Morbihan reste difficile et surtout empirique. Le traitement par diuretique est une alternative therapeutique interessante dans les formes severes de cette affection.

La cute umana, ben lungi dall’essere una superficie piana e liscia, presenta, al contrario, un rilievo complesso e vario, che ha un significato fisiologico o, anche, patologico. Sono, in effetti, le caratteristiche biomeccaniche del derma e dello strato corneo che si esprimono attraverso questo rilievo, dal microrilievo impercettibile che si puo trovare nel bambino fino alle rughe profonde e marcate della persona anziana. La quantificazione precisa e affidabile di questo rilievo esige di prendere sempre in considerazione queste due situazioni estreme, che hanno, come vedremo, ognuna i suoi limiti tecnici e le sue specificita pratiche. Il testo che segue deriva dalla nostra pratica dermatologica e cosmetologica negli ultimi dieci anni. Questa presentazione e volontariamente limitata alla proiezione di frange, attualmente la tecnica di profilometria ottica piu diffusa in biometrologia. Essa rende possibile una valutazione realistica, obiettiva e, soprattutto, riproducibile della cute. Permette anche delle misurazioni in vivo senza contatto, che sono particolarmente ricercate e richieste nella valutazione clinica. L’esposizione, quanto piu semplice possibile, insiste sui limiti pratici e sul rigore necessario all’implementazione di questo tipo di tecnologia. L’insieme del testo e disseminato di esempi di analisi provenienti direttamente da studi clinici o da test di fattibilita.

Resume But L’objectif de ce travail est, d’une part, d’analyser l’evolution de l’usage de la membrane amniotique humaine (MAH) dans le traitement des ulceres veineux au travers des etudes realisees ; et, d’autre part, de rapporter differents modeles d’ingenierie cutanee bases sur la MAH en vue d’un usage therapeutique ulterieur en cicatrisation. Methodes Cette revue s’appuie sur des articles provenant de la base de donnees PubMed, identifies avec les mots cles suivants : « Amnion »[Mesh] AND « Leg Ulcer »[Mesh] ; « Amnion »[Mesh] AND « Dermatology »[Mesh]. Les articles selectionnes, de langue anglaise ou francaise, traitent de l’utilisation de la MAH seule, sur des ulceres de jambe de type uniquement veineux. Resultats La MAH semble avoir un effet favorable sur l’evolution des ulceres veineux chroniques puisqu’elle favorise la formation du tissu de granulation, limite la fibrose et induit une re-epithelialisation. De nouvelles etudes comparatives randomisees sont cependant necessaires pour confirmer ces resultats. En parallele, les modeles developpes en ingenierie tissulaire pourraient permettre, par un apport de cellules, de reduire les delais de cicatrisation et ainsi engendrer un renouveau de l’utilisation de la MAH. Conclusion Compte tenu de ses proprietes et des differentes etudes cliniques analysees, la MAH semble etre utile pour le traitement des ulceres veineux.

La peau seche, ou xerose, est extremement frequente. Elle se traduit generalement par une peau rugueuse, squameuse et ayant perdu de sa flexibilite, pouvant etre accompagnee de sensations d’inconfort (tiraillements, demangeaisons, etc.). Certains facteurs predisposent a la peau seche : le manque d’eau des corneocytes, directement sous la dependance des facteurs naturels d’humidification (natural moisturizing factors [NMF]), une anomalie des processus de desquamation ou de keratinisation engendrant un retentissement sur la cohesion intercorneocytaire, une acceleration du cycle de renouvellement cellulaire et/ou une hyperproliferation, une modification de la composition en lipides du stratum corneum ou de la secretion de sebum. Qu’elle soit constitutionnelle ou liee a une maladie cutanee, la xerose necessite des soins particuliers, dont l’efficacite peut desormais etre precisement evaluee par des scores cliniques et par la mesure de parametres cutanes specifiques.

Resume Introduction La depigmentation volontaire (DV) est une pratique tres frequente dans la population a peau noire. Le nom donne localement a la pratique reprend souvent directement le nom d’une marque de produit tres utilisee : c’est le cas a Mayotte ou la DV est appelee « pandalao ». Patients et methodes Nous avons realise une etude descriptive sur un echantillon de la population feminine mahoraise, d’âge superieur a 15 ans, de peau noire. L’enquete par questionnaire a ete realisee aupres de 163 femmes entre le 12 novembre 2007 et le 24 janvier 2008. L’objectif de notre travail etait de connaitre la prevalence et les caracteristiques de la DV telle qu’elle se pratique a Mayotte. Resultats Cent pour cent des femmes interrogees connaissaient la DV et 95 % d’entre elles connaissaient dans leur entourage quelqu’un qui se depigmentait. La prevalence des utilisatrices de depigmentants etait de 33 %, mais 74 % d’entre elles en appliquaient de facon intermittente et 89 % des femmes limitaient les applications aux zones exposees (au regard d’autrui). Soixante-trois pour cent des femmes appliquaient simultanement Diproson® (dipropionate de betamethasone) et Pandalao®, dont le composant essentiel est l’acide salicylique. Cinquante-quatre pour cent des utilisatrices avaient presente un ou plusieurs effets secondaires a la suite des applications de produits, parmi lesquelles 28 % avaient cesse leur pratique a cause de ses effets secondaires (acne et dyschromies notamment). Discussion L’illegalite du commerce des depigmentants ne freine pas l’essor de ce phenomene qui represente un marche prospere et profite pleinement du succes de l’ethnocosmetique. La DV est a Mayotte, comme en France metropolitaine ou en Afrique, une realite notoire mais taboue. Quelques particularites doivent etre soulignees a Mayotte : la faible frequence de la DV sur le corps entier ; une application intermittente ; l’adjonction d’acide salicylique au dermocorticoide ; l’utilisation du masque traditionnel mahorais, le « msindzano », comme photoprotecteur.

Resume Le developpement remarquable de la photographie numerique a ete rendu possible par les progres conjoints de l’informatique et des logiciels de traitement et de retouche photo. L’utilisation scientifique de la photographie est desormais possible, a condition de comprendre ses limitations intrinseques, notamment dans le cadre temporel bien particulier d’un essai clinique. Nous detaillerons dans ce texte les 2 principales limitations inherentes a cette methode, a savoir la calibration geometrique et la calibration colorimetrique. Ces limitations seront abondamment illustrees a partir d’images tirees de notre pratique a Besancon depuis une dizaine d’annees.

In clinical evaluation, digital photography is a valuable low-cost and easy to use tool to illustrate assessments; hence the temptation to use it for analysis purposes, particularly in the assessment of facial wrinkles (forehead wrinkles, crow's feet). We review different methods to quantify the volume from 2D images, most of them directly adapted from algorithms initially developed in 3D profilometry. The 3D representation of these photographs is also detailed using several examples. Finally, the limits and drawbacks of this 3D "pseudo quantification" are listed and compared with those usually found in classic profilometry.

Medical literature is rich with new and relevant information, resulting from basic or applied research. Some strong arguments are presented in this document. Firstly, the discovery and role of a virus, the polyomavirus, in the development of Merkel tumours. It is a small virus with double bit DNA strand, coding for a oncoprotein. If the polyomavirus plays a causal role in the tumorigenesis, it acts by various mechanisms. The micro-RNAs represent an abundant class of small RNA not coding for proteins, but which control the gene expression coding for proteins on a post-transcriptional level. The first obvious sign of the role of the micro-RNAs in the inflammatory dermatoses appeared recently, in particular when these micro-RNAs associated with psoriasis and atopic dermatitis were identified through a broad genomic analysis of the expression of these micro-RNAs. A new giant virus strain sheltering another unknown tiny virus to date has just been discovered. This virus infinitely small called Sputnik enables to deteriorate a much larger virus baptized Mama, at the point of preventing it to manufacture normal viral particles and also preventing it from reproducing. This discovery raises a crucial question: Is Sputnik a new system of transfer of genes of a species of one virus to another? A group of blood cells expressing E-cadherin, the dot cells, found in the fetal blood of the dermis, contributes to tissue repair through the mechanisms of cellular differentiation and their action allows healing without scar. CD4+ T helper lymphocytes producing interleukin 17 (IL17) play a pathogenic part in atopic dermatitis. The genes of the beta defensins could be involved in the genetic susceptibility of the psoriatic disease. The autoimmune origin of the alopecia areata is supported by a great number of observations, the role of neuropeptides in the initiation of the autoimmunity during alopecia areata has just been demonstrated. The dendritic cells are cells presenting antigens which play a crucial role in the adaptive immunological response. It was shown that activation of the proliferation of the lymphocytes T after the migration of dendritic cells on the level of the lymphatic ganglion depended not on Langerhans cell, but of the dendritic cell. A new way appears to control the autoimmunity in the psoriasis and involves the plasmacytoid dendritic cells which are sensitized with the DNA itself when it is coupled with an antibacterial peptide. Mast cells express cathelicidin, which acts like an antibiotic with broad spectrum and influences the defence system of the epitheliums. We have perhaps found a new therapeutic target for rosacea by disclosing high rates of cathelicidin and a series of associated proteases in skin lesions. The sebocytes express antibacterial functional peptides deriving from cathelicidin which can have a bactericidal effect against P. Acnes. A vast genomic study in the androgenetic alopecia highlighted the existence of new loci localized on the 20p11 chromosome, associated with the risk of androgenetic alopecia. New alleles to determine the color of hair and the cutaneous pigmentation were identified. Two loci (IRF 4 and SLC24A4) are highly associated with the color of hair, like three other areas. The blue color of the eyes could be due to a change of an element located in gene HERC2 preventing of the expression of OCA2. Thus, many fields of dermatology were the object of research which opens new prospects for diagnosis and treatment.

Resume Introduction La prise de phenylbutazone expose a des effets indesirables frequents, tres varies et parfois graves. Nous rapportons pour la premiere fois une observation de syndrome de Sweet associe a une sialadenite, induite par la prise de phenylbutazone. Observation Une femme de 54 ans traitee pour des lombalgies, neuf jours auparavant par de la phenylbutazone durant trois jours, voyait apparaitre une parotidite et une sous-maxillite bilaterale, puis une eruption febrile erythemateuse, œdemateuse et pustuleuse, resistant aux antibiotiques. Les examens biologiques montraient un syndrome inflammatoire majeur avec hyperleucocytose a polynucleaires neutrophiles, thrombocytose, anemie et cytolyse hepatique. Le bilan infectieux et auto-immun etait negatif. L’examen histologique d’une biopsie cutanee confirmait le diagnostic de syndrome de Sweet. Une corticotherapie generale entrainait la disparition de la symptomatologie clinique et biologique. Discussion Une sialadenite induite par la phenylbutazone est un effet secondaire rare et meconnu, qui peut s’accompagner d’une reaction systemique. Dans notre observation, le syndrome de Sweet correspond aux criteres bien definis de syndrome de Sweet medicamenteux. Il correspond vraisemblablement a une reaction systemique par hypersensibilite medicamenteuse, au meme titre que la sialadenite.

The friction coefficient, the wettability and the surface free energy of lingual mucosa while deprived of its natural removable salivary layer were evaluated ex vivo and the influence of a salivary coating on these characteristics assessed. Piglet tongue was used as support for the experiments due to its known similarities with human tongue and the availability of a large number of specimens. Whole stimulated saliva (fresh human saliva) was collected and used as such. The friction and wettability properties of the oral mucosal tissue were tested before and after organic salivary layer formation using devices developed to characterise human skin properties. Tongue surface wettability was determined by advancing contact angle measurements. Distilled water, diiodomethane and ethylene glycol were used as probe liquids. Under experimental conditions, the tongue surface has a hydrophobic tendency and is weakly polar. When coated with a salivary layer, the surface of the tongue becomes significantly more hydrophilic. Salivary coatings increase the total surface free energy of the dorsal surface of the tongue and at the same time impart a more basic character. Moreover, the presence of salivary layers reduces the dynamic coefficient of friction by a factor of 1.6, underlying the lubricant function of saliva. In conclusion, friction and wetting properties of tongue surface provide valuable insight into how the tongue interacts with other surfaces as a function of the coating.

Dry skin is estimated to be present in about 75% of people aged 75 and over. It has been known for many years that this condition is more frequent in winter, in cold and dry weather conditions. With technological progress, people are now mostly exposed to multiple indoor and outdoor pollutants and environment parameters (air-conditioning, chemicals, noise) which can interact which each other and affect human health, and particularly the skin. All these phenomena are intensified with skin aging and can be aggravated by seasons, the way of life, habits (nutrition, dust, allergens, air-conditioning, noise, smoking, unadapted cosmetic use, some treatments) and working conditions (visual display unit, stress). In fact, this environment can be defined as the whole ensemble of external factors which could have an influence on a subject’s health. This means material (climate, geography), organical (biosphere, fauna, flora), physicocultural (techniques), biocultural (nutritional habits, hygiene, medical use) and psychocultural (stress) elements. The aim of this article is to make a review in order to check which of these elements have a major impact on dry skin, in particular among seasons, working/living conditions and cosmetic or hygienic products.

Trimethylpsoralen (TMP) is often used to treat skin diseases (i.e., psoriasis, vitiligo, etc.). This drug permeates moderately the skin barrier. In the present study, we investigated the effect of formulation on the improvement of TMP skin bioavailability. Three formulations were performed. Each form (liposomes, nanospheres, and EtOH solution) contained 0.05% of TMP. For each preparation, the quantity deposited on the skin surface was 250 µg (Q0). The TMP percutaneous penetration through ex-vivo human skin was processed by Franz® cells (n=4) using a human albumin solution (1.4% w/v) as receiver medium. The percentages of the extracted TMP that permeated through the skin and that were retained in the skin over 24 h, were calculated with respect to Q0. The values obtained were reported, respectively, as follows: EtOH solution (1.33 vs. 0.08%), liposomes (0.93 vs. 0.93%), and PLG-nanospheres (0.79 vs. 3.01%). So, considering the correlation between the cumulated amounts of TMP permeated through the skin and the TMP stocked in the skin, the nanosphere form showed the higher quantity of TMP accumulated in the skin structures. On the other hand, the maximum value of the flux (ng/cm2/h) in the steady state of TMP incorporated in each formulation was at 6 h for all formulations: 173.5±1.06 (EtOH solution) > 120.4±1.06 (liposomes) > 93.82±0.88 (PLG-nanospheres). These results indicate that the controlled release of TMP by incorporation in PLG-nanospheres may increase drug content in the skin, while maintaining a minimal percutaneous absorption. Finally, this work shows that the PLG-nanospheres could constitute a promising approach for controlling TMP release in order to maintain its topical activity. Drug Dev. Res. 61:86–94, 2004. © 2004 Wiley-Liss, Inc.

The purpose of the present study was to compare Franz cells (FC) and microdialysis (MD) for monitoring the skin absorption of salicylic acid (SA). The influence of pH on SA flux was also assessed by these two techniques. Excised abdominal human skin was used in the experiments. SA was dissolved in phosphate buffer solutions of pH 2, 5 and 7 (2 mg/ml). SA concentrations in the receptor FC solutions and in MD samples were assessed by high performance liquid chromatography (HPLC). The results demonstrate that the flux of SA decreased with increased pH. The profiles permeation determined by Franz cells and microdialysis were similar. However, whatever the pH, the SA flux was higher with microdialysis than with Franz cells. The results showed that SA percutaneous permeation conformed to the pH partition hypothesis. The flux of SA was different when it was determined by the two techniques. The collect of SA, by these two techniques is different. The results of the two techniques are compared and discussed.

Objective: We compared the effects on cultured human fibroblasts of a new non-adhesive wound dressing, Urgotul, with five other wound dressings. Urgotul is a hydrocolloid dressing; the comparator dressings included impregnated gauze and modern wound dressings. Method: Cultures in monolayer were used to study the morphology and growth of fibroblasts. The Bell model of cultured dermis equivalents was used to investigate myofibroblast differentiation. These cultures were labelled a-SM actin and F-actin. Results: Two of the tested dressings induced cytotoxic effects. They were found to inhibit cell growth (greater than 60%) and to disturb cell shape and cytoskeletal differentiation. Urgotul and the remaining three dressings showed no effect on proliferation. However, some of them modified fibroblast morphology and affected F-actin distribution. Conclusion: Depending on their nature and components, wound dressings may respect or affect fibroblast behaviour in vitro (proliferation, morphology and a-SM actin and F-actin distribution). The significance of these in vitro observed findings require further investigations. Declaration of interest: This study was supported by Urgo Laboratories.

Nowadays, the determination of human skin microtopography is usually carried out by methods based on mechanical techniques (profilometry and surfometry), or founded on optical conception (shadowing method and profilometry). Negative skin replicas made of a silicone rubber material (Silflo((R))) or positive casts performed from an epoxy resin (Araldite((R))), are used to assess the skin microstructure. Skin surface microtopography is quantified by measuring furrows depths and spaces between them. An original application using confocal scanning laser microscope (CLSM) is described in this paper. The CLSM gives simultaneously images of the skin surface associated with quantitative measurements of the microtopography. With this apparatus, it is easy to achieve perfect skin replica images with assessment of its microstructure, before and after applications of topical medicines or cosmetic products to evaluate the skin surface restoration. It is worth to mention that it is indispensable to analyse the same skin surface (same plateaux and same furrows). For this reason, it is necessary to localize exactly and to replicate the same skin surface area (4 mm(2)) before and after the cosmetic use, whatever the extended period of the topical application.

Detection and mass estimation of fissile material are important tasks. The aim of this paper is to show how one can try to solve such an inverse problem with an iterative forward approach.

Until now, the wettability of the skin has been only estimated through the measurement of its critical surface tension (Zisman), or surface free energy. These methods give information on the behaviour of the surface with water, but cannot quantify its behaviour with other polar liquids. In this paper we propose to express both the hydrophilia of the skin (Hi) by the ratio of its critical surface tension (gamma(c)) to the water surface tension (gamma(H(2)O)), and its hydrophobia (Ho) by the ratio of the difference between the critical surface tension (gamma(c)), and the value of the water surface tension (gamma(H(2)O)) normalized by the latter. By using this proposed parameter, it should be possible to classify skin surfaces according to their affinities to water, which is of major importance in Cosmetology as well as in biology. We also discuss the relationship between surface hydrophilia (Hi) and polarity (P) as defined by Wu, and water adhesion tension (tau(o)) as described by Vogler. The gamma(c) of untreated skin was 27.3 +/- 3.6 mJ m(-2), confirming previous data, and consequently basal Hi was 38%. Either cleaning with ether or hydration by occlusion induced a diminution of the wetting capacity of the surface and consequently a decrease of Hi to 29% and 33%, respectively. In contrast, washing the skin surface with soap and water increased surface Hi to 43%.

Introduction: Quality of smoothness of the skin is the combine result of its mechanical and frictional properties. Methods: A device was developed to characterize such a property in measuring the friction force between a reference material and the skin of the volar forearm. Results: The instrument showed a good reliability in using on steel roughness calibration plate, with the ability of the measuring unit to recognize different roughness from R a =0.4–50 μm. Validation of the device was realized on dental silicone with the determination of a friction coefficient μ ≈0.42. Preliminaries tests in vivo on a 42 year-old woman showed a friction coefficient in the axis of the volar forearm of μ ≈0.7. In this study, each curve was the mean of ten tests for each load applied and for all curves the variation coefficient was found Conclusion: This device provides an accurate quantitative measurement of the skin friction force. It can help us in further investigations to correlate each change with aging cosmetic product application, in relation to mechanical and microrelief properties.

The presence of tyrosinase mRNA in the peripheral blood cells of melanoma patients has been recently studied as a possible marker of haematogenous dissemination. However, considerable variations in the rates of detection have been noted. We determined the presence of tyrosinase mRNA-positive circulating cells using reverse transcriptase-polymerase chain reaction (RT-PCR) in 35 patients with stage I melanoma, two patients with stage II melanoma and two patients with stage III melanoma. Among the patients with stage 1, 13 were tested before and after surgery (< 1 h). Twenty healthy subjects served as negative controls. Out of the melanoma patients, the tyrosinase gene was expressed in three of the 52 samples tested. Tyrosinase mRNA was present in the circulating cells of only one patient with stage I melanoma after intra-congenital naevi resection. However, two other stage I patients developed rapidly lethal metastasis within the following 6 months, despite the lack of detectable tyrosinase mRNA. None of stage II patients were positive for the tyrosinase transcripts, while both patients with stage III melanoma showed enzyme expression. Our results confirm those of previous studies, showing that a small proportion of stage I melanoma patients have tyrosinase-positive circulating cells. Moreover, the lack of tyrosinase mRNA detection in the blood does not necessarily exclude metastatic progression. Therefore, this study indicates that the detection of tyrosinase mRNA-positive circulating cells by RT-PCR is not a predictive biomarker of a metastasis risk in patients with stage I melanoma.

Background: HIV-infected patients, like renal transplant recipients, are at increased risk of developing skin cancer in photoexposed areas. Previous studies demonstrated that prolonged ultraviolet (UV)-induced erythema and a decreased and delayed tanning could be correlated with an increased risk of skin cancers. Objective: As HIV-infected patients are at an increased risk of developing skin cancers, we aimed to assess the cutaneous response to UV irradiation in these patients. Methods: Twelve HIV-infected patients and 12 healthy volunteers were included in a prospective case-control study. No patient or volunteer had a history of skin cancer or photodermatosis. The minimal erythemal dose (MED) was determined using a solar simulator UV source, and, then, each subject underwent an exposure of 6 MED. The erythemal and pigmentation responses were studied using a visual scale and a tristimulus colorimeter over a 4-week period. Results: We failed to demonstrate any significant differences between HIV-infected patients and controls for erythema and delayed pigmentation. No difference was found for MED between the two groups although most HIV-infected patients received potentially photosensitive drugs. Conclusions: Our results suggest that, as a group, the HIV-infected patients without a history of photosensitivity or skin cancer did not demonstrate a greater susceptibility to intense UV irradiation in terms of erythema and pigmentation induced by intense UV exposition.

Background: Retinaldehyde, the natural precursor of retinoic acid, should exert similar effects on photoaged skin. Objective: To establish the efficacy and safety of topical retinaldehyde on photoaged skin. Methods: Open and controlled clinical studies using image analysis of silicone skin replicas. Results: Retinaldehyde proved efficient and safe. Conclusion: Retinaldehyde is efficient and well tolerated for the improvement of the signs of photoaging.

The forehead skin sebum casual (or usual) level, which is remarkably stable in a given individual, is responsible for the monopolar basic character of the skin surface. However, the significance of this finding, in terms of the physicochemical behaviour and wettability of the skin surface, remains unexplained. How does this vary during sebum casual level restoration following skin washing and what is its relationship with so-called “dry skin”? The present work was aimed at answering these questions. Forehead surface free energy components were assessed before and during the sebum casual level restoration following skin washing by nonionic soap and water, in 12 healthy volunteers: four oligo- (OS), four normo- (NS), and four hyper-seborrheic (HS) skins. Skin contact angles of water, formamide and diiodomethane were measured at intervals, and surface free energy components (i.e. Lifshitz–van der Waals, electron acceptor and electron donor components) were calculated using the contact angle values and acid–base theory of C.J. van Oss et al. The results showed that a low sebum-level does not deprive the skin surface of a normal Lifshitz–van der Waals component. This suggests that a low sebum-level is sufficient to render the skin normally lipophilic. The very low acidic component of the skin surface seemed to be due to the masking of acidic moieties by adsorbed water. The basic component was sebum-level dependent below a threshold value and remained to be related to the sebum free fatty acids and especially to their outward carboxylic group orientation. We conclude that the wetting properties of the skin surface could be defined by a “surface free energy component balance” or SEB. The SEB of NS and HS skins was around 0.22, and that of OS skin was 0.07. This low SEB stems from a weak hydrophilic component, allowing OS skin to be called dry skin, or better, a dry skin surface. This approach may provide a new insight into so-called “skin hydration”.

The purpose of this work was to assess the surface free energy (SFE) of bare and bile-salt-precontacted pellet surfaces of psoralens (lipophilic molecules). This study was carried out according to the approach of van Oss et al. to the solid-liquid interfacial free energy using the Lifshitz-van der Waals component, electron acceptor and electron donor parameters of the SFE. With the help of a hydraulic press, powders of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP) were compacted sufficiently to obtain smooth and glossy disc surfaces. One set of pressed discs was used directly after preparation and another set was treated with a bile salt (sodium cholate/sodium deoxycholate mixture) aqueous solution of 0.1 mol l −1 for 2 h at 37°C before droplet deposition. The surface free energies of bare and bile-salt-treated discs were determined by advancing contact angles using polar (water and formamide) and apolar (diiodomethane) standard liquids. The measurements were carried out at 21.5 ± 1.5°C using a surgical microscope fitted with a slanted mirror and equipped with a video camera linked to a computer. In addition, the surface and interfacial tensions of a biphasic system of octanol and water in which psoralens were solubilized were measured using the De Nouy ring method. The results were correlated with the lipophilicity and solubility of these drugs. The data of contact angle values of psoralen bare surfaces indicated the hydrophobicity order 8-MOP γ s LW ) components corroborated this. 8-MOP showed the same acidic and basic values ( γ s AB = 6.5 mJm −2 , while γ s AB was equal to 1.8 and 0.4 mJm −2 for 5-MOP and TMP respectively. However, when the psoralens were treated with sodium cholate sodium deoxycholate ( NaC NaDC ) mixture, the presence of micelles on the surface modified the previous data by decreasing the contact angles with polar solvents and γ s LW . In contrast, the total surface free energy of all the psoralens increased, especially the electron onor component ( γ − ) and γ s AB . When comparing the three psoralens, 5-MOP behaved peculiarly as it had the lowest γ s − (29.5 mJm −2 ) and γ s AB (21.4 mJm −2 ). Theoretical explanations concerning the reactivity of the psoralens vis a vis standard liquids were assumed. The results of this work enabled us to understand qualitatively and quantitatively the types of interaction between the molecules of each studied psoralen and to predict their behaviour when they permeate through a given biological membrane (e.g. human skin). From this work the adsorption of bile salts on to the hydrophobic surface was confirmed for the psoralen case. This result could constitute the beginning of a physicochemical explanation of the digestion step for orally taken psoralens.

Skin surface wettability is an important factor of the skin protective function, e.g. ecosystem preservation, smoothness and resiliency, barrier to chemicals, but surprisingly it has received little attention. Hence, this work aimed at calculating the surface free energy components of human skin, on the volar forearm, a sebum-poor area, and on the forehead, a sebum-rich area, and at assessing the influence of skin lipids on surface wettability using advancing contact angle measurements of water, glycerol, formamide and diiodomethane. Contact angles on the forearm and the forehead of ten healthy volunteers were measured, using a surgical microscope fitted with a slanted mirror and equipped with a video camera linked to a computer. Both skin areas were examined before and after ether treatment. According to the approach of van Oss et al. to solid-liquid interfacial interactions, the surface free energy components, i.e. Lifshitz-van der Waals, electron acceptor and electron donor components, were calculated. From the contact angle measurements and calculations of surface free energy, the forearm skin surface was found to be an almost apolar surface and the forehead skin surface a monopolar basic surface (electron donor). Ether treatment caused both surfaces to become more apolar, mostly by reducing the electron donor component. These results would suggest that skin surface lipids, mainly sebum, give the skin surface a hydrophilic character. However, no correlation was found between the skin lipid level and the basic component level which raises the question of the mechanism of the obvious wetting-enhancing effect of sebum. This could be due to the free fatty acids, which are especially abundant in the sebum.

8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP) are commonly used in PUVA therapy [psoralen (P) + ultraviolet light A (UVA) irradiation] to treat skin diseases such as psoriasis and vitiligo. In order to predict the choice of the suitable drug(s) for topical applications, with appropriate dosage, percutaneous permeation of the psoralens, in connection with their solubilities and partition coefficients in an octanol/water system, were investigated. The percutaneous penetration experiments were accomplished by the deposit of ethanolic psoralen solution onto human skin and epidermis fragments mounted on Franz cells. Six cells were employed for each psoralen solution and for the whole skin layer as well as for the epidermis. The diffused psoralens in the receptor solution (1.4%, of human serum albumin) were quantified by using high performance liquid chromatography. The solubilities and the partition coefficients (PC) were carried out in an octanol/water system, in triplicate by using spectrofluorimetry. The results demonstrated that cumulated permeated quantities (ng/cm2) over 24 h, across the whole skin and the epidermis were in the following order for the three psoralens: 8-MOP > 5-MOP > TMP. The lipophilicity, expressed via the log PC, was as follows: 1.93 +/- 0.01 (8-MOP), 2.00 +/- 0.01 (5-MOP) and 3.14 +/- 0.01 (TMP). It was inversely correlated with cumulated penetrated amounts over 24 h in both whole skin and epidermis. From these results, TMP could be predicted as the most convenient psoralen for topical applications, because of its weak penetrability. Considering the relationship between psoralens lipophilicity and permeation, only 5-MOP and 8-MOP could be used, topically or orally, especially in the case of generalised skin disorders.

Background/purpose Contact between skin surface and external environment induces a microclimate at the skin surface. That microclimate affects skin interaction with xenobiotics substances. We have developed a new device to explore the influence of environmental parameters, on percutaneous absorption. The aim of this study was to study the influence of external humidity and temperature on percutaneous absorption of caffeine. Methods Six exposure conditions were tested: four by combining two temperatures (27°C and 42°C) with two relative humidities (28% and 70%), performed by our device and two others by using Franz diffusion cell (unoccluded conditions, with skin surface in contact with ambient laboratory environment (27°C/33%) and in occluded conditions with skin surface covering by impermeable membrane). Results Kinetic curve profile of percutaneous absorption of caffeine revealed different shapes characteristics depending on environmental exposure conditions. These profiles were related to evaporative process, of deposited preparation on skin surface combined with water uptake resulting from water flux through skin. Conclusion Our results highlight a preponderant role of microclimate above the skin on percutaneous absorption of caffeine. The device used in this study will be a useful tool to investigate ex vivo, the influence of microclimate on percutaneous absorption.

Background/aims: Surface energy phenomena result from molecular interaction between substances. On the skin, they are involved in sweat and sebum dispersion, and in foreign substances, in spreading and absorption. However, they are unknown due to the scarce number of studies. The aim of this work was to find the skin critical surface tension (CST), an index of wettability, through a reliable technique, and to study the influence of skin lipid and of some oil-in-water (O/W) and water-in-oil (W/O) preparations. Method: The CST was calculated using the Zisman equation, from the contact angle at equilibrium, of droplets of liquids whose surface tension was known. Contact angles were computed from the base and the height of the droplets viewed from their side through an operating microscope provided with a slanted mirror. Both volar forearm and forehead were studied. Results: On volar forearm, the skin CST was 27.5±2.4 dyne/cm (n=12) and normally distributed. Forehead CST was above 50.7 dyne/cm. On both areas, defatting with ether reduced CST down to 21.6±2.6 dyne/cm, and 29.3±1.7 dyne/cm, respectively (p

Percutaneous absorption and cutaneous bioavailability of zinc and copper from zinc 2-pyrrolidone 5-carboxylate (ZnPC), zinc oxide (ZnO), zinc sulfate (ZnSO4), copper 2-pyrrolidone 5-carboxylate (CuPC) and copper sulfate (CuSO4) were compared using 5 formulations (3 emulsions and 2 ointments) that were applied topically on human skin in vitro. After application for 72 h, percutaneous absorption of zinc from ointments containing ZnO and ZnSO4 was found to be lower than that from a ZnPC-containing emulsion (0.36 and 0.34 versus 1.60% of applied dose). In the case of copper, the flux after a 72-hour treatment period showed that there had been minimal release from CuPC- and CuSO4-containing formulations (approximately 5 ng/cm2/h). All formulations used in this study effected an increase in zinc and copper concentrations in whole skin and epidermis. Bioequivalence of the 5 formulations based on pharmacokinetic results was assessed, and salt and vehicle effects were discussed.

Summary Cutaneous warts are caused by infection of the epidermis with human papillomavirus (HPV). Cryotherapy using liquid nitrogen is one of the most common local treatments. In this study, we used a novel ex vivo approach to compare the efficacy of a new product with conventional liquid-nitrogen cryotherapy by studying epidermal histology and assessing the presence of HPV types 1 and 2 DNA in plantar warts. The studied formulation, which acts by tissues mummification, is a combination of nitric acid, organic acids and metallic salts. We found that, similar to liquid nitrogen, the studied product induced alterations in the wart structure. In addition, unlike liquid nitrogen, this product also reduced the amount of HPV DNA. The results suggest that there is a poor correlation between the histological response and the antiviral efficacy of standard wart treatment.

5-geranoxypsoralen (5-GOP), commonly called bergamottin, is a highly photoreactive psoralen, which in contrast to most furocoumarins, does not strongly interact with DNA. 5-GOP gives the opportunity to study, in a more selective way, the mechanisms of phototoxic and immunological activities induced by psoralen and UVA radiation. We investigated the effects of repetitive treatments with 5-GOP plus UVA radiation (320–400 nm) on the number of ATPase+ epidermal Langerhans cells and on the induction of photoreactivity. These effects were compared with those of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP) plus UVA radiation and UVA radiation alone. C3H HeN mice were treated topically with the psoralen three times/week for 4 consecutive weeks followed each time by 1 J/cm2 of UVA radiation. At the end of the treatment, mice treated with 8-MOP or 5-MOP plus UVA radiation exhibited severe gross phototoxicity and nearly total depletion of ATPase-stained Langerhans cells. Both treatments produced severe morphological alterations of Langerhans cells. No gross but a microscopic phototoxic effect was observed after 5-GOP plus UVA radiation treatment, while the number of ATPase+ Langerhans cells was also greatly reduced. Interestingly the latter treatment induced no morphological alterations of the remaining Langerhans cells in contrast to treatment with 8-MOP or 5-MOP plus UVA radiation. We conclude that phototoxicity and decrease in the number of ATPase-stained epidermal immune cells observed after treatment with 5-GOP plus UVA radiation are not related to the DNA binding activity of the psoralen. A second type of photoreaction which is oxygen mediated may be involved.

Summary Background Provoked vestibulodynia is difficult to treat. The beneficial effects of botulinum toxin A are being considered because of the muscular anomalies observed in this pathology. Objective To evaluate the efficacy of botulinum toxin A in the treatment of provoked vestibulodynia. Methods Patients aged between 18 and 60 years presenting with provoked vestibulodynia (according to the 2003 International Society for the Study of Vulvar Disease classification) received 50 U of botulinum toxin A bilaterally in the bulbospongiosus muscle under electromyographic monitoring. Pain was evaluated by a visual analogue scale (VAS), quality of life was evaluated by the Dermatology Life Quality Index and sexual function by the Female Sexual Function Index. Results Twenty patients received the injections. Sixteen patients presented with a muscular hyperactivity on electromyography. After 3 months, 80% of the patients improved in terms of pain. Mean ± SD VAS values significantly decreased from 8·37 ± 1·22 (range 4·5–10) to 2·57 ± 2·67 (0–9; P

International audience; In clinical evaluation, digital photography is a valuable low-cost and easy to use tool to illustrate assessments; hence the temptation to use it for analysis purposes, particularly in the assessment of facial wrinkles (forehead wrinkles, crow's feet). We review different methods to quantify the volume from 2D images, most of them directly adapted from algorithms initially developed in 3D profilometry. The 3D representation of these photographs is also detailed using several examples. Finally, the limits and drawbacks of this 3D "pseudo quantification" are listed and compared with those usually found in classic profilometry.

International audience

International audience; Background/aims: The purpose of this work was to develop a new sensor for objective in vivo measurement of the cutaneous temperature based on micro-electro-mechanical systems (MEMS), and to compare these performances with those of a classical thermocouple. Research on this new sensor was carried out to allow the quantification of the thermal properties of the made-up skin. Methods: Sixteen female subjects divided into two different age groups (18–35 and >50 years old) were recruited for this study. Several zones of the face and forearms were made up at random with foundations containing or not a thermoregulator raw material. The quantity of foundation applied on the skin was standardized and measurements were carried out first before make-up, and then 10 s and 5 min after make-up. The new sensor and the thermocouple were used successively on each zone. The cutaneous temperature was expressed in degrees celsius. Results/conclusion: The two systems are similar in terms of repeatability and reproducibility, with some differences in sensibility. The data measured by the MEMS sensor appear lower than those measured by the thermocouple. After make-up, the MEMS sensor detects a progressive increase of the temperature in time whereas the thermocouple detects a decrease. We found the same evolution on the face but in a more attenuated way. These results tend to show that the devices do not measure the same phenomenon. The thermocouple appears more sensitive to the thermal response of the made-up surface whereas the MEMS sensor appears more sensitive to the heat transfers in the interface between the skin and make-up.

Objective: The tissue contraction phenomenon associated with wound healing is of prime importance for wound closure. Contractile properties of human fibroblasts from chronic venous leg ulcers were compared with those of normal fibroblasts using in vitro models. Method: Biopsies were taken from the uninvolved skin of the thigh, the epithelialised ulcer edge and the non-epithelialised ulcer centre in four patients (average age: 78 years). Fibroblasts were obtained by an explant technique and expanded in vitro in Dulbecco’s Modified Eagle’s Medium supplemented with 10% foetal calf serum and used for the assays at their fourth passage. Intracellular alpha-smooth muscle actin expression (αSM-actin) was studied by immunofluorescence labelling of cells cultured in monolayer. Contractile properties were evaluated using three-dimensional collagen lattices. Results: Fibroblasts from the ulcer centre were the richest cells in actin filaments. Both populations of venous ulcer fibroblasts contracted more rapidly and to a greater extent than normal fibroblasts. The peak contractile forces developed by fibroblasts from the ulcer centre and the ulcer edge were 30% and 18% greater than normal fibroblasts respectively. Conclusion: Some functions of fibroblasts, in particular the generation of contractile forces and the formation of cytoplasmic actin filaments, seem not to be affected in chronic venous ulcers. Declaration of interest: This study was supported by the Fondation Coloplast pour la Qualite de la Vie of France.