19043850 2008 11 28 2009 02 02

1600-0625 17 12 2008 Dec Exp. Dermatol. The skin: an indispensable barrier. 1063-72 The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes. In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses. The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains. The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements. During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers. The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC. Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils. Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis. A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis. Department of Dermatology, University Hospitals of Schleswig-Holstein, Kiel, Germany. eproksch@dermatology.uni-kiel.de Proksch Ehrhardt E Brandner Johanna M JM Jensen Jens-Michael JM eng Journal Article Review

Denmark Exp Dermatol 9301549 IM Animals Cell Communication physiology Epidermis cytology physiology physiopathology Humans Intercellular Junctions physiology Models, Biological Permeability Signal Transduction physiology Skin Diseases metabolism physiopathology Skin Physiological Phenomena 107 2008 12 2 9 0 2009 2 3 9 0 2008 12 2 9 0 ppublish 19043850 17603506 2007 07 02 2007 09 06

1465-7392 9 7 2007 Jul Nat. Cell Biol. p63: revving up epithelial stem-cell potential. 731-3 Blanpain Cédric C Fuchs Elaine E eng News

England Nat Cell Biol 100890575 0 Phosphoproteins 0 Protein Isoforms 0 Trans-Activators 0 Trp63 protein, mouse 0 Tumor Suppressor Protein p53 IM Animals Cell Differentiation Cell Proliferation Epidermis cytology embryology Epithelial Cells physiology Mice Mice, Knockout Phosphoproteins genetics physiology Protein Isoforms genetics physiology Stem Cells physiology Trans-Activators genetics physiology Tumor Suppressor Protein p53 genetics metabolism 2007 7 3 9 0 2007 9 7 9 0 2007 7 3 9 0 ppublish ncb0707-731 10.1038/ncb0707-731 17603506 12210515 2002 09 04 2002 10 30 2005 11 17

0265-9247 24 9 2002 Sep Bioessays Epithelial barrier function: assembly and structural features of the cornified cell envelope. 789-800 Terminally differentiating stratified squamous epithelial cells assemble a specialized protective barrier structure on their periphery termed the cornified cell envelope (CE). It is composed of numerous structural proteins that become cross-linked by several transglutaminase enzymes into an insoluble macromolecular assembly. Several proteins are involved in the initial stages of CE assembly, but only certain proteins from a choice of more than 20 different proteins are used in the final stages of CE reinforcement, apparently to meet tissue-specific requirements. In addition, a variable selection of proteins may be upregulated in response to genetic defects of one of the CE proteins or tissue injury, in an effort to maintain an effective barrier. Additionally, in the epidermis and hair fiber cuticle, a layer of lipids is covalently attached to the proteins, which provides essential water barrier properties. Here we describe our current understanding of CE structure, a possible mechanism of its assembly, and various disorders that cause a defective barrier. Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Kalinin Andrey E AE Kajava Andrey V AV Steinert Peter M PM eng Journal Article Review

England Bioessays 8510851 0 Cytoskeletal Proteins 0 Lipids 0 Membrane Proteins 0 PPL protein, human 0 Plakins 0 Protein Precursors 0 envoplakin 147-85-3 Proline 60108-77-2 involucrin EC 2.3.2.13 Transglutaminases IM Animals Cytoskeletal Proteins chemistry Epithelial Cells cytology Epithelium metabolism physiology Humans Lipids chemistry Membrane Proteins chemistry Models, Biological Models, Chemical Models, Molecular Plakins Proline chemistry Protein Precursors chemistry Transglutaminases chemistry 74 2002 9 5 10 0 2002 11 1 4 0 2002 9 5 10 0 ppublish 12210515 10.1002/bies.10144 16864974 2006 11 22 2007 01 04 2008 11 21

1660-5527 19 6 2006 The pH of the skin surface and its impact on the barrier function. 296-302 The 'acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e.g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e.g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Departments of Dermatology and Allergology, Rheinische Friedrich Wilhelm University, Bonn, Germany. Monika-Hildegard.Schmid-Wendtner@ukb.uni-bonn.de Schmid-Wendtner M-H MH Korting H C HC eng Journal Article Review 2006 07 19

Switzerland Skin Pharmacol Physiol 101188418 IM Handwashing Humans Hydrogen-Ion Concentration Skin chemistry Skin Diseases metabolism Skin Physiological Phenomena 58 2005 9 2 2005 12 22 2006 7 19 2006 7 26 9 0 2007 1 5 9 0 2006 7 26 9 0 ppublish SPP2006019006296 10.1159/000094670 16864974 2436413 1987 04 27 1987 04 27 2006 11 15

0001-5555 67 1 1987 Acta Derm. Venereol. Influence of repeated washings with soap and synthetic detergents on pH and resident flora of the skin of forehead and forearm. Results of a cross-over trial in health probationers. 41-7 Ten healthy individuals washed their forehead and forearm twice a day over consecutive periods of four weeks with soap and synthetic detergents or vice versa (cross-over design). In general the pH values were higher during the period when soap was applied (the mean pH differed by 0.3 units, p less than 0.01). As a rule the counts of coagulase-negative staphylococci were not much altered. The number of propionibacteria, however, was markedly higher when soap was used (p = 0.02 and 0.01 resp.). At the forehead there was a clear correlation between bacterial counts and skin pH both with propionibacteria (0.56, p less than 0.001) and staphylococci (0.51, p less than 0.001). At the forearm only the former proved true (0.24, p less than 0.05). Thus the skin pH seems to be open to long-standing changes according to the preferred washing habits which may also be of major influence on the composition of the cutaneous bacterial flora. Korting H C HC Kober M M Mueller M M Braun-Falco O O eng Comparative Study Journal Article

SWEDEN Acta Derm Venereol 0370310 0 Detergents 0 Soaps 0 Surface-Active Agents IM Adult Detergents Female Forearm Forehead Humans Hydrogen-Ion Concentration Hygiene Male Skin microbiology Soaps Surface-Active Agents 1987 1 1 1987 1 1 0 1 1987 1 1 0 0 ppublish 2436413 8462378 1993 05 06 1993 05 06 2008 11 21

0149-5992 16 4 1993 Apr Diabetes Care Skin surface pH in intertriginous areas in NIDDM patients. Possible correlation to candidal intertrigo. 560-3 OBJECTIVE--To compare skin surface pH and moisture in intertriginous areas in diabetic patients and healthy control subjects and to study the relationship between these parameters and candidal infection. RESEARCH DESIGN AND METHODS--We measured the skin surface pH and moisture in the axillary, inframammary, inguinal, and forearm skin with a pH meter with a flat-glass electrode and skin corneometer. The subjects were 50 NIDDM patients from the diabetic outpatient clinic at Beilinson Medical Center, Petah Tiqva, Israel, and 40 healthy control subjects from hospital personnel. The main outcome measures were skin surface pH, skin moisture, and skin culture for Candida. RESULTS--Skin pH in the inguinal and axillary regions was significantly higher in diabetic patients compared with healthy control subjects (P < 0.0001), whereas no difference was noted in the forearm. In the inframammary region, diabetic women had significantly higher pH than nondiabetic women (P < 0.01). No difference was noted in men in this region. Six patients (12%) had candidal infection in intertriginous areas. CONCLUSIONS--Our study indicates that in intertriginous regions, skin surface pH of diabetic patients is significantly higher than in normal control subjects and implies the significance of skin pH as a possible factor promoting host susceptibility to skin candidal infection. Department of Internal Medicine B, Beilinson Medical Center, Petah Tiqva, Israel. Yosipovitch G G Tur E E Cohen O O Rusecki Y Y eng Journal Article

UNITED STATES Diabetes Care 7805975 IM Adult Aged Analysis of Variance Axilla Breast Candida isolation & purification Diabetes Mellitus, Type 2 physiopathology Female Forearm Groin Humans Hydrogen-Ion Concentration Intertrigo physiopathology Male Middle Aged Reference Values Sex Factors Skin physiopathology Skin Physiological Phenomena 1993 4 1 1993 4 1 0 1 1993 4 1 0 0 ppublish 8462378 1865448 1991 09 06 1991 09 06 2008 11 20

0141-0768 84 7 1991 Jul 'Skin failure'--a real entity: discussion paper. 412-3 South East Thomas Regional Health Authority. Irvine C C eng Journal Article

ENGLAND J R Soc Med 7802879 IM Burns physiopathology Humans Skin physiopathology Skin Diseases physiopathology therapy Skin Temperature physiology PMC1293332 1991 7 1 1991 7 1 0 1 1991 7 1 0 0 ppublish 1865448 PMC1293332 1831060 1991 09 19 1991 09 19 2004 11 17

0007-1064 46 1 1991 Jul Disability in dermatology. 33-6 To be unwelcome is the greatest disability of all. On the other hand, to be confident is a passport for success. Beauty is what people like. If one is ugly one has a significant chance of not being liked and one's chances of achieving one's potential are greatly reduced. Skin failure should rate with heart failure, respiratory failure, liver failure or any other failure as worthy of intensive care. Department of Dermatology, Slade Hospital, Oxford. Ryan T J TJ eng Journal Article

ENGLAND Br J Hosp Med 0171545 IM Dermatology Disability Evaluation Disabled Persons Humans Skin Diseases pathology physiopathology psychology 1991 7 1 1991 7 1 0 1 1991 7 1 0 0 ppublish 1831060 15715523 2005 02 17 2005 05 27 2008 11 20

0248-4900 97 3 2005 Mar Biol. Cell Epidermal stem cells: the cradle of epidermal determination, differentiation and wound healing. 173-83 The field of epidermal stem cells has dramatically advanced in the last decade, leading to a better understanding of the molecular factors, signalling pathways and cellular events that identify and characterize stem cells, thus revealing their immense potential for therapeutic use. Furthermore, multipotent epidermal stem cells present the major advantage of easy accessibility with the discovery of their specific location within the bulge of the hair follicle. This review focuses on the most recent findings on epidermal stem cells, and their potential role in initial epidermal commitment, differentiation and wound healing processes in the skin. Developmental Skin Biology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. morassom@mail.nih.gov Morasso Maria I MI Tomic-Canic Marjana M eng AR45974 AR NIAMS NIH HHS United States NR08029 NR NINR NIH HHS United States Z01 AR041124-06 AR NIAMS NIH HHS United States Journal Article Research Support, U.S. Gov't, P.H.S. Review

England Biol Cell 8108529 IM Animals Cell Differentiation Epidermis anatomy & histology cytology physiology Humans Keratinocytes physiology Mice Stem Cells physiology Wound Healing 90 NIHMS5474 PMC1283090 2005 2 18 9 0 2005 5 28 9 0 2005 2 18 9 0 ppublish BC20040098 10.1042/BC20040098 15715523 PMC1283090 NIHMS5474