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1.
Hautarzt ; 67(11): 907-921, 2016 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-27770133

RESUMO

The permeability barrier plays an important role in numerous skin diseases. Particularly well known is the importance of this barrier in eczema. In irritative-toxic contact dermatitis, the first step in the pathogenesis is the disturbance of the permeability barrier by irritative-toxic noxious substances. Only after damage to the barrier is achieved can irritants and allergens penetrate into the living epidermis. In atopic eczema due to an impaired barrier, allergens penetrate from the environment into the skin and cause or worsen the eczema. In psoriasis-the other common chronic inflammatory dermatosis-the role of the permeability barrier is only partly understood. In exanthema, infectious agents or drugs cause systemic inflammation, whereby the inflammation of the skin is followed by a barrier disorder. In principle, disturbed permeability of the skin barrier is present in all inflammatory diseases.


Assuntos
Epiderme/imunologia , Absorção Cutânea/imunologia , Dermatopatias/imunologia , Pele/imunologia , Animais , Proteínas Filagrinas , Humanos , Modelos Imunológicos
2.
Z Gerontol Geriatr ; 48(4): 325-30, 2015 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-25117860

RESUMO

BACKGROUND: Aged skin is the sum of chronological und UV-induced aging. Light-exposed skin is unattractive, with irregular pigmentation, roughness und scaliness. The skin is often dry and itches. METHODS: The present paper provides an overview of diseases of aging skin and describes how to prevent or reduce disease by prophylactic and therapeutic skin care. RESULTS: Aged skin can develop into several skin diseases, e.g., different types of eczema and skin cancer. In the body folds we often find an irritant contact eczema caused by friction from skin to skin, sweating, and urinary and fecal incontinence. In the bedridden, bed sores can also develop. Furthermore, there is a delay in wound healing owing to old age. Use of adequate creams and ointments is very helpful in preventing and improving most skin diseases of mature skin. However, the knowledge of aged people and healthcare professionals about the importance of skin care is low. Older people are often unable to care for their skin because they are lacking the physical and mental ability. CONCLUSION: Healthcare professionals are not sufficiently trained about the value of proper skin care. Adequate studies on the role of skin care and selection of the correct preparation in various aged-related diseases are lacking.


Assuntos
Envelhecimento da Pele/fisiologia , Higiene da Pele/métodos , Idoso , Humanos , Pomadas , Transtornos de Fotossensibilidade/fisiopatologia , Transtornos de Fotossensibilidade/terapia , Envelhecimento da Pele/efeitos da radiação , Creme para a Pele
3.
Mycoses ; 57(3): 147-52, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23952012

RESUMO

In superficial tinea and pityriasis versicolor, the causative fungi are for the most part confined to the stratum corneum which is barely reached by leukocytes. Therefore, a role of non-cellular components in the epidermal antifungal defence was suggested. To investigate the presence of such factors in these infections, the expression of human beta defensins 2 and 3 (hBD-2, hBD-3), RNase 7, psoriasin, toll-like receptors 2, 4 and 9 (TLR2, TLR4 and TLR9) and dectin 2 was analysed by use of immunostainings in skin biopsies. We found that hBD2, hBD3, psoriasin, RNase7, TLR2 and TLR4 were significantly more often expressed in distinct layers of lesional epidermis as compared with uninfected epidermis. In both infections but not in normal skin, hBD2 and hBD3 were commonly expressed within the stratum corneum and in the stratum granulosum. Similarly, psoriasin was seen more often in the upper skin layers of both infections as compared with normal skin. No significant differences between normal and infected skin were found for the expression of TLR9 and dectin 2. Our findings clearly show the expression of specific antimicrobial proteins and defence-related ligands in superficial tinea as well as in pityriasis versicolor, suggesting that these factors contribute to fungal containment.


Assuntos
Ribonucleases/metabolismo , Proteínas S100/metabolismo , Tinha Versicolor/metabolismo , Tinha/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , beta-Defensinas/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Estudos Retrospectivos , Ribonucleases/genética , Proteína A7 Ligante de Cálcio S100 , Proteínas S100/genética , Pele/microbiologia , Pele/patologia , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Trichophyton/isolamento & purificação , beta-Defensinas/genética
4.
Skin Pharmacol Physiol ; 27(1): 47-55, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23949208

RESUMO

Various dietary supplements are claimed to have cutaneous anti-aging properties; however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of collagen hydrolysate (CH) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind, placebo-controlled trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH or placebo once daily for 8 weeks, with 23 subjects being allocated to each treatment group. Skin elasticity, skin moisture, transepidermal water loss and skin roughness were objectively measured before the first oral product application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo. After 4 weeks of follow-up treatment, a statistically significantly higher skin elasticity level was determined in elderly women. With regard to skin moisture and skin evaporation, a positive influence of CH treatment could be observed in a subgroup analysis, but data failed to reach a level of statistical significance. No side effects were noted throughout the study.


Assuntos
Colágeno/farmacologia , Suplementos Nutricionais , Peptídeos/farmacologia , Pele/efeitos dos fármacos , Administração Oral , Adulto , Método Duplo-Cego , Elasticidade , Feminino , Humanos , Pessoa de Meia-Idade , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Propriedades de Superfície , Água/metabolismo
5.
Skin Pharmacol Physiol ; 27(3): 113-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24401291

RESUMO

Dietary consumption of food supplements has been found to modulate skin functions and can therefore be useful in the treatment of skin aging. However, there is only a limited number of clinical studies supporting these claims. In this double-blind, placebo-controlled study, the effectiveness of the specific bioactive collagen peptide (BCP) VERISOL® on eye wrinkle formation and stimulation of procollagen I, elastin and fibrillin biosynthesis in the skin was assessed. A hundred and fourteen women aged 45-65 years were randomized to receive 2.5 g of BCP or placebo, once daily for 8 weeks, with 57 subjects being allocated to each treatment group. Skin wrinkles were objectively measured in all subjects, before starting the treatment, after 4 and 8 weeks as well as 4 weeks after the last intake (4-week regression phase). A subgroup was established for suction blister biopsies analyzing procollagen I, elastin and fibrillin at the beginning of the treatment and after 8 weeks of intake. The ingestion of the specific BCP used in this study promoted a statistically significant reduction of eye wrinkle volume (p < 0.05) in comparison to the placebo group after 4 and 8 weeks (20%) of intake. Moreover a positive long-lasting effect was observed 4 weeks after the last BCP administration (p < 0.05). Additionally, after 8 weeks of intake a statistically significantly higher content of procollagen type I (65%) and elastin (18%) in the BCP-treated volunteers compared to the placebo-treated patients was detected. For fibrillin, a 6% increase could be determined after BCP treatment compared to the placebo, but this effect failed to reach the level of statistical significance. In conclusion, our findings demonstrate that the oral intake of specific bioactive collagen peptides (Verisol®) reduced skin wrinkles and had positive effects on dermal matrix synthesis.


Assuntos
Colágeno/farmacologia , Peptídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Administração Oral , Idoso , Colágeno/administração & dosagem , Colágeno Tipo I/metabolismo , Método Duplo-Cego , Elastina/metabolismo , Feminino , Fibrilinas , Humanos , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
6.
Hautarzt ; 65(3): 192-6, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-24419476

RESUMO

Topical therapy should always be adapted to patients' age due to changes in skin physiology. This is particularly applicable when choosing a cream or ointment and the active substances. The expectations for therapy also change with age. The motivation to perform therapy as well as the physical ability to do so also changes with age. Children and elderly patients often need help in applying topical agents. In addition, range and cause of diseases varies considerably within age groups. Finally, the penetration of the active substance from creams and ointments may also change with age.


Assuntos
Envelhecimento/fisiologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacocinética , Absorção Cutânea/fisiologia , Dermatopatias/tratamento farmacológico , Dermatopatias/metabolismo , Administração Cutânea , Animais , Medicina Baseada em Evidências , Humanos , Modelos Biológicos
8.
Allergy ; 67(3): 413-23, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22142306

RESUMO

BACKGROUND: Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD. OBJECTIVE: This study elucidates the mode of action of topical BM and pimecrolimus cream in AD. METHODS: Lesional AD skin samples after topical treatment with either BM or pimecrolimus were subjected to gene expression profile analysis. RESULTS: Betamethasone valerate resulted in a significant reduction in mRNA levels of genes encoding markers of immune cells and inflammation, dendritic cells, T cells, cytokines, chemokines, and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. CONCLUSION: The gene expression profiles are consistent with our previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Corticosteroids are still the main treatment for severe and acutely exacerbated AD; pimecrolimus may be preferable for long-term treatment and stabilization.


Assuntos
Betametasona/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Perfilação da Expressão Gênica , Pele/efeitos dos fármacos , Tacrolimo/análogos & derivados , Adulto , Betametasona/farmacologia , Calcineurina/farmacologia , Calcineurina/uso terapêutico , Inibidores de Calcineurina , Permeabilidade da Membrana Celular/efeitos dos fármacos , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Método Duplo-Cego , Feminino , Proteínas Filagrinas , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Proteínas/genética , Proteínas/metabolismo , Pele/metabolismo , Pele/patologia , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Resultado do Tratamento , Adulto Jovem
9.
Hautarzt ; 62(12): 900-5, 2011 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-22160225

RESUMO

Many persons in the developed countries report sensitive skin. Persons with sensitive skin have a predisposition to several skin diseases, most importantly dry skin, but also atopy, seborrheic dermatitis, acne vulgaris, rosacea, and perioral dermatitis. Their complaints may be triggered by environmental factors such as low temperature, wind, high temperature, sun exposure and stress. Various skin care products and cosmetics are not tolerated. A disturbed skin barrier function and reduced stratum corneum water content are most important in the pathophysiology of sensitive skin. Environmental factors and cosmetics may induce irritation of the skin because of the disturbed skin barrier. Of further importance for the pathogenesis are neurogenic factors including stress and hyper-excitability. Mechanisms in signal transduction involve cytokines and neurotransmitters, but the exact pathways are unknown.


Assuntos
Dermatite/fisiopatologia , Modelos Biológicos , Dor Nociceptiva/fisiopatologia , Células Receptoras Sensoriais/metabolismo , Pele/fisiopatologia , Humanos , Absorção Cutânea , Síndrome
10.
Hautarzt ; 62(9): 699-708; quiz 709, 2011 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-21882101

RESUMO

Diaper dermatitis is one of the most common skin diseases during infancy and childhood. It is a type of irritant contact eczema resulting from a complex interaction between urine and feces under occlusive conditions in combination with the hyperhydration of the stratum corneum, pressure and friction under the diaper. These conditions pave the way for Candida albicans infection, which is often associated with diaper dermatitis. The anogenital region can be involved by a variety of dermatoses, so a precise skin examination, detailed history and sometimes histologic examination are needed for a precise diagnosis. Therapeutically, frequent diaper changes and adequate skin care are most important.


Assuntos
Candidíase Cutânea/diagnóstico , Dermatite das Fraldas/diagnóstico , Biópsia , Candidíase Cutânea/etiologia , Candidíase Cutânea/patologia , Pré-Escolar , Diagnóstico Diferencial , Dermatite das Fraldas/etiologia , Dermatite das Fraldas/patologia , Humanos , Lactente , Fatores de Risco , Pele/patologia , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Superinfecção/diagnóstico , Superinfecção/etiologia , Superinfecção/patologia
11.
Klin Padiatr ; 222(6): 388-90, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21058226

RESUMO

Patients with Wiedemann-Beckwith syndrome (WBS, MIM 130650), a congenital overgrowth syndrome, have a known increased tumor risk especially for embryonic tumors. WBS belongs to the "imprinting" syndromes caused by overexpression of IGF2 and/or loss of CDKN1C on chromosome 11p15.5. A 13-year-old boy with WBS developed a spitzoid malignant melanoma (Clark level V, Breslow index 4.8 mm) on the right cheek. Genetic analyses of the patient's blood showed hypermethylation at the H19 locus on chromosome 11p. The (epi)genetic changes of the WBS locus might have played a role in the pathogenesis of melanoma development.


Assuntos
Síndrome de Beckwith-Wiedemann/diagnóstico , Cromossomos Humanos Par 11/genética , Metilação de DNA/genética , Neoplasias Faciais/diagnóstico , Impressão Genômica/genética , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Síndrome de Beckwith-Wiedemann/genética , Bochecha , Neoplasias Faciais/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Melanoma/genética , RNA Longo não Codificante , RNA não Traduzido/genética , Neoplasias Cutâneas/genética
12.
J Eur Acad Dermatol Venereol ; 23(4): 388-93, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19175487

RESUMO

BACKGROUND: Allergies to latex or 'rubber chemicals' in medical or other occupationally used gloves are not uncommon. In contrast, very few articles have reported on latex allergy (type I) or allergic contact sensitization to additives (type IV) associated with household gloves, in spite of some 44 million pairs sold in Germany in, e.g., 2006. OBJECTIVE: We seek to determine the frequency of allergies to household gloves by providing own data and we reviewed the literature. METHODS: The study was based on 105083 consultations of patients with suspected contact allergy (Type IV) in the Information Network of Departments of Dermatology (IVDK) in Germany in the years 1995 to 2006 and on the PubMed databases (last access 7/2008). RESULTS: 1221 patients were identified in whom protective gloves were considered as a possible cause of contact dermatitis and who did not work in occupations associated with above average risk of contact allergy to rubber chemicals. In 178 cases positive reactions to rubber components were reported, while 13 additional cases reacted only to a previously used rubber glove brand, but not to commercial allergens. In the literature only two publications on type I and two on type IV reactions were found in which allergies to rubber household gloves were explicitly reported. CONCLUSIONS: Allergies to rubber household gloves seem to be rare. Factors presumably counteracting contact sensitization by household gloves, compared to occupational use, comprise short intermediate use, loose fitting and the incorporation of e.g. an inner cotton surface reducing skin contact with rubber chemicals.


Assuntos
Luvas Protetoras , Hipersensibilidade ao Látex/epidemiologia , Alemanha/epidemiologia , Humanos
13.
Skin Pharmacol Physiol ; 22(1): 3-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18832866

RESUMO

Facial skin is unique in that it gets far more exposure to the external environment than skin on other areas of the body and paradoxically, because it contains the thinnest epidermis and stratum corneum, especially on the eye lid. Environmental attacks contribute to drying of facial skin and damage to the stratum corneum. In recent years, there has been an explosion of new products that contain ingredients that claim to benefit facial skin and protect against environmental damage. This review critically examines the scientific basis, rationale and evidence for inclusion of these ingredients in products for protection of facial skin.


Assuntos
Emolientes/administração & dosagem , Dermatopatias/prevenção & controle , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Clima , Face , Humanos , Pele/patologia , Pele/fisiopatologia , Dermatopatias/patologia , Dermatopatias/fisiopatologia , Resultado do Tratamento , Perda Insensível de Água/efeitos dos fármacos
14.
G Ital Dermatol Venereol ; 144(6): 689-700, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19907407

RESUMO

The skin provides an effective barrier between the organism and the environment, preventing the 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, as well as how barrier function is regulated and altered in association with dermatoses. The physical barrier localized primarily 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, with its tight, gap and adherens junctions, additional desmosomes and cytoskeletal elements, also contributes to the barrier. Lipids are synthesized in the keratinocytes during epidermal differentiation and are then extruded into the extracellular domains, where they form lipid-enriched extracellular layers. The cornified cell envelope, a robust protein/lipid polymer structure, is located below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides A and B, forming the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC, are covalently bound to cornified envelope proteins. Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils. Cytokines, cAMP and calcium influence the formation and maintenance of barrier function. Changes in lipid composition and epidermal differentiation 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 an important component in the pathogenesis of contact dermatitis, ichthyosis, psoriasis, and atopic dermatitis.


Assuntos
Fenômenos Fisiológicos da Pele , Animais , Água Corporal/metabolismo , Diferenciação Celular , Conexinas/fisiologia , Desmossomos/ultraestrutura , Epiderme/fisiologia , Epiderme/ultraestrutura , Proteínas Filagrinas , Humanos , Proteínas de Filamentos Intermediários/fisiologia , Queratinócitos/fisiologia , Queratinócitos/ultraestrutura , Lipídeos/fisiologia , Camundongos , Permeabilidade , Pele/imunologia , Pele/microbiologia , Pele/ultraestrutura , Dermatopatias/fisiopatologia
15.
Skin Pharmacol Physiol ; 21(2): 75-80, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18187966

RESUMO

Dry skin is a common skin condition as well as a key aspect of a number of diseases such as atopic dermatitis and psoriasis but also of other diseases and systemic conditions. Dry skin has an impact on the patient in terms of discomfort, pruritus and impaired quality of life. Within the overall treatment regimen for these diseases, the use of emollients to manage dry skin plays a considerable role in managing skin conditions. In atopic dermatitis and psoriasis, emollients help to improve skin condition and to reduce pruritus alongside more potent pharmacological agents. It is important to choose an emollient that not only soothes and rehydrates the skin but also offers numerous other dermatological supporting roles, especially induction of proper epidermal differentiation. This review will explain the role of emollients within the management of diseases with dry skin as a major symptom and the components of an ideal emollient.


Assuntos
Emolientes/uso terapêutico , Ictiose/tratamento farmacológico , Administração Tópica , Doença Crônica , Dermatite Atópica/complicações , Dermatite Atópica/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Emolientes/farmacologia , Humanos , Ictiose/etiologia , Falência Renal Crônica/complicações , Bicamadas Lipídicas/metabolismo , Psoríase/complicações , Psoríase/tratamento farmacológico
16.
J Clin Invest ; 85(3): 874-82, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2312730

RESUMO

Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl-containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state.


Assuntos
Epiderme/enzimologia , Hidroximetilglutaril-CoA Redutases/análise , Acetona/farmacologia , Animais , Colesterol/biossíntese , Ativação Enzimática , Ácidos Graxos Essenciais/deficiência , Masculino , Camundongos , Camundongos Pelados , Permeabilidade , Fosforilação , Dodecilsulfato de Sódio/farmacologia
17.
J Clin Invest ; 87(5): 1668-73, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2022737

RESUMO

We examined the possibility that the cutaneous permeability barrier regulates epidermal DNA synthesis in two acute and two chronic models of barrier perturbation. In animals treated topically with acetone, DNA synthesis is increased 102%, in tape-stripped animals 127%, in essential fatty acid deficient animals 50%, and in animals chronically treated with topical lovastatin 64%. This linkage between disturbances in barrier function and increased DNA synthesis is further supported by specific and correlative observations: (a) in these disparate models, artificial replacement of the barrier with a water-impermeable membrane inhibits the expected increase in DNA synthesis; (b) the extent of the burst in DNA synthesis is proportional to the degree of barrier abrogation; (c) the inhibition of DNA synthesis by membranes is directly related to the degree of permeability of these occlusive membranes, i.e., the more impermeable the greater the degree of inhibition; (d) topical treatment with lipids that restore barrier function corrects the increase in DNA synthesis; and (e) barrier abrogation with acetone produces an increase in epidermal DNA synthesis without altering bulk protein synthetic rates in contrast to events known to follow injury or cell replacement. Autoradiographic studies show that the increase in DNA synthesis after acetone treatment is limited to the epidermal basal layer. This constellation of findings strongly suggests that cutaneous barrier function is one factor that regulates epidermal DNA synthesis.


Assuntos
DNA/biossíntese , Epiderme/metabolismo , Animais , Água Corporal/metabolismo , Epiderme/patologia , Hiperplasia , Lovastatina/farmacologia , Camundongos , Camundongos Pelados , Permeabilidade
18.
J Clin Invest ; 104(12): 1761-70, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10606630

RESUMO

Epidermal TNF expression increases in response to cutaneous permeability barrier disruption and wound healing. TNF signaling is mediated by acid and neutral sphingomyelinases (A- and N-SMase), which generate ceramide, an important regulator of proliferation, differentiation, and apoptosis. In the epidermis, ceramide is known to be an integral part of the extracellular stratum corneum (SC) lipid bilayers that constitute the permeability barrier of the skin. We show here that topical application of TNF after experimental injury to the SC of hairless mice (hr(-/-)) enhances barrier repair. In TNF receptor p55-deficient (TNF-R55-deficient) mice (hr(+/+)), cutaneous barrier repair was delayed compared with wild-type (hr(+/+)) or TNF-R75-deficient (hr(+/+)) animals. After barrier disruption in hairless (hr(-/-)) and wild-type (hr(+/+)), but not in TNF-R55-deficient (hr(+/+)) mice, the enzymatic activities of both A-SMase and N-SMase were significantly enhanced. Stimulation of SMase activities was accompanied by an increase in C(24)-ceramide levels. Most A-SMase activity in hairless mice (hr(-/-)) was found in the outer epidermal cell layers and colocalized in the lamellar bodies with A-SMase and sphingomyelin. Reduction of epidermal A-SMase activity by the inhibitor imipramine resulted in delayed permeability barrier repair after SC injury. Together, these results suggest that TNF-R55 signaling pathways contribute to cutaneous permeability barrier repair through SMase-mediated generation of ceramide.


Assuntos
Antígenos CD/fisiologia , Receptores do Fator de Necrose Tumoral/fisiologia , Pele/metabolismo , Esfingomielina Fosfodiesterase/fisiologia , Animais , Ceramidas/análise , Glucosilceramidase/fisiologia , Imipramina/farmacologia , Masculino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos C57BL , Permeabilidade , Receptores Tipo I de Fatores de Necrose Tumoral , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Esfingomielinas/análise , Fator de Necrose Tumoral alfa/farmacologia
19.
J Clin Invest ; 89(2): 530-8, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1737844

RESUMO

Topical solvent treatment removes lipids from the stratum corneum leading to a marked increase in transepidermal water loss (TEWL). This disturbance stimulates a variety of metabolic changes in the epidermis leading to rapid repair of the barrier defect. Using an immersion system we explored the nature of the signal leading to barrier repair in intact mice. Initial experiments using hypotonic to hypertonic solutions showed that water transit per se was not the crucial signal. However, addition of calcium at concentrations as low as 0.01 mM inhibited barrier repair. Moreover, both verapamil and nifedipine, which block calcium transport into cells, prevented the calcium-induced inhibition of TEWL recovery. Additionally, trifluoroperazine or N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide, which inhibit calmodulin, prevented the calcium-induced inhibition of TEWL recovery. Although these results suggest an important role for calcium in barrier homeostasis, calcium alone was only modestly effective in inhibiting TEWL recovery. Potassium alone (10 mM) and phosphate alone (5 mM) also produced a modest inhibition of barrier repair. Together, however, calcium and potassium produced a synergistic inhibition of barrier repair (control 50% recovery vs. calcium + potassium 0-11% recovery in 2.5 h). Furthermore, in addition to inhibiting TEWL recovery, calcium and potassium also prevented the characteristic increase in 3-hydroxy-3-glutaryl CoA reductase activity that occurs after barrier disruption. Finally, the return of lipids to the stratum corneum was also blocked by calcium and potassium. These results demonstrate that the repair of the epidermal permeability barrier after solvent disruption can be prevented by calcium, potassium, and phosphate. The repair process may be signalled by a decrease in the concentrations of these ions in the upper epidermis resulting from increased water flux leading to passive loss of these ions.


Assuntos
Água Corporal/metabolismo , Cálcio/fisiologia , Epiderme/metabolismo , Homeostase , Potássio/fisiologia , Animais , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Calmodulina/antagonistas & inibidores , Hidroximetilglutaril-CoA Redutases/análise , Queratinócitos/metabolismo , Lipídeos/análise , Masculino , Camundongos , Camundongos Pelados , Potássio/farmacologia
20.
Biochim Biophys Acta ; 1083(1): 71-9, 1991 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-2031940

RESUMO

Recent studies have shown that epidermal cholesterol synthesis is regulated by HMG CoA reductase activity and that this activity is modulated by changes in the cutaneous permeability barrier. Here, we quantitated HMG CoA reductase activity after acute and chronic barrier disruption in the upper and lower layers of murine epidermis. In unperturbed epidermis, 13 and 87% of enzyme activity localized to the upper and lower epidermis, respectively, with the majority of activity in the stratum basale. Acute barrier disruption with either acetone or sodium dodecylsulfate provoked an increase in HMG CoA reductase activity (54% and 30%) in the lower layers, but only a small change in the upper layers. However, the activation state of the enzyme was increased 50% in the upper epidermis. Correction of barrier function by occlusion with an impermeable Latex wrap prevented the increase both in enzyme activity and activation state. After chronic barrier disruption; i.e., essential fatty acid deficient (EFAD) diet, HMG CoA reductase activity was increased in the upper epidermis (161%); a change prevented by occlusion. These results show: (1) that HMG CoA reductase activity is present in both the upper and lower cell layers; (2) that acute insults to barrier integrity stimulate enzyme activity in both the upper and lower epidermis; and (3) that chronic insults provoke an increase in enzyme activity in the upper layers. These studies provide further insights into the linkage of the permeability barrier with epidermal cholesterol metabolism.


Assuntos
Epiderme/enzimologia , Hidroximetilglutaril-CoA Redutases/metabolismo , Pele/enzimologia , Animais , Colesterol/biossíntese , Epiderme/efeitos dos fármacos , Epiderme/patologia , Exfoliatinas/toxicidade , Cinética , Camundongos , Camundongos Pelados , Microssomos/enzimologia , Permeabilidade , Valores de Referência , Pele/efeitos dos fármacos , Pele/patologia
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