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IntroductionSkin provides critical barrier properties that enable terrestrial life. Myriad research has focused on the "water barrier" to transepidermal water loss (TEWL) despite there being a multitude of skin barrier properties. We asked what other barrier properties may have been overlooked and compiled data demonstrating the "electrolyte barrier" to be of potential clinical relevance.MethodsA literature search was conducted through PubMed, Embase, Google Scholar, and Web of Science databases for the following keywords: "transepidermal" or "epidermal" or "cutaneous" or "skin" or "percutaneous" and "ion" or "sodium" or "chloride" or "potassium" or "electrolyte" and "flux" or "egression." Textbooks at the University of California, San Francisco were also hand reviewed. Experimental studies quantifying in vivo or ex vivo percutaneous egression of ions in response to human skin barrier perturbation were included.ResultsExperimental damage to skin, mostly by tape-stripping, frequently induced increased ion flux rates through the epidermis, in addition to increases in TEWL values. Interestingly, barrier perturbation did not always result in a concomitant rise in TEWL and transepidermal ion flux rates, such as in delipidization, indicating a distinction between the two barriers.ConclusionQuantifying the percutaneous egression of ions in response to physical or chemical alterations may offer additional data that are not to be captured with TEWL studies exclusively. Continued efforts should be made to: (1) advance this technique as a method of assessing skin status and (2) enhance our understanding of other barriers and mechanisms.

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3β-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3β-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.

Almonds have long been studied as a rich source of fatty acids, phytochemical polyphenols and antioxidants such as vitamin E. A recent study compared almond supplementations to a calorie-matched intervention for 16 weeks, yielding statistically significant improvement in wrinkle severity in postmenopausal women with Fitzpatrick skin types I and II that received almonds. This study furthers that assessment with a larger population and duration of 24 weeks to assess the influence of almond consumption on wrinkle severity, skin pigmentation and other skin biophysical profiles. To investigate the effects of almond consumption on photoaging such as wrinkles and pigment intensity as well as facial biophysical parameters such as sebum production, skin hydration and water loss. A prospective, randomized controlled study assessed postmenopausal women with Fitzpatrick skin types I or II who consumed 20% of their daily energy consumption in either almonds or a calorie-matched snack for 24 weeks. A facial photograph and image analysis system was used to obtain standardized high-resolution photographs and information on wrinkle width and severity at 0, 8, 16 and 24 weeks. Measurements of transepidermal water loss (TEWL), skin pigmentation, skin hydration and sebum production were also completed at each visit. The average wrinkle severity was significantly decreased in the almond intervention group at week 16 and week 24 compared to baseline by 15% and 16%, respectively. Facial pigment intensity was decreased 20% in the almond group at week 16 and this was maintained by week 24. There were no significant differences in skin hydration or TEWL in the almond group compared to the control, although sebum excretion was increased in the control group. The daily consumption of almonds may improve several aspects of photoaging such as facial wrinkles and pigment intensity in postmenopausal women. In conclusion, the daily consumption of almonds may contribute to the improvement of facial wrinkles and reduction of skin pigmentation among postmenopausal women with Fitzpatrick skin types I and II.

Nitric oxide (NO) regulates a variety of epidermal functions, including epidermal proliferation, differentiation and cutaneous wound healing. However, whether nitric oxide (NO) and its synthetic enzymes regulate epidermal permeability barrier homeostasis is not clear. In the present study, we employed inducible nitric oxide synthase (iNOS) KO mice to explore the role of iNOS in epidermal permeability barrier homeostasis. Our results showed that iNOS mice displayed a comparable levels of basal transepidermal water loss rates, stratum corneum hydration and skin surface pH to their wild-type mice, but epidermal permeability barrier recovery was significantly delayed both 2 and 4 hours after acute barrier disruption by tape stripping. In parallel, expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes were lower in iNOS KO mice versus wild-type controls. Topical applications of two structurally unrelated NO donors to iNOS KO mice improved permeability barrier recovery kinetics and upregulated expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes. Together, these results indicate that iNOS and its product regulate epidermal permeability barrier homeostasis in mice.

BackgroundAdverse cutaneous reactions to skin care products (SCP) are becoming increasingly common and may be indicative of defective permeability barrier function.AimTo determine the differences in transepidermal water loss rates (TEWL) between skin patch positive vs negative to skin care products in normal Chinese females.MethodsSkin patch test reactions to nine skin care products were assessed in 65 normal Chinese females. Correlations of cutaneous reactions to a panel of nine foreign and domestic SCP with permeability barrier function and stratum corneum (SC) hydration levels were analyzed.ResultsOut of 65 subjects, 24 (37%) displayed positive reactions to one or more SCP. However, the occurrence of positive reactions to patch tests did not correlate with either transepidermal water loss rates or SC hydration levels.ConclusionsThough a substantial proportion of normal females display adverse reactions to SCP, this problem cannot be attributed to differences in the qualities of their epidermal permeability barriers, and therefore, these reactions more likely reflect the potential adverse events of the SCP themselves. However, further studies in large cohort of both males and females would be helpful to ascertain whether TEWL levels can predict cutaneous reactions to SCP.

Studying skin barrier function is central to our understanding of many skin disorders. The past decade has seen a surge of skin barrier related investigative work. Genetic, biochemical and cell biology experiments have added much evidence to the importance of the barrier in disease pathogenesis of a variety of disorders including ichthyosis, atopic dermatitis and psoriasis. However, functional assays prove ever more important to demonstrate relevance of any of these findings. A paper published by Monash and Blank 60 years ago describes a stress test of the skin barrier, measuring skin barrier recovery, a functional test of tremendous implications. This seminal paper has not been cited for almost 15 years, time to acknowledge its critical importance and to review the relevance of this method today.

BackgroundTransient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood.ObjectiveTo investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice.MethodsFollowing daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions.ResultsCompared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45+ leukocytes, mast cells as well as CD3+ T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice.ConclusionsIn summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.

O estudo da barreira cutânea e de suas propriedades ganhou impulso a partir da década de 60, com estudos que apontaram sua resistência de forma isolada e suas propriedades com relação à permeação cutânea. Paralelamente, a descrição dos corpos de Odland auxiliou a compreensão da manutenção da estabilidade da camada córnea. O modelo brick & mortar, em que os corneócitos são os tijolos e o cimento são os lipídeos intercelulares, é o mais aceito, até o momento. Atualmente, há evidências consistentes de que o estrato córneo é uma estrutura metabolicamente ativa e exerce funções adaptativas. A barreira cutânea também tem um papel na resposta inflamatória, com ativação de melanócitos, angiogênese e fibroplasia, cuja intensidade depende, basicamente, da intensidade da agressão. As anormalidades da barreira cutânea da dermatite atópica são clinicamente observáveis pela presença de pele seca, achado muito frequente e significativo, que constitui parâmetro iagnóstico e de acompanhamento. O grau de hidratação da camada córnea, assim como a perda de água transepidérmica (transepidermal water loss - TEWL), estão relacionados com o grau de dano à barreira, constituindo parâmetros biofísicos que permitem acompanhar os pacientes de maneira não invasiva e com maior grau de sensibilidade.Research about the skin barrier and its properties has increased significantly since the 60s, with studies that indicated its resistance when isolated, as well as its particularities in relation to skin permeability. At the same time, description of Odland bodies helped to understand how stratum corneum stability is maintained. The “brick and mortarâ€� model is the most accepted so far. In this analogy, the corneocytes are the bricks and the intercellular lipids are the mortar. Currently, there is concrete evidence that the stratum corneum is an active metabolic structure that holds adaptive functions, interacting dynamically with the underlying epidermal layers. The skin barrier also plays a role in the inflammatory response through melanocyte activation, angiogenesis, and fibroplasia. The intensity of this response will essentially depend on the severity of the injury. Skin barrier abnormalities in atopic dermatitis are clinically observed by the presence of dry skin, a common and significant symptom which constitutes a diagnostic and monitoring parameter. The stratum corneum hydration level and transepidermal water loss are associated with the level of damage to the barrier, representing biophysical parameters. These parameters help doctors monitor patients in a less invasive and more sensitive manner.