Basal Transepidermal Water Loss Research Articles

Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients

Introduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA²LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects’ general well-being, bronchial, nasal, and ocular symptoms were documented. Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. Conclusion: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.

Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice

Introduction: Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production. Objective: The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin. Materials and Methods: One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes. Results: Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.

Mutations in 3β-hydroxysteroid-δ8, δ7-isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice.

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.

Inducible nitric oxide synthase is required for epidermal permeability barrier homeostasis in mice.

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 4hours 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.

A Genome-Wide Association Study of Basal Transepidermal Water Loss Finds that Variants at 9q34.3 Are Associated with Skin Barrier Function

A Genome-Wide Association Study of Basal Transepidermal Water Loss Finds that Variants at 9q34.3 Are Associated with Skin Barrier Function

A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice.

Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora, have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm2 and UVB 40 mJ/cm2 three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v/v) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation.

Acidic Water Bathing Could Be a Safe and Effective Therapeutic Modality for Severe and Refractory Atopic Dermatitis.

Acidic Water Bathing Could Be a Safe and Effective Therapeutic Modality for Severe and Refractory Atopic Dermatitis.

Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier.

Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers.

Application of Topical Acids Improves Atopic Dermatitis in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids.

BackgroundThe acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD).ObjectiveWe performed an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions and to find out if the therapeutic effect of vinegar is attributable to its herbal contents, rather than its acidity.MethodsFive groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity: vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and pH 3.5 hydrogen chloride (HCl) cream. Also, we have compared two groups of Ox-AD mice treated with pH 5.5 vehicle cream or pH 5.5 vinegar cream.ResultsOx-AD mice treated with acidic creams exhibited fewer AD-like lesions, had significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference in eczema score, basal TEWL and SC hydration.ConclusionApplication of topical acids, regardless of their source materials, inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model.

Pseudoceramide stimulates peroxisome proliferator-activated receptor-α expression in a murine model of atopic dermatitis: molecular basis underlying the anti-inflammatory effect and the preventive effect against steroid-induced barrier impairment.

Topical pseudoceramides are successfully used in skin barrier repair therapy for atopic dermatitis (AD) and demonstrated to reduce the adverse effects of topical glucocorticoids (GC). However, the molecular mechanisms involved are not fully understood. We investigated whether PC-9S (myristoyl/palmitoyloxostearamide/arachamide MEA, Neopharm, Daejeon, Korea), one of the synthetic pseudoceramides, could stimulate peroxisome proliferator-activated receptor (PPAR)α expression in a hapten [oxazolone (oxa)]-induced AD murine model (oxa-AD mice) and subsequently improved permeability barrier, reduced inflammation, and increased antimicrobial peptides (AMPs) expression. Normal hairless mice and oxa-AD mice were topically treated twice daily with either PC-9S-containing physiologic lipid mixture (PLM), vehicle (PLM), or PPARα agonist for 4days. Topical PC-9S significantly increased PPARα expression in mouse epidermis in vivo and in oxa-AD mice skin comparable with PPARα agonist. Topical PC-9S-containing PLM significantly reduced basal trans-epidermal water loss (TEWL), surface pH, and mast cell infiltrates and prevented the decline of AMPs expression in oxa-AD mice, which were abrogated by PPARα antagonist. Then, oxa-AD mice were treated with super-potent topical GC twice daily for 4days with or without PC-9S co-applications. Co-treatment with PC-9S-containing PLM suppressed GC-induced increase in basal TEWL, epidermal thinning, reduced loricrin expression, and impaired barrier recovery and these effects were attenuated by PPARα antagonist. Collectively, our findings suggest that pseudoceramide PC-9S-induced stimulation of PPARα expression provides a new mechanism by which pseudoceramides show anti-inflammatory property, improve the permeability and antimicrobial barrier function, and prevent the negative effects of topical GC.

Facial skin pigmentation is not related to stratum corneum cohesion, basal transepidermal water loss, barrier integrity and barrier repair.

Hypotheses have been developed for the evolutionary selection of skin pigmentation one of which relates to improved skin barrier function. The aim of this study was to compare facial skin condition on photoexposed (cheek) and photoprotected (post-auricular) sites of naturally pigmented subjects of different ethnicities (Fitzpatrick skin phototypes II/III and V/VI) and Albino African subjects to understand better the relationship between facial stratum corneum (SC) barrier function, skin surface pH and skin pigmentation. Expert grading of skin conditions, capacitance, skin surface pH and skin barrier function measurements were performed. For the latter, transepidermal water loss (TEWL) measurements before (basal TEWL), after 3, 6 and 9 consecutive tape strippings (SC integrity) and 3.5 and 24 h post tape stripping (barrier recovery) were taken. Amounts of SC protein removed during stripping were estimated using infrared densitometry (SC cohesion). Firstly, correlation analysis of the biometric data of the Black African and Caucasian subjects showed there to be no relationship between skin surface pH and ITA° values nor pH and ITA° with basal TEWL. Neither skin surface pH nor ITA° correlated with SC integrity and barrier recovery measurements, but skin surface pH correlated with SC cohesion. ITA° values were correlated with skin hydration. Secondly, on comparing the three ethnic groups, severe skin photodamage was observed in the Albino African subjects and their SC was thicker. Whereas their basal TEWL was elevated, superior values for SC integrity and barrier recovery were measured. No differences in basal TEWL, SC integrity and barrier recovery were found between the other two subject groups. Equally, SC cohesion and skin surface pH values were similar among the three groups. There was no relationship between ITA° values and basal TEWL, SC integrity, SC cohesion and barrier recovery, but ITA° was correlated with skin hydration. Skin surface pH, irrespective of ITA° values, correlated with SC cohesion, indicating a greater intracorneal cohesion at lower pH values. Thus, pigmentation has no effect on SC barrier properties but was related to skin hydration. On comparing the three ethnic groups, Albino African SC was found to be superior to the Caucasian and Black African subjects in terms of SC integrity and barrier recovery but not basal TEWL. The Albino African subjects also have a thicker SC which contributes to their better SC integrity. No differences in skin barrier functionality or skin surface pH were observed for the other two groups. Skin hydration was, however, greatest in the Black African subjects. Our data support the evolutionary hypothesis that pigmentation protects the skin from UV irradiation and thereby the skin barrier but not the skin pigmentation-/pH-driven adaptive skin barrier hypothesis.

Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis

BackgroundDry skin in atopic dermatitis (AD) mainly results from barrier impairment due to deficiency of ceramide and natural moisturizing factors including pyrrolidone carboxylic acid (PCA) in stratum corneum (SC). Caspase-14 cleaves filaggrin monomers to free amino acids and their derivatives such as PCA, contributing natural moisturizing factors. Cytokines in the corneocytes represent cutaneous inflammation severity of AD patients. ObjectTo analyze the correlations of PCA, caspase-14 and cytokines in corneocytes with clinical severity, barrier function and skin inflammation, those were quantitated. MethodsA total of 73 persons were enrolled: 21 patients with mild AD, 21 with moderate-to-severe AD, 13 with X-linked ichthyosis (XLI) as a negative control for filaggrin gene (FLG) mutation, and 18 healthy controls. Skin barrier functions such as basal transepidermal water loss (TEWL), stratum corneum (SC) hydration and skin surface pH were measured. To collect corneocytes, stripping with D-squame® discs was done on lesional and non-lesional skin. And then PCA was isolated from D-squame® discs and quantitated by LC–MS/MS. Cytokine assays were performed. ResultsThe quantity of PCA and caspase-14 was decreased in inflammatory lesions compared to non-lesion in AD patients. And the amounts of PCA and caspase-14 in the lesion of AD patients correlated with clinical severity as determined by eczema area and severity index score and the skin barrier functions. Also, the expressions of TNF-α and IL-13 inversely correlated with PCA quantity. ConclusionThe quantity of PCA or caspase-14 in the corneocytes of the lesional skin of AD patients reflects the clinical severity, skin barrier function and the degree of lesional inflammation.

Differential effects of topical corticosteroid and calcineurin inhibitor on the epidermal tight junction

Tight junction (TJ) is one of the functional barriers present in the skin. Although topical corticosteroids and calcineurin inhibitors are used widely for atopic dermatitis, the effect of these agents on TJs has not been reported. We investigated the structural changes of TJs in mice skin after application of 0.05% clobetasol propionate or 0.1% tacrolimus ointment for 10days. Clobetasol caused epidermal thinning and decreased collagen density. Basal transepidermal water loss was significantly increased in clobetasol-treated versus vehicle- or tacrolimus-treated skin. Confocal immunofluorescence showed that clobetasol altered the structure of claudin-1,-4 and occludin. Tacrolimus also caused morphological alteration of occludin. Western blot and real-time PCR revealed that clobetasol significantly decreased claudin-1,-4 and occludin, whereas tacrolimus did not significantly affect claudin-1 and -4 but downregulated occludin to a lesser extent compared to clobetasol. In conclusion, we suggest that downregulation of TJ proteins expression is another pathomechanism of corticosteroid-induced permeability barrier disruption.

Topical hesperidin improves epidermal permeability barrier function and epidermal differentiation in normal murine skin.

Orange peel extract appears to exhibit beneficial effects on skin whitening, inflammation, UVB protection, as well as keratinocyte proliferation. In the present study, we determine whether topical hesperidin influences epidermal permeability barrier function and its underlying mechanisms. Hairless mice were treated topically with 2% hesperidin or 70% ethanol alone twice daily for 6 days. At the end of treatment, basal transepidermal water loss (TEWL) was measured 2 and 4 h post barrier disruption. Epidermal proliferation and differentiation were evaluated by immunohistochemical staining and Western blot analysis. Additionally, lamellar body density and secretion were assessed by electron microscopy. Although there were no significant differences in basal barrier function, in comparison with control animals, topical hesperidin significantly accelerated barrier recovery at both 2 and 4 h after acute barrier abrogation. Enhanced barrier function in hesperidin-treated skin correlated with stimulation of both epidermal proliferation and differentiation, as well as enhanced lamellar body secretion. These results indicate that topical hesperidin enhances epidermal permeability barrier homeostasis at least in part due to stimulation of epidermal proliferation, differentiation, as well as lamellar body secretion.

Defective barrier function in melasma skin

Melasma is characterized by increased pigmentation and photodamaged features, which include solar elastosis. Recently, we detected the downregulation of the genes most associated with lipid metabolism using microarray analysis in melasma. These findings suggested that lesional skin may have different biophysical characteristics, and, in particular, an altered skin barrier function. To determine the cutaneous biophysical characteristics of melasma. The melanin index, erythema index, stratum corneum hydration, sebum content and transepidermal water loss (TEWL) were measured for lesional and perilesional normal skin of 16 melasma patients and then compared. In addition, a skin biopsy was performed on 11 of the 16 study subjects to measure stratum corneum thickness and to study the protein expressions of PPAR-α and ALOX15B. Melanin index, erythema index and stratum corneum hydration were significantly higher in lesional skin than in perilesional normal skin. No significant difference was found between lesional and normal skin in terms of basal TEWL level or sebum content. However, the rate of TEWL after barrier perturbation was significantly higher for lesional skin, and the barrier recovery rate was significantly delayed. Furthermore, a trend towards thinned stratum corneum was observed for lesional skin, and this was correlated with barrier recovery rate. The expressions of PPAR-α and ALOX15B were variable in the samples. Melasma skin is characterized by impaired stratum corneum integrity and a delayed barrier recovery rate.

Efficacy of Combined Peroxisome Proliferator-Activated Receptor-α Ligand and Glucocorticoid Therapy in a Murine Model of Atopic Dermatitis

Although topical glucocorticoids (GCs) display potent anti-inflammatory activity in inflamed skin, they also can exert numerous harmful effects on epidermal structure and function. In contrast, topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) not only reduce inflammation, and also improve cutaneous barrier homeostasis. Therefore, we examined whether sequential topical GCs followed by topical Wy14643 (a ligand of PPARα) might be more effective than either alone for atopic dermatitis (AD) in a hapten (oxazolone)-induced, murine model with multiple features of AD (Ox-AD). Despite expected anti-inflammatory benefits, topical GC alone induced: i) epidermal thinning; ii) reduced expression of involucrin, loricrin and filaggrin; and iii) allowed outside-to-inside penetration of an epicutaneous tracer. While Wy14643 alone yielded significant therapeutic benefits in mice with mild or moderate Ox-AD, it was less effective in severe Ox-AD. Yet, topical applications of Wy14643 after GC was not only significantly effective comparable to GC alone, but it also prevented GC-induced structural and functional abnormalities in permeability barrier homeostasis. Moreover, rebound flares were largely absent after sequential treatment with GC and Wy14643. Together, these results show that GC and PPARα ligand therapy together is not only effective but also prevents development of GC-induced side effects, including rebound flares, in murine AD.

Irritability of the skin barrier: A comparison of chronologically aged and photo-aged skin in elderly and young adults

Purpose The epidermal barrier resides in the stratum corneum (SC). Compared to young adults baseline barrier function of aged skin is comparable. Stress to the aged barrier results in decreased rates of repair. Barrier irritability of young vs. old, chronologically aged vs. photo-aged skin has not been examined in direct comparison. Patients and methods Geriatric patients (mean age 81 ± 7 SD; n = 104) underwent a dermatological examination. The irritability of young (24 ± 3; n = 21) vs. old (82 ± 5; n = 21), chronologically aged (ventral side of the upper arm) vs. photo-aged (dorsal aspect of the lower arm) skin was assessed, including transepidermal water loss (TEWL), SC hydration before and after 10 minutes irritation with 0.5 N NaOH under occlusion. Results Clinical examination of aged subjects revealed a correlation between excessive dry skin and photo-aged, but not chronologically aged skin ( P < 0.05). Compared to young adults’ SC hydration was lower in photo-aged skin sites of the elderly ( P < 0.001). Basal TEWL was comparable in young, chronologic and photo-aged skin. Only photo-aged skin of old subjects revealed increased irritability to the alkaline irritant compared to chronologic aged and young skin ( P < 0.001). Conclusion Skin dryness and irritability in the elderly is enhanced only in photo-aged skin.

Is there any barrier impairment in sensitive skin?: a quantitative analysis of sensitive skin by mathematical modeling of transepidermal water loss desorption curves

Sensitive skin is a vague, subjective and difficult to characterize affliction. It affects a large part of the population and is accompanied with great interest by the cosmetic industry. Some studies have suggested that sensitive skin is the result of impaired barrier function, which leads to the exposure of immune system cells and sensitive nerves, resulting in marked cutaneous responses to otherwise harmless stimuli. This study aimed to investigate the cutaneous barrier integrity of individuals with sensitive skin by a novel approach: a plastic occlusion stress test followed by measurement of transepidermal water loss (TEWL) desorption curves. The study was conducted in volunteers with sensitive skin in the hands and a control group with no sensitivity complaints. A previously developed mathematical model was adjusted to the TEWL data points and two parameters were calculated: dynamic water mass and the evaporation half-life period. Statistically significant differences have been detected in the parameters obtained in the sensitive skin group, which supports the thesis that individuals with an increased skin susceptibility have impaired barrier function. Whereas in the studies based in basal TEWL measurements only discrete differences were reported, the dynamic approach followed in this study provided unequivocal evidence of barrier impairment. The methodology enabled a more objective characterization of sensitive skin and can potentially be applied to the diagnosis/prediction of sensitivity; as well as the efficacy assessment of cosmetic products that are specifically designed to fulfill the needs of consumers with this skin condition.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure.

Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function

Topical calcineurin inhibitors (TCIs) such as pimecrolimus and tacrolimus have recently been used for dermatologic diseases including atopic dermatitis instead of topical glucocorticoids, because they display comparable efficacy, but less-frequent side effects. Although even short-term topical glucocorticoid compromise epidermal permeability barrier homeostasis, the effects of TCI on barrier function have not yet been reported. However, viral infections such as eczema herpeticum and molluscum contagiosum, which could indicate an impaired skin barrier, continue to occur with TCI use in atopic dermatitis. We determined here whether TCIs disrupt epidermal permeability barrier and antimicrobial function, and whether these effects can be prevented. In normal humans, topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery without an increase in basal transepidermal water loss was observed. Co-application of physiologic lipid mixture (PLM) containing an equimolar ratio of ceramides, cholesterol and free fatty acids normalized barrier homeostasis in the face of topical TCIs. In hairless mice, 4 days of TCI treatment also disrupted barrier function significantly. TCIs-treated epidermis showed the decrease of epidermal lipid content, lamellar body number and secretion, and lipid synthesis-related enzymes such as 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, serine-palmitoyl transferase and fatty acid synthase, implying decreased lipid synthesis. TCIs also suppressed expression of IL-1alpha and antimicrobial peptides, CRAMP and mouse beta-defensin 3. However, these TCI-induced abnormalities can be overridden by topical replacement with PLM. Our results demonstrate that TCIs induce negative effects on the skin barrier including permeability and antimicrobial functions, which are mediated by decreasing epidermal lipid synthesis, lamellar body secretion and antimicrobial peptides expression through suppression of cytokine such as IL-1alpha, therefore co-treatment with PLM would be helpful to overcome these negative effects.