Correlation between the properties of the lipid matrix and the degrees of integrity and cohesion in healthy human Stratum corneum

The correlation between the degrees of integrity and cohesion in healthy human Stratum corneum (SC) and the properties of the SC lipid matrix could be examined non-invasively in vivo using ATR-FTIR spectroscopy and measurements of pH, conductance, and transepidermal water loss (TEWL) taken in the course of tape-stripping. The change of TEWL following the removal of a SC layer with a predefined thickness served as a measure for the SC integrity, and the amount of protein removed by predefined number of tapes - as a measure for the SC cohesion. The extent of lipids organized in orthorhombic lattices and the pH in the inner SC emerged as the main factors that determine the degree of integrity. The amounts and molecular organization of the SC lipids did not correlate with the degree of cohesion, while the pH and the hydration of SC correlated well with the degree of cohesion in the superficial but not in the inner SC layers. This study evidenced the variability of SC integrity and cohesion existing in healthy human skin, demonstrated the importance of the lipid molecular organization for the SC integrity, and illustrated the limitations in the determination the degree of corneodesmolysis in SC based only on the protein content of tape-strips.     

Noninvasive bioengineering assessment of the skin barrier function in patients with chronic venous insufficiency

Background  Chronic venous insufficiency (CVI) comprises all symptoms caused by permanent venous and capillary hypertension. While the clinical manifestations of the disease have been well characterized, there is little knowledge on the skin barrier function in the affected patients. Objectives  The aim of the study was to assess noninvasively the barrier function in patients with CVI stage C2 and stage C4 according to the CEAP classification in comparison with healthy controls (stage C0). Methods  Thirty patients with CVI without concomitant diseases and 15 healthy, aged‐matched controls were recruited for the study. The skin barrier function was assessed by measuring transepidermal water loss (TEWL), capacitance and skin colour symmetrically on the calf, medial and lateral malleolus, posterior arch (arcus venosus) and volar forearm. Results  Compared with the forearm, there was a tendency for increased TEWL and significant reduction of capacitance on all measurement sites on the lower limb. Compared with the control group, the patients with CVI had significantly higher TEWL values on all measurement sites on the lower extremities while no difference in capacitance between patients and controls was observed. Conclusions  Changes in the epidermal barrier function in patients with CVI are readily detectable by bioengineering methods as early as stage C2 and are manifested by significantly increased TEWL. Our results suggest that the reduced stratum corneum hydration in patients with CVI is due to anatomical differences rather than venous disease. These findings may help better understand the factors contributing to disease progression and its complications.     

Efficacy of stratum corneum lipid supplementation on human skin

Recent studies suggest that supplementing intercellular lipids of the stratum corneum in ageing populations or in people with dry skin can stimulate the functioning of the skin. This work lends support to the reinforcement capacity of two different stratum corneum lipid mixtures (synthetic stratum corneum lipid mixtures, SSCL, and internal wool lipid extracts, IWL) formulated as liposomes on healthy skin of two differently aged groups of individuals. Protection of healthy skin against detergent-induced dermatitis was evaluated. Transepidermal water loss and capacitance were used to evaluate the effect of these formulations in in vivo long-term studies. Increase in water-holding capacity is obtained only when the formulations applied are structured as liposomes. This is slightly more pronounced for aged skin. Subsequent SLS exposure reflected the protection of healthy human skin against detergent-induced dermatitis. Slightly better results were obtained with IWL containing a mixture of natural ceramides than with SSCL with only one ceramide present in the formulation. All these results support the beneficial effects of skin lipid supplementation given their resemblance to the lipids in the stratum corneum both in composition and in the structuring of the formulation.     

Neuroimmunomodulatory compound for sensitive skin care: in vitro and clinical assessment

Background The pathophysiology of sensitive skin consists of an inflammatory reaction resulting from the abnormal penetration in the skin of potentially irritating substances, which occurs due to skin barrier dysfunction and changes in the production of local neuromediators. Aims The therapeutic potential of l ‐carnosine and Rhodiola rosea, as antioxidant and neuromodulatory, respectively, leads us to investigate the effects of the R. rosea extract/l ‐carnosine–associated compound (RCAC) on sensitive skin alterations. Methods A double‐blind comparative study was conducted on 124 volunteers with sensitive skin, who were selected by their reactivity to stinging test. Two randomized groups of 62 each received either a formulation containing 1% of RCAC or placebo, which was applied twice a day for 28 consecutive days. One perceptibility questionnaire was applied at the onset and at the end of the treatment to evaluate the subjective response to test product. Additionally, in vitro studies were performed to investigate RCAC neuroimmunomodulatory mechanisms. Results RCAC treatment produced in vivo protective effects in skin barrier function and a positive subjective response of sensitive skin volunteers. In vitro treatment promoted the release of proopiomelanocortin peptides and restored to normal the increased levels of neuropeptides and cytokines produced by keratinocytes exposed to ultraviolet radiation. Clinical effectiveness was measured by reduction of transepidermal water loss, positive perceptions of improvements in skin dryness and skin comfort sensation, and reduction of discomfort sensation after stinging test. Conclusions The protective effect of RCAC in skin barrier function and the positive response produced in human subjects with sensitive skin could be partially explained by our in vitro results showing a significant increase in opioid peptides release, an inhibitory effect on neuropeptides production, and modulation of cytokines production by keratinocytes under ultraviolet stress.     

International guidelines for the in vivo assessment of skin properties in non‐clinical settings: Part 2. transepidermal water loss and skin hydration

Background

There is an emerging perspective that it is not sufficient to just assess skin exposure to physical and chemical stressors in workplaces, but that it is also important to assess the condition, i.e. skin barrier function of the exposed skin at the time of exposure. The workplace environment, representing a non‐clinical environment, can be highly variable and difficult to control, thereby presenting unique measurement challenges not typically encountered in clinical settings.

Methods

An expert working group convened a workshop as part of the 5th International Conference on Occupational and Environmental Exposure of Skin to Chemicals (OEESC) to develop basic guidelines and best practices (based on existing clinical guidelines, published data, and own experiences) for the in vivo measurement of transepidermal water loss (TEWL) and skin hydration in non‐clinical settings with specific reference to the workplace as a worst‐case scenario.

Results

Key elements of these guidelines are: (i) to minimize or recognize, to the extent feasible, the influences of relevant endogenous‐, exogenous‐, environmental‐ and measurement/instrumentation‐related factors; (ii) to measure TEWL with a closed‐chamber type instrument; (iii) report results as a difference or percent change (rather than absolute values); and (iv) accurately report any notable deviations from this guidelines.

Conclusion

It is anticipated that these guidelines will promote consistent data reporting, which will facilitate inter‐comparison of study results.     

Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial

BACKGROUND: Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. OBJECTIVES: To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. METHODS: Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. RESULTS: Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. CONCLUSIONS: Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.     

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium‐induced colitis mouse model

Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease‐induced skin disruption, we used a dextran sulphate sodium (DSS)‐induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS‐treated mice compared to controls. Tumor necrosis factor‐alpha (TNF‐α), interleukin 6 and levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS‐treated mice. However, when administered TNF‐α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase‐expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion‐blocking agent) was administered to DSS‐treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon‐to‐skin signal transduction, as DSS‐induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS‐induced colitis, and the activation of mast cells via mAChRs is critical to this association.