A new dexpanthenol-containing liquid cleanser for atopic-prone skin: Results from two prospective clinical studies evaluating cutaneous tolerability, moisturization potential, and effects on barrier function.

BACKGROUND: Gentle cleansing of the skin without further compromising its barrier function and moisture content and being simultaneously devoid of adverse effects on the skin microbiome are important features of body cleansers for atopic-prone skin sufferers. For this population, a new dexpanthenol-containing liquid cleanser (DCLC) was developed. METHODS: Two prospective 4-week studies have been conducted. Study 1 investigated the effect of once-daily DCLC on stratum corneum (SC) hydration, transepidermal water loss (TEWL), skin pH, and skin microbiome (all on the volar forearm) in adult subjects with dry skin (N = 44). Study 2 explored the cutaneous tolerability of DCLC and its effect on the microbiome biodiversity of the volar forearm skin in infants/children with atopic-prone skin (N = 33, aged 6 months to 6 years). In the latter study, DCLC was applied 2-3 days/week in combination with an emollient applied at least twice daily. RESULTS: In Study 1, on Day 29, the mean change in skin surface capacitance from baseline was significantly greater in the forearm test area treated with DCLC than in the contralateral test area (control) treated with water only (5.16 vs. 3.65 a.u.; p = 0.011), suggesting long-term SC hydration. DCLC use was not associated with changes in TEWL, skin pH, or microbiome biodiversity if compared to control. In Study 2, the 4-week use of DCLC in combination with an emollient was well tolerated according to pediatrician skin assessment, and no flare-ups were recorded. The microbiome biodiversity did not shift during the study. CONCLUSION: These findings support the use of DCLC in subjects with atopic-prone skin.

Targeted dry skin treatment using a multifunctional topical moisturizer.

OBJECTIVE: The development of dry skin is a complex process, with a wide variety of factors each playing different roles in its evolution. Given this, it is important when designing a formulation to tackle dry skin that these varied aspects of skin behaviour are addressed. Presented here are the results of a 3-week moisturization study carried out on dry legs. A wide range of traditional and more recently developed biophysical measurement methods have been combined with visual assessment of skin condition to enable multiple aspects of skin function to be determined. The observed changes in the skin are discussed in terms of the ingredients used in the moisturizing formulation. METHODS: A range of novel and traditional skin assessment methods and techniques were used to assess the effects of an oil in water-based moisturizing product compared to an untreated site during a 3-week in vivo study on dry lower leg skin. RESULTS: Statistically significant improvements were observed in a range of skin parameters as a result of product usage. Skin hydration assessed using Corneometer®, Epsilon® and visual dry skin grading all increased after 3 weeks of use. Skin barrier function measured using transepidermal water loss also improved. Levels of cholesterol, free fatty acids and Ceramide NH increased, as well as the average length of the stratum corneum (SC) lipid lamella bilayers, and the ratio of lipid to protein increased (measured using Lipbarvis® and in vivo Confocal Raman Spectroscopy). Increases in the levels of Ceramide EOS and NP were also observed, along with an improvement in corneocyte maturity, although these were not statistically significant. CONCLUSIONS: Using a variety of traditional and novel skin assessment techniques, a wide range of factors associated with the evolution of dry skin have been assessed upon treatment with a new topical moisturizer. Product usage resulted in significant improvements to skin hydration and barrier function, the levels and morphology of SC barrier lipids, and overall epidermal differentiation. As a result there was a significant reduction in the characteristics associated with the development of dry skin after use of the test product.

OBJECTIF: le développement de la sécheresse cutanée est un processus complexe, une grande variété de facteurs jouant chacun des rôles différents dans son évolution. De ce fait, il est important d'aborder ces différents aspects du comportement de la peau lors de la conception d'une formulation pour lutter contre la sécheresse cutanée. Les résultats d'une étude de 3 semaines sur l'hydratation des jambes sèches sont présentés ci-dessous. Un large éventail de méthodes de mesure biophysiques traditionnelles et plus récemment développées ont été combinées à une évaluation visuelle de l'état de la peau pour permettre de déterminer de multiples aspects de la fonction cutanée. Les changements observés sur la peau sont abordés en termes des ingrédients utilisés dans la formulation hydratante. MÉTHODES: une série de méthodes et de techniques nouvelles et traditionnelles d'évaluation de la peau ont été utilisées pour évaluer les effets d'un produit hydratant à base d'émulsion huile dans eau par comparaison à un site non traité au cours d'une étude in vivo de 3 semaines sur la peau sèche de la partie inférieure des jambes. RÉSULTATS: des améliorations statistiquement significatives ont été observées au niveau d'une gamme de paramètres cutanés suite à l'utilisation du produit. L'hydratation cutanée évaluée à l'aide de Corneometer®, Epsilon® et de la cotation visuelle de la sécheresse cutanée s'est améliorée selon toutes ces méthodes après 3 semaines d'utilisation. La fonction de barrière cutanée mesurée d'après la perte d'eau transépidermique s'est également améliorée. Les taux de cholestérol, d'acides gras libres et de céramides NH ont augmenté, ainsi que la longueur moyenne des bicouches des lamelles lipidiques de la couche cornée (CC), et il en a été de même pour le rapport lipide/protéine (mesuré à l'aide du Lipbarvis® et de la spectroscopie confocale de Raman in vivo). Des augmentations des taux de céramides EOS et NP ont également été observées, ainsi qu'une amélioration de la maturité des cornéocytes, bien qu'elles n'aient pas été statistiquement significatives. CONCLUSION: à l'aide d'une gamme de techniques d'évaluation de la peau traditionnelles et nouvelles, un large éventail de facteurs associés à l'évolution de la sécheresse cutanée a été évalué lors du traitement avec un nouveau produit hydratant topique. L'utilisation du produit a entraîné une amélioration significative de l'hydratation et de la fonction de barrière de la peau, des taux et de la morphologie des lipides de la barrière SC , et de la différenciation épidermique globale. Cela a entraîné une amélioration significative des facteurs associés au développement de la sécheresse cutanée.

αPIX Is a Trafficking Regulator that Balances Recycling and Degradation of the Epidermal Growth Factor Receptor.

Endosomal sorting is an essential control mechanism for signaling through the epidermal growth factor receptor (EGFR). We report here that the guanine nucleotide exchange factor αPIX, which modulates the activity of Rho-GTPases, is a potent bimodal regulator of EGFR trafficking. αPIX interacts with the E3 ubiquitin ligase c-Cbl, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation. We show that EGF stimulation induces αPIX::c-Cbl complex formation. Simultaneously, αPIX and c-Cbl protein levels decrease, which depends on both αPIX binding to c-Cbl and c-Cbl ubiquitin ligase activity. Through interaction αPIX sequesters c-Cbl from EGFR and this results in reduced EGFR ubiquitination and decreased EGFR degradation upon EGF treatment. However, quantitatively more decisive for cellular EGFR distribution than impaired EGFR degradation is a strong stimulating effect of αPIX on EGFR recycling to the cell surface. This function depends on the GIT binding domain of αPIX but not on interaction with c-Cbl or αPIX exchange activity. In summary, our data demonstrate a previously unappreciated function of αPIX as a strong promoter of EGFR recycling. We suggest that the novel recycling regulator αPIX and the degradation factor c-Cbl closely cooperate in the regulation of EGFR trafficking: uncomplexed αPIX and c-Cbl mediate a positive and a negative feedback on EGFR signaling, respectively; αPIX::c-Cbl complex formation, however, results in mutual inhibition, which may reflect a stable condition in the homeostasis of EGF-induced signal flow.