Aging-Associated Changes in the Adult Human Skin Microbiome and the Host Factors that Affect Skin Microbiome Composition.

Understanding the changes in the skin microbiome and their relationship to host skin factors during aging remains largely unknown. To better understand this phenomenon, we collected samples for metagenomic and host skin factor analyses from the forearm, buttock, and facial skin from 158 Caucasian females aged 20‒24, 30‒34, 40‒44, 50‒54, 60‒64, and 70‒74 years. Metagenomics analysis was performed using 16S ribosomal RNA gene sequencing, whereas host sebocyte gland area, skin lipids, natural moisturizing factors, and antimicrobial peptides measurements were also performed. These analyses showed that skin bacterial diversity increased at all the skin sites with increasing age. Of the bacterial genera with an average relative abundance >1%, only Lactobacillus and Cutibacterium demonstrated a significant change (decrease) in abundance at all sampled skin sites with increasing age. Additional bacterial genera demonstrated significant age- and site-specific changes in abundance. Analysis of sebocyte area, natural moisturizing factors, lipids, and antimicrobial peptides showed an age-related decrease in sebocyte area and increases in natural moisturizing factors/antimicrobial peptides/skin lipids, all of which correlated with changes in specific bacterial genera. In conclusion, the human skin microbiome undergoes age-associated alterations that may reflect underlying age-related changes in cutaneous biology.

Improving newborn skin health: Effects of diaper care regimens on skin pH and erythema.

BACKGROUND/OBJECTIVE: Newborn infant skin is functional but immature, and diapering products can play a significant role in infant diapered skin health. Previous work demonstrated a regimen consisting of a diaper with an emollient and apertures on the inner liner (topsheet) with an acidic, pH-buffered wipe (Regimen A) lowered newborn skin pH and reduced the enzymatic activity on skin post-stool cleaning versus a regimen without these features (Regimen B). This study extends these findings to determine the impact of Regimen A on diaper area erythema severity over a 2-week use period. METHODS: This IRB-approved, blinded, randomized, crossover study enrolled newborn infants >7 days and ≤8 weeks. Participants exclusively used two unique diaper and wipe combinations, Regimen A and Regimen B (non-emollient, non-aperture containing topsheet and wipe with limited buffering capacity), each for 14 days and preceded by a 3-day washout regimen. RESULTS: Diapered skin pH was reduced during Regimen A use to values similar to that of a non-diapered control site (chest), while use of Regimen B was associated with a more alkaline skin pH. Regimen A resulted in significantly fewer severe erythema episodes. At the site of highest erythema, the perianal space, the average erythema score was significantly lower and more newborns were free of erythema while using Regimen A vs. Regimen B (P < .05). CONCLUSIONS: These findings demonstrate that diapering products can have a significant impact on newborn skin. They reinforce the need to support the physiological normalization of skin pH and protection from skin irritation and damage.

Effects of petrolatum, a petrolatum depositing body wash and a regular body wash on biomarkers and biophysical properties of the stratum corneum.

BACKGROUND: An important trend in the personal care industry involves the development of body wash products that not only clean the skin without damage but deposit conditioning ingredients to improve skin barrier function. OBJECTIVE: The objective of this study was to develop skin biomarker measures to quantify the treatment effects of body wash products. METHODS: We employed analysis of structural proteins (keratin 1,10,11 and involucrin), a natural moisturizing factor (pyrrolidone carboxylic acid) and an inflammatory mediator (IL-1ra/IL-1α) from adhesive discs with dry skin grading, TEWL and capacitance measurements to compare the effects of direct application of petrolatum, a high petrolatum depositing body wash, and a regular body wash on dry leg skin in a standard leg-wash treatment protocol. RESULTS: High depositing body wash and petrolatum had positive effects on stratum corneum barrier function as judged by biomarker analysis, biophysical measurements and skin grading compared to the regular body wash product. CONCLUSIONS: The results clearly indicate that a combination of biomarker and biophysical property measurements is effective for determining the skin benefits of moisturizing body wash products.

CONTEXTE: Une tendance importante dans l'industrie des soins personnels inclut le développement de produits de lavage corporel qui non seulement nettoient la peau sans l'endommager, mais déposent des ingrédients de traitement pour améliorer la fonction de la barrière cutanée. OBJECTIF: L'objectif de cette étude était de développer des mesures de biomarqueurs cutanés permettant de quantifier les effets du traitement des produits de lavage corporel. MÉTHODES: Nous avons utilisé l'analyse de protéines structurelles (kératine 1,10,11 et involucrine), un facteur hydratant naturel (acide carboxylique de pyrrolidone) et un médiateur inflammatoire (IL-1ra/IL-1a) provenant de disques adhésifs avec cotation de la sécheresse cutanée, mesures de perte d'eau transépidermique (transepidermal water loss, TEWL) et de capacitance pour comparer les effets de l'application directe de vaseline, d'un produit de lavage corporel avec dépôt élevé de vaseline et d'un produit de lavage corporel ordinaire sur la peau sèche des jambes, dans un protocole de traitement de lavage des jambes standard. RÉSULTATS: Le produit de lavage corporel à dépôt élevé et la vaseline avaient des effets positifs sur la fonction de barrière de la couche cornée, comme évalué par l'analyse des biomarqueurs, les mesures biophysiques et la cotation de la peau, comparé au produit de lavage corporel ordinaire. CONCLUSIONS: Les résultats indiquent clairement qu'une combinaison de mesures des biomarqueurs et des propriétés biophysiques est efficace pour déterminer les bienfaits pour la peau des produits de lavage corporel hydratants.

Use of an emollient-containing diaper and pH-buffered wipe regimen restores skin pH and reduces residual enzymatic activity.

BACKGROUND/OBJECTIVES: Diaper dermatitis is one of the most frequent skin conditions affecting infants and is associated with elevated skin pH, exposure to urine and feces, and increased fecal protease and lipase activity, resulting in stratum corneum barrier damage and increased risk of infection. The study aim was to determine the impact of two diaper and wipe regimens on newborn infant skin pH and residual enzyme activity after stool cleaning. METHODS: Two diaper and wipe regimens were compared in a randomized, single-blinded crossover study. Regimen A paired an emollient-containing diaper with an acidic, pH-buffered wipe. Regimen B was a non-emollient diaper and wipe with limited buffering capacity. A 3-day washout period preceded each 3-day regimen use period. Skin pH at the perianal/buttocks interface (PBI), genital region, and undiapered chest control were measured at baseline and day 3. Skin swabs were collected for residual enzyme activity after a stool cleaning event. RESULTS: Diapered skin pH at the PBI was similar to undiapered skin after 3 days of use for Regimen A, while PBI pH for Regimen B was elevated versus control. PBI pH was lower for Regimen A versus Regimen B. After a stool cleaning, PBI skin pH for Regimen A was lower immediately and had lower residual enzyme activity versus Regimen B (P < .05), and the pH-lowering effect was sustained up to 60 minutes. CONCLUSIONS: These results suggest that the use of an emollient-containing diaper with a pH-buffered wipe creates conditions favorable to optimum diapered skin health.

Effects of season stratum corneum barrier function and skin biomarkers.

The skin on the lower legs of 25 female subjects was evaluated first in the winter, and then again in the summer of the same subjects. Barrier function was determined by measuring transepidermal water loss (TEWL), and skin hydration and dryness were evaluated by electrical measurements (Corneometer ® CM825) and visual grading. Stratum corneum (SC) was sampled using 10 sequential D-Squame sampling discs and analyzed for 2-pyrrolidone-5-carboxylic acid (PCA), keratin-1,10,11, interleukin 1α (IL-1α), interleukin 1 receptor antagonist (IL-1ra), selected ceramides, cholesterol, cholesterol sulfate, and selected free fatty acids. TEWL as well as the visual dryness grades were significantly lower in the summer while hydration was higher. PCA was significantly higher in the summer as were the keratins. The ratio IL-1ra:IL-1α, an indicator of skin inflammation, was significantly lower in the summer. The amount of protein removed by the tape strips was also significantly lower in summer indicating better SC cohesion. Among the SC lipids measured, total ceramides, individual ceramides, total fatty acids, and cholesterol were higher in summer compared to winter. Stearic acid and cholesterol sulfate were not significantly different between winter and summer.

Epidermal changes associated with symptomatic resolution of dandruff: biomarkers of scalp health.

BACKGROUND: Dandruff is a common scalp condition characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect underlying histopathologic and biochemical events that must be reversed if treatment is to be effective. OBJECTIVES: This study aimed to better characterize the state of the epidermis in dandruff and to determine how a defined set of skin surface biomarkers of this state change during a successful course of treatment with a potentiated zinc pyrithione (ZPT) shampoo. METHODS: A population of dandruff sufferers was treated for 3 weeks with a commercial ZPT shampoo or a non-medicated product, and the effect of treatment on adherent scalp flake (ASF) scores was evaluated. Biopsies were taken from lesional sites at baseline and at the end of the study for histomorphometric and histopathologic analysis. Stratum corneum (SC) samples were likewise obtained for evaluation of biochemical markers of inflammation (IL-1α, IL-1RA, IL-8) and barrier integrity (keratin 1, 10, 11; involucrin; SC lipids; human serum albumin). The biomarker profile was evaluated first by comparison with that in non-dandruff subjects at baseline, and then to determine whether any treatment-induced changes were correlated with reductions in flaking in dandruff sufferers. RESULTS: Taken together, our studies showed that treatment with the ZPT shampoo led to an improvement in the overall scalp condition as assessed by the resolution of flaking, reduction in epidermal thickness and inflammatory biomarkers, and a dramatic improvement in biomarkers of epidermal barrier integrity. CONCLUSIONS: The combination of biomarkers examined appears to be a good overall descriptor of the health of the scalp in dandruff, and changes in these biomarkers track with tissue-level events that underlie clinical efficacy in the treatment of dandruff by ZPT shampoo. For the first time, we demonstrate a set of tools that extend beyond flaking scores to provide insight into specific biological changes occurring on the scalp to enable an objective assessment of scalp health.

Evolution of thiazolidine-based blockers of human Kv1.5 for the treatment of atrial arrhythmias.

Blockade of the Kv1.5 ion channel is a potentially atrial-selective avenue for the treatment of atrial fibrillation and atrial flutter. The development and biological evaluation of a series of thiazolidine-based blockers of Kv1.5 is described.

Discovery and in vitro/in vivo studies of tetrazole derivatives as Kv1.5 blockers.

A novel class of tetrazole-derived Kv1.5 blockers is disclosed. In in vitro studies, several compounds had IC(50)s ranging from 180 to 550 nM. In vivo studies indicated that compounds 2f and 2j increased right atrial ERP about 40% without affecting ventricular ERP.

Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1.5 blockers.

A novel class of tetrahydroindolone-derived semicarbazones has been discovered as potent Kv1.5 blockers. In in vitro studies, several compounds exhibited very good potency for blockade of Kv1.5. Compound 8i showed good selectivity for blockade of Kv1.5 vs hERG and L-type calcium channels. In an anesthetized pig model, compounds 8i and 10c increased atrial ERP about 28%, 18%, respectively, in the right atrium without affecting ventricular ERP.

Discovery and synthesis of tetrahydroindolone-derived carbamates as Kv1.5 blockers.

A novel class of tetrahydroindolone-derived carbamates has been discovered whose members are potent Kv1.5 blockers. The in vitro data show that compounds 6 and 29 are quite potent. They are also very selective over hERG (>450-fold) and L-type calcium channels (>450-fold).

Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones as Kv1.5 channel blockers for the treatment of atrial fibrillation.

A series of novel (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones were prepared and examined for utility as Kv1.5 channel blockers for the treatment of atrial fibrillation.