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Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-β1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers' breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities. [ABSTRACT FROM AUTHOR]

Leonardo Celleno,1 Alessandra D’amore,1 Wai Kwong Cheong2 1Department of Dermatology, Catholic University of Rome, Rome, Italy; 2Specialist Skin Clinic, Singapore, SingaporeCorrespondence: Leonardo Celleno, Via Cesare Beccaria 98, Rome, 00196, Italy, Tel +390636006629, Email lcelleno@gmail.comPurpose: Urea as an ingredient in topical skin applications can aid skin integrity and hydration and have keratolytic, anti-fungal, anti-bacterial, and anti-pruritic effects. Skin conditions that urea-containing formulations have been utilized to treat include hand eczema/dermatitis, seborrheic dermatitis and psoriasiform dermatoses of the scalp. Two monocentric, simple blind, observational studies were carried out in healthy participants to examine the efficacy and safety of two urea-containing products in these skin conditions.Patients and Methods: Study 1 tested the actions of a commercially available 30% urea topical cream on hand eczema. The product was applied ≥ 2/day for 28 ± 2 days. Transepidermal water loss, skin redness, skin hydration, and participant ratings of efficacy and qualities were assessed prior to first product application and on days 14 and 29. Study 2 tested the actions of a commercially available foaming product containing 10% urea on seborrheic dermatitis and scalp psoriasiform dermatoses. The product was applied ≥ 2/day for 28 ± 2 days. Desquamation index and surface occupied by squames, analysis of extracted squames, microscopic assessment of scalp photos and participant ratings of product efficacy and qualities was carried out prior to first product application and on days 14 and 29.Results: In Study 1 (n = 20 females), results showed a significant (p < 0.05) decrease in transepidermal water loss, with an increase in hydration level of the upper skin layers, and a decrease in skin redness. In Study 2 (n = 13 females, 7 males), product use led to significant (p < 0.05) decreases in desquamation measures and dryness. In both studies, the majority of participants “agreed” or “slightly agreed” that the product had good efficacy and was easy to apply. No adverse reactions were reported.Conclusion: These findings point to the utility of urea in topically applied vehicles for hand eczema, seborrheic dermatitis, and psoriasiform dermatoses.Keywords: natural moisturizing factor, anti-pruritic, transepidermal water loss, keratinocytes, topical formulations

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra‐uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra‐uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria—a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier. [ABSTRACT FROM AUTHOR]

Fabrizio Spada, Tanya M Barnes, Kerryn A Greive Research and Development, Ego Pharmaceuticals Pty Ltd, Braeside, VIC, Australia Background: Moisturizers are topical products designed to improve and maintain the skin barrier function and to help prevent dry skin.Materials and methods: A new moisturizer (Ceramide cream) was formulated containing ingredients which mimic the skin’s own natural moisturizing systems. Corneometry was performed at baseline, 2, 4, 6 and 24 hours following a single application of Ceramide cream to healthy skin, and compared to three reference moisturizers available over-the-counter, and placebo. Transepidermal water loss (TEWL) was also measured following a single application of Ceramide cream compared to baseline, and its safety was assessed by repeat insult patch test, ophthalmologist and pediatric testing.Results: A single topical application of either the Ceramide cream or the three reference moisturizers resulted in a significant increase in skin hydration over time (P

Although barrier function of psoriatic skin is shown to be decreased by measuring transepidermal water loss ( TEWL), few reports exist examining other physical skin properties and components including stratum corneum hydration, natural moisturizing factor ( NMF), free fatty acids ( FFA), β-sheet and α-helix ratio of structural protein(s), and sebum content. We compared the skin properties and components of normal, involved and uninvolved skin of psoriasis. Using a corneometer and attenuated total reflection-infrared spectrometer, we measured TEWL, stratum corneum hydration, NMF, FFA, β/α ratio and sebum in psoriasis vulgaris patients and healthy controls. TEWL and β/α ratio of involved psoriatic skin were significantly increased compared with uninvolved skin and normal control skin. In contrast, stratum corneum hydration , NMF and FFA, but not sebum, are significantly decreased in the involved skin compared with uninvolved skin and normal skin. TEWL and stratum corneum hydration returned to the normal levels following clinical improvement of the lesion. Barrier function and hydration of psoriatic skin are defective and secondary structure in stratum corneum protein is altered in the involved psoriatic skin. [ABSTRACT FROM AUTHOR]

The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of the study was to evaluate the effect of pure lecithins in comparison to a conventional surfactant on skin in vivo. (2) Methods: Physiological skin parameters were evaluated at the beginning and the end of the study (day 1 and day 4) (n = 8, healthy forearm skin) with an Aquaflux®, skin-pH-Meter, Corneometer® and an Epsilon® sensor. Confocal Raman spectroscopy was employed to monitor natural moisturizing factor, urea and water content of the participants' skin. Tape strips of treated skin sites were taken and the collected corneocytes were subjected to atomic force microscopy. Circular nano objects were counted, and dermal texture indices were determined. (3) Results: Transepidermal water loss was increased, and skin hydration was decreased after treatment with SDS and LPC80. Natural moisturizing factor and urea concentrations within the outermost 10 µm of the stratum corneum were lower than after treatment with S75 or water. Dermal texture indices of skin treated with SDS were higher than skin treated with water (control). (4) Conclusions: Results suggest very good (S75) or good (LPC80) skin-tolerability of lecithin-based surfactants in comparison to SDS and encourage further investigation. [ABSTRACT FROM AUTHOR]

Background: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD FLG ) compared with that seen in patients with AD without these mutations (AD NON-FLG ). Objectives: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD FLG versus patients with AD NON-FLG . We also sought to examine the same profiles in a murine model of filaggrin deficiency (Flgft/Flgft [FlgdelAPfal ] mice). Methods: One hundred thirty-seven patients were studied. NMF levels were ascertained using confocal Raman spectroscopy; transepidermal water loss and skin surface pH were measured. IL-1α, IL-1β, IL-18, IL-1 receptor antagonist (IL-1RA), and IL-8 levels were determined in SC tape strips from 93 patients. All subjects were screened for 9 FLG mutations. Flgft/Flgft (FlgdelAPfal) mice, separated from maFlgft/maFlgft (flaky tail) mice, were used for the preparation and culture of primary murine keratinocytes and as a source of murine skin. RT-PCR was performed using primers specific for murine IL-1α, IL-1β, and IL-1RA. Results: SC IL-1 levels were increased in patients with AD FLG ; these levels were inversely correlated with NMF levels. NMF values were also inversely correlated with skin surface pH. Skin and keratinocytes from Flgft/Flgft mice had upregulated expression of IL-1β and IL-1RA mRNA. Conclusions: AD FLG is associated with an increased SC IL-1 cytokine profile; this profile is also seen in a murine homologue of filaggrin deficiency. These findings might have importance in understanding the influence of FLG mutations on the inflammasome in the pathogenesis of AD and help individualize therapeutic approaches. [Copyright &y& Elsevier]

Background: Filaggrin (FLG) has a central role in the pathogenesis of atopic dermatitis (AD). FLG is a complex repetitive gene; highly population-specific mutations and multiple rare mutations make routine genotyping complex. Furthermore, the mechanistic pathways through which mutations in FLG predispose to AD are unclear. Objectives: We sought to determine whether specific Raman microspectroscopic natural moisturizing factor (NMF) signatures of the stratum corneum could be used as markers of FLG genotype in patients with moderate-to-severe AD. Methods: The composition and function of the stratum corneum in 132 well-characterized patients with moderate-to-severe AD were assessed by means of confocal Raman microspectroscopy and measurement of transepidermal water loss (TEWL). These parameters were compared with FLG genotype and clinical assessment. Results: Three subpopulations closely corresponding with FLG genotype were identified by using Raman spectroscopy. The Raman signature of NMF discriminated between FLG-associated AD and non–FLG-associated AD (area under the curve, 0.94; 95% CI, 0.91-0.99). In addition, within the subset of FLG-associated AD, NMF distinguished between patients with 1 versus 2 mutations. Five novel FLG mutations were found on rescreening outlying patients with Raman signatures suggestive of undetected mutations (R3418X, G1138X, S1040X, 10085delC, and L2933X). TEWL did not associate with FLG genotype subgroups. Conclusions: Raman spectroscopy permits rapid and highly accurate stratification of FLG-associated AD. FLG mutations do not influence TEWL within established moderate-to-severe AD. [Copyright &y& Elsevier]