A high glycerol-containing leave-on scalp care treatment to improve dandruff.

Dandruff is a common cosmetic condition associated with flaky scalp skin and pruritus. It is generally treated with regular use of antifungal-based shampoos. Research into factors underlying the characteristic skin lesions has revealed perturbations in epidermal differentiation and a dramatic deterioration in the associated process of stratum corneum (SC) maturation. These observations suggest that directly addressing the quality of the SC could have a scalp benefit. In this study, the authors investigated the efficacy of a moisturising leave-on lotion (LOL) containing a high concentration of glycerol (10%) and other known skin benefit agents (saturated fatty acid and sunflower seed oil) to reduce dandruff over an 8-week treatment period with 3 applications per week. Results of expert visual grading and biophysical measurements of SC parameters (transepidermal water loss and hydration) revealed a significant reduction in the dandruffcondition over this period, with significant improvement in both SC water barrier function and hydration. These scalp skin benefits were maintained for up to a week following cessation of the treatment. This study indicates that use of a glycerol-rich substantive LOL, designed to directly improve the quality of the SC barrier can have a significant impact on the dandruff condition.

Amino acid composition, including key derivatives of eccrine sweat: potential biomarkers of certain atopic skin conditions.

The free amino acid (AA) composition of eccrine sweat is different from other biological fluids, for reasons which are not properly understood. We undertook the detailed analysis of the AA composition of freshly isolated pure human eccrine sweat, including some of the key derivatives of AA metabolism, to better understand the key biological mechanisms governing its composition. Eccrine sweat was collected from the axillae of 12 healthy subjects immediately upon formation. Free AA analysis was performed using an automatic AA analyser after ninhydrin derivatization. Pyrrolidine-5-carboxylic acid (PCA) and urocanic acid (UCA) levels were determined using GC/MS. The free AA composition of sweat was dominated by the presence of serine accounting for just over one-fifth of the total free AA composition. Glycine was the next most abundant followed by PCA, alanine, citrulline and threonine, respectively. The data obtained indicate that the AA content of sweat bears a remarkable similarity to the AA composition of the epidermal protein profilaggrin. This protein is the key source of free AAs and their derivatives that form a major part of the natural moisturizing factor (NMF) within the stratum corneum (SC) and plays a major role in maintaining the barrier integrity of human skin. As perturbations in the production of NMF can lead to abnormal barrier function and can arise as a consequence of filaggrin genotype, we propose the quantification of AAs in sweat may serve as a non-invasive diagnostic biomarker for certain atopic skin conditions, that is, atopic dermatitis (AD).

Regulatory role for the profilaggrin N-terminal domain in epidermal homeostasis.

It is well known that profilaggrin, after its release from keratohyalin granules through dephosphorylation, becomes enzymatically processed into individual filaggrin monomers. The roles for filaggrin monomers in aggregating keratin filaments, as a component of the cornified cell envelope, and as a source of natural moisturizing factor are well established. A specific N-terminal fragment, called the PF-AB domain, becomes proteolytically released as well, but much less is known about its functional role in epidermal development. Here, the functional role of profilaggrin N-terminal (PF-N) domain was addressed by overexpressing three overlapping fragments from a lentiviral expression vector in the epidermis of living skin equivalents. The PF-N domain expression impaired the epidermal development through reducing keratinocyte proliferation and impairing differentiation. The expression of well-known differentiation markers profilaggrin, loricrin, and keratin 10 was considerably downregulated in PF-N domain overexpressing-skin equivalents. The activation of caspase 14 was also substantially affected. In contrast, total silencing of profilaggrin expression, obtained with a lentiviral miR vector, resulted in a hyperproliferative epidermis. We propose a hypothesis that profilaggrin AB domain provides a key feedback mechanism that controls epidermal homeostasis.

Filaggrin repeat number polymorphism is associated with a dry skin phenotype.

Profilaggrin is a key epidermal protein, critical for the generation and maintenance of the stratum corneum barrier. It is encoded by a gene located in the epidermal differentiation complex of Chromosome 1q21 and is composed of multiple filaggrin repeats connected by highly conserved linker peptides. Within the human population the number of filaggrin repeats encoded by this gene varies between 10, 11 or 12 repeats. Using a PCR-based approach we have determined individual profilaggrin allelotypes in a group of 113 subjects and identified preliminary evidence of an inverse association between the 12 repeat allele and self-perceived frequent dry skin (P=0.0293). This is the first demonstration of a potential association between a genetic marker and cosmetic skin condition and suggests that cosmetic skin dryness may in part be genetically determined and associated with specific profilaggrin allelotypes.

The stratum corneum: structure and function in health and disease.

Our understanding of the formation, structure, composition, and maturation of the stratum corneum (SC) has progressed enormously over the past 30 years. Today, there is a growing realization that this structure, while faithfully providing a truly magnificent barrier to water loss, is a unique, intricate biosensor that responds to environmental challenges and surface trauma by initiating a series of biologic processes which rapidly seek to repair the damage and restore barrier homeostasis. The detailed ultrastructural, biochemical, and molecular dissection of the classic "bricks and mortar" model of the SC has provided insights into the basis of dry, scaly skin disorders that range from the cosmetic problems of winter xerosis to severe conditions such as psoriasis. With this knowledge comes the promise of increasingly functional topical therapies.