Protective effects of glycerol and xylitol in keratinocytes exposed to hyperosmotic stress.

Purpose: Our goal was to study whether glycerol and xylitol provide protection against osmotic stress in keratinocytes. Methods: The experiments were performed on HaCaT keratinocytes. Hyperosmotic stress was induced by the addition of sorbitol (450, 500 and 600 mOsm). Both polyols were applied at two different concentrations (glycerol: 0.027% and 0.27%, xylitol: 0.045% and 0.45%). Cellular viability and cytotoxicity were assessed, intracellular Ca2+ concentration was measured, and the RNA expression of inflammatory cytokines was determined by means of PCR. Differences among groups were analyzed with one-way ANOVA and Holm-Sidak post-hoc test. When the normality test failed, Kruskal-Wallis one-way analysis of variance on ranks, followed by Dunn's method for pairwise multiple comparison was performed. Results: The higher concentrations of the polyols were effective. Glycerol ameliorated the cellular viability while xylitol prevented the rapid Ca2+ signal. Both polyols suppressed the expression of IL-1α but only glycerol decreased the expression of IL-1ß and NFAT5. Conclusions: Glycerol and xylitol protect keratinocytes against osmotic stress. Despite their similar chemical structure, the effect of these polyols displayed differences. Hence, joint application of glycerol and xylitol may be a useful therapeutic approach for different skin disorders.

Beyond the physico-chemical barrier: Glycerol and xylitol markedly yet differentially alter gene expression profiles and modify signalling pathways in human epidermal keratinocytes.

Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.

Effects of Locally Applied Glycerol and Xylitol on the Hydration, Barrier Function and Morphological Parameters of the Skin.

Glycerol and xylitol hydrate the skin and improve its barrier function over a short period. We studied the effects of glycerol and xylitol on the physiological properties and morphology of the skin after longer-term application. Twelve volunteers with dry skin were examined. Three areas on the arms were determined. Area 1 served as untreated control. The vehicle was applied to area 2, while area 3 was treated twice daily with a formulation containing glycerol (5%) and xylitol (5%) for 14 days. Transepidermal water loss (TEWL), hydration and biomechanical properties of the skin were monitored. Biopsies were taken for routine histology and immunohistochemistry for filaggrin and matrix metalloproteinase-1 (MMP-1). The polyols increased the skin hydration and protein quantity of filaggrin, elevated the interdigitation index, decreased the TEWL and improved the biomechanical properties of the skin, but did not change the protein expression of MMP-1. A combination of glycerol and xylitol can be useful additional therapy for dry skin.

Antiirritant properties of polyols and amino acids.

BACKGROUND: Antiirritants are used in cosmetic products to prevent or to treat skin irritations that arise during daily life. Data were published earlier on the efficacy of the best-known humectant, glycerol, in reducing irritation. OBJECTIVE: The aim of the present study was to examine the effects of different polyols (including glycerol, xylitol, and mannitol) and the amino acids taurine and glycine on sodium lauryl sulfate (SLS)-induced skin irritation. METHODS: Healthy adult volunteers were patch-tested with 0.1% SLS in the presence or absence of one or another polyol or amino acid. Skin reactions were evaluated via measurements of transepidermal water loss (TEWL). RESULTS: Glycerol and xylitol significantly suppressed the SLS-induced increase in TEWL, whereas mannitol had no effect on the SLS-induced skin irritation. Taurine also inhibited the SLS-induced increase in TEWL, but glycine was not effective in reducing the SLS-induced irritative response. CONCLUSION: Similar to the action of the well-known antiirritant glycerol, SLS-induced skin irritation is suppressed by xylitol and taurine. These results suggest that these agents might also be effective in preventing irritative dermatitis.

Canine meibometry: establishing baseline values for meibomian gland secretions in dogs.

Meibomian lipid secretions are essential in preventing tear evaporation. Disorders of the meibomian glands may therefore play an important role in the pathogenesis of some forms of keratoconjunctivitis sicca (KCS). Until now, meibomian lipid secretions have never been quantitatively evaluated in dogs. With the aim of establishing baseline values of canine meibomian lipid secretions, meibometry was conducted in 42 healthy dogs, 16 of which were Miniature Schnauzers. The mean meibomium level in 84 eyes of the 42 dogs was 179+/-60 Meibometer units. Age, gender and side did not affect the results. However, meibomium levels were significantly lower in the Miniature Schnauzers, a breed that is susceptible to KCS, compared to other breeds. This report demonstrates that meibometry is a simple and minimally invasive technique that may be readily used in conscious dogs to quantify meibomian gland secretions and explicate tear film dynamics in normal and dry canine eyes.

The influence of eyelid temperature on the delivery of meibomian oil.

The aim of this study is to establish the effect of heating and cooling of the eyelid on the delivery of oil from the meibomian glands, as indicated by the extent of re-establishment of the reservoir of meibomian oil on the human eyelid margin, resulting from 10 conscious blinks, following pre-cleaning by a hexane swab. A standard handling sequence was followed. Step 1. Both upper and lower eyelids of both eyes of human volunteers were cleaned by a hexane swab and measured by a Meibometer to show satisfactory removal of the pre-existing oil (initial reading less than 60 instrumental units (IU)). The volunteers were then asked to blink 10 times at their normal rate. Then the eyelid was re-measured by the Meibometer. Step 2. The closed eyelids were heated for 5 min by a 250 W infrared lamp from a distance of 50 cm. The eyelid temperature was measured by an infrared thermometer, then Step 1 was repeated. Step 3. The eyelids were cooled for 5 min by an ice-pack (crushed ice in a towel). The eyelid temperature was measured, then Step 1 was repeated. Both eyes of 20 female subjects, aged 68 +/- 3 S.E.M. (range 52-84) years were examined. The mean instrumental reading (IU +/- S.E.M.) after 10 blinks at 33.4 +/- 0.1 degrees C was 154 +/- 12. On increasing the eyelid surface temperature by 4.9 +/- 0.3 degrees C we obtained an increase of 49 +/- 9 IU. On decreasing it by 7.6 +/- 0.4 degrees C we obtained a decrease of 46 +/- 9 IU. We conclude that temperature significantly influences the delivery of the meibomian gland secretion. Our results are in agreement with the 10-blink recovery value of 191 +/- 9.3 IU previously reported. They also agree with the reported benefit of warm compresses to improve delivery from dysfunctional glands. The most likely explanation for our findings is a change in the viscosity of the meibomian oil.

A novel in vivo model in guinea pigs for dry skin syndrome.

BACKGROUND/AIMS: The lack of a suitable, validated animal model for the comparison of the pharmacological effectiveness of known and potential moisturizers in the treatment of "dry skin syndrome" led us to develop such an in vivo model. METHODS: "Dry skin syndrome" was induced in guinea pigs by daily application of 2% sodium lauryl sulphate (SLS) in deionized water on one of the two shaved flanks for three consecutive days. After ascertaining skin dryness, that side was treated with an agent for 6 days. The in vivo humectant effect was measured by a Corneometer CM 825(R), erythema was measured by a Mexameter MX 16(R). In some cases histological studies were carried out. RESULTS: The treatment with the 2% SLS led to a consistent "dry skin syndrome" for 2 weeks. Glycerol, Vaseline, urea and ammonium lactate treatments validated the model, since the Corneometer CM 825(R) readings of the treated dry side was equal to that of the control untreated side after 1 week of treatment. Mexameter MX 16(R) measurements showed abolishment of the erythema by glycerol only. Histological study showed that SLS treatment creates acanthosis that is partially reversed by Vaseline and fully reversed by glycerol treatment. CONCLUSION: The guinea pig dry skin model is a relevant model of the human "dry skin syndrome". The instrumental results combined with the histological findings indicate that erythema measurements are relevant for the determination of curative effect.