Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders.

BACKGROUND: A large number of skin diseases, including atopic dermatitis and psoriasis, appear to be precipitated or exacerbated by psychological stress. Nevertheless, the specific pathogenic role of psychological stress remains unknown. In 3 different murine models of psychological stress, it was recently shown that psychological stress negatively impacts cutaneous permeability barrier function and that coadministration of tranquilizers blocks this stress-induced deterioration in barrier function. OBJECTIVES AND METHODS: The relationship between psychological stress and epidermal permeability barrier function was investigated in 27 medical, dental, and pharmacy students without coexistent skin disease. Their psychological state was assessed with 2 well-validated measures: the Perceived Stress Scale and the Profile of Mood States. Barrier function was assessed simultaneously with the stress measures at periods of presumed higher stress (during final examinations) and at 2 assumed, lower stress occasions (after return from winter vacation [approximately 4 weeks before final examinations] and during spring vacation [approximately 4 weeks after final examinations]). RESULTS: The subjects as a group demonstrated a decline in permeability barrier recovery kinetics after barrier disruption by cellophane tape stripping, in parallel with an increase in perceived psychological stress during the higher vs the initial lower stress occasions. During the follow-up, presumed lower stress period, the subjects again displayed lower perceived psychological stress scores and improved permeability barrier recovery kinetics, comparable to those during the initial lower stress period. Moreover, the greatest deterioration in barrier function occurred in those subjects who demonstrated the largest increases in perceived psychological stress. CONCLUSION: These studies provide the first link between psychological status and cutaneous function in humans and suggest a new pathophysiological paradigm, ie, stress-induced derangements in epidermal function as precipitators of inflammatory dermatoses.

Factors defining sensitive skin and its treatment.

BACKGROUND: Users of cosmetics and skin care products often report adverse reactions ranging from itching and dryness to intense inflammatory responses such as erythema or wheal and rash. Self-assessment is not always an accurate parameter for categorizing skin as sensitive or nonsensitive, although it can be valuable. For this reason, it is important to define sensitive skin by more objective factors. OBJECTIVE: Studies were undertaken to determine if objective biophysical measurements could detect differences in barrier function between those individuals who identified themselves as having sensitive skin and those self-identified as having normal skin. In addition, the effects of treatment on barrier functions of individuals with sensitive skin were determined. METHODS: Three main factors that contribute to cutaneous reactivities were observed for the estimation of skin sensitivity: barrier functions, reactivity to irritants, and neuronal responses manifested as sensory reactions. Barrier functions of the skin was tested by gentle removal of the stratum corneum with simple cellophane tape stripping followed by measurement of transepidermal water loss (TEWL) as a marker of barrier loss. The onset and intensity of skin reaction against an irritant, balsam of Peru, was tested on the same individuals to observe the reactivity of their skin. Using the lactic acid sting test, additional information regarding skin sensitivities was obtained. RESULTS: Sensitive skin individuals exhibiting easy barrier damage possess delicate skin that is also highly reactive to irritants. When these individuals used a regimen of products that contained minimal preservatives and no surfactants for 8 weeks, the skin barrier and reactivity changed such that it was similar to nonsensitive skin. CONCLUSIONS: Skin sensitivity is observed because of a combination of factors, including a disrupted barrier and a tendency to hyperreact to topical agents. Treatment with special topical skin care formulations can reduce overall skin sensitivity.

Effect of topical application of antioxidants and free radical scavengers on protection of hairless mouse skin exposed to chronic doses of ultraviolet B.

BACKGROUND/AIMS: Within the past three decades, there has emerged a greater awareness of the molecular effects of solar rays especially ultraviolet radiation (UV-R), to the extent that the harmful effects of solar radiation are recognized not only by molecular biologists and physicians, but also by the general public (1). Various sunscreen molecules that effectively block the UVB component of the sun are available; however, a large part of Western populations elicits adverse reactions against chemical sunscreens (2). This study was designed to observe the protective effect of antioxidants against the damaging effects of chronic UVB exposure of skin in an attempt to introduce antioxidants and free radical scavengers as topical sun protective agents. METHODS: Jackson hairless mice were exposed to suberythemal doses of UVB, three times a week, and topically treated with a cream containing the anti-oxidants vitamin E, butylated hydroxy-toluene, nordihydroguaradinic acid and vitamin C. RESULTS: Treatment with vehicle alone along with UVB exposure resulted in an increase in epidermal thickness showing a 38%, 77% and 112% increase after 4 weeks, 8 weeks and 12 weeks, respectively. Chronic UVB exposed skin treated with the material containing free radical scavengers and antioxidants mix (AO mix) exhibited 39%, 73% and 124% thicker epidermis than the un-treated control after, respectively, 4 weeks, 8 weeks and 12 weeks of treatment. The vehicle did not appear to protect skin against UV irradiation, since there appeared to be more (16%) sunburn cells in vehicle treated skin than the untreated, UV exposed skin after 4 weeks of treatment. After 8 weeks and 12 weeks, there were 33% and 36% less sunburn cells in the vehicle treated skin than the untreated, UV exposed skin. The antioxidant mix was significantly effective (P=<0.001) in protecting against UVB irradiation, having 63%, 71 % and 79% fewer sunburn cells than the untreated, UV exposed skin after 4 weeks, 8 weeks and 12 weeks of treatment, respectively. CONCLUSION: Data from these studies suggest that low level chronic exposures to UV can lead to alteration of the skin, like epidermal thickening and appearance of sunburn cells. The data also indicates that a mix of common antioxidants and free radical scavengers are photoprotective against chronic skin damage in the hairless mouse skin model.

Cellulite. Etiology and purported treatment.

Much research must be undertaken before any of the treatments discussed can be validated as clinically effective. At present, it can be safely stated that there is no topical medication or manipulative process to which advanced cellulite visibly responds in a treatment period of less than 2 months.

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations.

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.

Antikeratin antibody staining on ultrathin sections of epidermal cells prepared by low-denaturation embedding.

Direct immunological identification of cellular components has not been possible in tissues prepared for electron microscopy by conventional methods. This may be attributed, in part, to the relatively harsh reagents employed. Using an approach to preparation of biological specimens for transmission electron microscopy that aims for minimal perturbation of native protein conformation, we have obtained specimens that may be stained with antibodies. Recent investigations using these methods have revealed new information regarding the organization of epidermal cells.

Discrimination of collagen types by methionine-specific stain.

Chloroglycyl-L-methioninatoplatinum (II) (Pt-GLM) specifically labels methionine residues in collagen. Rat Type I and calf Type III collagen segment long spacing aggregates show differences in Pt-GLM bands, in agreement with known methionine positions. Reconstituted fibers formed from the same two collagens again demonstrate some differences in band pattern, which can be understood in terms of the amino acid sequences and the known packing of molecules in the fiber. Native collagen fibers have been extracted from rat and chick tendon (predominantly Type I collagen). These have been stained with Pt-GLM and studied in the Johns Hopkins STEM and a CTEM. Density profiles along the collagen fibers have been obtained, and those for successive 670-A repeats averaged, by computer programs. The position of peaks in the average density profiles for these various fibers show very good correlation with the known locations of Met residues. The band patterns and density profiles for native and reconstituted Type I fibers are very similar and differ from those of reconstituted Type III fibers.