These new results as well as our earlier results with diabetic mice suggest that patients with diabetes mellitus tend to show a reduced hydration state of the SC together with decreased sebaceous gland activity, without any impairment of the SC barrier function.

We investigated the role of stratum corneum (SC) trypsin-like and chymotrypsin-like serine proteases in the degradation of desmoglein-1 (DSG-1) in the SC sheet. DSG-1, whose presence in the SC sheet was confirmed by Western blot analysis, was degraded completely during incubation of the SC sheet in Tris buffer. The degradation of DSG-1 was inhibited by the addition of protease inhibitors, such as aprotinin or a mixture of leupeptin and chymostatin. Either leupeptin or chymostatin alone did not inhibit its degradation. These results indicated that both trypsin-like and chymotrypsin-like serine proteases are involved in the degradation of DSG-1. We further examined the activities of the two proteases in the SC obtained from patients with ichthyosis vulgaris, in whom SC desquamation is abnormal. The enzymatic activities measured using synthetic substrates were significantly decreased in these ichthyotic SC samples. This result supports the idea that these proteases play an important role in normal SC desquamation.

Skin disorders such as atopic dermatitis, psoriasis and senile xerosis show a tendency to exacerbate in winter. We investigated the seasonal influence on the functional parameters of the skin in healthy female volunteers of different age groups. Biophysical noninvasive measurements, including transepidermal water loss (TEWL) as a parameter for the barrier function of the stratum corneum (SC), high-frequency conductance as a parameter for the hydration state of the SC, temperature, color and casual surface lipid levels, were conducted during the later summer and winter months in 39 healthy adult Japanese females ranging in age from 24 to 78 years. The measurements were made on the cheek, the exposed area, and flexor forearm, the semicovered area, in the same climate-controlled chamber. The barrier function of the SC was found to be significantly impaired in winter both on the cheek and flexor forearm. This difference between summer and winter was much larger on the cheek than on the forearm. The hydration state of the SC was significantly lower in winter on the flexor forearm, whereas no such seasonal change was apparent on the cheek where sebum levels did not show any seasonal change. We measured the corneocyte size in 24 out of the 39 subjects to estimate a seasonal change of the turnover rate of the SC. It tended to be smaller only on the exposed cheek skin, suggesting an enhanced turnover of the SC in winter, whereas it was somewhat larger on the semicovered flexor forearm. The skin surface temperature and redness were also significantly higher on the cheek in winter. We think that subclinical inflammation resulted in the enhanced turnover rate of the SC associated with elevated TEWL levels observed on the face in winter. In conclusion, the obtained data suggest that the exposed facial skin becomes more irritable under the influence of the dry and cold environment of winter even in healthy individuals where the barrier function of the SC is relatively poor as compared to the skin of other areas.

The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring.

No abstract