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

Background: Patients with atopic dermatitis (AD) are well known to be sensitive to irritation from the environment due to the impaired function of the stratum corneum (SC). Electrical current perception threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of the sensory nerves. Objective: To study the CPT in a noninvasive fashion using Neurometer^® CPT/C, together with measurements of various functions of the SC. Methods: We measured the CPT on the flexor forearm and cheek of AD patients and normal individuals. Subsequently, we evaluated the CPT and skin sensitivity to a 30% aqueous solution of lactic acid after the infliction of various mildly disruptive measures on the SC on the flexor forearm of healthy individuals by the following three methods: (1) removal of the superficial sebum with acetone/ether, (2) scarification with a needle and (3) tape stripping of the SC. Finally, we examined the effect of topical applications of emollients such as petrolatum or a moisturizing cream to the scratched skin. Results: AD patients showed a lower barrier function and lower CPT than normal individuals. In subsequent studies conducted in normal individuals, the CPT was found to be inversely correlated with transepidermal water loss (TEWL) levels after tape stripping. However, most of all, the partial superficial scarification with a needle decreased the CPT and increased the lactic acid stinging response. Prolonged removal of lipids from the SC with acetone/ether for 30 min that increased the TEWL levels for only 1 day decreased the high-frequency conductance value for 2 days and the CPT only on the 2nd day after treatment. Topical applications of emollients were effective to prevent the increased sensitivity caused by scratching. Conclusions: AD patients showed functional abnormalities of the SC and tended to have more sensitive skin on the cheek and flexor forearm than healthy controls. Even focal SC damage caused by superficial cracking may lead to further disruption of the already damaged SC in AD patients, by eliciting scratching and facilitating the permeation of various environmental allergens and also the induction of hypersensitive skin.

We conducted a cohort study to determine whether the barrier dysfunction of the stratum corneum that facilitates the penetration of various exacerbating agents from the environment is inherent in atopic dermatitis patients as suggested by some dermatologists. Clinical observation and biophysical measurements of the skin were performed on the cheek and on the flexor forearm of 24 newborn infants once between 2 and 14 days postnatally and 1, 3, and 6 months later. Nineteen had atopic family histories. Most of the infants had physiologic neonatal xerosis that was observed as a reduced high-frequency conductance without any impairment in the stratum corneum barrier function assessed by transepidermal water loss. Four of the 24 neonates developed atopic dermatitis around 2 to 3 months after birth. In all of them, barrier impairment noted as increased transepidermal water loss was observed only after the development of skin lesions. During their neonatal period, their transepidermal water loss and skin surface hydration state were indistinguishable from those of the neonates whose skin remained lesion-free during the observation period. Therefore, we concluded that the barrier impairment found in atopic dermatitis is not inherent but represents a phenomenon secondary to dermatitic skin changes.

Objective: Based on our previous findings that, reflecting mild inflammation, the exposed facial skin shows much poorer functional properties of the stratum corneum (SC) in the dry and cold winter than those evaluated in the same individuals in the warm and humid summer time, we conducted a half-side test on the face to determine how the facial skin changes induced by a winter environment are improved by daily applications of a moisturizing cream as assessed by non-invasive biophysical and cytological methods. Methods: One side of the face of 16 young females was treated with a moisturizing cream twice daily for 6 weeks, with the other side serving as the non-treated control. Before treatment, 3 and 6 weeks after the start of the treatment, high-frequency conductance as a parameter of the skin surface hydration, transepidermal water loss (TEWL), a parameter of the water barrier function of the skin, and the skin surface lipid level were measured on the cheeks. Obtaining the SC from the skin surface by adhesive tape, interleukin (IL) 1α and IL-1 receptor antagonist (IL-1ra) in the SC and cornified envelope (CE) maturation were determined. Results: At first, baseline measurements conducted before treatment showed rather high TEWL values suggestive of an impaired skin barrier. During the treatment with the moisturizing cream, significantly higher conductance values and lower TEWL values were found on the moisturizer-treated side, accompanied by a decreasing IL-1ra/IL-1α ratio and immature CEs. Conclusion: These results suggested that the daily application of a moisturizing cream is effective in improving mild subclinical inflammation that is induced on the facial skin by the winter environment.