The repetitive exposure of skin to ultraviolet B (UVB) preferentially elicits wrinkling while ultraviolet A (UVA) predominantly elicits sagging. In chronically UVB or UVA-exposed rat skin there is a similar tortuous deformation of elastic fibers together with decreased skin elasticity, whose magnitudes are greater in UVB-exposed skin than in UVA-exposed skin. Comparison of skin elasticity with the activity of matrix metalloproteinases (MMPs) in the dermis of ovariectomized rats after UVB or UVA irradiation demonstrates that skin elasticity is more significantly decreased in ovariectomized rats than in sham-operated rats, which is accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV. Clinical studies using animal skin and human facial skin demonstrated that topical treatment with a specific inhibitor or an inhibitory extract of skin fibroblast-derived elastase distinctly attenuates UVB and sunlight-induced formation of wrinkling. Our results strongly indicated that the upregulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity.

Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

Clinical Characteristics as a Recurrent Dermatits The skin of patients with atopic dermatitis (AD) is mainly characterized by a clinically normal appearance but which exhibits a high susceptibility to irritants and allergens, dry skin and deficient innate immunity. Thus, as shown in Figure 1, an increased transepidermal water loss (TEWL) and decreased water content, even in the clinically normal skin of patients with AD suggest a marked down-regulation of both the barrier and the water holding functions. AD skin also shows a high frequency of S. aureus colonization even in the nonlesional skin, compared with no colonization in healthy control (HC) skin [1-4]. Abnormality in Cutaneous Permeability Barrier Function There is a general consensus that disruption of the barrier function of the stratum corneum (SC) is an essential etiologic factor for skin inflammation in patients with AD. Thus, AD could be considered as a barrier disease in which antigens and irritants that permeate the skin trigger and worsen the dermatitis. Since TEWL, which is frequently evaluated as an indication of barrier function, is not necessarily a precise reflection of cutaneous permeability, we determined whether chemical penetration is really enhanced or not in the nonlesional skin of AD patients compared with HC skin [5]. To evaluate in vivo cutaneous permeability, we used photoacoustic spectrometry by which chemical concentrations present through the layers of the SC can be measured using the intensity of photoacoustic signals derived from the chopped expansion of air due to chemical heat released from chemical molecules

Our previous studies strongly indicated that the up-regulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. Fortunately, we succeeded in identifying human skin fibroblast-derived elastase as a previously known enzyme, neprilysin or neutral endopeptidase (NEP). We have also characterized epithelial-mesenchymal paracrine cytokine interactions between UVB-exposed-keratinocytes and dermal fibroblasts and found that interleukin-1α and granulocyte macrophage colony stimulatory factor (GM-CSF) are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate the expression of neprilysin by fibroblasts. On the other hand, direct UVA exposure of human fibroblasts significantly stimulates the secretion of IL-6 and also elicits a significant increase in the gene expression of matrix metallo-protease(MMP)-1 as well as neprilysin (to a lesser extent), which is followed by distinct increases in their protein and enzymatic activity levels. Direct UVA exposure of human keratinocytes also stimulates the secretion of IL-6, IL-8 and GM-CSF but not of IL-1 and endothelin-1. These findings suggest that GM-CSF secreted by UVA-exposed keratinocytes as well as IL-6 secreted by UVA-exposed dermal fibroblasts play important and additional roles in UVA-induced sagging and wrinkling by up-regulation of neprilysin and MMP-1, respectively, in dermal fibroblasts.

Acne is a common skin disease that involves the seborrheic area of the face and results from the obstruction of hair follicles followed by inflammation. Careful face washing helps to improve and prevent acne; however, intensive washing has a risk of inducing skin barrier impairment and dry skin, especially in sensitive skin. We hypothesized that skin care combining mild skin cleansing and intensive moisturizing ("combination skin care") may be effective in the care of acne in subjects with dry skin and/or sensitive skin. We developed a combination skin care with a weakly acidic foaming facial skin cleanser based on a mild detergent, an aqueous lotion with eucalyptus extract and a moisturizing gel containing pseudo-ceramide and eucalyptus extract. To optimize an ideal facial skin care system for mild acne on sensitive skin, we performed a 4-week clinical trial with 29 post-adolescent Japanese women with mild acne with dry and sensitive skin. The acne significantly decreased after this trial accompanied by the improvement of dry skin, a significantly increased endogenous ceramide level in the stratum corneum and an elongated alkyl chain length of the non-hydroxy acyl sphingosine type ceramide. No adverse events due to the test samples were observed. Based on diagnosis by a dermatologist, 97% of the subjects found the combination skin care to be "useful" or "slightly useful". Based on these findings, the combined use of a facial skin cleanser and moisturizers is safe and effective for the care of acne in post-adolescent Japanese women with sensitive skin.

Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis and their impaired skin barrier and water-holding functions. We studied those characteristics following topical treatment with a designed synthetic pseudoceramide (pCer) and analyzed that pathophysiological linkage by microanalyzing ceramides using normal phase liquid chromatographyeelectrospray ionization mass spectrometry. Four weeks of treatment with pCer significantly reduced skin symptoms, accompanied by significant decreases in transepidermal water loss and increases in water content. In the SC ceramide profiles, ceramides containing nonhydroxy fatty acids and 6hydroxysphingosines (Cer[NH]) and ceramides containing nonhydroxy fatty acids and phytosphingosines (Cer[NP]) increased, whereas ceramides containing nonhydroxy fatty acids and sphingosines (Cer[NS]) and ceramides containing a-hydroxy fatty acids and sphingosines (Cer[AS]) decreased, with larger alkyl chain lengths in Cer[NS], distinctly representing a switch from an atopic dermatitis to a healthy skin phenotype. The level of pCer that penetrated into the SC was significantly correlated with the SC water content but not with transepidermal water loss. The level and the average carbon chain length of Cer[NS] were closely correlated with the pCer level in the SC. These findings indicate that the penetrated pCer contributes to shift the ceramide profile from an atopic dermatitis to a healthy skin phenotype. Taken together, the observed clinical efficacy of treatment with pCer provides a deep insight into the pathogenesis of atopic dermatitis as a ceramide-deficient disease.

We determined whether compensating ceramides in the stratum corneum (SC) may ameliorate the impaired barrier function and subsequently attenuate the enhanced skin sensitivity. Treatment for 4 weeks with the ceramide complex cream or the placebo cream significantly ameliorated the intensity of lactic acid sensations in 39 female subjects with sensitive skin, the degree of which was attenuated to a greater extent at 1 week by the ceramide complex cream compared with the placebo cream. The amelioration of skin sensations was accompanied by a significant increase in total ceramide content in the SC elicited by the ceramide complex cream that was significantly more effective than the placebo cream at 4 weeks. Consistently, TEWL and conductance values were significantly decreased or increased at 1 and 4 weeks, respectively, to a greater extent by the ceramide complex cream than by the placebo cream. TEWL levels were significantly correlated with the increased levels of SC total ceramide in the ceramide complex cream-treated skin but not in the placebo cream-treated skin. Thus, the amelioration of lactic acid sensations by topical application of a ceramide complex cream, provides a deep insight into the pathophysiology of sensitive skin as a reduced barrier function-dependent sub-clinical sensory response.

Background Diaper rash, also known as diaper dermatitis (DD), is a very common skin condition in infants, and use of disposable diapers with breathable materials is an effective approach for the management of diaper rash. In China, new material diapers and standard diapers are currently the two most commonly used disposable diapers. This study aimed to compare the effectiveness of new material diapers versus standard diaper for the prevention of diaper rash in Chinese babies. Methods A total of 80 eligible babies admitted to Shanghai Skin Diseases Hospital during the period from June through July, 2016, were enrolled and randomized into two groups. Babies in Group A (n = 41) used the new material diapers, and babies in Group B (n = 39) used standard diapers. Two weeks after the use of the diaper, the babies used the alternate product for the next 2 weeks. Skin conditions were assessed on the front and back waist, right and left buttock, pubic region, anal region, and right and left groin using a 6-point scoring system based on four parameters in 0, 2, and 4 weeks after use of the diapers. Results There were changes of the mean skin assessment score in each of the six regions after the use of the diapers. There were significant differences, in the mean skin assessment score of the front waist in Group A between weeks 2 and 4 (P = 0.006) and in Group B between weeks 0 and 2 (P = 0.004), and no significant differences were detected in the mean skin assessment score of the back waist and buttock in both Group A and Group B on weeks 0, 2, and 4. A higher mean skin assessment score of the pubic region was assessed in Group A on week 4 than on week 2 (P = 0.036), with a higher score seen on week 2 than on week 0 (P = 0.048), while no significant differences were found in Group B among weeks 0, 2, or 4. There was a higher mean score of the anal region assessed in Group A on week 2 than on week 0 (P = 0.01), while a higher mean score was found in Group B on week 2 than on weeks 0 (P = 0.036) and 4 (P = 0.01). In addition, a higher mean skin assessment score of the groin was detected on week 2 than on week 0 in both Group A (P = 0.00001) and Group B (P = 0.0001). Conclusion The new material diaper is superior to the standard diaper for the prevention of diaper rash in Chinese babies.