Efficacy of Pseudo-Ceramide-Containing Steroid Lamellar Cream in Patients with Mild to Moderate Atopic Dermatitis: A Randomized, Double-Blind Study.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure. METHODS: We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms. RESULTS: The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small- and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the double-blind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p < 0.01) and significant decrease in transepidermal water loss (p < 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group. CONCLUSION: The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.

Association between Visceral Fat and Brain Structural Changes or Cognitive Function.

Visceral fat accumulation is an independent risk factor for cardiovascular disease and mortality. Visceral fat is a causal risk factor for hypertension and type 2 diabetes, which was reported as one of the risk factors for dementia. Visceral fat areas (VFA) might be clinically important to prevent dementia; however, the association between VFA and cognitive function in the elderly remains unknown. We aimed to evaluate the association between brain structural abnormalities using magnetic resonance imaging (MRI) and VFA, and the association between cognitive function and VFA, in the elderly. A total of 2364 healthy individuals were enrolled, and we excluded those diagnosed with dementia. Participants were divided into a high-VFA and a low-VFA group based on median VFA. The high-VFA group had significantly lower cognitive function than the low-VFA group (p = 0.025), after adjustment for related factors using a linear regression model. Regarding brain structure in MRI, VFA remained significantly associated with white matter lesions (odds ratio (OR), 1.90; 95% confidence interval (1.33-2.70); adjusted p < 0.001) and perivascular space (OR, 1.28; 95% confidence interval (1.02-1.61); adjusted p = 0.033). Further follow-up studies are needed, but reducing visceral fat might be important, not only to prevent cardiovascular disease but also to prevent dementia.

Improvement of crow's feet lines by topical application of 1-carbamimidoyl-L-proline (CLP).

Wrinkles, one of the characteristics of chronic sun-damaged and/or aged skin, are associated with psychological distress. Apart from the deterioration of collagen and elastic fibers in the dermis, which induces the loss of skin elasticity, it has been recently proposed that decreased flexibility or elasticity of the stratum corneum (SC) is also correlated with wrinkle formation. The elasticity of the SC has been shown to be regulated, at least in part, by the amounts and types of amino acids. To evaluate the ability of our newly developed amino acid-derivative (1-carbamimidoyl-L-proline; CLP), which recovers the elastic properties of the SC ex vivo, to improve wrinkles, a clinical test was performed with 126 Japanese female subjects aged 32-50 years who had crow's feet lines on their faces. Three eligible dermatologists evaluated the study according to authorized grades by the Japanese Cosmetic Science Society and scored the subjects who were much improved or improved as 29.7% and 57.8% of all CLP-treated subjects at 4 and 8 weeks, respectively. In contrast, only 1.5% and 8.1% of subjects improved with the placebo lotion at 4 and 8 weeks, respectively. These results suggest a significant efficacy of CLP to improve wrinkles. In parallel with the dermatologists' assessments, skin surface roughness in the CLP-treated group was significantly reduced after treatment with CLP for 4 and 8 weeks compared to the placebo-treated group. The sum of these data suggests that CLP is a promising and useful ingredient for the improvement of wrinkles through its ability to enhance the elasticity of the SC.

Gender-dependent differences in degree of facial wrinkles.

BACKGROUND/PURPOSE: This study aimed to reveal gender-dependent differences in the degree of facial wrinkles. METHODS: Subjects comprised 173 Japanese men and women, divided into four groups according to age. Photographs were taken from nine facial regions and used to classify the intensity of wrinkles into five grades. In addition, replicas were taken from five facial sites and used to measure surface roughness. Data were compared between men and women within each age group. RESULTS: In all age groups, men showed increased forehead wrinkles compared with women. In contrast, no gender-dependent differences were found in upper eyelid wrinkles. Other facial wrinkles were greater in men than in women in all except the oldest group (age, 65-75 years), in which wrinkles in women were greater than or equal to those in men. CONCLUSION: Our results showed that gender-dependent differences exist in the degree of facial wrinkles. In general, men tend to have more severe wrinkles than women. This tendency disappeared or was reversed in some regions of the face and in individuals more than 60 years old.

Structure and rheology of a self-standing nanoemulsion.

A stable nanoemulsion consisting of nanometer-sized oil droplets in water having a self-standing capability was prepared by high-pressure emulsification. The nanoemulsion does not flow and has a yield stress. This nonfluidity is ascribed to the crystal-like lattice structure of nanodroplets. The lattice structure was observed by transmission electron microscopy of a freeze-fractured surface of the specimen. Small-angle neutron scattering (SANS) revealed the presence of an ordered structure in addition to spherical domains with a radius of 17 nm. This long-range order is, in principle, due to electrostatic repulsive interaction between charged nanodroplets. Dynamic light scattering (DLS) showed two relaxation modes, one for the collective motion of the lattice and the other for the translational diffusion of the nanodroplets. Dilution of the nanoemulsion resulted in a transition from a crystal-like structure to a typical colloidal solution.

Long-term alteration in the expression of keratins 6 and 16 in the epidermis of mice after chronic UVB exposure.

The influences of chronic UVB exposure on epidermal differentiation have been poorly studied compared to dermal photo-aging although those effects are very important in terms of photo-damage to the skin. The purpose of this study was to investigate the effects of chronic UVB exposure on keratin expression in the epidermis. The effects on murine skin of chronic exposure to weak UVB (below 1 MED) was examined by immunoblotting for keratins K10, K5, K6, and K16, by immunohistochemistry using antibodies to K6, K16, and Ki67 as well as by conventional HE staining of skin sections. Alterations of keratin expression induced by the chronic UVB exposure were distinct from those elicited by a single acute UVB exposure. The expression of keratins K6 and K16 was quite long-lasting, continuing for 7 weeks after 6 weeks of chronic UVB exposure and for 6 weeks after 9 weeks of chronic UVB exposure. In contrast, K6 and K16 expression induced by a single UVB exposure at 0.5 MED or 3 MED almost ceased within 2 weeks after that exposure. Furthermore, the expression of the constructive keratins, K5 and K10, remained almost unchanged by chronic UVB exposure. Epidermal thickness was increased significantly immediately after the 9 weeks of chronic UVB exposure; however, it had returned to normal level 6 weeks later. The alterations in keratin expression accompanied the marked disruption of the ordered ultrastructure of keratin intermediate filaments, which were observed by TEM. Thus, chronic exposure to UVB has a deep impact on the biosynthetic regulation of different keratins in the epidermis, thereby interfering with the ordered ultrastructure of keratin intermediate filaments. Those events could have relevance to the mechanism of photo-damage, such as fine wrinkles observed in chronically UV-exposed skin in addition to dermal photo-aging.

In situ small-angle neutron scattering and rheological measurements of shear-induced gelation.

The microscopic structure of shear-induced gels for a mixed solution of 2-hydroxyethyl cellulose and nanometer-size spherical droplets has been investigated by in situ small-angle neutron scattering (SANS) with a Couette geometry as a function of shear rate gamma. With increasing gamma, the viscosity increased rapidly at gamma approximately 4.0 s(-1), followed by a shear thinning. After cessation of shear, the system exhibited an extraordinarily large steady viscosity. This phenomenon was observed as a shear-induced sol-gel transition. Real-time SANS measurements showed an increase in the scattering intensity exclusively at low scattering angle region. However, neither orientation of polymer chains nor droplet deformation was detected and the SANS patterns remained isotropic irrespective of gamma. It took about a few days for the gel to recover its original sol state. A possible mechanism of gelation is proposed from the viewpoint of shear-induced percolation transition.

The formation of wrinkles caused by transition of keratin intermediate filaments after repetitive UVB exposure.

It has been reported that the formation of wrinkles involves changes in the elastic properties of the dermis due to the denaturation of elastic fibers. Several studies have shown that the hydration condition of the stratum corneum is also important in wrinkle formation. It is, however, still unclear how the stratum corneum contributes to wrinkle formation. Here we investigated the relationship between the formation of wrinkles and changes in the physical properties and condition of the skin after repetitive ultraviolet B (UVB) irradiation of hairless mice (HR/ICR). Repetitive UVB irradiation caused wrinkles on the dorsal skin of the mice. The elasticity (E') of the stratum corneum of UVB-irradiated mice was significantly lower than that of age-matched control (unirradiated) mice. UVB exposure also caused a deterioration of the fibrous ultrastructure of keratin intermediate filaments (KIFs) in the skin. We conclude that the deterioration of KIFs in the stratum corneum caused by repetitive UVB irradiation decreases the elastic properties of the stratum corneum, resulting in the formation of wrinkles.