The investigation of the skin characteristics of males focusing on gender differences, skin perception, and skin care habits.

BACKGROUND/PURPOSE: Various studies have examined the properties of male skin. However, because these studies mostly involved simple measurement with non-invasive devices, a lack of understanding of the properties of male skin remains. METHODS: In this study, we focused and investigated not only on simple instrumental measurements but also on gender differences and men's subjective perceptions of skin and daily skin care habits. RESULTS: Barrier function depends on corneocyte maturation level as well as sebum amount. Irrespective of the skin type, a high percentage of male subjects perceived a 'tacky feeling'. However, the percentage of men perceiving a 'shiny feeling' differed by skin type. Furthermore, there was a relationship between skin care habits and skin function. Men who did not perform a daily skincare regimen demonstrated a significantly higher sebum amount and transepidermal water loss value than those who did perform a daily skincare regimen. CONCLUSION: The results of this study indicate that male skin has two specific characteristics: impaired barrier function because of the excess amount of sebum and a lack of an appropriate skin care regimen because of the 'tacky feeling' caused by excess sebum.

Orally available pyridinylpyrimidine derivatives as novel RANKL-induced osteoclastogenesis inhibitors.

An HTS campaign led to the identification of 4-pyrroldino-2-(pyridin-2-yl)pyrimidine compound 1 as an RANKL-induced osteoclastogenesis inhibitor. The compound 1 showed high clearance values in microsomes, however. Modification of the pyrrolidino group to a benzylamino group improved human microsomal stability with a slight loss of in vitro activity. Substitution at the ortho position of the benzyl group ameliorated in vitro activity, and further fluorination of the benzyl group improved microsomal stability in rodents. Representative members of this series, compounds 20 and 23, exhibited efficacy in RANKL-induced osteopenic mice when administered orally at 0.3 mg/kg.

Relevance of the directionality of skin elasticity to aging and sagging of the face.

BACKGROUND: Forces acting in facial skin have been suggested to show directionality. Non-invasive methods of measuring this directionality may thus provide information related to aging processes. The Reviscometer(®) RVM600 device is capable of measuring directionality of forces on the skin. This device has not been used previously in a published study to evaluate changes in directionality of forces on facial skin with aging. AIM: The first objective of this pilot study was to investigate relationships between mechanical directionality using the Reviscometer(®) RVM600, the Cutometer(®) MPA580, and aging of the facial skin in a supine position. In addition, the study investigated relationships between mechanical directionality and 'skin sagging,' which may be caused by gravity. To validate this as a new measurement of mechanical directionality, we also performed double-blinded trials on two groups of subjects, with one group using a product containing an anti-aging substance and the other group using a placebo product without an anti-aging substance. METHODS: We examined 91 healthy Japanese women with a mean age of 48.5 years (range, 20-79 years) at the three sites on the face using the Reviscometer(®) RVM600 and the Cutometer(®) MPA580, and evaluation was performed for skin sagging in September and November 2008, and January 2009. The Reviscometer(®) RVM600 was used to measure resonance-running time (RRT) every 10° from 0° to 350°. Evaluation of skin sagging was undertaken by making marks on the face and using face photographs taken in both sitting and supine positions to calculate the sagging index. Usage testing was conducted on 38 healthy Japanese women in a double-blinded study with one group, using a preparation containing Yomogi AGEs Clearing (YAC) extract and another group using the same preparation without the YAC extract from October 2008 to April 2009. Mean age of these subjects was 44.0 years (range, 30-60 years). Measurements were taken at the three sites on the face using the Reviscometer(®) RVM600 and the Cutometer(®) MPA580 and sagging index. RESULTS: A significant correlation was identified between RRT parameters and subject age at all three measurement sites. Significant correlations between sagging index and RRT values were found for 110-170° and 290-350° only at the center of the cheek. Significant differences in RRT values were noted for 110-150° and 300-350° at this site between subjects with and without the use of YAC extract. A similar trend was found in sagging index for this site alone between subjects with and without YAC extract. CONCLUSION: The use of non-invasive procedures to measure skin mechanical parameters on the face in all directions may evaluate aging and effective preventive and restorative support.

Structural requirements for the stability of novel cephalosporins to AmpC beta-lactamase based on 3D-structure.

AmpC beta-lactamase is one of the leading causes of Pseudomonas aeruginosa (P. aeruginosa) resistance to cephalosporins. FR259647 is a cephalosporin having a novel pyrazolium substituent at the 3-position and exhibits excellent activity (MIC=1 microg/mL) against the AmpC beta-lactamase overproducing P. aeruginosa FP1380 strain in comparison with the third-generation cephalosporins FK518 [Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 454; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 455; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 456; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 457] (MIC=16 microg/mL) and ceftazidime (CAZ) (MIC=128 microg/mL). The stability of FR259647 and FK518 to AmpC beta-lactamase was evaluated using MIC assays against both the P. aeruginosa PAO1 strain and a PAO1 mutant strain overproducing AmpC beta-lactamase as a differential assay, which indicates that the main difference derives from their stability to AmpC beta-lactamase. A structural analysis using computer simulations indicated that the difference in stability may be due to steric hindrance of the 3-position substituents causing differential affinity. This steric hindrance may disturb entry of the cephalosporins into the binding pocket. We predicted the possibility of inhibition of entry as a potential means of enhancing stability by conformational analysis. In order to validate this speculation, novel FR259647 derivatives 4-9 were designed, calculated, synthesized, and evaluated. As a result, we demonstrated that their probability of entry correlated with the MIC ratio of the mutant strain to the parent strain and supports the validity of our model.

New efficient route for solid-phase synthesis of benzimidazole derivatives.

A simple and efficient method for the solid-phase synthesis of benzimidazole libraries is described. Monoalkylation of various o-phenylenediamines on resin-bound bromoacetamide proceeded smoothly to give the monoalkyl resin-bound o-phenylenediamines in high yields. Subsequent cyclization of the diamines with various aldehydes afforded solid-supported benzimidazoles. Cleavage from the resin gave benzimidazoles in good yields. The present method enabled the introduction of the diversity on the benzene ring of imidazoles. Azabenzimidazoles, such as 4-azabenzimidazoles, 5-azabenzimidazoles, and purines, were also synthesized in good yields with high purities by the same procedure.