Ozonized glycerin (OG)-based cosmetic products lighten age spots on human facial skin.

BACKGROUND: Few cosmetic ingredients are shown to be able to safely remove or lighten facial dark spots once they have formed. OG has been reported to possess oxidation power and exhibit various biological activities such as antibacterial, antiviral, and wound healing promotion. AIMS: This study aimed to clarify the effects of OG on human skin, especially on age spots on the face. METHODS: OG formulations (80 and 800 ppm) were mixed with synthetic melanin in vitro for 4 weeks and then assessed for its ability to degrade the melanin. OG also investigated its effect on gene expression of keratinocyte differentiation markers in vitro to explore the cell maturation. In clinical study for the evaluation of effects of OG formulations on age spots on facial skin, 48 women were measured for the melanin content of them by a Mexameter at 4 and 8 weeks after daily twice application of OG formulations. Adverse events were monitored during the study. RESULTS: Both OG formulations showed direct melanin degradation in a time-dependent manner, with significant effects observed as early as 6 h. OG formulation at 800 ppm showed higher activity than OG formulation at 80 ppm, and the amount of melanin was decreased by about 40% on Day 14 of the mixing reaction. Differentiation marker studies using human keratinocytes showed that the gene expression of involucrin and serine palmitoyltransferase was upregulated by OG, which was almost equivalent concentration to OG formulation 80 ppm, suggesting that OGs can enhance turnover of the skin epidermis. In clinical study, OG formulations 80 and 800 ppm showed larger decreases in melanin contents at 8 weeks compared with those at 4 weeks and their mean values of △melanin index were -16.7 and -15.2, respectively. Statistically significant differences were detected against respective controls. Number of subjects with a decrease in melanin index from baseline to 4 or 8 weeks increased in both OG formulations 80 and 800 ppm, especially prominent at 8 weeks. There were no adverse events related to treatments of OG 80 and 800 ppm during the study. CONCLUSION: The result indicated that applications of OG formulations are safe and effective in lightening age spots on the facial skin.

Roles of GP33, a guinea pig cytomegalovirus-encoded G protein-coupled receptor homolog, in cellular signaling, viral growth and inflammation in vitro and in vivo.

Cytomegaloviruses (CMVs) encode cellular homologs to evade host immune functions. In this study, we analyzed the roles of GP33, a guinea pig CMV (GPCMV)-encoded G protein-coupled receptor (GPCR) homolog, in cellular signaling, viral growth and pathogenesis. The cDNA structure of GP33 was determined by RACE. The effects of GP33 on some signaling pathways were analyzed in transient transfection assays. The redET two-step recombination system for a BAC containing the GPCMV genome was used to construct a mutant GPCMV containing an early stop codon in the GP33 gene (Δ33) and a rescued GPCMV (r33). We found the following: 1) GP33 activated the CRE- and NFAT-, but not the NFκB-mediated signaling pathway. 2) GP33 was dispensable for infection in tissue cultures and in normal animals. 3) In pregnant animals, viral loads of r33 in the livers, lungs, spleens, and placentas at 6 days post-infection were higher than those of Δ33, although the viruses were cleared by 3 weeks post-infection. 4) The presence of GP33 was associated with frequent lesions, including alveolar hemorrhage in the lungs, and inflammation in the lungs, livers, and spleens of the dams. Our findings suggest that GP33 has critical roles in the pathogenesis of GPCMV during pregnancy. We hypothesize that GP33-mediated signaling activates cytokine secretion from the infected cells, which results in inflammation in some of the maternal organs and the placentas. Alternatively, GP33 may facilitate transient inflammation that is induced by the chemokine network specific to the pregnancy.

Development and evaluation of a novel dry-coated tablet technology for pellets as a substitute for the conventional encapsulation technology.

Pellet formulations as represented by multiparticulate systems are often contained in hard capsules. We examined the use of a different approach to the making of compressed tablets containing pellets, OSDRC-technology. OSDRC-technology employs a double-structure punch (center punch and outer punch) allowing for dry-coated tablets to be assembled in a single run. We examined the effects of the thickness of the outer punch, formability of pellets, and diameter of tablets on pellet filling. The results revealed that thinner outer punches are not always better for filling small tablets with large amounts of pellets. We considered that this was because the core pellets spread in a cone shape within the formulating tablets at filling, requiring a thickness of the outer punch and a particle density of the diluents at which pellets would not exude from the formulating tablets. It was suggested that the formability of core pellets affects the maximum number of layers of pellets, and higher formability would yield better results. However, we found that pellets with poor formability (tensile strength of < or =2 kPa) could be used in tablets. For the tablets, the larger the diameter, the greater the maximum number of layers. We considered this to be due to the friction between the pellets and punch wall. We concluded that OSDRC-technology could be applied to capsule-like forms containing pellets > or =50 wt% through an unconventional approach.

Effects of pulmonary surfactant system on rifampicin release from rifampicin-loaded PLGA microspheres.

Pulmonary surfactants little affected the release ratio of rifampicin from rifampicin-loaded poly(lactide-co-glycolide) PLGA microspheres. The release ratio of rifampicin was depending on pH of pulmonary surfactant solution, showing that rifampicin-loaded PLGA microspheres have an ideal property to deliver rifampicin into alveolar macrophages inside of which Mycobacterium tuberculosis bacilli reside and to kill them. That is, little amount of rifampicin is released in alveolar lining liquid before the microspheres are phagocytosed by alveolar macrophages, then rifampicin is released in phagosome or cytoplasm, but little amount of rifampicin is released in lysosome of alveolar macrophages after the microspheres are internalized. Pulmonary surfactants also little affected the changes in molecular weight of residual PLGA during its hydrolytic degradation process. From the electrophoretic mobility measurements of PLGA microspheres, it was shown that pulmonary surfactants changed the surface charge density of PLGA microspheres by adsorbing on their surfaces.