Plasticizer-gelatin mixed solutions as skin protection materials with flexible-film-forming capability.

To demonstrate the feasibility of plasticizer-gelatin solutions as novel skin protection materials from a physical aspect, we evaluated the rheological properties of the solutions and the mechanical properties and textures of their dried sheets and films. Three types of sugars and polyols were employed as organic plasticizers and mixed with gelatin in solutions at plasticizer/gelatin weight ratios of 0.13-1.67. The plasticizers minimally affected the viscosities and gelation temperatures of the gelatin solutions, but they remarkably softened dried gelatin sheets, except for propylene glycol. Glycerol exhibited the best plasticizing effects, but the sheets obtained using glycerol showed tacky textures. Preliminary investigations on the film-forming properties of the solutions on the human skin showed that the fructose-gelatin solution at a weight ratio of 1.0 formed a flexible thin film with a texture and mechanical properties similar to those of a commercially available polyurethane-based flexible film dressing. In terms of physical properties, we conclude that the fructose-gelatin solution has potential as a skin protection material that transforms from a solution to a film on the skin.

A novel administration route of edaravone--II: mucosal absorption of edaravone from edaravone/hydroxypropyl-beta-cyclodextrin complex solution including L-cysteine and sodium hydrogen sulfite.

We examined the pharmacokinetics of edaravone when edaravone/hydroxypropyl-beta-cyclodextrin (HPbetaCD) complex solution, including L-cysteine (L-Cys) and sodium hydrogen sulfite (SHS), was administered intravenously, rectally and via the oral mucosa. In oral mucosal administration, atomized edaravone/HPbetaCD complex solution that contained L-Cys and SHS was sprayed into the mouth of Wistar rats. Oral mucosal and rectal administration of edaravone/HPbetaCD complex solution that contained L-Cys and SHS was compared with that for edaravone/HPbetaCD complex solution without L-Cys and SHS. When edaravone 0.25-1.0 mg was administered intravenously, C(0) and AUC(0-60) were linear. In oral mucosal and rectal administration, C(max) and AUC(0-60) of edaravone/HPbetaCD with L-Cys and SHS were significantly higher than those of edaravone/HPbetaCD without L-Cys and SHS. On the other hand, bioavailability of oral mucosal, rectal and oral administration was about 100, 63.5 and 26.6%, respectively. This study suggested that L-Cys and SHS were useful for the oral mucosal and rectal administration of edaravone.

A novel administration route for edaravone: I. Effects of metabolic inhibitors on skin permeability of edaravone.

We examined the effects of metabolic inhibitors on skin permeation of edaravone. SKF-525A, diclofenac sodium (DIC) and indomethacin (IND) were added to supernatant fluid (SF) of hairless rat (HR) skin homogenate. L-Cysteine (L-Cys) and benzotriazole (BTA), as pharmaceutical additives, were added to HR skin homogenate SF, and incubated at 37 degrees C for 30 min. K(m) and V(max) values were calculated. For determination of edaravone skin permeation from edaravone/hydroxypropyl-beta-cyclodextrin (HPbetaCD) complex solution, HR skin was placed in a Franz diffusion cell, and kept at 37 degrees C. Edaravone/HPbetaCD solution that contained L-Cys was put into the donor side. The relative activity in skin homogenate SF after co-treatment with IND and SKF-525A decreased to 40.8% of the control. However, DIC and IND had a weak inhibitory effect. For inhibition of edaravone metabolism, L-Cys and BTA had no effect on K(m) value, but V(max) was significantly decreased compared with controls (*P<0.05, Tukey-Kramer test). The edaravone skin permeation rate and permeability coefficient from edaravone/HPbetaCD complex solution with inhibitor were significantly increased compared with those without inhibitor. We suggest that the metabolism inhibitor was useful for the transdermal delivery of edaravone.

In vitro metabolism study of edaravone in Wistar and hairless rat skin.

We investigated the skin metabolism of edaravone as a radical scavenger in Wistar and hairless rat skin. Approximately 1 g of abdominal skin was excised from 10-week-old Wistar and hairless rats, homogenized in 10 ml saline, and centrifuged at 10000 g for 20 min. The supernatant fluid was used for the examination of edaravone metabolism in the skin, and we also used supernatant fluid that was heated at 80 degrees C. Edaravone solution (0.05 ml, 2.4 micromol/ml) was added to 0.95 ml Wistar rat and hairless rat skin homogenate supernatant fluids. In Wistar rats, the residual amount of edaravone in skin homogenate supernatant fluid at 37 degrees C after 0, 5, 10, 20 and 30 min was 61.58+/-1.65, 41.84+/-8.52, 35.54+/-8.62, 19.73+/-5.99 and 13.89+/-4.40%, respectively. In hairless rats, the residual amount of edaravone in skin homogenate supernatant fluid at 37 degrees C after 0, 5 and 10 min was 50.19+/-14.17, 6.71+/-5.82 and 0.89+/-0.80%, respectively, and edaravone was not detected after 20 min. Although it was thought that metabolic enzyme activity in skin homogenate supernatant fluid was lost following heat treatment at 80 degrees C, the residual amount of edaravone in our skin homogenate supernatant fluid decreased with time. It is suggested that edaravone metabolism in the skin is necessary for non-enzymatic reactions.

Sarcomatoid acquired cystic disease-associated renal cell carcinoma.

In this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for anti-mitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.