AimsTo determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population. MethodsThree hundred and fifty-eight healthy Korean subjects were studied. CYP2C9 alleles were detected by polymerase chain reaction-restriction fragment leng th polymorphism assays and direct sequencing assays. ResultsThe allele frequencies were 0.934 for CYP2C9 * 1 , 0.060 for CYP2C9 * 3 and 0.006 for CYP2C9 * 13 . The CYP2C9*2, * 4, * 5 and * 11 alleles were not detected. The frequencies of the CYP2C9 * 1/ * 1 , * 1/ * 3 and * 1/ * 13 genotypes were 0.869, 0.120 and 0.011, respectively. ConclusionThe frequency of the CYP2C9 * 3 allele in the Korean population studied was significantly higher than reported elsewhere, and a novel allele, CYP2C9 * 13 , was found at a frequency of 0.006 (95% confidence interval 0, 0.012). Only three genotypes of CYP2C9, CYP2C9

Background and Aims Currently there is no Food and Drug Administration–approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut‐liver axis in their pathogenesis, we investigated the therapeutic effect of a long‐acting dual agonist of glucagon‐like peptide (GLP)‐1 and GLP‐2 receptors in mice with NAFLD/NASH. Approach and Results C57BL/6J mice were fed a choline‐deficient high‐fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1‐Fc, GLP2‐Fc, or GLP1/2‐Fc fusion (GLP1/2‐Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well‐developed NASH phenotypes. GLP1/2‐Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2‐Fc were found in in vitro cell systems. GLP1/2‐Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2‐Fc–mediated protection. We confirmed that FMT exerted an additive effect on GLP1‐Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis. Conclusions A long‐acting dual agonist of GLP‐1 and GLP‐2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

Eperisone hydrochloride is widely used for the treatment of plasticity to relieve muscle stiffness and back pain. However, oral eperisone has a very low bioavailability and short muscle relaxant activity, because of the profound intestinal first-pass metabolism. To improve the efficacy and compliance of eperisone, we designed a new dosage form, a transdermal patch, and evaluated the efficacy of the eperisone patch with the muscle relaxant activity of rats. The muscle relaxant activity was assessed by the measurement of forelimb grip strength and hanging test in rats. The transdermal patch of eperisone showed significantly enhanced muscle relaxant activity at 0.5 1.5 and 3 cm²/200 g rat (1.39, 4.17 and 8.33 mg of eperisone hydrochloride/kg, respectively) in a dose-dependent manner and the effects lasted over 24 h. Even though oral eperisone hydrochloride showed significant muscle relaxant activity at 12.5, 25 and 50 mg/kg in a dose-dependent manner, the activity lasted only 1 or 2 h after administration. These results suggest that eperisone as transdermal patch form showed efficient absorption with more potent and longer-lasting muscle relaxant activity than oral solution. The transdermal patch form of eperisone will increase the efficacy and compliance in the clinical use of eperisone.

Our data suggest that ATXN8 -62 G/A polymorphism plays a role in Taiwanese PD susceptibility.

No abstract