Effects of UGT1A, CYP2C9/19 and ABAT polymorphisms on plasma concentration of valproic acid in Chinese epilepsy patients.

Aim: To evaluate the association between genetic polymorphisms and plasma concentration-to-dose ratio of valproic acid (CDRV) in Chinese epileptic patients. Methods: A total of 46 epileptic patients treated with valproic acid therapy were enrolled. 18 SNPs in nine genes related to valproic acid were directly sequenced with Sanger methods. Results: Patients carrying UGT1A6 heterozygous genotypes had significantly lower CDRV than those carrying the wild-type genotypes. In contrast, patients with the homozygote genotypes of CYP2C9 and ABAT had higher CDRV than those with the wild-type genotypes and patients with the heterozygous genotypes of CYP2C19 had higher CDRV. Conclusion: Detection of genetic polymorphism in these genes might facilitate an appropriate dose of valproic acid for epileptic patients. Further studies with larger cohorts are necessary to underpin these observations.

Abnormal anthropometric measurements and growth pattern in male adolescent idiopathic scoliosis.

PURPOSE: The progression of adolescent idiopathic scoliosis is closely correlated with longitudinal growth during puberty. A decreased incidence of curve progression has been found in male patients with adolescent idiopathic scoliosis compared with female patients with the condition. This finding implies that there might be a sexual dimorphism in the pubertal growth patterns of adolescent idiopathic scoliosis patients. Abnormal pubertal growth in female adolescent idiopathic scoliosis patients has been well characterized; however, the pubertal growth patterns of male adolescent idiopathic scoliosis patients have not been reported. We conducted a cross-sectional study of anthropometric measurements to compare the growth patterns of male patients with adolescent idiopathic scoliosis with those of healthy boys during puberty and explore the difference in the pubertal growth patterns of female and male patients with adolescent idiopathic scoliosis. METHODS: A total of 688 subjects were involved in the study, including 332 male adolescent idiopathic scoliosis patients and 356 age-matched healthy boys. The subjects were categorized according to their chronological ages. Their body weights, heights and arm spans were obtained using standard methods; the corrected body heights of the adolescent idiopathic scoliosis boys were determined using Bjour's equation. The inter-group differences in the anthropometric parameters were analyzed. Multivariate regression analysis was carried out in the adolescent idiopathic scoliosis patients to identify the anthropometric parameters that influence curve severity. RESULTS: The corrected standing heights and arm spans of male adolescent idiopathic scoliosis patients were similar to those of the matched controls during puberty. However, the body weights of the adolescent idiopathic scoliosis patients who were more than 14 years old were significantly less than those of the control group. The body mass index of the adolescent idiopathic scoliosis patients between the ages of 15 and 17 were also significantly less than those of the control subjects. Moreover, a significantly higher incidence of underweight was found in adolescent idiopathic scoliosis patients (8.6%) than in the controls (3.4%). Upon multivariate regression analysis, body weight and chronological age were identified as independent predictors of curve magnitude in male adolescent idiopathic scoliosis patients. The male adolescent idiopathic scoliosis patients with variable curve patterns exhibited no significant differences in their anthropometric parameters. CONCLUSIONS: The results showed abnormal pubertal growth in the male adolescent idiopathic scoliosis patients compared with their age- and gender-matched normal controls. Despite similar longitudinal growth, the male patients with adolescent idiopathic scoliosis exhibited significantly lower body weights and a higher incidence of underweight during the later stage of puberty compared with their normal controls. These abnormalities in the pubertal growth of male patients were different from those observed in female patients with adolescent idiopathic scoliosis. Body weight could be an important parameter for further longitudinal studies on the prognostication of curve progression in adolescent idiopathic scoliosis.

Metabolic profiling of mice plasma, bile, urine and feces after oral administration of two licorice flavonones.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is an ancient food and medicinal plant. Liquiritigenin and liquiritin, two kinds of major flavonoes in licorice, are effective substances used as antioxidant, anti-inflammatory and tumor-suppressive food, cosmetics or medicines. However, their in vivo metabolites have not been fully explored. AIM OF STUDY: To clarify the metabolism of liquiritigenin and liquiritin in mice. MATERIALS AND METHODS: In this study, we developed a liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry approach to determine the metabolites in mice plasma, bile, urine and feces after oral administration of liquiritigenin or liquiritin. The structures of those metabolites were tentatively identified according to their fragment pathways, accurate masses, characteristic product ions, metabolism laws or reference standard matching. RESULTS: A total of 26 and 24 metabolites of liquiritigenin or liquiritin were respectively identified. The products related with apigenin, luteolin or quercetin were the major metabolites of liquiritigenin or liquiritin in mice. Seven main metabolic pathways including (de)hydrogenation, (de)hydroxylation, (de)glycosylation, (de)methoxylation, acetylation, glucuronidation and sulfation were summarized to tentatively explain their biotransformation. CONCLUSION: This study not only can provide the evidence for in vivo metabolites and pharmacokinetic mechanism of liquiritigenin and liquiritin, but also may lay the foundation for further development and utilization of liquiritigenin, liquiritin and then licorice.