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This article is available online at http://dmd.aspetjournals.org ABSTRACT:The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNAexpressed cytochrome P450 (P450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Cl int ) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9-and 2.4-fold higher than those from the R-form, respectively. The sums of formation Cl int of both metabolites were 13.5 and 57.3 l/min/mg protein for R-and S-lansoprazole, respectively, suggesting that S-lansoprazole would be cleared more rapidly than the R-form. The P450 isoform selective inhibition study in liver microsomes, and the incubation study of cDNA-expressed enzymes, demonstrated that the stereoselective sulfoxidation is mediated by CYP3A4 and that the hydroxylation is mediated by CYP2C9 and CYP3A4 as well as by CYP2C19. Total Cl int values of hydroxy and sulfone metabolite formation catalyzed by all these P450 enzymes were consistently higher for S-lansoprazole than for the R-form. The CYP3A4 produced the greatest difference of Cl int between Sand R-enantiomers, mainly due to a difference of sulfoxidation metabolism (Cl int 76.5 versus 10.8 l/min/nmol of P450, respectively), whereas CYP2C19-catalyzed hydroxylation resulted in a minor difference of Cl int between S-and R-enantiomers (179.6 versus 143.3 l/min/nmol of P450, respectively). However, the affinity of CYP2C19 on hydroxylation was 5.7-fold higher for S-enantiomer than for the R-form (K m 2.3 versus 13.1 M), suggesting that the role of CYP2C19 on stereoselective hydroxylation would be more prominent at concentrations around the usual therapeutic level. These findings suggest that both CYP2C19 and CYP3A4 are major enzymes contributing to the stereoselective disposition of lansoprazole, but stereoselective hydroxylation of lansoprazole enantiomers is mainly influenced by CYP2C19, especially at the usual therapeutic doses.

Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.

Background The COVID-19 pandemic has affected various facets of health. While mental health became a major concern during the COVID-19 outbreak, the impact on the migrants’ mental health has still been neglected. The purpose of this study was to examine the COVID-19 outbreak's impact on the mental health of immigrants in South Korea. Methods A total number of 386 immigrants in South Korea participated in this quantitative cross-sectional study. The standardized e-questionnaire, including the General Anxiety Disorder (GAD-7) scale, was used to measure the anxiety level. Logistic regression analysis was performed to find out the determinants of anxiety disorders among immigrants. Results The prevalence of severe anxiety among immigrants was found to be 47.2%. Female immigrants (28.6%) had a lower anxiety disorder than males (71.4%). Immigrants who were married, living alone, had a low income, had a history of health problems were suffered from moderate to severe anxiety. Immigrants who were unemployed (OR 2.302, 95% CI = 1.353–3.917) and lost their jobs due to the COVID-19 outbreak (OR 2.197, 95% CI = 1.312–3.678) have a higher anxiety disorder. Immigrants aged over 30 years were found to suffer from a high level of anxiety (OR 2.285, 95% CI = 1.184–4.410). Relief support from the government was significantly associated with anxiety disorder among immigrants (p < 0.01, OR = 3.151, 95% CI = 1.962–5.061). Conclusion With very limited studies on immigrants’ mental health during the COVID-19 pandemic, this paper provides scientific research evidence of the COVID-19 outbreak's impact on the mental health of migrants. Our study has consequences for implementing integrated psychological interventions and health promotion strategies for the well-being of immigrants’ mental health.