結晶酵母りんグリセリン酸ムターゼに関する研究

京都大学0048新制・論文博士農学博士論農博第17号新制||農||18(附属図書館)学位論文||S38||N37(農学部図書室)422(主査)教授 満田 久輝, 教授 小野寺 幸之進, 教授 緒方 浩一学位規則第5条第2項該当Kyoto UniversityDA

Population pharmacokinetics of everolimus in adult liver transplant patients: Comparison to tacrolimus disposition and extrapolation to pediatrics

Everolimus has recently been used to prevent graft rejection in liver transplantation and reduces the incidence of kidney dysfunction caused by calcineurin inhibitors. In this study, a population pharmacokinetic analysis was conducted to improve the individualization of everolimus therapy. Japanese post-liver transplant patients whose blood everolimus concentrations were measured between March 2018 and December 2020 were included in this study. A nonlinear mixed-effect modeling program was used to explore covariates that affect everolimus pharmacokinetics. Individual everolimus pharmacokinetic parameters estimated by the post-hoc Bayesian analysis using the final model were compared with the tacrolimus dose per trough concentration (D/C) ratio in each patient. The final model was extrapolated to pediatric liver transplant patients for external evaluation. A total of 937 concentrations from 87 adult patients were used in the model-building process. Everolimus clearance was significantly affected by the estimated glomerular filtration rate, concomitant use of fluconazole, sex, as well as total daily dose of everolimus (TDM effect). The estimated individual apparent clearance of everolimus by the post-hoc Bayesian analysis was moderately correlated with the D/C ratio of tacrolimus in each patient (R² = 0.330, p < 0.0001). The estimation accuracy in pediatric patients was considerably high, except for one infant out of 13 patients. In conclusion, population pharmacokinetic analysis clarified several significant covariates for everolimus pharmacokinetics in liver transplant patients. Everolimus pharmacokinetics moderately correlated with tacrolimus pharmacokinetics and could be extrapolated from adult to pediatric patients by body size correction, except for infants

Effects of childhood experience with nature on tolerance of urban residents toward hornets and wild boars in Japan

<div><p>Urban biodiversity conservation often aims to promote the quality of life for urban residents by providing ecosystem services as well as habitats for diverse wildlife. However, biodiversity inevitably brings some disadvantages, including problems and nuisances caused by wildlife. Although some studies have reported that enhancement of nature interaction among urban children promotes their affective attitude toward of favorable animals, its effect on tolerance toward problem-causing wildlife is unknown. In this study, we assessed the tolerance of 1,030 urban residents in Japan toward hornets and wild boar, and analyzed the effects of childhood experience with nature on tolerance using a structural equation model. The model used sociodemographic factors and childhood nature experience as explanatory variables, affective attitude toward these animals as a mediator, and tolerance as a response variable. The public tolerance toward hornets and boars was low; over 60% of the respondents would request the removal of hornets and wild boar from nearby green spaces by government services, even when the animals had not caused any damage. Tolerance was lower in females and elderly respondents. Childhood experience with nature had a greater influence on tolerance than did sociodemographic factors in the scenario where animals have not caused any problems; however, its effect was only indirect via promoting positive affective attitude toward wildlife when the animals have caused problems. Our results suggest that increasing people’s direct experience with nature is important to raise public tolerance, but its effect is limited to cases where wildlife does not cause any problems. To obtain wider support for conservation in urban areas, conservationists, working together with municipal officials, educators and the media, should provide relevant information on the ecological functions performed by problem-causing wildlife and strategies for avoiding the problems that wildlife can cause.</p></div