失眠对老年大鼠行为和糖代谢的影响

目的探讨失眠对老年大鼠行为和糖代谢的影响。方法采用小平台水环境的睡眠剥夺方法建立动物失眠模型,18只雄性老年大鼠随机分为对照组(C)、每天6小时睡眠组(S6h)和每天4小时睡眠组(S4h)。结果试验组大鼠的修饰行为次数、中央格停留时间、粪便颗粒数,高于C组,差异具有显著性(P0.05);旷场实验得分,S6h组C组S4h组,差异具有显著性(P0.05)。与C组比较,试验组大鼠的FPG水平显著升高(P0.05);与C组比较,大鼠血清INS水平,S6h组,差异无显著性(P0.05);S4h组,差异具有显著性(P0.05)。大鼠的ISI水平,S4h组S6h组C组,差异具有显著性(P0.05)。结论失眠可以导致老年大鼠行为和糖代谢的改变。     

Physiologically-Based Pharmacokinetic Modeling of Benzene in Humans: A Bayesian Approach

Benzene is myelotoxic and leukemogenic in humans exposed at high doses (>1 ppm, more definitely above 10 ppm) for extended periods. However, leukemia risks at lower exposures are uncertain. Benzene occurs widely in the work environment and also indoor air, but mostly below 1 ppm, so assessing the leukemia risks at these low concentrations is important. Here, we describe a human physiologically-based pharmacokinetic (PBPK) model that quantifies tissue doses of benzene and its key metabolites, benzene oxide, phenol, and hydroquinone after inhalation and oral exposures. The model was integrated into a statistical framework that acknowledges sources of variation due to inherent intra- and interindividual variation, measurement error, and other data collection issues. A primary contribution of this work is the estimation of population distributions of key PBPK model parameters. We hypothesized that observed interindividual variability in the dosimetry of benzene and its metabolites resulted primarily from known or estimated variability in key metabolic parameters and that a statistical PBPK model that explicitly included variability in only those metabolic parameters would sufficiently describe the observed variability. We then identified parameter distributions for the PBPK model to characterize observed variability through the use of Markov chain Monte Carlo analysis applied to two data sets. The identified parameter distributions described most of the observed variability, but variability in physiological parameters such as organ weights may also be helpful to faithfully predict the observed human-population variability in benzene dosimetry.