Lipophilicity in PK design: methyl, ethyl, futile

Lipophilicity, often expressed as distribution coefficients (log D) in octanol/water, is an important physicochemical parameter influencing processes such as oral absorption, brain uptake and various pharmacokinetic (PK) properties. Increasing log D values increases oral absorption, plasma protein binding and volume of distribution. However, more lipophilic compounds also become more vulnerable to P450 metabolism, leading to higher clearance. Molecular size and hydrogen bonding capacity are two other properties often considered as important for membrane permeation and pharmacokinetics. Interrelationships among these physicochemical properties are discussed. Increasing size (molecular weight) often gives higher potency, but inevitably also leads to either higher lipophilicity, and hence poorer dissolution/solubility, or to more hydrogen bonding capacity, which limits oral absorption. Differences in optimal properties between gastrointestinal absorption and uptake into the brain are addressed. Special attention is given to the desired lipophilicity of CNS drugs. In examples using -blockers, Ca channel antagonists and peptidic renin inhibitors we will demonstrate how potency and pharmacokinetic properties need to be balanced.     

Hepatobiliary excretion and brain distribution of caffeine in rats using microdialysis

To investigate the pharmacokinetic mechanism of hepatobiliary excretion and brain distribution of caffeine, this study uses a method based on microdialysis technique and liquid chromatography that allows continuous and concurrent in vivo monitoring of extracellular caffeine in the blood, brain and bile of anesthetized rats following the administration of caffeine (3 or 10 mg/kg, i.v.) through the femoral vein. Dialysates of the blood, brain and bile were directly injected onto the liquid chromatographic system and no further clean-up procedures were required. The study design consisted of two groups of six rats in parallel: the rats of the control group received caffeine (3 or 10 mg/kg, i.v.) alone and those of the cyclosporine treated-group were injected cyclosporine (10 mg/kg, i.v.) 10 min prior to caffeine administration (3 or 10 mg/kg, i.v.). The decline of caffeine in the blood, brain striatum and bile suggested that caffeine had rapid exchange and equilibration between the peripheral compartment and the central nervous system. In addition, the results indicated that caffeine underwent hepatobiliary excretion and was distributed into brain. When cyclosporine was co-administered, the pharmacokinetic parameters were not significantly altered. The results of this study reveal that the pharmacokinetic mechanism of hepatobiliary excretion and brain distribution of caffeine might not relate to P-glycoprotein.     

Repleteness and regular lattice measures

Let X be an abstract set and L a lattice of subsets of X. To each lattice regular measure µ, we associate two induced measures and on suitable lattices of the Wallman space IR(L) and another measure µ on the spaceIR(L). We will investigate the reflection of smoothness properties of p onto , and µ; and try to set some new criterion for repleteness and measure repleteness.     

基于生态足迹模型的贵州可持续发展能力定量评价

定量测度可持续发展能力是目前可持续发展研究的重要课题和前沿领域．其核心是确定人类是否生存于生态系统的承载力范围内．本文介绍了Wackemagel M等1996年以来提出和发展的可持续发展的定量测度方法——生态足迹法，并运用此方法计算和分析了贵州省2001年的生态足迹．其生态足迹由三个部分组成：1)生物资源；2)能源消费；3)贸易调整．按照这种方法计算，贵州省2001年人均生态足迹为1．49525hm^2，人均生态足迹赤字为1．153433hm^2．反映出目前贵州的生产、生活强度已经超过了生态系统的承载能力，区域生态系统处于人类的过度开发利用和压力之下．在此基础上作者提出了提高贵州省可持续发展能力的途径，最后还讨论了方法本身存在的一些缺陷．     

信用证诈骗分析及其防范对策

随着世界经济一体化和高科技的发展,信用证已成为国际贸易中重要的信用支付工具,然而信用证诈骗案件也随之不断增加.本文通过对信用证诈骗方式及原因进行分析,并提出了相应的防止利用信用证进行金融诈骗的对策.     

专用铁路安全管理问题探讨

文章针对当前专用铁路安全管理方面存在的问题，提出了加强专用铁路安全管理的具体措施。     

村民自治的政治绩效分析--以广东省村民自治的实践为例

村民自治在实践中取得了较好政治绩效,出现了较高的村民选举参与率,初步建立了以村民为决策主体的民主决策体制,同时出现了多元民主管理主体和多样化的民主管理和民主监督方式。另一方面村民自治实践中仍存在一些问题,影响了村民自治政治绩效的提高。要提升村民自治的政治绩效,必须要加强制度建设,要利用多种渠道,提高村民自治主体的民主、法制意识和文化素质。要加强村民自治组织的建设,提升其管理能力和服务能力。同时要求村民自治营造良好的社会法制环境。本文以广东省为例,对村民自治的政治绩效进行了分析,并提出了作者自己的见解。     

电流补偿法测电阻

常用的补偿法测电阻是通过电压补偿法来实现的。本文将通过分析、演变，巧妙设计出一种使用电流表，电压表进行电流补偿的测电阻的方法，通过实验测量的有关数据进行误差分析与计算。     

绿色住宅建筑物理环境的要求及技术措施

随着生活水平的不断提高，人们选择住宅更注重住宅的内在品质，绿色住宅正是顺应社会形势的发展和市场的需求而及时提出来的。对绿色住宅声、光、热工等建筑物理环境做了一个初步的研究，指出住宅的功能已由原来的栖息地转变为人们用来缓解工作压力、调节情绪、陶冶情操、保持身心健康的重要场所。     

多量子比特纯态纠缠刻画研究的一些进展

对多量子比特纯态纠缠刻画研究的一些进展作了介绍．首先介绍了三量子比特纯态情形对称正则形式的特点和LU多项式不变量与随机LOCC分类的关系．随后对多量子比特纯态的分类和纠缠的度量作了一些讨论，并指出紧致相对熵纠缠度不具有LU不变性以及Wei的几何纠缠度的不足．