SPSS估算一级并行米氏消除药物药动学参数的方法

目的 估算一级并行米氏消除药物静脉注射给药的药动学参数. 方法 利用四阶Runge-Kutta算法得到血药浓度的模拟数据,对模拟取样点的药-时数据进行转化,以⊿C/⊿t近似地代替微分式dC/dt,血药浓度C采用调和均数C_iC_i+1或算术均数（C_i+C_i+1）/2;采用SPSS软件中的非线性回归（nonlinear regression）对⊿C/⊿t调和均数（或算术均数）数据对拟合一级并行米氏消除药物静脉注射给药的药动学参数. 结果 SPSS估算的药动学参数准确可靠. 结论 SPSS可以用于估算一级并行米氏消除药物静脉注射给药的药动学参数.     

米氏消除药物血管外给药血药浓度的数值解

目的获得(一级并行)米氏消除药物血管外给药时的血药浓度近似值。方法根据四阶Runge Kutta算法，采用Excel软件编写基于药动学参数的血药浓度近似解表格程序。结果通过实例演示，可以输出第n周期(或稳态)第s次血管外给药后每间隔0.005 h的预期血药浓度。结论该法是(一级并行)米氏消除药物血管外给药动力学方程的一种可靠的数值解法。     

利用SPSS估算血管外给药的药动学参数

目的 利用SPSS估算血管外给药室模型的药动学参数。方法使用SPSS的非线性回归(nonlinear regression)拟合模拟的两室模型血管外给药的药-时数据；依据95％置信区间决定是否在模型中保留滞后时间(tlag)项。结果SPSS估算的药动学参数：住确可靠；根据tlag95％置信区间决定是否在模型中保留flag项是合理的。结论SPSS适用于估算血管外给药室模型的药动学参数。     

基于Excel软件的静脉滴注给药(一级并行)米氏消除药动学方程的数值解

目的获得静脉滴注给药时(一级并行)米氏消除药物的血药浓度近似解.方法根据四阶龙格-库塔算法,采用Excel软件编写(一级并行)米氏消除药动学方程数值解的表格程序.结果输入药动学参数(Vm,Km,Vd,ke)后,Excel表格输出任一次给药后某时刻的预期血药浓度.结论这一表格程序是静脉滴注给药(一级并行)米氏消除药动学方程一种可靠的数值解法.     

米氏消除药物静脉给药的药动学方程数值解

的：获得(一级并行)米氏消除药物静脉注射给药时的血药浓度近似解。方法：根据四阶Runge-Kutt。算法，采用Excel软件编写基于药动学参数的程序。结果：输出某周期或稳态任一次给药后的预期血药浓度。结论：方法操作简单，结果可靠，可作为(一级并行)米氏消除药物静脉注射给药时药动学方程的数值解法。     

两种软件对血管外给药一二室模型 药动学参数的拟合效果

［摘要］目的比较两种软件对血管外给药一、二室模型药动学参数的拟合效果。方法采用DAS2.0软件药动学模块和SPSS12.0软件的非线性回归方法对一系列时间 血药浓度模拟数据，以及实测数据进行拟合。结果模拟结果显示SPSS12.0非线性回归方法拟合效果优于DAS2.0软件，但实测数据的拟合结果两者一致。结论SPSS12.0和DAS2.0软件的拟合效果均良好，可以作为血管外给药一、二室模型药动学参数的拟合方法。     

利用SPSS和Excel拟合血管外给药药动学参数的效果比较

目的：考察SPSS和Excel对血管外给药的药动学参数的拟合效果。方法：采用SPSS，Excel对参数理论值产生的血药浓度和实测血药浓度进行曲线拟合。结果：通过理论参数和实例分析，显示Excel规划求解法的拟合效果良好，基本上与SPSS法相近。结论：Excel规划求解法可作为获取血管外给药药动学参数有效而简便的方法。     

静注Michaelis-Menten消除动力学稳态浓度的理论研究

Michaelis- Menten消除动力学 (下称米氏型消除 )是非线性药物动力学中的重要部分。大量临床研究表明 [1 ] ,呈药动学非线性特征的药物 ,尤有必要进行血药浓度监测。本文对静注多次给药情况下的稳态动力学特征进行了研究 ,得到了稳态浓度存在的必要条件及稳态浓度的精确表达式 ,为临床用药提供了理论依据。1　稳态浓度单室模型、快速静注某药剂量 D时 ,呈米氏消除的血药浓度 C随时间 t的变化规律为 :Vmt=Co- C+ K mln( Co/ C) ,t≥ 0 ( 1)其中 ,Vm为药物消除的理论最大速度 ,K m为米氏常数 ,Co=D/ V为初始浓度 ,V为表观分布容积。记 …     

非线性混合效应模型法处理癫痫患者苯妥英血药浓度数据

目的:估算癫痫患者苯妥英群体药动学参数,考察各因素对最大消除速率常数Vm及米氏常数Km的影响.方法:83例癫痫患者口服苯妥英钠片,FPIA法监测血药浓度数据96个,应用非线性混合效应模型进行计算.结果:按照米氏方程计算苯妥英药动学参数,Km=12.8 mg·L-1, Vm=499.0 mg·d-1.结论:性别、年龄、体重、合并用药等对药动学参数均无显著性影响,Km个体差异极大并呈现双相分布.     

三点法测定一室模型血管外给药的药动学参数

目的获得一室模型药物血管外给药的药动学参数;方法给予单次剂量X0,3个采样点时间为t、2t和3或4t,根据给定的药动学参数（ka、k和V/F）计算各取样点的理论血药浓度（c1、c2和c3）,推算ka、k和V/F值。结果参数推算值与给定值一致。结论三点法可以用于获取一室模型血管外给药的药动学参数。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.