An evaluation of numerical integration algorithms for the estimation of the area under the curve (AUC) in pharmacokinetic studies

Six numerical integration algorithms based on linear and log trapezoidal methods as well as four cubic-spline methods were proposed for estimation of area under the curve (AUC). These six different algorithms were implemented using IMSL/IDL^TM command language and evaluated using data simulated under five different dosing conditions and two different sampling conditions. Comparisons between AUC estimations using these six different algorithms and the theoretical results were made in terms of both overall AUC values and the superimposability of the concentration-time profiles. In well designed studies with ample data points, the algorithm based on IMSL/IDL^TM function CSSHAPE with concavity preservation gave the best performance. In contrast, when the frequency of blood collection was limited, the algorithm based on the log trapezoidal rule proved to be stable with reasonable accuracy, and is recommended as the practical method for numerical interpolation and integration in pharmacokinetic studies. Algorithms based on the combination of the log trapezoidal rule and cubic-spline methods using IMSL/IDL^TM function CSSHAPE can be developed to enhance overall performance.     

PHA对单产和联产白细胞介素-2活性的影响

本文研究了用人外周血白细胞在细胞浓度为5×10~5个/ml、培养时间为24h,PHA加量对单独生产白细胞介素_2(单产)及联合生产a_干扰素、白细胞介素-2(联产)的影响.单产中,以25μg/mlPHA刺激量为宜;联产中以100μg/ml刺激量最好.联产比单产所得白细胞介素-2产量高10倍以上,且纯度高.     

中医药学研究方法的解构与特性分析

将中医药学研究方法从观念理论、核心方法和技术手段3个方面进行解构，并对其内在特性进行详细分析。明确提出中医药学研究方法的范式特性、观念理论的思辨性、核心方法的主观性以及整体刚性和局部柔性的特性，揭示了中医药研究方法的优势与不足，为中医药研究方法论的创新提供理论依据。     

Effect of the NK3 receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans

Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK(3) receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK(3) receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants.     

反坦克武器击中坦克时舱室内有害气体测试方法的探讨

为探讨在模拟实验条件下，坦克受到反我武器攻击后舱室内有害气体的取样方法和分析方法，用3种武器发射3种弹药攻击坦克，在远距离控制取样设备，取样后在实验室进行坦克舱室内有害气体浓度分析，结果取样成功，坦克被击中后，一氧化碳气体含量有明显的增高，氮氧化物、二氧化硫增高幅度不大，氧含量无明显变化，说明对坦克舱室进行远距离现场控制气体采样是可行的；坦克的受反坦克武器打击后，除弹片和冲击波等致伤因素外，还会造成坦克内乘员一氧化碳中毒。     

Fluctuations in Tumor Blood Flow under Normotension and the Effect of Angiotensin II-induced Hypertension

To elucidate the significance of angiotensin II (AID-induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly-developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor Wood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under All-induced hypertension seemed to be greater than that under normotension, because the All-increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no-flow or low-flow areas, resistant to delivery of anti-cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by All-induced hypertension.     

圆形分布法在蝇类季节消长规律中的应用

目的确定蝇类季节消长的高峰日和高峰时段,为制定蝇类防制措施提供科学依据。方法用圆形分布法统计分析绍兴市区2003-2004年蝇类密度监测数据。结果绍兴市区2003-2004年蝇类平均密度高峰日为8月4日,高峰时段为6月8日至9月30日。其中2003年蝇类密度高峰日为8月11日,高峰时段为6月17日至10月5日;2004年蝇类密度高峰日为7月29日,高峰时段为6月1日至9月26日。结论绍兴市区2年中蝇类消长有明显的季节性规律。     

社区卫生服务信息系统功能建模研究

理顺功能关系、理清业务流程是构建社区卫生服务信息系统的前提和基础,功能建模是理顺功能关系的一个重要手段。在研究现有的各种功能分析方法的基础上,本文以IDEF0模型方法为基础,提出了社区卫生服务信息系统功能建模方法。通过建立功能、数据和约束之间的内在联系,为系统的功能设计和数据分析提供了基础。     

Distribution of calcium-activated neutral protease inhibitor in the central nervous system of the rat.

The ubiquitous existence of calcium-activated neutral protease (CANP, calpain), an enzyme whose activity is regulated by calcium ions and a specific endogenous CANP inhibitor (calpastatin), is well known. Although there has been much investigation concerning the distribution and role of CANP, investigations of the distribution of the CANP inhibitor using immunohistochemical techniques are rare. We made antiserum against a 40K fragment of cDNA corresponding to two C-terminal repeats of rat liver CANP inhibitor expressed in Escherichia coli. Using this antiserum, we examined the distribution of CANP inhibitor in the rat central nervous system by the ABC technique and compared it with the distribution of CANP. Neurons and glias were stained, with the cytosol stained diffusely and the cell membranes stained clearly and strongly. Axons and myelin were stained faintly, but nuclei and vessels were not stained. The distribution of CANP inhibitor was thus found to be similar to that of CANP.     

硒对沙土鼠脑缺血再灌注的保护作用及其作用机制研究

目的 研究亚硒酸钠对沙土鼠脑缺血再灌注损伤的保护作用及其机制。方法 将50只沙土鼠随机分为5组，Ⅰ组：假手术组；Ⅱ组：缺血灌注1天处死组；Ⅲ组：缺血再灌注4天处死组；Ⅳ组：硒处理、缺血再灌1天处死组；Ⅴ组：硒处理、缺血再灌注4天处死组。采用夹闭双侧颈动脉法制备沙土鼠脑缺血再灌注模型，焦油紫染色，光镜下观察各组海马CAl区神经细胞的形态变化，电镜下超微结构变化。同时测定脑组织中丙二醛(MDA)、谷胱甘肽过氧化酶(GSH-PX)、超氧化物歧化酶(SOD)的含量。结果 硒处理组沙土鼠脑缺血再灌注后，神经细胞病理形态损伤较轻，SOD、GSH-PX含量较高，MDA含量较低。结论 硒对沙土鼠脑缺血再灌注损伤具有保护作用，其机制可能和增强脑缺血再灌注早期脑组织中SOD、GSH-PX的活性，抑制氧自由基损伤，减轻脂质过氧化反应有关。