A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

缩窄门静脉主干1／2加丝线慢性栓塞术制备犬门静脉高压症模型

目的:探索操作简便且效果满意的门静脉高压症动物模型制备方法.方法:缩窄门静脉主干1/2加丝线慢性栓塞术,通过22条犬进行实验.结果:除1条死亡外.其余21条术后3～4周时门静脉压力升高至2.83±0.66kPa(术前1.33±0.28kPa,P<0.001):胃镜、门静脉造影及病理学检查证实,17条犬有食管胃底曲张静脉形成,形成率80.95%(其中方法完善后制备的14条、形成率100%),12条发生门脉高压性胃病,发生率57.14%.1条观察至术后4月.门静脉高压症表现仍然存在.结论:该法简便易行、建立模型周期短、成功率高且质量可靠并较持久.     

A new and highly sensitive method for measuring 3-methoxytyramine using HPLC with electrochemical detection. Studies with drugs which alter dopamine metabolism in the brain

3-Methoxytyramine (3-MT) is a minor metabolite of dopamine which is suggested to reflect the turnover and utilization of dopamine. A novel, isocratic HPLC method has been developed which can be used to analyse 3-MT in homogenates of rat brain without the need for additional purification procedures. Furthermore, the coulometric electrochemical detection system is sensitive enough to measure 3 pg of 3-MT (equivalent to 0.6 ng/g tissue wet weight). 3-Methoxytyramine was measured in the striatum and n. accumbens after decapitation and rapid freezing, using 3-methoxy-4-hydroxybenzylamine as the internal standard. The effects of dopaminergic and other drugs on this metabolite were examined using this method. -Methyl-p-tyrosine (200 mg/kg i.v.) produced parallel linear decreases in dopamine and 3-MT in naive rats, but not those pretreated with tranylcypromine (5 mg/kg i.p.). Methamphetamine (0.3–10 mg/kg i.p.) and amphetamine (0.3–10 mg/kg i.p.) both dose-dependently increased 3-MT in naive and tranylcypromine-pretreated rats. In naive animals, 3-MT was not altered by intraperitoneal injection of the dopamine reuptake inhibitors, bupropion (10 mg/kg) and nomifensine (10 mg/kg) or by sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg) and zimeldine (10 mg/kg). 3-Methoxy-tyramine was decreased by apomorphine (5 mg/kg i.p.) and also by large doses of the selective D₂ antagonist, BRL 34778 (5 mg/kg i.p.) or -DOPA (50 mg/kg i.p.). The selective D₁ antagonist, SCH 23390 (0.1 or 5 mg/kg i.p.) was without effect. In tranylcypromine-pretreated rats, 3-MT was dose-dependently reduced and increased by apomorphine (0.01–5 mg/kg i.p.) and BRL 34778 (0.1–5 mg/kg i.p.), respectively. The drug SCH 23390 (0.1–5 mg/kg i.p.) produced much smaller increases in 3-MT which were probably mediated through the striatonigral pathway. Overall, the data suggest that measurement of 3-MT, after inhibition of monoamine oxidase, is a useful index of the release and utilization of dopamine. However, after substantial and prolonged depletion of dopamine, levels of 3-MT in naive animals are a better index. Also, the formation of 3-MT in naive rats provides a sensitive method for distinguishing between dopamine releasing agents and reuptake inhibitors.     

Optimal Selection of Sib Pairs from Random Samples for Linkage Analysis of a QTL Using the EDAC Test

Percentages of extremely concordant and extremely discordant sib pairs are calculated that maximize the power to detect a quantitative trait locus (QTL) under a variety of circumstances using the EDAC test. We assume a large fixed number of randomly sampled sib pairs, such as one would hope to find in the large twin registries, and limited resources to genotype a certain number of selected sib pairs. Our aim is to investigate whether optimal selection can be achieved when prior knowledge concerning the QTL gene action, QTL allele frequency, QTL effect size, and background (residual) sib correlation is limited or absent. To this end we calculate the best selection percentages for a large number of models, which differ in QTL gene action allele frequency, background correlation, and QTL effect size. By averaging these percentages over gene action, over allele frequency, over gene action, and over allele frequencies, we arrive at general recommendations concerning selection percentages. The soundness of these recommendations is subsequently in a number of test cases.     

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

过度训练的病理生理及康复 Ⅰ.大鼠过度训练模型的建立

实验表明,运用大鼠跑台运动,以心电图、体重、饮食量、精神状况、毛发脱落、尿蛋白、血清睾酮、皮质醇等为监测指标建立大鼠过度训练模型的方法是可行的。本文并首次模拟出大鼠运动性心律失常心电图。     

The use of experimental studies to reveal suspected neurotoxic chemicals as occupational hazards: acute and chronic exposures to organic solvents.

The nervous system differs from many other body organs by its central control of vital functions and its low regeneration capacity. Organic solvents have, as a group, been suspected to have neurotoxic effects. Because of their similar physical properties and the fact that in industrial uses, they are often present in various mixtures, organic solvents have also been regarded, unfortunately, to induce common neurotoxic effects. However, it is evident from experimental studies using specified exposure conditions that different organic solvents have very diverse neurotoxic effects and also that the toxic mechanism may differ between acute and chronic exposure. No specific method used to describe a neurotoxic effect or single toxic response can be used for the overall occupational risk assessment of all organic solvents. Each solvent has to be considered as having its own unique toxic effects.     

河南省地方性高碘甲状腺肿的发现、流行特征及其干预研究

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Model parameters of the smooth pursuit eye movement system with electrooculogram

The visual pursuit test is a method that collects and analyzes the characteristics of pursuit eye movements and examines the function of the eye movement system. This paper analyzes the model parameters of the smooth pursuit eye movement system in order to explore a method for improving the analysis. The input-output relationship of the smooth pursuit system can be expressed by a quasilinear model. We compute the model parameters (gain, phase, spectral purity, cross covariance) by digital signal processing. Eye movement is recorded by electrooculogram. Both eyes are tested individually. The visual target moves at frequencies of 0.2, 0.4, 0.8, 1.2, and 1.6 Hz. Ranges are gain, 1.01 to 0.70; phase, -0.1 ° to -66 °; spectral purity, 0.97 to 0.70; and cross covariance, 0.99 to 0.26. We tested 40 normal subjects as well as patients with ataxia (8), vertigo (18), and ophthalmoplegia (9). The oculomotor system of normal subjects functions as a linear system in the performance of this test at 0.2 to 0.8 Hz. The spectral purity dropped to about 0.70 at 1.6 Hz. The variability of all measures increases greatly at 1.6 Hz, which indicates that this target motion exceeds the tracking ability of many normal subjects and that the oculomotor system of normal subjects functions as a nonlinear system in this condition. Statistical tests show no significant differences between sex, age, and the two eyes. The model parameters tentatively proved effective in clinical application.     

"吃食堂"的认知生成机制

以认知语法的行为链模式为分析工具,就汉语中的表工具、处所、方式等题元的介词宾语移位至动词宾 语位置的“吃食堂”等句法现象的成因作认知方面的解释说明。