132例男性不育患者遗传学病因分析

目的：对男性不育患者进行遗传学病因分析，并探讨其遗传效应。方法：采取132例男性不育患者外周血进行染色体核型分析。结果：132例男性不育患者中，染色体异常24例，染色体变异22例。其中大Y20例，47，XXY18例，45．XY，t(13；14)3例，小Y和46，XY，inv(9)各2例，46，XY，t(9；22)1例。结论：染色体异常是男性不育的重要原因，并建议男性不育患者进行基因诊断，以便确诊是否属于遗传病，为生育提供指导，避免盲目治疗。     

A simple and reliable method for rapidly harvesting split skin grafts in rats

A technique is presented which allows the rapid precise harvesting of split-skin grafts in rats. This technique uses the skin which would have been discarded in the formation of an open wound as a donor site thus reducing the overall assault on the animal.     

Development of HPLC plasma assays for CAM 4515 and CAM 4750, two new nonpeptide tachykinin antagonists, and application to bioavailability studies

CAM 4515 and CAM 4750 are new nonpeptide tachykinin NK₁ receptor antagonists with different lipophilicities. Two separate, simple, and sensitive HPLC methods for the quantitation of these two compounds in plasma and the evaluation of their oral bioavailability in rats were developed and validated. Extraction of CAM 4515 from plasma involved protein precipitation with acetonitrile, while that for CAM 4750 involved a one-step liquid-liquid extraction with methylene chloride. The analytes in extracts were chromatographed on a C18 column using two different separation buffers, 47% 0.02 M sodium citrate (pH 3.5)-53% acetonitrile for CAM 4515 and 59% 0.02 M potassium phosphate dibasic (pH 7.0)-41% acetonitrile for CAM 4750, and both compounds were detected by fluorescence (excitation 278 nm; emission 342 nm). Stability profiles of both drugs at −20°C or room temperature in plasma and in reconstituted buffers were good. The limit of quantitation for both drugs was 5 ng ml⁻¹ with good linearity from 5 to 1000 ng ml⁻¹ using 100–200 μl of plasma. Excellent precision (relative standard deviation < 8.3%) and accuracy (relative error ± 9.2%) were observed for both CAM 4515 and CAM 4750. Oral bioavailability studies were conducted for each compound in rats receiving a p.o. dose of 20 mg kg⁻¹ and an i.v. dose of 5 mg kg⁻¹. The absolute oral bioavailability of CAM 4750 (80%) was estimated to be 40-fold greater than that of CAM 4515 (2%). The experimental results suggest that incorporation of a pyridine group into the structural backbone may greatly improve bioavailability.     

热休克反应对大鼠感染性脑水肿脑组织诱生型一氧化氮合酶mRNA表达的影响

:探讨热休克反应 (HSR)对百日咳杆菌所致的大鼠感染性脑水肿诱生型一氧化氮合酶 (iNOS)mRNA表达的影响。方法 :从大鼠左侧颈内动脉注入百日咳菌液制备感染性脑水肿 (感脑 )模型 ,采用组织细胞原位杂交技术检测脑组织iNOSmRNA的表达。结果 :生理盐水组、4h感脑组及 4h热休克处理组均未见iNOSmRNA表达 ,8h ,2 4h时感染性脑水肿组均有明显的杂交信号 ,以 2 4h更为明显 ;而 8h ,2 4h热休克处理组仅有少数细胞有阳性信号。结论 :热休克反应对感染性脑水肿的保护作用可能与抑制iNOSmRNA的表达有关     

The interaction of cocaine and alcohol on schedule-controlled responding

 Within a number of physiological preparations, the effects of alcohol and cocaine in combination are reported to be greater than the effects of either drug given alone. Little has been reported, however, on the behavioral effects of the interaction. The present study investigated this issue by assessing the effects of cocaine and alcohol (alone and in combination) on schedule-controlled responding. Specifically, rats were trained to respond on an FR20 schedule for a water reinforcer. They were then administered cumulative doses of cocaine or alcohol. Following this, subjects were administered ineffective doses of alcohol prior to further dose-response assessments with cocaine and with ineffective doses of cocaine prior to further dose-response assessments with alcohol. Cocaine and alcohol alone produced dose-related decreases in responding. Furthermore, the dose-response function for cocaine was shifted to the left by alcohol and the dose-response function for alcohol was shifted to the left by cocaine. An isobolographic analysis revealed that the interaction between cocaine and alcohol was additive in nature. The possible bases for the interaction (e.g., changes in cocaine pharmacokinetics by alcohol and the formation of cocaethylene following co-administration of cocaine and alcohol) were discussed. Received: 22 February 1996 / Final version: 23 August 1996     

Effects of 5-HT3 agonists on reproductive behaviors in rats

Activity at 5-HT₁ and 5-HT₂ receptor sites influences sexual behavior in male and female rats. 5-HT₃ antagonists reportedly have no effect on copulatory activity in rats of either sex although they influence a variety of other behaviors. The effects of 5-HT₃ agonists on sexual behavior are unknown. The following experiments were undertaken to assess the influence of the 5-HT₃ agonists 1-phenylbiguanide (PBG) and 2-methyl-serotonin (2-Me-5-HT) on sexual behavior, when administered intracerebroventricularly. Consistent with earlier reports indicating that 5-HT₁ and 5-HT₂ receptor activity influences reproductive activity in a sex-dependent manner, PBG was found to facilitate male, but not female, rat sexual behavior. 2-Me-5-HT, however, failed to modify either female or male rat sexual activity. Evidence that PBG, but not 2-Me-5-HT, induces carrier-mediated dopamine release suggests that the effect of PBG in male rats is due to dopaminergic mediation. Overall, the present data indicate that 5-HT₃ receptor activation has only slight effects on rat sexual behavior.     

Reversal of stress-induced anhedonia by the dopamine receptor agonist,pramipexole

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of a palatable (1%) sucrose solution, and to attenuate food-induced place preference conditioning. In this study the effects of pramipexole (SND-919), a dopamine D₂ agonist, were studied during 7–9 weeks of chronic treatment. Pramipexole (1.0 mg/kg per day) reversed the suppression of sucrose intake in stressed animals, increasing sucrose intakes above the levels seen in untreated nonstressed controls. Pramipexole also increased sucrose intake in nonstressed animals; these effects were accompanied by increases in water intake and tended to correlate with weight loss. Drug-treated stressed animals also lost weight, but in this case water intake was unaffected. A second group of animals received a higher dose of pramipexole (2.0 mg/kg per day). The effects of the two doses were very similar. After three weeks of treatment, these animals were switched to a lower dose of pramipexole (0.1 mg/kg per day). Increases in sucrose intake were maintained over three weeks of treatment at the lower dose, with significant recovery of body weight. Two further groups received the same doses of pramipexole (1.0 mg/kg for 6 weeks or 2.0 mg/kg for 3 weeks followed by 0.1 mg/kg thereafter), but received intermittent (twice-weekly) drug treatment. Intermittent pramipexole treatments also tended to increase sucrose intakes, but the results were less consistent from week to week. Following 6–8 weeks of pramipexole treatment, food-induced place preference conditioning was studied in all animals. Untreated stressed animals showed no evidence of place conditioning. Normal conditioning was seen in both groups of stressed animals treated daily with pramipexole (at 1.0 and 0.1 mg/kg) and in the group treated twice weekly at the higher dose (1.0 mg/kg); intermittent treatment at the lower dose (0.1 mg/kg) was ineffective. The results indicate that pramipexole exerts rapid anti-anhedonic effects in the chronic mild stress model. This conclusion is complicated, but not undermined, by drug-induced weight loss and by the presence of significant drug effects in nonstressed control animals.     

精子顶体酶活性检测对诊断男性不育症的价值

目的比较各种质量精液的精子顶体酶活性。方法分光光度比色法检测顶体酶活性。结果各种质量精液的精子顶体酶活性均显著低于对照组P<0.001。结论精子顶体酶可作为了解精子生育力的一项可靠指标。     

实验性糖尿病早期大鼠背根神经节一氧化氮合酶基因表达的变化

目的：观察糖尿病早期(2周)大鼠背根神经节(DRG)中一氧化氮合酶(nNOS、iNOS、eNOS)的表达变化以及胰岛素对其的影响。方法：按60mg／kg一次性腹腔注射链脲佐菌素(STZ)制备胰岛素依赖性糖尿病大鼠模型(16只)，造模成功后随机分成2组(模型组和治疗组)，治疗组于造模成功后第2天开始给予胰岛素治疗，正常对照组(8只)与模型组予皮下注射同样体积的生理盐水。2周后取各组大鼠背根神经节，Trizol法提取总RNA，应用RT—PCR法测定3种NOS mRNA的表达。结果：在糖尿病早期大鼠DRG中，iNOS表达明显上调，胰岛素能有效逆转此变化。而nNOS和eNOS的表达无明显变化。结论：在早期糖尿病DRG中iNOS基因表达异常，可能与糖尿病外周神经病变的发生发展有关。