POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Objective. Angiotensin-converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion-deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness.Methods. A case-control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho-provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P＜0.05; odd ratio 4.98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P＜0.05; odd ratio 3.8). Accordingly, the mean values of FEV1% and FEV1/FVC were higher in asthmatics carrying non-DD alleles than patients with DD genotype (73.78% vs 56.56%, P＜0.05; 79.19% vs 69.29%, P＜0.05, respectively).Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.     

持续顺行灌注温血停搏液对心肌的保护作用

研究持续灌注温血停搏液对心肌的保护作用,探讨理想的心肌保护策略,方法６９只猫随机分为对照组、损伤组和保护组。观察测各组不同时间点心功能、心肌细胞膜ＡＴＰａｓｅ活性心肌细胞膜蛋白颗粒的形态变化。结果组Ⅰ各时间点各项指标无明显变化。升主动脉阻断期间,组Ⅱ－ⅢａＫ－ＡＴＰａｓｅ活性均显著下降（ＡＣＣ１５ｍｉｎ ｕｓ ＡＣＣ６０ｍｉｎ,Ｐ〈０．０１）,组ⅡＣａＭｇ－ＡＴＰａｓｅ活性单位面积心肌细胞膜蛋白颗     

妊娠早期人巨细胞病毒感染与妇女自然流产的关系探讨

目的：探讨妊娠早期人巨细胞病毒（ＨＣＭＶ）感染和妇女自然流产的关系。方法：采用ＥＬＩＳＡ和ＰＣＲ分别为４０例自然流产妇女和４０例人工流产妇女和血清中人巨细胞病毒ＩｇＭ抗体（ＨＣＭＶ－ＩｇＭ）胎盘组织中人巨细胞病毒核酸（ＨＣＭＶ－ＤＮＡ）进行检测。结果自然流产组妇女ＨＣＭＶ－ＩｇＭ检出率为５５％（２２／４０）,人工流产组妇女为２５％（１０／４０）,自然流产组妇女胎盘组织ＨＣＭＶ－ＤＮＡ检出率为１０％     

玻璃体内注射庆大霉素致视网膜损伤的实验研究I．组织病理学观察

为探讨庆大霉素对视网膜的毒性作用和评估玻璃体内注射庆大霉素的安全剂量,采用眼底镜观察及光镜、电镜技术对注射5种不同剂量庆大霉素的青紫蓝兔视网膜标本进行观察。结果： 3 ooo/μg庆大霉素注射后眼底表现为视盘水肿,后极部视网膜大片坏死,镜下视网膜组织形态严重破坏;50～500μg剂量注射引起后极部视网膜色素改变,组织损伤早期局限在视网膜内层,晚期全层受累。提示庆大霉素对视网膜的损伤程度随注入剂量增加而加重,即使50μg的微小剂量仍可产生视网膜损伤。 （中华眼底病杂志,1994,10：167-169）     

Type-I and type-iii procollagen metabolites and ca 125 in epithelial ovarian-cancer

The clinical courses of 24 patients with advanced epithelial ovarian cancer were monitored with serial serum CA125, PIIINP and PICP determinations before, during and after treatment. Initial serum CA125, PIIINP and PICP concentrations were pathologic in 93%, 80% and 11% of the cases, respectively. Eight patients responded to therapy with complete remission and 16 patients died of the malignancy. Initial serum PIIINP concentration, but not that of CA125 or PICP, was significantly lower in responders than in nonresponders. The pathologic serum CA125 and PIIINP levels of the responders decreased to normal within two months, whereas in patients with a poor prognosis they remained elevated. Serum CA 125 and PIIINP responded to progression with an increase and to remission with a decrease. The changes in the serum PICP concentration took place predominantly within the reference interval. In seven patients with progressive malignancy, it increased to a pathologic level during the final stage of the disease. Our results indicate that extensive ovarian malignancy strongly affects the metabolism of type I and type III collagens. The PIIINP assay is clinically useful. PIIINP and PICP determinations also have potential to increase our understanding of the mechanisms of invasion and spread of malignant tumours.     

Minimal changes with long-term administration of anxiolytics on septal driving of hippocampal rhythmical slow activity

In free-moving male rats, the function relating frequency to the threshold current required to drive hippocampal rhythmical slow activity (RSA; theta) with septal stimulation has a minimum at 7.7 Hz. Classical anxiolytics all increase thresholds in the region of 7.7 Hz, and so does the novel anxiolytic buspirone. However, unlike classical anxiolytics, 2 or 3 weeks are normally required for the onset of the clinical effects of buspirone. This study tested the effects of long-term administration of chlordiazepoxide and buspirone on septal driving of RSA. Separate groups of naive rats received three IP injections per day of chlordiazepoxide (0.4 mg/kg), buspirone (0.1 mg/kg) or saline for 50 days. Both chlordiazepoxide and buspirone increased thresholds at 7.7 Hz, as expected. These acute effects were not significantly changed with chronic administration. Buspirone and chlordiazepoxide produced similar, statistically significant, but small cumulative reductions in thresholds at 6.9 Hz. The present experiments suggest that if the effects of anxiolytic drugs on septally driven RSA provide any basis for their clinical action, then classical anxiolytics may have two actions: an immediate effect on euphoria and tension and a delayed effect on anxiety proper — with buspirone sharing only the latter effect.     

小鼠颗粒子宫腺细胞的组织学与超微结构的研究

对昆明种小鼠颗粒子宫腺细胞（ＧＭＧ细胞）进行光镜及电镜观察,结果显示：ＧＭＧ细胞以其胞浆中含耐淀粉酶消化的ＰＡＳ阳性颗粒为特点,而该种颗粒在电镜下为带有帽状结构的膜包颗粒。ＧＭＧ细胞有特殊的形态,其出现和消失与妊娠过程同步。     

Pharmacokinetic-pharmacodynamic (PK-PD) modeling for a new antihypertensive agent (neutral metalloendopeptidase inhibitor SCH 42354) in patients with mild to moderate hypertension

SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the link model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid E_max PD model. For the 300 mg BID dose, PD parameters were: maximum effect (E_max), 8.1mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC₅₀), 0.87 g·ml^–1; and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple E_max PD model. PD parameters obtained over the dose range were: E_max, 10.3 mmHg; Eo, 2.0 mmHg; and EC₅₀, 0.7 g·ml^–1. These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 g·ml^–1.     

十一酸睾酮对人精浆蛋白的影响

本文采用SDS—PAGE法,测定7例健康育龄男子在肌肉注射十一酸睾酮(TU)前,用药后l、2、3个月及停药后精子计数恢复正常时的精浆蛋白浓度和组份变化,并结合血清测定激素水平及常规精液分析,以探讨TU对上述指标的影响及其相互关系。结果显示:用药早期精浆总蛋白浓度开始逐步降低,在停药后精子计数恢复正常时仍未达到正常水平。精浆总蛋白浓度的变化与精子活动率、前向运动率及LH呈正相关(r值分别为0.8975、0.7776、0.6406,P<0.01或0.05)。精浆蛋白组份也发生变化,其中51KD、37KD的蛋白条带变化最为明显,其变化除与精子活动率相关外(r=0.9094,P<0.01),其中51KD蛋白条带的变化还与精子前向运动率相关(r=0.7660,P<0.05)。上述结果提示TU可能在抑制生精之前即通过改变精浆蛋白而影响精子的功能,说明单用睾酮(T)的避孕机理是多因素的。     

综合治疗对脑梗塞相关危险因素的影响

目的　探讨综合治疗对脑梗塞复发的相关危险因素的影响。方法　随机选择85 例脑梗塞伴各类危险因素患者在综合治疗前后,对他们进行血压、空腹血糖、胆固醇、甘油三酯及血液流变学等8 项指标的测定。结果　经过1 ～3 年临床观察随访,有50 % 以上高血糖、高血脂、高粘滞血症患者检验指标趋于正常,94 .3 % 的高血压得到控制与稳定,经t 检验,血液流变学4 项P 值< 0 .05 ,差异有显著意义,高血压、空腹血糖、胆固醇、甘油三酯的P 值< 0 .01 ,差异有非常显著意义。结论　综合治疗对控制相关危险因素,预防脑梗塞复发有重要临床意义