氯丙醇对大鼠的毒性研究

进行氯丙醇对大鼠毒作用研究 ,并进行氯丙醇暴露对健康影响评价的生物效应标志物探讨 ,为进行人群氯丙醇暴露对健康的影响评价提供科学依据。选用健康雄性断乳SD大鼠 1 76只 ,随机分为 8组 ,经口灌胃给予 0、0 2 5、0 5、1 0、2 0、4 0、8 0、1 6 0mg kg的 3 氯 1 ,2 丙二醇 (3 MCDP) 90天 ,进行体重、食物利用率、血液学指标、血生化指标、尿液中N 乙酰 β D 氨基葡萄糖苷酶 (NAG)、γ 谷胺酰转肽酶 (GGT)和总蛋白、精子数目、精子存活率和畸形率、睾丸组织中乳酸脱氢酶 (LDH)和乳酸脱氢酶同工酶 X(LDH X)、脏体比及其病理组织学测定和分析。结果表明 ,不同暴露剂量的氯丙醇对动物体重、食物利用率、血红蛋白、红细胞、白细胞、血丙氨酸氨基转移酶 (AST)、天冬氨酸氨基转移酶 (ALT)、肌酐、尿素氮、血清碱性磷酸酶 (ALP)、乳酸脱氢酶 (LDH)、总蛋白、白蛋白、尿GGT酶和总蛋白及睾丸LDH酶均未见显著影响。在 4 0、8 0和 1 6 0mg kg剂量组 ,动物尿N 乙酰 β D 氨基葡萄糖苷酶 (NAG)活性显著增加 ,肾体比增大 ,并出现肾毒性病理改变 ,精子数目也降低。在 8 0和 1 6 0mg kg剂量组 ,精子存活率和睾丸LDH X显著降低 ,睾丸和附睾出现病理改变 ,3 MCDP无致精子畸变作用。由此可见尿液中NAG酶活性和精子     

顺铂对结直肠癌肿瘤浸润淋巴细胞杀伤活性的影响

为在临床选择有效的免疫化疗方案提供一定的理论依据，作者以结直肠癌肿瘤浸润淋巴细胞（ＴＩＬ）和顺铂（ＣＤＤＰ）为研究对象，对１６名手术治疗的结直肠癌患者，分别观察ＣＤＤＰ体内注射及体外预处理ＴＩＬ和Ｒａｊｉ细胞对ＴＩＬ表面标志和杀伤活性的影响。流式细胞仪检测结果显示，静脉注射ＣＤＤＰ能增加结直肠癌ＴＩＬ中ＣＤ３＋／ＣＤ４＋和ＣＤ３＋／ＣＤ８＋细胞含量，同时增强ＴＩＬ体外杀伤Ｒａｊｉ细胞的活性；而体外以ＣＤＤＰ处理Ｒａｊｉ细胞能增强其对结直肠癌ＴＩＬ杀伤的敏感性。作者认为，对于联合应用ＴＩＬ和ＣＤＤＰ治疗结直肠癌的临床效果有必要进一步研究。     

An Appraisal of Different Cardiac Risk Reduction Strategies in Vascular Surgery Patients

OBJECTIVES: to summarize existing evidence regarding the benefits and the risks of all available interventional and medical means aimed at cardiac risk reduction in patients undergoing vascular surgery. DESIGN: review of the literature. MATERIALS AND METHODS: a critical review of all studies examining the impact of various prophylactic cardiac maneuvers on perioperative outcome following vascular surgery was performed. Overall mortality, cardiac mortality and myocardial infarction rate were used as the outcome measures. RESULTS: coronary artery bypass grafting is associated with a 60% decrease in perioperative mortality in patients undergoing vascular surgery, but in most of the cases this decrease does not outweigh the combined risk of the cardiac and the subsequent noncardiac vascular procedure. Data supporting the cardioprotective effect of percutaneous transluminal angioplasty in the perioperative setting are insufficient. beta-blockade has been shown to decrease perioperative mortality and cardiac morbidity in both high-risk (strong evidence) and low-risk (weak evidence) patients. CONCLUSIONS: coronary revascularization is rarely indicated to simply get the patient through vascular surgery and should be reserved for patients who would need it irrespective of the scheduled vascular procedure. Among all available pharmacological agents, including beta-blockers, alpha-agonists, calcium channel blockers and nitrates, only beta-blockers have been proven to reduce the cardiac risk of vascular surgery.     

Acute toxicity of two pyrethroids,permethrin, and cypermethrin in neonatal and adult rats

The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X²=5.97;p<0.05) and PERM (X²=4.37;p<0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.     

POSITIVE INTERACTION OF ETHANOL AND KAVA RESIN IN MICE

1. The lipid soluble extract of the psychoactive beverage kava has hypnosedative properties which can be measured by the length of time that the righting reflex is lost. 2. Ethanol and the lipid soluble extract (kava resin) have been shown greatly to increase each others hypnotic action in mice. Ethanol also increases the toxicity of kava markedly. 3. This interaction of kava and alcohol has important clinical and social consequences since, in contrast to traditional usage, kava is now often taken in conjunction with alcoholic drinks.     

Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.     

Effect of omeprazole on the anticoagulant activity and the pharmacokinetics of warfarin enantiomers in rats

The effect of the proton pump inhibitor omeprazole on the anticoagulation and the pharmacokinetics of warfarin enantiomers was studied in rats. Omeprazole given intraperitoneally in a daily dose of 0.67 mg/kg over 8 days had no significant effect on the absorption, distribution and the total serum clearance values of the S- and R-enantiomers of warfarin. Omeprazole did not affect the pre-treatment baseline blood coagulation and the in vitro rat serum protein binding of warfarin enantiomers. In vitro study with rat liver microsomes showed that omeprazole had an inhibitory effect on the hydroxylation of warfarin enantiomers. Results obtained from in vivo urinary excretion study revealed that omeprazole inhibited the formation clearance of both S- and R-form oxidative metabolites, but increased that of the overall reductive metabolites, and the renal clearance of S- and R-enantiomers, of warfarin. As a consequence, the total serum clearance values for warfarin enantiomers remained unchanged and the hypoprothrombinaemic response produced by warfarin was not affected.     

几种中草药复配杀虫剂的急性毒性实验研究

为有效开发植物杀虫剂资源及今后的推广应用提供科学依据。用两种粉剂和两种醇剂的杀虫应用浓度给小白鼠灌,而家兔则行皮肤刺激试验。结果显示,除醒剂Y-13经口有中毒情况发生外,其它3种制剂均无中毒现象,醇剂Y-13的家兔皮肤也无刺激反应发生。作者认为:4种制剂在有杀虫效果的前提下,杀虫应用浓度对人和动物都较安全。有开发和推广应用价值。