农药唑呀威毒理及中毒治疗的实验研究

唑呀威（Ｔｒｉａｚｕｒｏｎ）系新型的高效杀蚜虫剂。目前，对其抑制胆碱酯酶活性的毒理尚报道不一。作者在进行毒性测试和发现１６名包装工夏季作业时８名出现明显症状的基础上，开展动物实验研究。结果发现，唑呀威有较有机磷农药更为快速的胆碱酯酶抑制作用，大鼠经口染毒１１２．５ｍｇ／ｋｇ仅３０ｍｉｎ内即见全血胆碱酯酶活性显著下降，Ｐ＜０．０１；且存在明显剂量－反应关系。高剂量（２００ｍｇ／ｋｇ）还可引起心血管系统的损害。注射阿托品有显著解救效果，染毒同时给药的解救效果明显优于染毒后５分钟给药，提示愈早给药解救效果愈好。作者由此提出了临床中毒急救措施的建议     

复方甘油注射液长期毒性试验

复方甘油注射液系新脱水药。为了确定该药反复使用有无蓄积性中毒作用及最大无作用量，作者以大鼠和狗进行为期２８天的长期毒性试验。两种动物皆设立生理盐水对照组，低剂量组（大鼠为１０ｍｌ／ｋｇ，狗为１．７ｍｌ／ｋｇ），高剂量组（大鼠为４５ｍｌ／ｋｇ，狗为１３ｍｌ／ｋｇ）。按规定剂量每天一次静注给药，连续２８天。结果表明，两种动物均未出现明显的机能性变化，以及特异性靶器官、靶细胞的损害。故认为大鼠和狗对受试物的最大无作用量分别大于４５ｍｌ／ｋｇ和１３ｍｌ／ｋｇ。     

环孢素A体外抗曼氏血吸虫作用的观察

ＭＦ１小鼠实验感染曼氏血吸虫尾蚴１周、３周和６周后，分别经肺静脉和门静脉灌注取虫。实验显示，药物体外抗曼氏血吸虫的作用呈时间、剂量和虫龄依赖方式，童虫和雄虫对药物更敏感。     

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     

移植肾彩色多普勒血流超声与肾穿刺活检的对照研究

将彩色多普勒血流超声与移植肾活检结果相对照。评价无创性ＣＤＦＩ对移植肾排异反应的诊断价值。结果：不同病理状态下移植肾的阻力指数有所不同。急性排异和慢性排异反应组的ＲＩ值明显高于正常组。两次肾活检提示由急性排异转为慢性排异反应的同一患者，ＣＤＦＩ的动态观察显示，ＲＩ值明显增高。     

硒对氟致雄性大鼠生殖损害的拮抗作用

目的 :探讨硒对高氟所致雄性大鼠生殖损害的拮抗作用。方法 :1 0 0只雄性Wistar大鼠随机分成对照组、氟 (NaF 1 5 0mg/L)组、氟加低硒 (0 .5mg/L亚硒酸钠 )组、氟 (NaF 1 5 0mg/L)加中硒 (2 .0mg/L亚硒酸钠 )组、氟(NaF 1 5 0mg/L)加高硒 (4 .0mg/L亚硒酸钠 )组 5组 ,通过饮水加氟、加硒的方法染毒 1 0周。观察氟、硒对大鼠体重、睾丸和附睾质量及其脏器系数 ,精子计数、活动率及畸形率 ,睾丸、附睾生化标志酶 ,血清性激素 ,睾丸组织病理切片以及初级精母细胞染色体畸形率的影响。结果 :①右侧睾丸质量对照组为 (1 .80± 0 .2 2 )g ,氟加高硒组为 (1 .6 1±0 .1 1 )g ,2者相比差异有统计学意义 (P <0 .0 5 )。②精子计数 :氟组 (9.2 3× 1 0 7ml-1 )、氟加中硒组 (37.6 7× 1 0 7ml-1 )与对照组 (2 8.6 0× 1 0 7ml-1 )比较 ,差异有统计学意义 (P <0 .0 0 1 ) ;精子畸形率 :氟组 (36 .33% )氟加中硒组 (1 2 .70 % )与对照组 (1 4 .83% )比较 ,差异有统计学意义 (P <0 .0 0 1 ) ;精子活动率 :氟组 (6 2 .0 7%± 6 .5 0 % )氟加中硒组 (6 8.2 1 %± 4 .99% )与对照组 (73.6 7%± 6 .5 1 % )比较 ,差异有统计学意义 (P <0 .0 0 1 )。③LDH :氟组 ((5 79.4 7± 97.1 6 )u/g)、氟加中硒组 ((72 6 .1 3± 1 1     

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.     

Evidence for delayed cytotoxicity effects following exposure of rat hepatoma-derived Fa32 cells: implications for predicting human acute toxicity

The delayed cytotoxicity of the Multicentre Evaluation of In vitro Cytotoxicity (MEIC) reference chemicals was investigated in rat hepatoma-derived Fa32 cells. The cells were treated for 24 h with the test chemicals, and were than further cultured for 5 days in normal culture medium. The cytotoxicity was measured by the neutral red uptake inhibition, and the results were quantified by determining the NI50del. This is the concentration of test compound required to decrease the neutral red uptake with 50% compared with control cells. The results were compared with the acute NI50, the corresponding value measured immediately after 24 h treatment of the cells. On a total of 44 chemicals, nine showed delayed cytotoxicity (NI50del lower than or equal to NI50), 11 a probably delayed, and 24 no delayed cytotoxicity (NI50del more than 1.5×NI50). When the NI50del was compared with human toxicity, a correlation coefficient r²⁼0.761 was obtained. For the same series of 44 chemicals this correlation was clearly higher than that for human hepatoma-derived Hep G2 cells (r²=0.695). The Hep G2 assay was the best acute in vitro assay for the prediction of human toxicity within the MEIC study. Consequently, the delayed cytotoxicity assay on cultured Fa32 cells has the best prediction value so far obtained for the human toxicity.