新抗疟化合物的临床前毒性研究——Ⅷ、5-对氟苯氧基伯喹柠檬酸盐毒性试验的病理形态观察

实验性5-对氟苯氧基伯喹柠檬酸盐(MP-0090)毒性试验对狗、猴及小鼠的心肌、肝脏和部分动物的脑进行了病理观察,并与等剂量的磷酸伯喹进行对比。观察结果为二者均可引起部分狗及小鼠的心肌轻度嗜酸性变,部分狗的肝脏有灶性气球样变及个别猴有脂肪变。上述病变均属可逆并无临床意义,此外,两种药物所引起的损害基本相似。     

急性一氧化碳中毒对心肌的损害

<正> 急性一氧化碳中毒对心肌的损害虽然很早就有人作过描述,也有人用急性一氧化碳中毒的方法引起狗心肌的变性和出血坏死,但是只有少数一氧化碳中毒的尸检报告提到心肌的病变。由于中枢神经系统症状的掩盖和心肌受损的症状常在中毒几天以后或急性中毒症状消退后出现,急性一氧化碳中毒的心肌损害常被忽视。我们最近在二例急性一氧化碳中毒,估计在5—6小时内死亡的病例就见到心肌变性和早期坏死。结合我们进行过一些急性一氧化碳中毒的动物实验,在几小时内重复进行急性一氧化碳中毒,经过一     

硝硫氰胺治疗晚期日本血吸虫病一例尸检报告

抗血吸虫病新药硝硫氰胺自湖北省医药工业研究所合成以来,曾对小白鼠、狗、猫、猴等动物进行了急、慢性中毒试验,均能造成中毒性肝炎,出现肝实质细胞变性、坏死和黄疸。实验证明,每公斤体重7毫克的硝硫氰胺能杀灭动物体内的血吸虫。用同样剂量试治大量急、慢性血吸虫病人也获得了令人满意的疗效。在治疗过程中约6.2％的病人出现黄疸,但停药或适当治疗后,黄疸     

丙泊酚对罗哌卡因所致大鼠中枢及心脏毒性的影响

目的探讨丙泊酚对罗哌卡因所致大鼠中枢及心脏毒性的影响。方法 30只雄性SD大鼠随机均分为3组（n=10）,生理盐水组（A组）、丙泊酚Ⅰ组（B组）、丙泊酚Ⅱ组（C组）。实验前5min,A组大鼠股静脉注射生理盐水5ml/kg,B组大鼠股静脉注射0.5%丙泊酚5ml/kg,C组大鼠股静脉注射1%丙泊酚5ml/kg。所有实验动物股静脉置管泵注0.5%罗哌卡因,速度为2.5ml/（kg.min）,并记录大鼠出现抽搐、心律失常和心跳停止的时间及罗哌卡因用量。结果 3组泵入罗哌卡因后均出现抽搐、室性心律失常及心跳停止的中枢及心脏毒性反应。B组、C组出现中枢及心脏毒性反应时的中毒剂量明显大于A组（P〈0.01）。C组出现中枢及心脏毒性反应时的中毒剂量大于B组（P〈0.01）。结论短时间内过量罗哌卡因引起大鼠的中枢及心脏毒性反应,预先给予丙泊酚可明显减轻罗哌卡因对大鼠的中枢及心脏毒性作用。     

香菇多糖注射液毒性实验

本文报导香菇多糖注射液对狗、大白鼠、小白鼠的急性毒性、亚急性毒性实验。急性毒性实验结果;小白鼠尾静脉注射LD_(50)及95％可信限为15O0(1061～212O)mg/kg。肌肉注射对狗的呼吸、血压、心电图均无明显影响。首次静脉注射均有迅速—过性降压作用,同时伴有快速耐受现象,这种降压效应部分可被大剂量异丙嗪所阻断。亚急性毒性实验结果:表明其对动物的心脏、肾脏功能无明显影响,对血清谷丙转氨酶明显下降。病理检查肝细胞有浊肿、水样变性,大剂量组偶有点状坏死,但在停药25天后肝细胞病理改变基本恢复。电子显微镜检查结果肝细胞超微结构基本正常。     

膦甲酸钠的毒性研究

膦甲酸钠毒性试验结果表明：小鼠经静脉注射LD50为395．7mg／kg；大鼠经腹腔注射LD50为1050.5mg／kg；大鼠腹腔注射、狗静脉注射3个月长期毒性试验，无毒反应剂量分别为150mg／kg、60mg／kg，毒性反应剂量分别为300mg／kg、120mg／kg，主要中毒表现为肝、肾功能异常，中毒性肾病及肾小管坏死等；Ames试验中膦甲酸钠对鼠伤寒沙门菌无致突变作用；微核试验中膦甲酸钠未诱发NIH小鼠微核率的增加。     

伯氨喹啉对大鼠的细胞遗传学效应

用体内姊妹染色单体互换法观察了抗疟药伯氨喹啉对大鼠的细胞遗传学效应,见大鼠骨髓细胞 SCE 频率明显增加,提示伯氨喹啉可能是一种潜在的诱变剂。     

强心甙在克山病心功能不全治疗中应注意的几个问题

<正> 目前强心甙已普遍成功地用于亚急型和慢型克山病的治疗。亚急型和慢型克山病,心脏扩大,用洋地黄后心肌氧耗量是净减少的。慢克并有窦性心动过缓的病人,在用洋地黄过程中,往往随着充血性心衰的好转、心率反由过缓逐渐转为正常或接近正常。慢克病人对洋地黄有较好的耐受性,可按一般剂量、根据个体化原则,长期维持治疗。但亚急克的心肌有大片新鲜坏死灶,其情况与急性心梗有些相似,对洋地黄敏感性较高,易于发生洋地黄中毒,尤其当并用强峻排钾利尿剂时,中毒发生率就更高。洋地黄的毒性反应可分为心外毒性反应和心脏毒性反应,而危及生命的主要是心脏毒性反应。洋地黄中毒临床上的最早表     

膦甲酸钠的毒性研究

膦甲酸钠毒性试验结果表明，小鼠经静脉注射ＬＤ５０为３９５．７ｍｇ／ｋｇ大鼠经腹腔注射ＬＤ５０为１０５０．５ｍｇ／ｋｇ，大鼠腹腔注射，狗静脉注射３个月长期毒性试验，无毒反应剂量分别为１５０ｍｇ／ｋｇ，６０ｍｇ／ｋｇ毒性反剂量分别为３００ｍｇ／ｋｇ，１２０ｍｇ／ｋｇ主要中毒表现为肝，肾功能异常，中毒性肾病及肾小管坏死等，Ａｍｅｓ试验中膦甲酸钠对鼠伤鼠寒沙门无致突变作用，微核试验中膦甲酸钠未诱发ＮＩＨ小     

缺血缺氧性心肌坏死的病理学及实验病理学研究

利用人体病理材料及动物实验方法,系统阐明了相对性缺血缺氧(冠状循环不全)时心肌坏死的一系列特点。总结了这类心肌坏死在病变性质、病灶分布、病灶与心壁内冠血管分支的关系、坏死灶的吸收形式与扩展方式等九个方面的形态学特征及其与心肌梗塞的区别。1.冠状循环不全时心肌坏死的性质有凝固性肌溶解和液化性肌溶解两种,根据缺血缺氧程度和发生急缓之不同而异,而心肌梗塞则主要为凝固性心肌坏死。2.冠状循环不全时多为多发性小灶状心肌坏死,病灶之间相隔以正常的心肌,而心肌梗塞时则多为少数大片状坏死。     

Cardiotoxic Effect of Primaquine in Mammals:Histological and Ultrastructural Investigation

It has been known that the antimalarial drugs of aminoquinolinesincluding 8-aminoquinolines may cause inhibition of heart conduction or evenAdams-Stokes syndrome,but their morphologic bases were obscure.The purposeof the present study is to define the histological and ultrastructural features ofprimaquine in mammals including dogs,monkeys and rats in the subacute toxicexperiments with the stress on the morphological alteration of the heart.In most(11/16)of the intoxicated dogs,granular degeneration,eosinophilic degeneration,coagulation necrosis,vacuolar degeneration and colliquative myocytolysis werefound in the myocardium and conduction systems.Under electron microscopicstudy,the myocardial cells of intoxicated dogs showed swelling of mitochondria,dilatation of transverse tubules and sarcoplasmic reticulum,fusion or dissolutionof myofibrils,deformity of nuclei,clumping of chromatin,and eventually cellnecrosis.The severities of lesions were dose dependent.These lesions weresupposed to be the morphologic evidence of the toxic symptoms and signs caused byprimaquine.A few rats also revealed myocardial eosinophilic degeneration.Noimportant cardiac lesions were found in the monkeys,but the pathologic changesin the liver were obvious.Different species of laboratory animals showed differentorgan sensitivities to primaquine,but the heart lesions should be considered as animportant toxic effect of primaquine.     

黄曲霉毒素B_1对大鼠肝脏毒性作用的病理学研究

用雄性Wistar大鼠,体重130～150 g,实验组31只,对照组10只,连续喂黄曲霉毒素B_1结晶品45周,每只大鼠受毒总剂量3.88 mg,分别在第8、9、11、12、13、14、15、16个月处死,每次处死给药组3只,对照组1只,第17个月后自然死亡7只。肝组织切片用HE染色;对28只大鼠肝组织进行了AFP免疫酶染色的形态学观察,15只鼠作了电镜观察,其结果:(1)光镜观察的主要表现为肝细胞的水样变性、嗜酸性变、嗜碱性改变、脂肪变性以及肝细胞的灶性坏死。其应答反应显示卵圆细胞和小胆管增殖、肝细胞的再生及炎细胞浸润。上述改变为慢性非特异性中毒性肝炎;(2)电镜观察主要改变有肝细胞核仁均质化,核样体形成,线粒体肿胀和基质均质化,继而形成空泡和灶性坏死;(3)85.71％(24/28)宿主肝细胞AFP免疫酶染阳性,多呈全胞浆型分布,阳性程度多为弱至中等度。AFP阳性肝细胞呈散在或灶性分布。这一改变表明,是由于AFB_1对肝细胞毒性损害所产生的返祖现象。     

大鼠心肌急性高原性损伤特征的形态学观察

本实验将大鼠由近海平面区在10天内携往高原,通过对其心脏标本的光,电镜观察,提出以(1)右心室为主的全心性损伤(2)心肌细胞混浊肿胀,空泡变性,溶解坏死,间质水肿及(3)心肌细胞膜系统改变,收缩成份破坏,细胞内外水肿和糖元颗粒减少等分别为急性高原性大鼠心肌损伤的组织学及超微结构特征。     

MYOCARDIAL LESIONS AFTER LONG-TERM ADMINISTRATION OF METHAMPHETAMINE IN RATS

Objective To demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats.
Methods The experimental models of intoxication of methamphetamine were established in Sprague-Dawley rats. Methamphetamine hydrochloride （3 mg·kg^-1·d^-1） was subcutaneously injected to rats in methamphetarnine-treated group （n = 16）, and normal saline at the same dose was injected to rats in control group （n = 16）. After 1 week and 8 weeks of injection, 8 rats in each group were sacrificed and their hearts were examined with light microscopy and electron microscopy, respectively.
Results After 1 week of methamphetamine exposure, loci of contraction band and cellular degeneration were present in subendocardial myocardium. Cellular degeneration, myocytolysis, and contraction band necrosis became prominent and extensive in methamphetamine-treated rats after 8 weeks. Hypertrophy, intracellular vacuolization, and fibrosis were also observed. The ultrastructural feature showed marked swelling and degeneration of mitochondria, enlargement of sarcoplasmic reticulum, and dissolution of myofilaments. No obvious cardiac myocyte lesions were observed in rats of control group.
Conclusion Methamphetamine abuse daily for a long time may result in an increased risk of cardiovascular lesions similar to cardiomyopatby.     

高原急性缺氧对大鼠心肌结构的影响

为明确早期高原实地缺氧对大鼠心肌结构的影响 ,对携至不同海拔高原地区大鼠心肌组织的光、电镜标本进行了观察。结果 :光镜下大鼠各室壁心肌细胞均可见不同程度的浊肿、空泡变性、溶解坏死及间质水肿等 ;电镜下可见心肌细胞线粒体肿胀 ,肌浆网扩张 ,肌原纤维溶解 ,细胞内外水肿等 ,上述改变右室壁较左室壁明显 (P <0 .0 1 )。结果提示 :高原急性缺氧造成大鼠以右心室为主的全心性损伤 ,应重视高原缺氧早期的全心性防护。     

古罗酸伯喹的毒性及其抗疟作用

Elslager 在研究长效伯喹时报道了几十个水不溶的伯喹盐,未显示有长效作用。我们也研究了几十个伯喹盐,同样未获长效。我们设想某些水不溶的伯喹盐有可能毒性较低而疗效与磷酸伯喹相当,因此选取对鼠疟疗效较好的古罗酸伯喹与磷酸伯喹作了比较。实验证明古罗酸伯喹毒性较低而疗效与磷酸伯喹相当。     

持续性动脉血压升高心肌局灶性纤维化的病理形态学观察

观察了两肾一夹型高血压Wistar大鼠心肌局灶性纤维化病变的病理形态。在16只高血压大鼠心脏整张切片中,发现纤维化病灶81个,其中与小血管伴行者38个(46.9％),纤维组织为主者28个(34.6％),肉芽组织为主者15个(18.5％)。大部分病灶中遗留着心肌细胞坏死的痕迹,炎细胞浸润见于少数病灶。认为持续性全身性动脉血压升高心肌局灶性纤维化可由小血管病变引发,但多由心肌梗死引起,心肌间质细胞及嗜酸性白细胞和嗜中性白细胞在某些情况下也可能起着一定的作用。     

达曲班对异丙肾上腺素诱导的心肌缺血及离体心肌的作用

观察新型血栓素A2(TXA2)受体拮抗剂达曲班对异丙肾上腺素(Iso)诱导的大鼠心肌缺血损伤的保护作用及对心肌四性的影响。方法静脉注射Iso诱发大鼠心肌缺血，记录缺血后心功能的变化及心肌细胞病理改变情况。用离体大鼠心房肌进行自律性、收缩性、兴奋性和不应性的研究。结果达曲班对缺血后心功能的下降有明显的抑制作用，并能明显减轻缺血捐伤后心肌细胞坏死和浊肿现象。对离体心房肌能明显延长功能性不应期，抑制肾上腺素诱发的自律性，而对收缩性和兴奋性无明显影响。结论达曲班有较强的抗心肌缺血作用。     

色甘酸二钠注射给药的毒性研究

小白鼠iv DSCG的LD_(50)为2800±17.8mg/kg在猫与兔的急性毒性实验中,DSCG可引起短暂心率加快和血压升高,对ECG与呼吸几无影响。在亚急性毒性实验中,大剂量的DSCG可引红、白细胞数减少、肝功能损伤、肺间质性炎症和脾淤血。     

EFFECTS OF HIGH DOSE NARCOTICS AND CONTROLLED HYPOTENSORS ON THE HEART CONDUCTION SYSTEM

The effects of narcotics on the heart conduction system were studied in 51 rabbits. It was found that at equal efficacy dosages, the effects of high dose morphine, pethidine and fentanyl on the heart con duction system differ. Morphine 3 mg/kg injected iv did not influence the heart conduction system; fentanyl 30 ug/kg might improve both sinus node automaticity and sino-atrial conduction and pethidine 30 Vg/kg might seriously harm the heart conduction system. So fentanyl may be an ideal narcotic in patients with sick sinus syndrome. But when the dosage of fentanyl was increased t0 75 yg/kg, the sinus node was inhibited. The degree of pethidine effect upon the heart conduction system depends upon the dosage and rate of injection. The effects of controlled hypotensors on the heart conduction system were studied in 48 dogs. Trimethaphan (TMTP), sodium nitroprusside (SNP) nitro-glycerine (NG) and phentolamine (PA) were dripped iv respectively to lower the blood pressure by 30-40%. Five and 60 minutes after TMTP ad- ministration the atrio-ventricular junction was in inhibited and at 60 minutes the sino-atrial conduction was also inhibited. NG had no influence on the heart conduction system but SNP might inhibit the sinus node automaticity PA may also inhibit the sino atrial conduction, so this agent contraindicated in patients with sick sinus syndrome or sino-atrial block.