Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

槲皮素磷酸酯钾对实验性心肌梗塞的影响

iv10～20mg/kg(木解)皮素磷酸酯钾使兔急性心肌梗塞范围明显缩小,ST段明显降低,并能对抗冠脉结扎后引起的血清CPK含量增加及心律失常,这些作用与普萘洛尔相似。但iv40mg/kg后作用不明显。     

肾脏疾病患者治疗前后血浆内皮素水平动态变化及其意义

目的 为了探讨肾脏疾病患者血浆内皮素水平与肾脏疾病病情程度的关系,为肾脏疾病治疗效果的评价提供依据.方法 采用放射免疫分析(RIA)观察了77例肾脏疾病患者治疗前后血浆内皮素水平的动态变化,并与60例正常对照组比较.结果 正常对照组血浆内皮素浓度为43.1±15.2ng/L,肾脏疾病患者治疗前血浆内皮素水平为161±83.8ng/L,治疗后为97.4±52.7ng/L,均高于正常对照组(P值均<0.001).肾脏疾病治疗后内皮素水平明显下降(P<0.001),与BUN,Cr水平的下降具有一定的相关性(相关系过分别为0.54,0.55).结论血浆内皮素水平随着肾脏疾病严重程度的增加而升高,血浆内皮素水平可作为肾脏疾病治疗效果评定的指标之一     

-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats

L-2-Hydroxyglutaric acid (LGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as L-2-hydroxyglutaric aciduria (LHGA). Although this disorder is predominantly characterized by severe neurological findings and pronounced cerebellum atrophy, the neurotoxic mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA, at 0.25-5mM concentrations, on total creatine kinase (tCK) activity from cerebellum, cerebral cortex, cardiac muscle and skeletal muscle homogenates of 30-day-old Wistar rats. CK activity was measured also in the cytosolic (Cy-CK) and mitochondrial (Mi-CK) fractions from cerebellum. We verified that tCK activity was significantly inhibited by LGA in the cerebellum, but not in cerebral cortex, cardiac muscle and skeletal muscle. Furthermore, CK activity from the mitochondrial fraction was inhibited by LGA, whereas that from the cytosolic fraction of cerebellum was not affected by the acid. Kinetic studies revealed that the inhibitory effect of LGA on Mi-CK was non-competitive in relation to phosphocreatine. Finally, we verified that the inhibitory effect of LGA on tCK was fully prevented by pre-incubation of the homogenates with reduced glutathione (GSH), suggesting that this inhibition is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of creatine kinase activity for energy homeostasis, our results suggest that the selective inhibition of this enzyme activity by increased levels of LGA could be possibly related to the cerebellar degeneration characteristically found in patients affected by L-2-hydroxyglutaric aciduria.     

Serum creatine kinase activity following forearm flexion isometric exercise

Summary The purpose of this study was to 1) compare serum creatine kinase (CK) activity following two forearm flexion isometric exercise regimens differing in work to rest ratio, and 2) examine the CK response to a repeated bout of isometric exercise. Eleven males were tested on two sessions (bouts) spaced 1 week apart. For bout 1, five subjects (group A) performed a forearm flexion isometric exercise consisting of 40 10-s maximal contractions with 20-s inter-trial rests (1020), while six (group B) performed 40 maximal 10-s contractions with 5-s inter-trial rests (105). The increase in serum CK activity following the 1020 exercise (143%) was significantly greater than that following the 105 exercise (52%). The 1020 exercise was also associated with greater tension generation over trials. One week later, both groups performed a bout of 1020 exercise. A substantial reduction in the serum CK response was found following this second bout. The data suggest that for bout 1 the isometric exercise associated with the greater overall tension levels resulted in the greater CK response. However, when the 1020 exercise was repeated 1 week later, a substantial reduction in the CK response was found which was unrelated to the tension generated.This study was supported by a University Faculty Research Grant No. 2-03021     

急性心肌梗死患者血清肌酸激酶同工酶高峰与充血性心力衰竭的关系

目的：了解急性心肌梗死（AMI）患血清肌酸激酶同工酶MB（CK－MB）高峰与充血性心力衰竭（下称“心衰”）的关系。方法：对34例AMI患采用免疫抑制法制定系列血清CK－MB,并观察其并发心衰的情况。结果：AMI并发心衰患9例（心衰组,其中约40％在24h后并发心衰）,AMI无心衰患25例（无心衰组）两组血清CK－MB高峰时间均在24h内,但心衰组血清CK－MB峰值比无心衰组明显增高（P＜0．01）。结论：测定血清CK－MB峰值有助于预测AMI并发心衰。     

磷酸肌酸停搏液对缺血心肌的保护作用

目的 探讨外源性磷酸肌酸（creatine phosphate,CP）在心脏直视手术中作为添加剂加入心脏停搏液中对缺血心肌的保护作用。方法 66例接受心内直视手术的患者分为对照组（I组）及试验组（Ⅱ组）,各33例。I组使用冷晶体停搏液,Ⅱ组在I组停搏液中加入CP。于不同时段取血样检测5种心肌酶的含量。结果 两组心肌酶含量,术前差异无显著性;术后Ⅱ组心肌酶谱上升幅度低于I组,而下降速度则快于I组。结论 外源性CP加入心脏停搏液中对心肌具有良好的保护作用。     

磷酸肌酸心脏停搏液心肌保护临床观察

目的研究磷酸肌酸对缺血/再灌注损伤心肌的保护机制.方法对16例进行双瓣膜替换术的患者,随机分成两组(各8例)对照组(单晶体停搏液组)和实验组(晶体停搏液中加入磷酸肌酸10mmol/L);分别于主动脉阻断前,开放后5、15、30、60、120min抽血测定乳酸(LA)、丙二醛(MDA)、超氧化物歧化酶(SOD)、黄嘌呤氧化酶(XOD);于阻断前,开放后2、24和48h测定心肌肌钙蛋白T(cTnT);两组部分患者于心脏阻断后即刻和主动脉开放前1min,取左心房心肌做电镜检查.结果开放后5、15、30min时实验组LA、MDA含量明显低于对照组(分别为P＜0.05、O.01),SOD活性保持明显高于对照组(P<0.05),XOD组间无明显差异;开放后2、24、48h实验组cTnT显著低于对照组(P＜0.01).心肌超微结构结果为对照组线粒体改变较实验组明显(2.725±0.832和l.872±0.542,P＜0.001).结论磷酸肌酸具有为心肌细胞提供能量、保护细胞膜完整、维持心肌收缩蛋白正常的作用,可减轻心肌缺血/再于灌注损伤.     

Investigations into the effects of various hepatotoxic compounds on urinary and liver taurine levels in rats

The effect of various hepatotoxicants on urinary taurine and urinary creatine has been studied in the rat. Several hepatotoxic agents, carbon tetrachloride, thioacetamide, galactosamine and allyl alcohol which all caused hepatic necrosis (sometimes accompanied by steatosis), resulted in a rise in urinary taurine and in some cases creatine, when administered to rats. Ethionine and hydrazine also raised urinary taurine but caused only steatosis and did not raise urinary creatine. Therefore urinary taurine and possibly creatine may be useful markers of liver injury and dysfunction. Liver taurine levels were also affected by some of the hepatotoxicants but in those cases where there was a rise in urinary taurine this could not be accounted for by the loss in liver taurine. It is suggested that the increase in urinary taurine is partly due to changes in protein synthesis and hence in sulphur amino acid metabolism caused by hepatotoxic agents. However, bromobenzene did not increase urinary taurine and-naphthylisothiocyanate and lithocholate caused reduced levels. It is suggested that this lack of increase in urinary taurine may be due to depletion of glutathione or interference with the biliary system.     

乳酸脱氢酶同工酶LD1/LD2比值测定在急性心肌梗塞诊断中的意义

目的与方法:用琼脂凝胶电泳法测定乳酸脱氢酶(LDH)同工酶LD1/LD2比值.结果:表明,急性心肌梗塞(AMI)组44例平均1.0464士0.2947,非心肌梗塞组35例平均0.7690±0.1333,二者比较差异显著.首次血清的敏感性为47.7%(21/44),特异性为97.1%(34/35).并与发病后不同时间LDH.CK-MB,GOT做了比较,探讨其对AMI的诊断价值.结论:本文亦表明LDH同工酶的测定可弥补心电图对AMI诊断上的不足.