-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.     

Phosphate end dialysis value : a misleading parameter of hemodialysis efficiency

Despite low end dialysis serum phosphate levels (P_e) the control of phosphate retention remains often unsatisfactory in dialyzed patients. In order to assess the value of P_e in dialyzed children as an indicator of dialytic phosphate removal, we studied serum phosphate kinetics over the period of dialysis and post dialysis and compared these with urea kinetics. A multicenter study was conducted in the 21 French pediatric hemodialysis units and included 144 children under 15 years of age. Blood urea and phosphate concentrations were measured at the beginning, at 45 min later, at the end of dialysis, and 30 min post dialysis. At 60 min and at 360 min post dialysis measurements were made only for a subgroup of 12 children. From the serum levels, reduction ratios for urea (URR) and phosphate (PRR) and post dialysis rebound for urea (PDUR) and phosphate (PDPR) were calculated. URR (over the dialysis session, 72%±9%) was higher than PRR (47%±12%). Moreover, urea removal continued throughout the dialysis period, while most of the reduction in phosphate occurred in the initial dialysis period. Post dialysis urea rebound was limited to the 60th min post dialysis, whereas post dialysis phosphate rebound occurred until the 360th min post dialysis; by this time the serum phosphate levels had almost reached the predialysis levels. In summary, serum phosphate kinetics over dialysis and post dialysis periods in children appear to be misleading for the quantification of phosphate removal, i. e., phosphate clearance is a poor indicator of dialytic phosphate removal. Received September 21, 1995; received in revised form and accepted June 11, 1996     

Z-3-(2-羟基丁烯基)苯酞的合成研究

研究目的探讨苯酞类天然产物的合成方法及其生物活性。研究方法以邻苯二甲酐为底物，首先引入丁烯基，再进行烯丙位氧化，制得目标化合物。结果通过丁基锂反应，得到了具有药物活性的丁烯基苯酞，然后利用SeO2烯丙位氧化，首次合成了Z－3－（2－羟基丁烯基）苯酞。结论此合成方法原料易得，方法简便，为苯酞类化合物的合成研究提供了一个新的途径。     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

安桃乐气体吸入在分娩镇痛中对母婴影响的观察分析

目的:探讨安桃乐(ENTONOX)气体吸入对分娩镇痛及母婴结局的影响。方法:将181名无产科或内科合并症的住院产妇随机分成两组,一组由家属全程陪护,另一组由家属全程陪护+安桃乐气体吸入,观察两组产妇的镇痛效果、产程进展、分娩方式、新生儿Apgar评分情况、产后出血量。结果:ENTONOX吸入对分娩镇痛有效率达98.2％,显效率达80.7％,对产程进展有促进作用,对分娩方式、围产儿结局、产后出血量无显著性差异。结论:ENTONOX吸入镇痛是一种安全、有效的辅助分娩技术,作用迅速、费用低廉,是产妇乐意接受的镇痛方法。     

Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia. METHODS: Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography. RESULTS: The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations. CONCLUSIONS: The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.     

医院消毒灭菌效果自我监测的情况及分析

目的 :探讨医院消毒灭菌效果自我监测能力的可靠性。方法 :回顾性总结了对医院消毒灭菌效果定期及不定期进行监测的情况 ,及上级防疫部门对医院消毒灭菌效果抽查的情况。结果 :医院自查物品合格率略高于防疫站抽查物品合格率。但两组资料比较P >0 0 5 ,差异不显著。结论 :医院自我监测能力是可靠的 ,必须在加强医院自我监测能力的基础上 ,被动监测变为主动监测 ,回顾性调查变为前瞻性监控 ,才能保证消毒灭菌质量 ,才能提高医疗质量 ,提高社会效益和经济效益。     

"提高意识"活动在大学英语精读课中的体现 --对医学护理专业学生精读课改革的重新思考

语法翻译教学法多年来一直主宰着大学英语精读课的教学。随着中国经济突飞猛进的发展,各行各业的人们与国外同行交流的机会和要求也随之增加。面对社会发展而带来的这种变化,显然,古老传统的教学方法已不能适应。通过具体详尽的理论分析,对语法翻译教学法提出了自己的看法。     

孟鲁斯特对哮喘模型IL-5mRNA和IL-5蛋白表达的影响

目的 探讨白三烯受体拮抗剂孟鲁斯特(MK)对哮喘小鼠IL-5mRNA、IL-5蛋白表达的影响。方法 采用原位杂交、免疫组化LSAB法,检测哮喘小鼠及孟鲁斯特治疗后哮喘小鼠骨髓细胞IL-5mRNA的表达及肺、骨髓、脾IL-5蛋白的表达情况。 结果 孟鲁斯特可显著减轻哮喘小鼠肺组织炎症细胞浸润、细支气管痉挛、粘液分泌等;亦可减少骨髓IL-5mRNA阳性细胞数(P<0.02),并使骨髓、肺、脾IL-5蛋白表达下降。 结论 白三烯受体拮抗剂孟鲁斯特不仅使肺部炎症显著减轻,也抑制骨髓细胞表达IL-5mRNA、IL-5蛋白,提示白三烯可能通过调节炎症细胞、细胞因子合成来应答过敏原反应。     

非穿透性小梁切除术治疗开角型青光眼

目的 研究非穿透性小梁切除术治疗开角型青光眼的手术效果。方法 对20例26眼开角型青光眼行非穿透性小梁切除术,术后观察眼压、结膜滤枕及前房反应等情况,随访1～12个月。结果 术后各期平均眼压均低于术前平均眼压,差异有显著性(P<0.05)术。前平均眼压26.26mmHg,术后3个月、6个月、9个月、12个月平均眼压分别为15.47mmHg、16.89mmHg、19.14mmHg、18.50mmHg。16眼结膜形成滤性手术典型滤过泡,10眼结膜疏松无滤过泡形成。26眼均无前房出血,术后前房反应轻。结论 非穿透性小梁切除术能有效地降低开角型青光眼的眼压,术后并发症少,可作为此类青光眼病人手术的选择。