Kentanserin对大鼠心肌缺血 再灌注损伤的影响

为探讨５ ＨＴ２受体与心肌缺血 再灌注损伤的关系,观察５ ＨＴ２受体阻断剂ｋｅｎｔａｎｓｅｒｉｎ对心肌缺血 再灌注大鼠室颤及左室内压＋ｄｐ／ｄｔｍａｘ及－ｄｐ／ｄｔｍａｘ的影响。结果表明,ｋｅｎｔａｎｓｅｒｉｎ可拮抗缺血性心功能障碍和再灌室颤。提示５ ＨＴ２受体参与了缺血性心功能障碍和再灌室性心律失常的发生。     

氟脲嘧啶乳剂直肠内给药治疗晚期直肠癌

氟脲嘧啶(5-FU)乳剂经直肠内灌注后,可于短期内在直肠壁、肝脏及门静脉血中保持较高的浓度[1]。1992年4月～1996年7月,笔者对16例无法手术切除肿瘤的晚期直肠癌患者应用5-FU乳剂直肠内给药,现报告如下。1　临床资料1.1　一般情况　5-FU组(直肠内给予5-FU)16例,男性11例,女性5例,年龄49±4岁(38～56岁)。对照组(未给予5-FU)14例,男性9例,女性5例,年龄52±6岁(27～64岁)。全部患者均经病理证实为直肠腺癌。病理类型:5-FU组中隆起型10例,溃疡型4例,缩窄型2例;对照组中隆起型7例,溃疡型5例,缩窄型2例。两组病例术后均有直肠局部疼痛、坠胀…     

Surgery of epilepsy associated with focal lesions in childhood

OBJECT: Surgery in children with epilepsy is a new, evolving field. The important practical issues have been to define strategies for choosing the most suitable candidates and the type and optimal timing of epilepsy surgery. This study was undertaken to elucidate these points. METHODS: To identify the factors that correlated with outcome, the authors analyzed a series of 200 children (aged 1-15 years (mean 8.7 years) who underwent surgery between 1981 and 1996 at the H?pital Necker-Enfants Malades. In 171 cases (85.5%) the epilepsy was medically refractory and was associated with focal cortical lesions. Surgery consisted of resection of the lesion without specifically attempting to identify and remove the "epileptogenic area. "In the group of children whose seizures were medically refractory, the mean follow-up period was 5.8 years. According to Engel's classification, 71.3% of these children became seizure free (Class 1a,) whereas 82% were in Class I. A multivariate statistical analysis revealed that among all the factors studied, the success of surgery in a patient in whom there was a good clinical/electroencephalogram/imaging correlation depended on the patient's having undergone a minimally traumatic operation, a complete resection of the lesion, and a short preoperative seizure duration. After the surgical control of epilepsy, behavior disorders were more improved (31% of all patients) than cognitive function (25%). The patient age at onset, duration and frequency of seizures, intractability of the disease to therapy, and seizure characteristics were correlated with cognitive, behavioral, and academic performance pre- and postoperatively. Multivariate statistical analysis revealed that cognitive dysfunction correlated highly with the duration of epilepsy prior to surgery, whereas behavioral disorders correlated more with seizure frequency. CONCLUSIONS: These data must be taken into account when selecting patients for surgical treatment and when deciding the timing of surgery. Early surgical intervention allows for optimum brain development.     

Clinical case observations: lessons for empirical research

Empirical studies of psychopathology are typically conducted in the goal of uncovering general characteristics of large samples of individuals. By contrast, the case study has remained a basic paradigm for understanding the causes of psychopathology as it is actually experienced by a given patient. However, by using case studies as an example, empirical researchers are rediscovering the importance of the individual. New data collection and analytic techniques have recently been applied to this effort, and considerable progress has been made to remove previous barriers to idiographic analyses. The present article describes these new applications, and discusses how empirical research can benefit from using case studies as a model for understanding the individual in a larger sample.     

重组人神经营养因子-4/5蛋白抗三氧化二砷神经毒作用

目的初步观察重组人神经营养因子-4／5（hNT－4／5）蛋白对三氧化二砷毒性的抑制作用。方法利用hNT－4／5蛋白具有抗神经毒性的特点,采用本实验室克隆表达及部分纯化的具有天然hNT－4／5蛋白生物学活性的重组hNT-4／5蛋白,以不同水平的重组hNT4／5蛋白（0－100μl）与不同浓度的As2O3（0－160μmol／L）同时加入各组鸡胚前脑神经细胞和PC12细胞培养液中共同孵育24－48小时,观察其对染毒鸡胚前脑神经细胞存活和PC12细胞突起生长的影响作用。结果在鸡胚前脑神经细胞和PC12细胞中与As2O3共同培养48小时后,对照组与实验组的细胞存活率差异有显著性,而且细胞存活率和突起数目随hNT－4／5浓度增高而提高和增加。结论初步观察到重组hNT4／5蛋白具有抑制As2O3的毒性作用,为从基因工程途径寻找抗环境毒物因子提供了依据。     

多普勒超声心动图评估左心室舒张末压的研究

目的探讨多普勒超声心动图评估左室舒张末压的有效方法与指标。方法对６８例病人采用左心导管测压及经胸多普勒超声心动图检测。结果对比研究显示,联合肺静脉与二尖瓣血流频谱分析优于二尖瓣血流频谱分析,肺静脉Ａ峰和二尖瓣Ａ峰时限差值（ＰＡｄ－Ａｄ）与左室舒张末压实测值呈最佳相关性（ｒ＝０．７２,Ｐ＜０．０１）。结论认为应用多普勒超声心动图测定ＰＡｄ与Ａｄ,并以其差值估测左室舒张末压,是一项简便、可靠的无创性评估左室舒张末压的方法。ＰＡｄ－Ａｄ≥０可作为临床判断左室舒张末压增高［≥２．０ｋＰａ（１５ｍｍＨｇ）］的一项半定量指标。     

Does glutathione-S-transferase dethiolate lens protein-thiol mixed disulfides?-A comparative study with thioltransferase.

Protein S-thiolation is a process in which under oxidative stress, vulnerable sulfhydryl groups of proteins are conjugated to non-protein thiols such as glutathione (GSH) or cysteine resulting in the formation of protein-thiol mixed disulfides, protein-S-S-glutathione (PSSG) and protein-S-S-cysteine (PSSC). This process spontaneously disrupts the redox homeostasis of the cells, which in turn leads to functional disturbances in the respective tissue. In the ocular lens, such modification of proteins may trigger a cascade of events starting with the alteration of protein conformation, protein/enzyme deactivation, protein-S-S-protein aggregation and eventually lens opacification or cataract. Generally, the first line of defense system in the cells protects the lens proteins against such damage. Recent studies in our laboratory have shown that in addition to this defense system, lens cells also possess a well developed system to repair the oxidative damage to the lens proteins. We have identified this repair system as thioltransferase (TTase) and have proved that TTase by its dethiolase activity reverses the protein S-thiolation process which returns the oxidatively damaged lens proteins/enzymes to their original reduced state and restores their physiological functions. We investigated if this repair mechanism was mediated by enzymes other than TTase. We studied glutathione S-transferase (GST) and report here for the first time the cloning, high level expression, and purification of human lens mu and pi isoforms of GST. A comparative study of recombinant human lens TTase and GST (mu and pi) on their dethiolating abilities using lens crystallin-thiol mixed disulfides showed that the lens TTase is 60-70% more efficient in the dethiolation/repair process than GST. When TTase and GST were tested in conjunction for the dethiolation of thiol mixed disulfides, there was no significant enhancement of dethiolase activity. These findings suggest that TTase by itself is an efficient enzyme in the dethiolation/repair process and hence can be considered a crucial system to counteract oxidative stress in the lens.     

Modulation of Ca2+/calmodulin-dependent protein kinase II activity by acute and chronic morphine administration in rat hippocampus: differential regulation of alpha and beta isoforms

Calcium/calmodulin-dependent protein kinase II (CaMK II) has been shown to be involved in the regulation of opioid receptor signaling. The present study showed that acute morphine treatment significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus, with little alteration in the protein level of either alpha or beta isoform of CaMK II. However, chronic morphine treatment, by which rats were observed to develop apparent tolerance to morphine, significantly down-regulated both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II and differentially regulated the expression of alpha and beta isoforms of CaMK II at protein and mRNA levels. Application of naloxone or discontinuation of morphine treatment after chronic morphine administration, which induced the withdrawal syndrome of morphine, resulted in the overshoot of CaMK II (at both protein and mRNA levels) and its kinase activity. The phenomena of overshoot were mainly observed in the beta isoform of CaMK II but not in the alpha isoform. The effects of both acute and chronic morphine treatments on CaMK II could be completely abolished by the concomitant application of naloxone, indicating that the effects of morphine were achieved through activation of opioid receptors. Our data demonstrated that both acute and chronic morphine treatments could effectively modulate the activity and the expression of CaMK II in the hippocampus.