Effect of Zonisamide (CI-912) on a Synaptic System Model

The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.     

酥胆麒麟膏用于痔瘘术后换药的药效学与毒理学研究（二）

本文通过设一个阳性对照组（马应龙鹰香痔疮膏），一个空白对照组（凡士林）及酥胆麒麟膏大、中、小三个剂量组（１０％、２０％、４０％浓度）进行三个方面的实验研究，证实酥胆麒麟膏具有止血、抗菌、生肌长皮等综合作用，局部外用无毒副作用，安全性高。其止血、生肌长皮作用，优于马应龙麝香痔疮膏；抗金葡萄茵的作用与银灰散相同；抗大肠杆菌的作用犹于银灰散。尤其是２０％酥胆麒麟膏的以上多种作用优于１０％浓度的，等效于４０％浓度的，可作为临床使用时的最佳浓度。     

Electrophysiologic mechanisms of ventricular arrhythmias

In this work the electrophysiologic mechanisms of ventricular arrhythmias have been briefly summarized. Ventricular arrhytmias can be caused either by pacemaker activity or by reentrant excitation. Enhancement of normal automaticy can generate a parasystolic rhythm in normal fibers. Abnormal automaticity may arise fom fibers in which maximum diastolic potential has been reduced by a variety of interventions. Triggered activity is caused by either an early (EAD) or delayed (DAD) afterdepolarization and requires a prior normal action potential for initiation. While there is growing evidence that EAD-induced triggered activity plays a significant role in the Long QTU syndrome and Torsade de Pointes, no clinical arrhythmias has definitely been ascribed to DADs, although DADs have been recorded in man after acute digoxin intoxication.Ventricular arrhytmias can be also caused by reentrant excitation, which can be subdivided into reflection or circus movement reentry (CMR). In the reflection model impulses in both directions are transmitted over the same pathway. In the CMR three models can be differentiated: the ring model, which requires a fixed anatomical obstacle; the figure-eight model and the leading circle model, where functional rather than fixed anatomical obstacles are involved.Abbreviations AV atrio-ventricular - CMR circus movement reentry - DAD delayed afterdepolarization - EAD early afterdepolarization - ECG electrocardiogram - LV left ventricle - MAP monophasic action potential - MF muscle fiber - PF Purkinje fiber - RV right ventricle - TdP Torsade de Pointes     

Acute actions of insulin-like growth factor II on glucose metabolism in adult rats

Summary The metabolic potency of recombinant human insulin-like growth factor II was studied in anaesthetized adult rats by obtaining dose-response curves for the hypoglycaemic action and for the stimulation of glucose metabolism during euglycaemic clamping. Compared to insulin, about 50 times higher doses of insulin-like growth factor II were required to result in identical in vivo responses, with half-maximally effective serum concentrations for the stimulation of glucose disposal during clamp studies of about 0.8 and 50 pmol/ml, respectively. A similar difference in potency was observed for the dose-dependent stimulatory actions on glucose metabolism in individual target tissues. Half-maximally effective serum concentrations in the range of 0.8 to 3.0 pmol/ml for insulin and of 40 to 70 pmol/ml for insulin-like growth factor II were seen to be required for 2-deoxyglucose uptake, glycogen formation in skeletal muscle and lipogenesis in epididymal fat. Maximal responses were identical with both peptides. These data suggest that in vivo acute metabolic actions of insulin-like growth factor II on carbohydrate metabolism occurred through insulin receptors.     

Dopamine antagonists reduce spontaneous electrical activity in cultured mammalian neurons from ventral mesencephalon

Mammalian neurons from ventral mesencephalon (VM) were grown in primary dissociated cell (PDC) culture. These neurons are predominantly non-dopaminergic. Many of these non-dopaminergic neurons have dopamine agonist and antagonist binding sites. Intracellular recordings were obtained from these neurons. When bathed in phosphate-buffered saline (PBS) solution they generated action potentials spontaneously. However, in the presence of haloperidol dissolved in PBS solution, the percentage of neurons which generated action potentials spontaneously was reduced in a dose-dependent manner (1–10 μM). This response was also obtained with (+) butaclamol (1 μM) but not with (−) butaclamol (1 μM). This neuroleptic inhibition of spontaneously generated action potentials was specific for neurons in PDC cultures of VM since neurons in PDC cultures of spinal cord did not demonstrate this phenomenon.     

中老年人24小时动态血压变化的研究

目的探讨血压正常老年患者和老年高血压患者24h动态血压波动规律及与靶器官损害的关系.方法采用无创伤袖带式动态血压监测仪检测36例中年人(对照组),50例血压正常老年患者,60例老年高血压患者的动态血压.结果血压正常老年患者较中年血压正常者24h动态血压呈杓型曲线的比例明显下降.血压正常老年患者,血压昼夜波动曲线与心、脑、肾损害无相关性.老年高血压患者,血压曲线呈非杓型者比例增高,血压昼夜节律消失较节律正常的高血压患者有更显著的靶器官损害.结论对于非高血压患者,随年龄的增加,血压昼夜节律消失者增多,血压曲线变化与心、脑、肾损害无关,可能与原发病有关.对于高血压患者,血压昼夜节律紊乱可作为靶器官损害的预测因子.     

原钒酸钠对Ⅱ型糖尿病的降糖作用研究

目的　观察原钒酸钠对Ⅱ型糖尿病大鼠的降糖作用。方法　用高脂饲料灌胃正常大鼠 ,引起肥胖 ,测定血中游离脂肪酸浓度。同时应用正糖钳技术检测胰岛素抗性 ,对产生胰岛素抵抗的大鼠腹腔注射小剂量链脲菌素 (5 5mg·kg-1) ,然后筛选空腹血糖值大于 11 1mmol·L-1大鼠为糖尿病模型组。连续灌胃原钒酸钠 7d后 ,测定空腹血糖值。结果　①大鼠喂食高脂饲料后 ,正糖钳实验中维持血糖稳态所需胰岛素量增多 ,为 (0 5 4± 0 0 2 )U·min-1,高于正常组 (P <0 0 1) ;同时血中游离脂肪酸浓度增加 ,从正常 (0 4 6 9±0 0 4 7)mmol·L-1至 (1 5 32± 0 2 91)mmol·L-1(P <0 0 1) ;②原钒酸钠对正常大鼠的血糖值无影响 ,而对Ⅱ型糖尿病大鼠的空腹血糖值及糖耐量曲线下面积有降低作用 (P <0 0 5 )。结论　实验结果证明了原钒酸钠可以明显降低Ⅱ型糖尿病大鼠的空腹血糖值 ,并且对糖耐量具有保护作用     

刺五加叶皂甙单体Sb对培养大鼠心肌细胞动作电位的影响

本研究中所用的刺五加叶皂甙单体Ｓｂ（５０、２００μｇ／ｍＬ），使培养的ｗｉｓｔａｒ大鼠心肌细胞动作电位的波幅、波宽、阈电位、最大舒张电位、超射、最大除极速度及复极（１０％、５０％、９０％）水平的动作电位波宽一致减小。Ｃａ２＋８０μｇ／ｍＬ能使之反转，Ｓｂ作用与尼莫地平作用相似。上述结果表明Ｓｂ具有钙通道阻滞作用。     

Control of feeding and sexual behaviors by neuropeptide Y: physiological implications

Recent evidence suggests that a variety of hypothalamic neuropeptides may mediate interneuronal communication to coordinate diverse neuroendocrine and behavioral functions. In this work, we describe the effects of neuropeptide Y (NPY) on feeding and sexual behaviors. We observed that central administration of bolus NPY stimulated a robust, dose-related feeding response in satiated male and female rats. Continuous NPY receptor activation also evoked dose-related, intermittent feeding in a manner normally observed during nocturnal feeding. It appears that the paraventricular nucleus in the hypothalamus may be the primary site of NPY action because the anticipated reciprocal changes in NPY concentrations, in response to food deprivation followed by ad libitum food intake, occurred only in this site. Additional findings revealed that NPY-induced feeding may follow either substantial reduction or complete restraint of an inhibitory influence on feeding mediated by alpha 2-adrenoreceptor systems in satiated rats. Further, NPY was found to suppress male and female sexual behaviors. The suppressive effects on sexual behavior were apparent prior to or at the time of the onset of feeding after NPY administration. These observations may provide a neurochemical basis for clinical and animal studies on disorders of feeding associated with diminished reproductive functions.