Increased Sensitivity to the Anticonvulsant Effect of Valproate in Aging BN/BiRij Rats

The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L^–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991.     

双氯灭痛药膜体外透皮速率的实验研究

作者选择乙基纤维素、聚乙烯醇等高分子材料制成涂膜剂，用大鼠皮进行双氯灭痛药膜的体外透皮速率测定。结果表明，氮酮与丙二醇可以促进药物渗透。不同的高分子材料可影响药物的扩散与释放，从而影响其透皮速率。与无膜无促透剂处方相比，药物在乙基纤维素中的透皮速率没有增加，在聚乙烯醇膜中的透皮速率有显著增加。     

紫外分光光度法测定甘氨酸茶碱钠中茶碱的含量

本文建立了用于甘氨酸茶碱钠中茶碱含量测定的紫外分光光度法。将样品溶于０．１ｍｏ１／Ｌ氢氧化钠溶液中，在２７４ｎｍ波长处测其吸收度，结果的相对标准偏差（ＲＳＤ）为０．２２％．与药典方法比较，Ｆ．ｔ检验均无显著性差异．本法简便，快速，结果可靠，准确．     

头孢噻肟钠聚合物测定实验条件的改进

目的:对中国药典收载的头孢噻肟钠聚合物测定条件进行改进。 方法 :采用高效液相色谱法 ,以Sephadex G- 10色谱柱 4 2 cm× 1.3cm对 6批样品进行分析 ,分别进样 5 0μl和 2 0 0μl,按外标法计算聚合物的量。结果:头孢噻肟钠在 10～ 6 0 μg/m l范围内线性关系良好 (r=0 .9995 ) ,高中低浓度的加样回收率分别为 10 0 .2 %、10 0 .4 %、99.7% ;RSD分别为 1.7%、1.5 %、1.9% (n =3)。该方法与药典方法比较 ,差异无统计学意义 (P >0 .0 5 )。 结论:本方法简便、快速、可行 ,具有实用价值     

用酶联免疫吸附术观察向附睾注射鱼肝油酸钠后抗精子抗体的变化

本研究用酶联免疫吸附术观察8只家兔在附睾注射鱼肝油酸钠后血清及精浆中的抗精子抗体。血清抗精子抗体阳性率为37.5～50.0%,最早检出率为术后2个月,6～7月达高峰。精浆抗精子抗体阳性率为25%,最早检出率为术后4个月,且此时己达高峰。与输精管结扎资料相比,发现血清抗精子抗体检出率偏低,而精浆相应抗体偏高,表明向附睾注射鱼肝油酸钠引起的免疫反应有别于结扎,以生殖道局部为主。     

二尖瓣置换术围手术期硝普钠的应用

本文介绍了20例二尖瓣置换术病人围手术期使用硝普钠的经验。术中和术后早期使用硝普钠可降低肾素-血管紧张素系统的活性、减轻外周血管阻力和后负荷,增强泵血功能,从而使心脏指数升高,降低术后高血压和肺水种的发生率。体外循环停止后,硝普钠与低浓度升压药并用可增强心肌收缩力,预防低排综合征     

Inhibition of rat hippocampal excitability by the plant alkaloid 3-acetylaconitine mediated by interaction with voltage-dependent sodium channels

The effects of the Aconitum alkaloid 3-acetylaconitine on neuronal activity were investigated in the slice preparation and on cultivated neurons of rat hippocampus by extracellular and patch-clamp recordings, respectively. 3-Acetylaconitine (0.01–1 μM) diminished the orthodromic and antidromic population spike in a concentration-dependent manner. The inhibitory action of the drug was preceded by a transiently enhanced excitability. The latency of onset of the inhibition was accelerated by increased stimulation frequency, whereas recovery during washout of the alkaloid was accelerated by decreased stimulation frequency. Moreover, the inhibitory effect of 3-acetylaconitine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors by bicuculline (10 μM) or by a nominal Mg²⁺-free bathing medium. In accordance with the activity-dependent mode of action, this compound abolished the synaptically evoked population spikes in the presence of bicuculline or nominal Mg²⁺-free bathing medium, respectively. Whole-cell patch-clamp recordings revealed an interaction of 3-acetylaconitine with the voltage-dependent sodium channel. At a concentration of 1 μM, 3-acetylaconitine did not affect the peak amplitude of the sodium current, but shifted the current-voltage relationship in the hyperpolarized direction such that sodium currents were already activated at the resting potential. Received: 22 July 1996 / Accepted: 14 October 1996     

Sodium Valproate-lnduced Cardiovascular Abnormalities in the JchlCR Mouse Fetus

Sodium valproate was administered to Jcl:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septal defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.     

Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis

It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.