ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

苯甲酸钠喷雾沸腾造粒

本文介绍一种用流态化技术与喷雾干燥相结合的方法将苯甲酸钠溶液在流化床内完成蒸发、干燥与造粒。     

Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (V˙_max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙_max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. Received: 25 July 1996 / Accepted: 14 October 1996     

二巯基丙磺酸钠对苯硫丹和多噻烷急性中毒小鼠的保护作用

用二巯基丙磺酸钠对苯硫丹、多噻烷急性染毒小鼠进行保护解救。结果表明：二巯基丙磺酸钠对该两农药急性染毒小鼠具有显著的保护作用（Ｐ＜０．０５）。本实验填补了以二巯基丙磺酸钠作为首选药物治疗沙蚕毒系现有全部品种急性中毒解毒谱的空白。     

高渗氯化钠高氧液对失血性休克家兔血乳酸和动脉血气的影响

目的:观察高渗氯化钠高氧液对失血性休克家兔动脉血气和血乳酸值的影响，评价其对失血性休克的早期救治效果。方法:制备高渗氯化钠溶液(HS)、生理盐水高氧液（NSO）和高渗氯化钠高氧液(HSO)。30只雄性家兔制备失血性休克模型［于10min内使平均动脉压（MAP）降至40mmHg（1mmHg＝0.133kPa），维持60min］，随机分为NSO，HS，HSO组3个治疗组。分别按6mL/kg剂量5min内静脉输入NSO,HS和HSO。记录休克前后及给药后心率（HR）、呼吸（RR）、MAP及尿滴（UD），测定休克前、休克60min，给药后30，60，120min时血乳酸（BL）和动脉血气值。最后观察尸肺，测定肺系数。结果:HS和HSO组均显著地改善MAP，HR和UD，降低BL，改善代谢性酸中毒,肺系数明显低于NSO组。HSO与NSO及HS比较，能更显著地降低血BL，提高动脉血氧饱和度（SaO2）和动脉血氧分压（PaO2）。结论:HSO较HS和NSO能更显著地降低血BL,提高SaO2和PaO2，对失血性休克的早期救治具有较高的使用价值。     

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     

羟丁酸钠对缺血缺氧性脑损伤新生大鼠大脑皮层神经细胞凋亡的影响

目的 观察羟丁酸钠对缺血缺氧性脑损伤新生大鼠大脑皮层神经细胞凋亡的影响。方法 新生7dSD大鼠随机分为假手术组（S组）、生理盐水对照组（C组）和羟丁酸钠组（71、坦和档组）。每组按Ⅲ（缺血缺氧）后不同时间点进一步分为1h、3h、1d、3d、7d5个亚组（n=6）。按Rice法制作缺血缺氧性脑损伤模型。C、γ1、γ2和γ3组HI后即腹腔分别注射生理盐水0．2ml／10g、羟丁酸钠50、100、200mg／kg，3次／日；S组术后吸空气2h，腹腔注射生理盐水0．2ml／10g，3次／日。TUNEL染色法检测HI后各时间点大脑皮层凋亡神经细胞。结果 HI后1h～7d，C、γ1、γ2、γ3组凋亡神经细胞数高于S组（P〈0．05），且于HI后1d达高峰；HI后3h-3d，C、γ3组凋亡神经细胞数多于γ1、γ2组（P〈0．05），而C组与γ3组之间凋亡神经细胞数差异无统计学意义（P〉0．05）；HI后7d，γ1组凋亡神经细胞数多于让组（P〈0．05）。结论 50、100mg／kg羟丁酸钠能抑制缺血缺氧性脑损伤新生大鼠大脑皮层神经细胞凋亡，且100mg／kg效果较好。