Barium-induced blockade of the inward rectifier in calf Purkinje fibres

The Ba-induced blockade of i_K1 in calf Purkinje fibres was studied in the low concentration range (3–1,000 M). The results showed that the blockade induced by hyperpolarizations was time-dependent, and that the rate of blockade increased with the Ba concentration and the negative pulse amplitude. At Ba concentrations higher than 1 mM the time course of i_K1 blockade was not separable from the capacity transient. At these concentrations, and in a limited voltage range, the Ba-sensitive instantaneous current displayed a marked inward rectification and behaved with external K as expected for a pure K⁺ current, suggesting that under these conditions the only current affected by Ba was i_K1. The Ba-sensitive current decreased with time during hyperpolarizations even when high external K was present, indicating that a voltage-dependent inactivation process could be at least in part responsible for the observed current decline.     

Cellular mechanism of ischemic acute renal failure: Role of Ca2+ and calcium entry blockers

Summary This presentation briefly reviews the cellular mechanism of ischemic acute renal failure (ARF) with particular emphasis on the role of Ca²⁺ and calcium entry blockers (CEB). Vascular consequences of an ischemic renal insult including vasoconstriction, diminished glomerular permeability, loss of autoregulation, and hypersensitivity to renal nerve stimulation may relate to increased cellular Ca²⁺ concentration in the renal afferent arteriole and glomerular mesangial cells. Evidence is also presented that the ischemic injury to tubular plasma membranes is associated with increased Ca²⁺ uptake. With an ischemic insult of a short duration, the renal mitochondria are able to buffer the increased cellular Ca²⁺. However, after an ischemic insult of long duration, the Ca²⁺ overloaded mitochondria deteriorate, adenosine triphosphate (ATP) synthesis decreases, and cell death follows. If a sufficient number of renal tubular cells undergo this cell death, tubular obstruction, i.e. the maintenance phase of ARF, occurs.     

山莨菪碱保护缺血小肠的机理探讨

山莨菪碱(654-2)具有保护缺血、缺氧组织细胞的作用,其机制尚不清楚。本工作观察654-2是否具有钙拮抗作用。研究发现,1.肠系膜动脉灌注654-2可显著减轻缺血小肠的粘膜损伤和组织内钙积聚。2.654-2可降低高钾去极化豚鼠回肠对钙的收缩反应,使钙拮抗作用曲线显著右移。3.连续静脉注射654-2 5mg/kg明显抑制心功能,病理检查显心衰样心肺损伤。结果提示,654-2具有钙拮抗样作用,可能是其具有细胞保护作用的重要机理之一。     

尼卡地平抗癫痫作用研究

目的　探讨二氢吡啶类钙拮抗剂尼卡地平的抗癫痫作用。②方法　制备大鼠戊四唑 (PTZ)化学性点燃模型 ,通过PTZ点燃发作实验、小鼠最大电休克实验和小鼠急性PTZ惊厥实验 ,观察尼卡地平的抗癫痫作用。③结果　腹腔注射尼卡地平 2～ 2 0mg/kg体质量显著抑制PTZ点燃发作 ,并呈量效关系 (t=2 .5 0 0～ 4.34 2 ,P <0 .0 5 ,0 .0 1) ;腹腔注射尼卡地平 2 0mg/kg体质量显著减少小鼠最大电休克强直发作时间 (F =5 .32 7,t=3.92 4,P <0 .0 1) ;腹腔注射尼卡地平 10 ,2 0mg/kg体质量对小鼠PTZ惊厥有保护作用 (F =7.30 0 ,t=3.436～ 4.45 7,P <0 .0 1)。④结论　尼卡地平有抗癫痫作用。     

尼卡地平和表皮生长因子对胶质瘤细胞增殖的影响

目的 :研究钙通道拮抗剂尼卡地平 (Nicardipine ,NC)和表皮生长因子 (EpidermalGrowthFactor,EGF)对恶性胶质瘤细胞系U2 5 1MG生长的作用。方法 :在含 10 %小牛血清和无血清培养基中 ,加入不同浓度的EGF ,NC及NC和EGF(10ng·ml-1)干预 ,应用MTT法观察其细胞生长效应。结果 :在无血清培养基中 ,EGF具有强大的剂量依赖性细胞生长刺激作用 ,10mg·ml-1接近最大效应。加入血清则掩盖EGF的作用。NC能抑制U2 5 1MG细胞的生长 ,在有血清培养基中作用更明显 ;且能完全阻断EGF的生长刺激效应。结论 :NC能抑制胶质瘤细胞的增殖 ,并能完全阻断EGF的生长刺激效应 ,在胶质瘤治疗中具有潜能     

SOD与尼莫地平对窒息幼兔脑组织的保护作用

４２只新西兰幼兔，随机分为对照、窒息、窒息＋ＳＯＤ及窒息＋尼莫地平４组。各组动物均于实验开始后２４ｈ心脏取血测ＯＦＲ，测脑组织水含量，并观察脑病理改变。窒息组织与对照组比较，血清ＬＰＯ、脑水含量明显增高，血中ＳＯＤ、ＧＳＨ－Ｐｘ活力明显降低，脑病理改变明显，且窒息组ＬＰＯ与脑水含量呈正相关关系。两用药组与窒息组相比，血清ＬＰＯ、脑水含量明显减少，ＳＯＤ、ＧＳＨ－Ｐｘ活力明显增高，脑病理改变减轻。提     

The effects of calcium and calcium channel blockers on sodium pump

The effects of 10 mM Ca²⁺ and Ca²⁺ channel blockers verapamil, diltiazem and flunarizine on the ouabain-sensitive electrogenic Na⁺, K⁺ pump activity of mouse diaphragm muscle fibres enriched with Na⁺ were compared with the changes in cytosolic [Ca²⁺]. The electrogenic Na⁺ pump activity produced by adding K⁺ to muscles previously bathed for 4 h in a K⁺-free, 2-mM [Ca²⁺] solution increased the resting membrane potential by about 18 mV. This hyperpolarization was completely inhibited after 10 min incubation in 10 mM Ca²⁺. Verapamil 10^–5M, 10^–5M diltiazem and 10^–7 M flunarizine effectively prevented the effect of elevated [Ca²⁺]. At these concentrations, these drugs did not affect the K⁺-induced hyperpolarization. In mouse diaphragm, the basal cytosolic [Ca²⁺] measured by the fluorescent indicator 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]2-(2-amino 5-methylphenoxy) ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester (fura-2/AM) was 261±6 nM. After 4 h in a Liley K⁺-free, 2 mM [Ca²⁺] solution, the cytosolic [Ca²⁺] increased to 314±28 nM. Increase in [Ca²⁺] from 2 to 10 mM caused a twofold increase of cytosolic [Ca²⁺] to 637±26 nM. This rise was, like the Ca²⁺-induced inhibition of electrogenic pump, prevented by 10^–5 M verapamil, 10^–5M diltiazem and 10^–7 M flunarizine. The results suggest that substances which block Ca²⁺ entry into the cell prevent the Ca²⁺ induced inhibition of the Na⁺ pump.     

麦冬加钙通道阻滞剂防止异丙肾上腺素副作用效果观察

为解决异丙肾上腺素长期用药不良作用问题,我们试验观察了麦冬加钙通道阻滞防止该副作用的效果,实验用断乳前经致癌剂处理的雄性ICR小鼠,断乳后每日皮下注射盐酸异丙肾上腺素和咖啡因造模。结果表明异丙肾上腺素用药达5个月以上时动物呈现明显病态,包括消瘦,反应性低下,肝间隙连接通讯显著抑制乃至死亡,饮水和饲料中添加麦冬水煎液和钙通道阻滞剂的动物则无上述病态。说明麦冬加钙通道阻滞剂可以完全防止异丙肾上腺素长期用药的不良副作用。     

Safety considerations surrounding use of treatment options for nausea and vomiting in pregnancy

Introduction: Nausea and vomiting of pregnancy (NVP) is the most prevalent medical condition during gestation, affecting up to 85% of pregnant women. Many of them hesitate to use medications due to perceived fetal risks.

Areas covered: There are two main aspects to medication safety in NVP: The fetal safety of drugs used to treat NVP symptoms, and the risks of untreated NVP.

While mild and moderate NVP are not associated with major increase in fetal or maternal risks, and may render protective fetal effects, they have major impact on the quality of life of the mother. In contrast, severe NVP and hyperemesis gravidarum (HG) are associated with increased maternal and fetal risks, from in utero growth restriction to developmental delay.

For the doxylamine/pyridoxine combination, H1blockers and metoclopramide there are large studies documenting fetal safety. There are also large reassuring studies on the fetal safety of ondansetron, but they are contrasted by some studies claiming increased fetal risk.

Expert opinion: Fetal safety of the doxylamine/pyridoxine combination, H1blockers and for metoclopramide has been documented. Reassuring studies on the fetal safety of ondansetron, are contrasted by some studies claiming increased teratogenicity. More studies are needed to quantify fetal risks of HG.