西咪替丁对林可霉素生物利用度的影响

通过8名健康志愿者服药后的对照实验,用微生物法检测血药浓度,按一室模型配置求算药物动力学参数,探讨西咪替丁对林可霉素体内过程的影响。结果表明,西咪替丁不能改变林可霉素的吸收速率(Ka)和消除速率(Ke),但可通过增加其吸收程度或改变其分布容积,使林可霉素的血药浓度和生物利用度分别增加约19％和27％。     

国产法莫替丁治疗消化性溃疡的近期疗效观察

本文报告应用国产法莫替丁治疗消化性溃疡45例的近期疗效。治疗组法莫替丁20mg,早晚各服一次;对照组甲氰咪胍400mg,早晚各服一次,两组疗程皆为6周。以胃镜检查为诊断和评价疗效的依据,两组愈合率分别为97.8%,89.9%,上腹疼痛用药后三日缓解率分别为60.9%,30.2%。两组均未出现明显毒副作用,由于抗溃疡新药疗效高,提示今后治疗无合并症消化性溃疡将以药物治疗为主。     

Effects of famotidine and cimetidine on plasma levels of epidurally administered lignocaine

The effects of two H2-receptor antagonists, famotidine and cimetidine, on the plasma levels of epidurally administered lignocaine were studied. Group A (n = 20) received famotidine 20 mg orally the night before surgery and 20 mg intramuscularly 60 minutes before induction of anaesthesia. Group B (n = 15) received cimetidine 200 mg orally the night before the surgery and 400 mg orally 60 minutes before the anaesthetic induction. Group C (n = 20) received neither famotidine nor cimetidine and served as controls. Twelve millilitres of 2.0% lignocaine with adrenaline 1:200,000 was injected into the epidural space in all patients, after the establishment of general anaesthesia with nitrous oxide, oxygen, and enflurane (0.3-0.5%). The patients who received cimetidine showed significantly higher plasma concentrations of lignocaine compared with either group A or group C at all investigation times (p less than 0.01). The mean peak plasma concentrations were 2.4 (SEM 0.1), 3.2 (SEM 0.2) and 2.3 (SEM 0.1) micrograms/ml in group A, B, and C, respectively. This study suggests that famotidine is preferable to cimetidine for control of gastric acidity before the use of lignocaine as the epidural anaesthetic.     

蛛网膜下腔注射神经降压素对大鼠血压和心率的影响

本文研究了蛛网膜下腔注射神经降压素（ｎｅｕｒｏｔｅｎｓｉｎ，ＮＴ）对大鼠血压和心率的影响，结果表明：注射ＮＴ后血压立即下降，继而有所回升，但不及正常水平，然后再次降低，持续６０ｍｉｎ；心率无明显改变。Ｈ１受体阻断剂苯海拉明能部分阻断ＮＴ的降血压效应，Ｈ２受体阻断剂甲氰咪胍无翻转作用。注射组胺释放剂Ｃｏｍｐｏｕｎｄ４８／８０使血压下降，待血压恢复正常水平后，再注射ＮＴ，其降压效应减弱。结果提示：蛛网     

西咪替丁对血浆氨茶碱浓度的影响

在１６例呼吸系疾病患者观察了西咪替丁对氨茶碱血浆浓度的影响。结果表明加服西咪替丁４００ｍｇ，３次／日，３天后血浆氨茶碱谷浓度和峰浓度均明显增高（ｐ＜０．０１），其中谷浓度升高４３．０±５１．１％，峰浓度升高２７．０±２９．０％。提示二者合用时，应适当减少氨茶碱用量，以避免氢茶碱中毒的发生。     

人三叶因子2治疗大鼠胃溃疡的效果评价

目的探讨人三叶因子2（hTFF2）治疗大鼠胃溃疡的疗效。方法将48只雄性Wistar大鼠随机分为Ⅰ、Ⅱ、Ⅲ组，冰乙酸法制作慢性胃溃疡模型。造模时Ⅰ、Ⅱ、Ⅲ组于胃黏膜下分别注射pcDNA3．1-hTFF2（人三叶因子2插入pcDNA3．1载体；pcDNA3．1为真核表达载体，有进入胃黏膜下细胞的特性）西米替丁及pcDNA3．1。造模后7、14d各组分别处死8只大鼠，测定溃疡面积、胃液总酸度及黏液糖蛋白水平。结果Ⅰ、Ⅱ组较Ⅲ组溃疡面积明显缩小，Ⅱ组较Ⅰ、Ⅲ组胃总酸度明显降低，Ⅰ组较Ⅱ、Ⅲ组黏液糖蛋白量明显增加，P均〈0．001。结论pcDNA3．1-hTFF2单次局部注射可通过增加黏液糖蛋白的分泌促进大鼠胃溃疡愈合。     

Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells

The effect of histamine on the phosphoinositide turnover andintracellular free calcium activity [Ca²⁺]_i was examined inhuman glomerular epithelial cells in culture. Addition of histamineto glomerular epithelial cells resulted in formation of inositolphosphates in a time- and dose-dependent manner. A transientmaximum of inositol trisphosphate (InsP₃) was observed within10 s. Stimulation of protein kinase C by short-term pretreatment(15 mm) of glom erular epithelial cells with phorbol 12-mynstate13-acetate caused a dose-dependent inhibition of the histamine-inducedinositol phosphate accumulation. The baseline of [Ca²⁺]_i inthe cells was 115 ±2.7 nmol/l (n=103). Histamine (ED₅₀:approx. 2x10^–7mol/l) caused a rapid and transient increasein [Ca²⁺]_i, as detected by fura-2 microfluorimetry studies.In a calcium-free extracellular solution the rapid increaseof [Ca²⁺]_i was still present. The H₁ receptor antagonist mepyramine(IC₅₀: approx. 8 x 10^–9 mol/l) inhibited the histamine(10^–6 mol/l) response on [Ca²⁺]_i Cimetidine, a potentH₂ receptor antagonist, showed no effect. This data indicates that H₁ receptor activation causes hydrolysisof phosphatidylinositol 4, 5-bisphosphate by phospholipase Cactivation, and consecutive mobil ization of intracellular calcium.Since histamine is a mediator of inflammation, antigen responseand cellular injury, these findings could be of importance forthe understanding of glomerular epithelial cell pathology.     

脂质体阿苯达唑及主要代谢产物的HPLC法和药代动力学研究

作者报道了动物(鼠)口服脂质体阿苯达唑后血浆、肝脏、包虫囊组织和囊液中阿苯达唑及主要代谢产物阿苯达唑砜和阿苯达唑亚砜的反相HPLC法。同时进行了药物动力学研究和并用西咪替丁后对血、肝药物浓度的影响。结果表明,阿苯达唑在血浆、囊液中的检出限为0.05μg/ml,在肝脏和囊组织中为0.10μg/g;砜和亚砜在血浆、囊液中均为0.01μg/ml,在肝脏和囊组织中均为0.02μg/g。药物动力学结果显示,阿苯达唑脂质体、混悬液及脂质体并用西咪替丁后的体内过程均符合二室模型,混悬液并用西咪替丁后符合单室模型。阿苯达唑脂质体具有一定的缓释及靶向的作用,西咪替丁可能增强阿苯达唑的缓释作用,同时可能加速阿苯达唑亚砜的代谢。     

Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children

Summary We have studied the mechanisms of the increased dosage requirements of the H₂-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study.Cimetidine (10–15 mg·kg^–1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis.The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 µg·ml^–1.The mean (SEM) clearance of cimetidine in burned children was 16.22 ml·kg^–1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml·min·kg^–1 and 2.21 h respectively.Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml·min^–1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r ²=0.85).The plasma concentration of cimetidine needed to increase gastric pH to 4.0 was 1.0 µg·ml^–1, which contrasts with the value of >0.5 µg·ml^–1 required for adult burned patients.These findings support the hypothesis that the higher dosage requirements of cimetidine in burned children is due both to enhanced elimination kinetics and to alterations in target organ sensitivity, requiring higher than normal plasma concentrations for the desired effect. In burned children Cimetidine should be given in higher doses and/or more frequently.     

Conservative surgery in Zollinger-Ellison syndrome: report of a case with an eight-year follow-up

The patient described here, with malignant non-beta islet cell tumor of the head of the pancreas, was treated by resection of the tumor and metastases. Additional pathology of perforated duodenal ulcer and pyloric stenosis required vagotomy and pyloroplasty. The maintenance of normal gastrin levels after the operation indicates a good prognosis. We believe that the low-risk Zollinger-Ellison patient should be treated surgically and the tumor removed. When no tumor can be detected, parietal cell vagotomy should be performed to assist the pharmacological control of the gastric acid hypersecretion. Extensive surgery, such as total gastrectomy, is no longer the treatment of choice and is reserved for the so-called "cimetidine failure."