示波极谱滴定法测定盐酸苯海拉明苯妥英钠及其制剂含量

采用示波极谱滴定法测定了盐酸苯海拉明、苯妥英钠及其制剂含量,所得结果均达到药典标准,与非水滴定法或提取后分光光度法比较,本法具有快速、准确、简单、操作方便、免用有机溶剂的优点。     

高碘摄入对SD大鼠钠/碘同向转运体蛋白表达影响的免疫组化研究

目的:动态观察长期高碘摄入对SD大鼠甲状腺细胞钠/碘同向转运体(NIS)蛋白表达的影响.方法:SD大鼠分别饲以去离子水及不同碘浓度的碘化钾水,给碘后1 d及1,2,4,8周处死.测定尿碘、组织碘含量,免疫组织化学方法观察甲状腺细胞NIS蛋白表达水平.结果:高碘摄入可引起甲状腺滤泡细胞膜表面NIS蛋白表达的下降.短期较低浓度的高碘摄入对NiS蛋白的表达无明显影响,而较高浓度的碘摄入则引起NIS蛋白表达的明显减少;长期高碘摄入对NIS蛋白表达的抑制作用,可在机体自我调节机制作用下得以部分恢复,但NIS蛋白表达仍处较低水平.结论:高碘摄入可导致甲状腺细胞表面NIS蛋白表达下降,随摄碘浓度的增加抑制作用增强;不同浓度的碘摄入对NIS蛋白表达的抑制作用表达时间不同.     

高危出血患者应用吉派林抗凝血液透析疗效观察

目的：观察危重型肾功能衰竭合并高危出血患者选择抗凝药物进行血液透析治疗的效果。方法：应用吉派林(低分子肝素钠)作为抗凝剂进行血液透析。结果：129例病人进行血液透析386次，均没有出血发生。结论：吉派林在高危出血患者血液透析中使用方便，安全，效果良好。     

头孢哌酮钠在醋酸钠平衡液中的稳定性

考察了头孢哌酮钠在醋酸钠平衡液中的稳定性。二药配伍后，置室温（２５℃）及３７℃水浴中，６ｈ内溶液无颜色改变，亦无沉淀、气体产生，头孢哌酮钠均在初始浓度的９５％以上。     

丙戊酸钠与尼莫地平治疗偏头痛的疗效比较

目的：观察丙戊酸钠与尼莫地平治疗偏头痛的疗效有否差别。方法：偏头痛１２９例，随机分为丙戊酸钠治疗组６６例（男性１７例，女性４９例；年龄２５±ｓ７ａ），丙戊酸钠开始剂量为０．２ｇ，ｐｏ，ｔｉｄ，以后根据发作频率及程度逐渐增量，最大量１．４ｇ／ｄ，共用３ｍｏ；尼莫地平对照组６３例（男性１８例，女性４５例，年龄２７±６ａ），尼莫地平３０ｍｇ，ｐｏ，ｔｉｄ，共用３ｍｏ。结果：丙戊酸钠组总有效率为８３％。尼莫地平组为８５％，２组无明显差异（Ｐ＞０．０５）．未见严重不良反应。结论：丙戊酸钠与尼莫地平治疗偏头痛安全有效、疗效相似。     

Interaction of Nucleoside Analogues with the Sodium–Nucleoside Transport System in Brush Border Membrane Vesicles from Human Kidney

The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na⁺-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na⁺-driven ³H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na⁺–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K _i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na⁺–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K _i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside.     

The effect of high sodium intake on bone mineral content in rats fed a normal calcium or a low calcium diet

The effect of high sodium intake on bone mineral content of rats fed a normal (0.6% Ca) or a low (0.02% Ca) calcium diet was studied. Rats on a normal calcium diet given 1.8% sodium chloride to drink showed persistent and significant hypercalciuria and subnormal bone mineral content. Total calcium content of femur was significantly lower after 4 months (p<0.02) and 12 months (p<0.001). In rats maintained on a low calcium diet (0.02% Ca), a high sodium diet for 8 weeks caused a significant loss of calcium in bone similar to that seen in animals fed a normal calcium diet for 4 months. We conclude that high sodium intake reduces bone mineral content, especially if the diet is low in calcium.     

Effects of acetylsalicylic acid on electromechanical activity ofin vivo rabbit ileum

Aspirin has antisecretory and ulcerogenic properties in the gastrointestinal tract. The aim of this study was to determine the effects of acetylsalicylic acid (ASA) on the electrical and mechanical activity of the ileum in anesthetized New Zealand White rabbits. Ileal electromechanical activity was recorded from serosal electrodes and a miniature intraluminal balloon. Thirty minutes after injection of ASA (30, 60 and 100 mg/kg intravenous) significant and dose-dependent increases in the percentage of slow waves with action potentials were observed when compared with saline-injected animals. The onset of action potentials correlated with phasic increases in intraluminal pressure, indicating the onset of circular muscle contractions. Injection of 15 mg/kg ASA, sodium salicylate (100 mg/kg intravenous) or saline had no effect on baseline action potential activity. Prostaglandin E ₂ (PGE ₂)(5 and 10 g/kg intravenous) significantly increased slow-wave frequency and decreased ASA-induced action potential activity. This study demonstrates that (1) ASA, but not sodium salicylate, stimulates phasic ileal action potential and contractile activity and (2) in ASA-treated animals, PGE ₂ produces differential effects on in vivoslow-wave frequency and action potential activity.     

Effect of a protein binding change on unbound and total plasma concentrations for drugs of intermediate hepatic extraction

For substances eliminated from blood by the liver, the effect of a change in unbound fraction of drug (fu _b )on steady state total (C _b )and unbound (Cu _b )blood concentrations has hitherto only been considered for the two limiting cases, i.e., at the upper and lower extremes of hepatic intrinsic clearance (CL _int ).For a substance of very low CL _int ,if fu _b changes, C _t will change and Cu _b will remain constant, whereas if CL _int isvery high, Cu _b will change and C _b will remain constant.The present study defines the effects of a change in fu _b on C _b and Cu _b over the whole CL _int range. Computer simulations were undertaken which predicted that, for a given change in fu _b ,absolute and relative changes in C _b would decreasenonlinearly with increasing CL _{int, twhile the relative change in} Cu _{b would} increasewith CL _int .The absolute change in Cu_b would be independent of CL _int .Significant changes in C_b and Cu _{b would be observed at intermediate values of} CL _{int not just at the high and low extremes. These theoretical predictions were investigated experimentally in the isolated perfused rat liver by examining the effects of a change in} fu _{b of sodium taurocholate a substance with intermediate} CL _int (such that at fu _b =0.27,hepatic extraction ratio=0.71) induced by concurrent administration of sodium oleate. Sodium 24- ¹⁴ C-taurocholate (specific activity 52 Ci/mmol) was infused into the reservoir in a recycling system at 30 mol/hr for 105 min (n=6). At 45 min a bolus dose of sodium oleate (50 mmol) was administered to the reservoir, followed by a constant infusion of 143 mmol/hr for 1 hr. Following the administration of oleate, taurocholate fu _{b fell promptly by 55% (0.27–0.12). There was a relative increase of taurocholate} C _{b of 22.7% and a relative decrease in} Cu _{b of 45.4%, in accordance with the simulations (p<0.05). We conclude that important changes in unbound steady-state concentration, the pharmacologically active moiety, can occur upon changes in unbound fraction with compounds of intermediate hepatic intrinsic clearance}.This study was supported by the National Health and Medical Research Council of Australia.     

The sodium channels of the neuroblastoma x glioma 108 CC 15 hybrid cell change their sensitivity for volatile and local anesthetics upon continuous passage

Summary We have studied the ion flux through the sodium channels of low passage number (<50p.) and high passage number (>150p.) neuroblastoma x glioma hybrid cells using [¹⁴C] guanidinium and specific neurotoxins to induce channel opening and closing. The sodium channels of low passage number hybrid cells could be opened by veratridine alone, suggesting the presence of voltage dependent channels in agreement with electrophysiological studies reported in the literature. The sodium channels of the high passage number hybrid cells, however, needed the synergistic action of veratridine and scorpion toxin for activation suggesting that these channels are silent. The [¹⁴C] guanidinium ion flux through the sodium channels of the high passage number hybrid cells was inhibited by significantly lower concentrations of the volatile anesthetics (halothane, isoflurane and enflurane) and the lcoal anesthetics (tetracaine and bupivacaine) than the comparable flux through the sodium channels of the low passage number hybrid cells.Dedicated to Prof. Dr. E. Wecker on the occasion of his 65th birthday.