维药毛菊苣根-种子不同比例配伍的90%乙醇提取物对小鼠急性肝损伤的保护作用及其机制

目的:研究毛菊苣根-种子药对不同比例配伍90%乙醇提取物的化学指纹谱与肝损伤保护作用的相关性,探索维药处方中"药对"的配伍机制。方法:将毛菊苣的根和种子按6个质量比例 (1:0,0:1,1:1,1:2,1:3,2:1)配伍,用90%乙醇提取,得到6个提取物;观察不同提取物对四氯化碳 (CCl₄)致小鼠急性化学性肝损伤模型,以及小鼠尾静脉注射卡介苗 (BCG)和脂多糖 (LPS)造成急性免疫性肝损伤模型,血清中天冬氨酸氨基转移酶 (AST),丙氨酸氨基转移酶 (ALT)水平的影响及肝脏组织病理改变。采用高效液相色谱法分析各提取物的化学谱图,观察与药效相关的化学物质变化。结果:毛菊苣根-种子以质量比1:2配伍能显著降低CCl₄致小鼠急性化学性肝损伤引起的血清AST (P<0.01)和ALT (P<0.01)升高,对BCG+LPS致急性免疫性肝损伤模型血清中AST (P<0.05)和ALT (P<0.01)也有明显的改善作用;另外,毛菊苣根-种子以质量比1:3配伍对CCl₄致小鼠急性化学性肝损伤引起的血清AST (P<0.01)和ALT (P<0.05)升高,以及对BCG+LPS致急性免疫性肝损伤引起的血清AST (P<0.05)和ALT (P<0.01)升高也有明显的改善作用。化学谱图中的色谱峰与提取物改善CCl₄致小鼠急性化学性肝损伤引起的血清AST和ALT 变化呈正相关。结论:用现代研究方法证实了维药毛菊苣不同药用部位配伍的科学性,进一步从化学角度探索了毛菊苣根-种子肝保护作用的临床经典比例1:2和1:3配伍的可能机制。     

黄花远志根和叶提取物对急性肝损伤小鼠的保护作用

目的：研究黄花远志根和叶提取物对四氯化碳（CCl4）所致急性肝损伤小鼠的保护作用。方法：采用 CCl4诱导化学性急性肝损伤模型,测定小鼠肝脏指数、血清丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）,观察小鼠肝脏病理学变化。结果：黄花远志根（4 g、2 g 生药／ kg）和叶（4 g、2 g 生药／ kg）提取物能显著降低 CCl4致小鼠急性肝损伤ALT 和 AST 的升高,明显改善 CCl4对肝组织的病理损伤。结论：黄花远志根和叶对 CCl4致小鼠急性肝损伤具有保护作用。     

河蚬提取物对小鼠急性化学性肝损伤的保护作用

目的 研究河蚬提取物对小鼠急性化学性肝损伤的保护作用.方法 采用灌胃给予乙醇或腹腔注射四氯化碳(CCl4)方法制备小鼠急性化学性肝损伤模型,检测血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性、肝脏指数.结果 连续6 d灌胃给予15.0.30.0,60.0mg/(kg·d)的河蚬提取物能明显抑制肝损伤小鼠血清ALT及AST活性的升高(P<0.05),降低增加的肝脏指数.结论 河蚬提取物对四氯化碳及乙醇引起的小鼠急性肝损伤具有保护作用.     

美味猕猴桃根提取物保肝降酶作用的研究

目的观察美味猕猴桃根不同极性溶剂的提取物对四氯化碳(CCl4)肝损伤小鼠血浆转氨酶活性的影响。方法采用CCl4建立小鼠急性肝损伤模型,以不同的提取物和阳性对照药甘草酸二铵灌胃治疗,测定小鼠血浆中丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)活性。结果美味猕猴桃根60%乙醇提取物(C部位),经乙酸乙酯萃取,萃余物上大孔树脂60%~90%乙醇洗脱部分(A部位)60 mg/kg对CCl4造成的小鼠急性肝损伤ALT、AST活性升高具有显著的降低作用。结论美味猕猴桃根提取物部位A对肝脏损伤有保护作用。     

水飞蓟素磷脂酰胆碱复合物对实验性肝损伤的保护作用

目的:观察水飞蓟素磷脂酰胆碱复合物(SIL-PC)对3种肝损伤模型小鼠肝功能的影响,并与水飞蓟素(SIL)进行比较.方法:采用CCl4,D-Galn及免疫性肝损伤模型,以AST及ALT为指标,观察SIL-PC对肝损伤小鼠的保肝效应.结果:SIL-PC可剂量依赖性降低CCl4致肝损伤小鼠血清AST和ALT活性.对D-Galn致肝损伤小鼠,800mg·kg-1 SIL-PC分别使肝损伤小鼠血清AST和ALT活性下降约61%和43%,与模型组比较,P＜0.01.在免疫性肝损伤模型,SIL-PC 100～800mg·kg-1剂量依赖性降低血清AST,ALT活性,且相同剂量的SIL-PC作用明显强于SIL.结论:SIL-PC对小鼠肝损伤有明显的保护作用,且其保护作用明显强于SIL.     

芹菜根提取物对CCl4所致急性小鼠肝损伤的保护作用

目的观察芹菜根提取物对CCl4所致小鼠急性肝损伤的影响。方法60只昆明小鼠随机均分为正常对照组、模型对照组、阳性对照组、芹菜根大、中、小剂量组。大、中、小剂量组按10.0、5.0、2.5 g.kg-1灌胃芹菜根提取物,阳性对照组按15 mg.kg-1灌胃联苯双酯滴丸,正常对照组及模型对照组以等体积生理盐水灌胃,共7 d。第7天,模型对照组、阳性对照组和给药组按10 m.lkg-1sc 1?l4花生油溶液,正常组注射等体积生理盐水。测定各组小鼠血清中无门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT),并观察肝组织的病理改变。结果芹菜根提取物能显著降低CCl4所致小鼠血清中AST、ALT含量的升高(P<0.05)。结论芹菜根提取物对CCl4所致的小鼠急性肝损伤具有一定的保护作用。     

刺山柑胶囊对肝损伤模型小鼠的保护作用及对大鼠胆汁分泌的影响

目的:研究刺山柑胶囊对急性肝损伤模型小鼠的保护作用及对大鼠胆汁分泌的影响。方法:腹腔注射CCl4以复制小鼠化学性肝损伤模型,腹腔注射氨基半乳糖(GaIN)以复制小鼠化学性肝损伤模型,尾静脉注射卡介苗(BCG)及脂多糖(LPS)以复制小鼠免疫性肝损伤模型。测定小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性;取小鼠肝脏作组织病理学检查。以胆总管插管引流法测定正常大鼠胆汁分泌量。结果:与正常对照组比较,模型组小鼠血清ALT、AST活性增强,差异有统计学意义(P<0.01),小鼠均出现较严重急性肝损伤反应;与模型组比较,刺山柑胶囊高、中、低剂量组小鼠肝脏ALT、AST活性减弱,差异有统计学意义(P<0.01或P<0.05),小鼠肝脏肝损伤有一定程度的改善。0.58 g/kg剂量下刺山柑胶囊给药2².5 h时可使大鼠胆汁分泌量明显增加。结论:刺山柑胶囊具有潜在的保肝利胆作用,其机制可能与抗炎和提高机体免疫功能有关。     

苷力康注射液对小鼠四氯化碳肝损伤的保护作用

目的：观察苷力康注射液对四氯化碳（CCl4）至小鼠化学性肝损伤的保护作用。方法：应用CCl4致动物化学性肝损伤模型，以小鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）为检测指标，对苷力康的降酶效果进行实验。结果：苷力康2，4，8g/kg可显降低CCl4所致化学性肝损伤小鼠血清中的ALT，AST含量（P＜0.01)。结论：苷力康对化学性肝损伤小鼠有较好的保护作用。     

黄芪提取物对小鼠急性化学性肝损伤的保护作用

目的探讨黄芪提取物（AE）对CCl4致小鼠急性化学性肝损伤模型的保护作用。方法采用CCl4诱导小鼠急性肝损伤模型,检测血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和肝匀浆中丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）含量,HE染色法对肝脏作病理检查。结果AE能显著降低小鼠血清ALT、AST、肝匀浆MDA水平,升高SOD和GSH-Px酶活性,减轻肝细胞损伤。结论AE对CCl4致小鼠急性化学性肝损伤模型具有保护作用。     

茵陈大孔树脂提取物对CCl4所致肝损伤的影响

目的 建立小鼠肝损伤模型,考察AB-8大孔树脂制备的茵陈提取物对CCl4所致肝损伤的保护作用.方法 利用AB-8大孔树脂制备30%醇提取物,作用于0.1% CCl4诱导肝损伤模型,观察不同浓度茵陈提取物对肝损伤小鼠ALT、AST等指标的影响.结果 与正常组比较,模型组小鼠血清液ALT、AST含量升高;与模型组比较,给药组中高、中剂量组小鼠血清中ALT、AST含量降低,低剂量组无显著性差异.结论 AB-8大孔树脂制备的茵陈提取物对CCl4诱导的肝损伤有保护作用.     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.