在体兔心肌顿抑模型中心肌酶谱的变化

目的:了解在体兔心肌顿抑模型心肌酶谱的变化。方法:家兔20只,随机分为两组,每组10只。假手术组(A组):只穿线,不结扎,旷置15min,再观察1h;缺血/顿抑组(B组);结扎左冠状动脉前降支15min,再灌注1h。结果:B组与A组比较:15min、30min、60min时心肌酶谱有明显变化(P<0.01)。结论:在体兔心肌顿抑模型心肌酶谱有显著变化。     

呋喃丙吡啶对再灌注心肌顿抑兔血小板聚集和血压的影响

目的：探讨心肌顿抑发生后血流动力学和血小板聚集率的变化，以及钙通道拮抗剂呋喃丙吡啶对心肌顿抑兔的保护作用。方法：经冠状动脉结扎法建立兔心肌顿抑模型。用药组缺血前用呋喃丙吡啶静脉给药。结果：对照组再灌注后１５ｍｉｎ血浆最大血小板聚集率达高峰（６１．７６％±９．２２％），用药组同一时间点血浆最大血小板聚集率较对照组低（４０．２３％±５．３９％，Ｐ＜０．０１）。对照组血压较缺血前明显下降（Ｐ＜０．０５），用药组：Ⅰ组（１ｍｇ·ｋｇ－１）血压变化与对照组无统计学差异，Ⅱ组（３ｍｇ·ｋｇ－１）缺血后舒张压下降明显与对照组相比差异显著，随着再灌注时间延长舒张压逐步回升。结论：心肌顿抑发生后伴有血流动力学变化及血小板聚集率增高，缺血前静脉应用呋喃丙吡啶治疗对心肌损伤具有保护作用。     

姜黄素对兔心肌缺血再灌注损伤的影响

目的:探讨姜黄素(curcumin)预处理对兔心肌缺血再灌注损伤(ischemia-reperfusion injury,IRI)的影响。方法:将40只新西兰大白兔随机分为两组:处理组(20只)于术前2h将60mg/kg的姜黄素静脉注射;对照组(20只)静脉注射等体积的DMSO。"二线二结"法结扎心脏左前降支动脉30min,然后恢复心肌灌注。两组分别于结扎前与再灌注后1.0h从股静脉取血2ml,测定血浆心肌肌钙蛋白I(cardiac troponin I,cTnI)与超氧化物岐化酶(superoxide dismutase,SOD)含量。结果:再灌注1.0h后,兔血浆cTnI较结扎前明显升高(P<0.05),SOD含量较结扎前降低(P<0.05),处理组cTnI水平较对照组明显降低(P<0.05),SOD含量较对照组明显增加(P<0.05)。结论:姜黄素对兔心肌IRI有保护作用,其机制可能与提高SOD含量、减少氧自由基生成有关。     

呋喃丙吡啶对心肌顿抑兔心肌肾素、血管紧张素Ⅱ及去甲肾上腺素的影响

目的研究心肌局部肾素、血管紧张素Ⅱ（ＡｎｇⅡ）及去甲肾上腺素（ＮＥ）在心肌顿抑发病中的作用，以及呋喃丙吡啶（Ｆ３）对心肌顿抑是否具有保护作用。方法采用冠状动脉结扎法建立兔心肌顿抑模型，用放射免疫法测定肾素、ＡｎｇⅡ及ＮＥ的变化，缺血前用呋喃丙吡啶静脉给药。结果心肌缺血后局部肾素活性有升高趋势，再灌注后心肌局部肾素活性显著高于正常对照组。心肌局部ＡｎｇⅡ含量明显高于正常对照组。心肌ＮＥ含量明显升高。缺血前静脉推注呋喃丙吡啶可以降低心肌顿抑时心肌局部ＡｎｇⅡ及ＮＥ的产生。结论心肌局部肾素，ＡｎｇⅡ及ＮＥ在心肌顿抑的发病中具有重要意义，缺血前静脉应用呋喃丙吡啶防治可能是有益的。     

呋喃丙吡啶对心肌顿抑兔心肌肾素,血管紧张素Ⅱ及去甲肾上？…

目的 研究心肌局部肾素、血管紧张素Ⅱ（Ａｎｇ Ⅱ）及去甲肾上腺素（ＮＥ）在心肌顿抑发病中的作用，以及呋喃丙吡啶（Ｆ３）对心肌顿抑是否具有保护作用。方法 采用冠状动脉结扎法建立兔心肌顿抑模型，用放射免疫法测定肾素、ＡｎｇⅡ及ＮＥ的变化，缺血前用呋喃丙吡啶静脉给药，结果 心肌缺血后局部肾活性有升高趋势，再灌注后心肌局部肾素活性显著高于正常对照组。心肌局部ＡｎｇⅡ含量明显高于正常对照组。心肌ＮＥ含量明显     

双氢青蒿素通过抑制蛋白激酶B和NF-κB P65磷酸化减轻缺血再灌注导致的小鼠心肌损伤

目的 探讨双氢青蒿素(DHA)对心肌缺血再灌注(I/R)小鼠心肌氧化应激损伤作用及其机制.方法 采用左冠状动脉前降支结扎法制备心肌I/R小鼠模型.结扎前20 min,模型+DHA 12.5,25.0和50.0 mg·kg-1组小鼠分别ig给予相应剂量DHA,假手术组和I/R模型组ig给予等量生理盐水,每天1次,连续7 ...     

冠心宁注射液对大鼠心肌缺血再灌注损伤的保护作用

目的:观察冠心宁注射液对大鼠心肌缺血再灌注损伤的保护作用,探讨冠心宁抗心肌缺血再灌注损伤的保护机理.方法:雄性SD大鼠30只随机分成假手术组(C组)、缺血再灌注组(I/R组)、冠心宁治疗组(G组),建立大鼠在体心肌缺血再灌注模型:C组丝线穿过冠状动脉前降支但不结扎,I/R、G组通过结扎心脏左冠状动脉前降支40 min,再灌注60 min制作缺血再灌注损伤动物模型.缺血前30 min,G组经腹腔注射冠心宁注射液10.0 ml·kg-1,余两组注射等量0.9%氯化钠注射液.测定再灌注60 min后心肌超氧化物岐化酶(SOD)活性及丙二醛(MDA)含量,同时取每组大鼠心肌检测梗死面积,电镜下观察缺血区心肌超微结构变化.结果:与I/R组相比,G组再灌注后60 min心肌MDA含量降低(P<0.01),SOD活性增高(P<0.01),梗死面积较小(P<0.01),心肌超微结构受损较轻.结论:冠心宁注射液对心肌缺血再灌注损伤有明显的保护作用,其机制与其增强心肌抗氧化作用有关.     

丹参酮对兔急性心梗再灌注损伤的心肌保护

目的 探讨丹参酮在心肌梗死再灌注损伤中的干预作用,为临床治疗提供实验依据。方法 将40只,♂,新西兰大白兔按成组设计应用随机列表法分成4组,每组10只：葡萄糖再灌注组、丹参酮再灌注治疗组、丹参酮冠脉结扎前治疗组和假手术组。建立再灌注模型后经耳缘静脉给药。分别于结扎前5 min、结扎后1 h、再灌注后2 h时,取血清检测肌酸激酶(CK)、肌酸激酶的同功酶(CK-MB)、肌钙蛋白Ⅰ(Tn-Ⅰ)。并于再灌注后2 h,以1%的四氮唑红溶液制作心肌切片,以AutoCAD 2002图形设计软件计算坏死心肌范围。结果 ①丹参酮再灌注组与葡萄糖再灌注组、丹参酮结扎前治疗组与葡萄糖再灌注组在再灌注后2 h的CK、CK-MB、Tn-Ⅰ有统计学差异(P<0.05);丹参酮再灌注组与丹参酮结扎前治疗组在再灌注后2 h的CK、CK-MB无统计学差异(P>0.05)、Tn-Ⅰ有统计学差异(P<0.05)。②丹参酮再灌注组与葡萄糖再灌注组、丹参酮结扎前治疗组与葡萄糖再灌注组心肌梗死范围比较有统计学差异(P<0.05)。丹参酮再灌注组与丹参酮结扎前治疗组无统计学差异(P>0.05)。结论 静脉注射丹参酮可以降低兔急性心肌梗死再灌注后CK、CK-MB、Tn-Ⅰ,并减少兔急性心肌梗死面积。     

维生素E对再灌注心肌损伤的保护作用

SD大鼠60只,分为对照(C)、维生素E(VitE)及超氧化物歧化酶(SOD)3组。结扎左冠状动脉(LCA)5min后开放,心肌再灌注60min。结果:再灌注后C组的左室收缩峰值压持续下降,VitE及SOD组均保持10.7～12.0kPa水平约30min。C及SOD组的室颤(VF)发生率及死亡率明显高于VitE组。心肌电镜形态计量表明VitE组的心肌细胞结构基本完整,证明VitE可保护心肌细胞不受再灌注损伤。     

松树皮提取物原花青素对心肌缺血再灌注损伤大鼠的保护作用

目的 探讨松树皮提取物原花青素对心肌缺血再灌注损伤(MIRI)大鼠的保护作用,为进一步研究此药对缺血性心血管疾病的防治提供依据.方法 用60只雄性SD大鼠随机分成6组,即假手术组、模型组、复方丹参对照组、松树皮提取物原花青素低剂量组(60 mg·kg-1)、中剂量组(80 mg·kg-1)和高剂量组(100 mg·kg-1).将麻醉大鼠冠脉结扎30 min后,再灌注120 min造成心肌损伤模型.均与结扎LAD前20 min给予药物和生理盐水.结果 松树皮提取物原花青素能降低缺血再灌注后血清内皮素(ET 1)浓度,而且能够升高一氧化氮(NO)的水平以及提高超氧化物歧化酶(SOD)活性.结论 松树皮提取物原花青素对心肌缺血再灌注损伤的大鼠具有保护作用.     

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.     

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。     

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.     

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.     

Study of potential in vitro and in vivo genotoxicity in hepatocytes of quinolone antibiotics

The genotoxicity of quinolone antibiotics has been evaluated in hepatocytes following in vitro and in vivo exposure. Unscheduled DNA synthesis (UDS) was induced in vitro in rat hepatocytes by norfloxacin, ofloxacin, pefloxacin, and ciprofloxacin but not by nalidixic acid. In vivo UDS was not observed in hepatocytes isolated 4 to 24 hr after exposure of adult male F344 rats to either a single dose (30 to 190 mg/kg) or repeated doses (40 mg/kg) of ciprofloxacin. Using the 32P-postlabeling technique, no modified bases were detected in hepatocytes exposed in vitro to ciprofloxacin. In summary, UDS was induced in hepatocytes by in vitro exposure to high concentrations of norfloxacin, ofloxacin, pefloxacin, or ciprofloxacin. There was no evidence of in vitro DNA adduct formation by ciprofloxacin or in vivo DNA damage under the conditions tested. These findings suggest that ciprofloxacin is not DNA reactive, but it induces in vitro UDS as a consequence of some indirect action.