血清妊娠相关血浆蛋白A与急性冠状动脉综合征的临床相关性的研究

目的研究急性冠状动脉综合征（ACS）患者血清妊娠相关血浆蛋白A（PAPP-A）的变化及其与血清高敏C-反应蛋白（hsCRP）和肿瘤坏死因子-α（TNF-α）水平的相关性。方法测定18例不稳定型心绞痛（UAP组）、37例急性心肌梗死（AMI组）和15例稳定型心绞痛（SAP组）及15例正常对照者的血清PAPP—A、hsCRP、TNF-α水平。结果SAP组血清PAPP—A水平与正常对照组相比,差异无统计学意义（P〉0．05）;UAP组和AMI组血清PAPP—A水平均显著高于正常对照组（P〈0．01）和SAP组（P〈0．01）,但UAP组与AMI组相比,差异无显著性。cTnT阴性ACS组患者血清PAPP—A水平也明显高于正常对照组（P〈0．01）和SAP组（P〈0．05）。SAP组血清hsCRP和TNF-α水平明显高于正常对照组;UAP组明显高于正常对照组和SAP组,但低于AMI组。单因素直线相关分析显示,ACS组患者的血清PAPP—A水平与hsCRP和TNF-α水平呈显著正相关（r=0．616、0．712,P〈O．01）。结论PAPP—A与炎症密切相关,在识别没有cT-nT升高的ACS患者方面有重要临床应用价值。     

血清淀粉样蛋白A与不同糖耐量人群血管内皮功能的关系探讨

目的探讨不同糖耐量人群血清淀粉样蛋白A的水平,及与血管内皮功能的关系。方法59例患者根据OGIT试验分为3组：19例NGT、20例IGT和20例T2DM。分别检测血清淀粉样蛋白A、生化指标、肱动脉内皮依赖性舒张功能（FMD）和含服硝酸甘油后肱动脉内皮依赖性舒张功能（NID）。结果①SAA随着血糖的升高而升高,DM组的SAA较IGT组、NGT组明显升高（P〈0．01）,IGT组的SAA较NGT组升高（P〈0．05）。②FMD随着SAA的升高而下降,DM组的FMD较IGT组和NGT组明显降低（P〈0．01）,IGT组的FMD较NGT组降低（P〈0．05）。③Spearman相关分析显示SAA与FBG、HbA1c、TC均呈正相关（r值分别为0．63、0．48、0．59,P〈0．01）,与FMD呈显著负相关（r值为-0．62,P〈0．01）。结论SAA与血管内皮功能损害密切相关。     

血清胆碱酯酶作为一种新的急性时相反应蛋白的探讨

目的探究血清胆碱酯酶（ChE）在创伤、心肌梗死、感染、肿瘤等情况下活性的变化，分析血清ChE作为一种新的急性时相反应蛋白的可行性。方法选择抚顺市中心医院收治的重症感染病患者37例、外伤及手术患者56例、急性心肌梗死患者45例、恶性肿瘤患者43例以及健康体检人员50例，分别进行血清ChE的测定，并对检测结果进行统计学分析。结果各疾病组ChE活性均低于对照组，其中，手术组ChE活性下降最为显著，对照组与不同组间比较，差异均有统计学意义（P〈0．01）。与治疗前比较，除了手术组患者治疗后的ChE活性下降外，其余各组患者的ChE活性均显著升高（P〈0．01）。结论血清ChE具有急性时相反应蛋白的特性。     

2型糖尿病患者急性时相蛋白与尿微量白蛋白的关系

目的探讨2型糖尿病患者急性时相蛋白与尿微量白蛋白的相关性。方法采用免疫比浊法检测100例2型糖尿病患者的尿微量白蛋白水平，并根据尿白蛋白排泄率（UAER）将其分为正常蛋白尿组（n=40）和微量清蛋白尿组（n=60）。采用免疫比浊法检测两组的血清高敏C反应蛋白（hsCRP）和α1-酸性糖蛋白（α1-AAG）水平，并分析hsCRP和α1-AAG与UAER的相关性。结果微量清蛋白尿组的UAER、血清hsCRP、α1-AAG水平和SBP均明显高于正常蛋白尿组，差异有统计学意义，均P〈0．01（t=6．585，7．383，2．896，9．989）。2型糖尿病患者UAER与血清hsCRP（1=0．410，P〈0．01）和α1-AAG（1=0．670，P〈0．01）呈显著正相关。多元逐步回归分析结果显示α1-AAG和SDP是UAER独立预期因子，均P〈0．01（γ=0．630，0．691）。结论2型糖尿病患者血急性时相蛋白与尿微量白蛋白密切相关，一定程度上可反映糖尿病肾脏病变程度。     

血清蛋白（a）测定的临床分析

目的：探讨血清脂蛋白（a）在临床诊断中的应用。方法：分别对冠心病、糖尿病肾病、急性感染、肝硬化患者进行血清脂蛋白（a）测定，并与正常对照组比较。结果：肝硬化患者组血清Lp（a）值明显低于对照组（P〈0．01），其余各组患者血清Lp（a）水平则明显高于对照组（P〈0．01）。结论：Lp（a）测定在早期诊断和预防糖尿病并发冠心病中有一定应用价值，同时Lp（a）是最敏感的急性时相蛋白。     

血清抵抗素和高敏C反应蛋白与急性生理学和慢性健康状况评分系统Ⅱ评分的变化在创伤患者病程监测中的意义

目的探讨血清抵抗素、高敏C反应蛋白（Hs-CRP）与急性生理学和慢性健康状况评分系统（APACHEⅡ）评分的变化在创伤患者病程监测中的意义。方法选择80例创伤患者,按照人院时APACHEⅡ评分分为轻度创伤组（34例）和重度创伤组（46例）,分别在人院的第1、3、5、7天动态检测血清抵抗素和Hs—CRP浓度的变化,采用酶联免疫吸附试验（ELISA）检测血清抵抗素含量,采用免疫比浊法对血清Hs-CRP进行测定;并同步进行APACHEⅡ评分,对所得结果进行统计学分析。结果患者入院时轻度创伤组与重度创伤组比较,血清抵抗素和Hs-CRP含量水平差异有统计学意义（P〈0．05）。轻度创伤组患者血清Hs-CRP水平在第3天开始下降,血清抵抗素水平在第5天开始下降,APACHEⅡ评分也逐渐下降;重度创伤组患者血清抵抗素和Hs—CRP水平以及APACHEⅡ评分虽经治疗仍持续上升,2组上述指标同时间比较,差异有统计学意义（P〈0．01或P〈0．05）。创伤患者血清抵抗素与Hs-CRP呈正相关（r=0．71,P〈0．01）,与APACHEⅡ评分呈正相关（r=0．64,P〈0．01）,Hs—CRP与APACHEⅡ评分呈正相关（r=0．61,P〈0．01）。结论动态检测创伤患者血清抵抗素和Hs．CRP水平结合APACHEⅡ同步评分,有助于准确及时地评估病情和判断预后。     

急性颅脑损伤患者血清中S100B蛋白的动态变化及临床意义

目的分析急性颅脑损伤患者血清中S100B蛋白的动态变化与疾病严重程度及预后的相关性。方法急性颅脑损伤患者60例按GCS评分分为轻型组10例,中型组35例,重型组15例。分别于发病后24h内,第3、7、14天抽取空腹外周静脉血,使用双抗体夹心ELISA法测定S100B蛋白的血清浓度。结果3组S100B蛋白水平差异有统计学意义（P〈0．01）,即中型组S100B蛋白水平明显高于轻型组（P〈0．01）,重型组S100B蛋白水平明显高于轻、中型组（P〈0．01）。结论S100B蛋白水平可以为急性颅脑损伤的早期诊断及预后评估提供有意义的信息。     

急性缺血性卒中患者血液中β-淀粉样肽的变化

目的研究β-淀粉样肽（β-amyloid，AB）代谢改变与急性缺血性卒中（acute ischemic stroke，AIS）的关系。方法选取40例急性缺血性卒中患者和40例年龄相当的正常人作为对照，应用双抗体夹心酶联免疫吸附法（ELISA），测定了血液中可溶性Aβ1-40及Aβ1-42的水平。结果AIS患者血清Aβ1-40水平较正常对照显著升高（P〈0．01），而血浆Aβ1-42水平较正常对照显著降低（P〈0．01），血液中Aβ1-42／Aβ1—40及总体AB水平较正常对照显著降低（P〈0．01）。结论急性缺血性卒中过程中存在的β淀粉样肽蛋白（β-amyloid precursor protein，APP）表达上调以及相伴随的短暂Aβ水平变化，可能是脑急性损伤和灌流不足的结果。     

急性脑梗死患者血清C反应蛋白测定及其临床意义

目的：探讨急性脑梗死患者血清C反应蛋白（CRP）的变化及其对预后的影响。方法：对91例脑梗死患者（脑梗死组）、32例腔隙性脑梗死患者（腔梗组）N53N健康体检者（对照组）血清CRP含量进行测定,计算其异常率并进行比较。结果：脑梗死组CRP含量高于腔梗组,腔梗组高于对照组（均P〈0．01）;脑梗死组中CRP异常率高于腔梗组（P〈0．05）,CRP异常的患者NDS评分的改善低于CRP正常组,且CRP异常者预后中无变化和死亡明显高于正常对照者组（均P〈0．01）。结论：CRP水平是临床评价脑梗死严重程度和预后的一个重要的生物学指标。     

超敏C反应蛋白对血液病患者细菌真菌感染鉴别的意义

目的探讨超敏C反应蛋白（hsCRP）在血液病患者细菌、真菌感染鉴别中的价值。方法回顾性分析我院2007年6月～2009年6月治疗过程中出现感染的各类血液病患者91例共计感染117例次,取每次抗感染治疗前hsCRP最高值作为研究对象,分析不同hsCRP值与相对应的细菌或真菌感染的关系。结果血液病患者细菌感染hsCRP值明显高于真菌感染（P〈0．01）,细菌感染中革兰阴性菌感染者hsCRP值又高于革兰阳性菌感染者（P〈0．01）,当细菌合并真菌感染时,其hsCRP值与革兰阳性菌感染相当,但明显高于单纯真菌感染（P〈0．01）。结论hsCRP可有效鉴别血液病患者治疗中出现的细菌和真菌感染,并对抗感染治疗有一定的指导意义。     

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.