IL-4、IFN-γ和TCF-β1与系统性红斑狼疮的关系

目的探讨系统性红斑狼疮（SLE）与白细胞介素4（IL-4）、γ干扰素（IFN-γ）、生长转化因子β1（TGF-β1）的关系。方法采用酶联免疫吸附试验（ELISA）测定36例SLE患者和17例健康对照组的外周血单个核细胞（PBMC）培养上清液中IL-4、IFN-γ、TGF-β1的含量。结果Th1／Th2升高组的IFN-γ测值高（P〈0.05），IL4与健康对照组相比无显著差异（P〉0.05）；Th1／Th2降低组的IFN-γ测值低（P〈0.05），IL-4测值高（P〈0.05）；Th1／Th2降低组的TGF-β1高于Th1／Th2升高组，但两组相比无显著差异（P〉0．05）。结论Th1和Th2细胞极化增强均参与了SLE的发病，TGF-β1可能与SLE患者的Th1、Th2细胞极化异常有关。     

慢性乙型肝炎病毒携带者外周血单个核细胞凋亡及细胞因子检测的意义

目的探讨外周血单个核细胞凋亡（PBMC）和Th1／Th2型细胞因子表达在乙型肝炎病毒慢性化中的作用。方法分离21例健康人、45例慢性乙型肝炎病毒携带者PBMC，在植物血凝素（PHA-P）刺激培养72h后，以酶联免疫吸附测定法检测细胞培养上清液中的γ-干扰素（IFN-γ）浓度，流式细胞仪以膜联蛋白V-异硫氰酸荧光素／碘化丙锭（AnnexinV-FITC／PI）法检测PBMC凋亡率。结果慢性乙型肝炎病毒携带者PBMC凋亡率明显高于对照组（P〈0．01），培养上清液IFN-γ水平低于对照组（P〈0．01），且与PBMC凋亡率呈负相关（r=-0．647，P〈0.01）；IL4水平高于正常对照组（P〈0.01），且与PBMC凋亡率呈正相关（r=0．598，P〈0．01）。结论严重活化诱导的淋巴细胞凋亡（AICD）和Th1／Th2失衡在乙型肝炎病毒慢性化中起一定的作用。     

血清白介素-4和干扰素-γ及尿白三烯 E4在婴幼儿喘息性疾病中的变化及意义

目的：探讨血清IL-4、IFN-γ及尿LTE4在婴幼儿喘息性疾病中的变化及临床意义。方法选取2014年3月至2015年3月收治的喘息性疾病患儿30例为喘息组;急性非喘息性下呼吸道感染患儿30例为非喘息组,体检健康婴幼儿30例为对照组,采用酶联免疫吸附法（ ELISA）检测血清IL-4、IFN-γ及尿LTE4水平,血清IL-4、IFN-γ与尿LTE4之间的关系采用Pearson相关性分析。结果（1）喘息组急性期患儿血清IL-4水平明显高于非喘息组及对照组,血清IFN-γ水平明显低于非喘息组及对照组,差异有统计学意义（ P ＜0．05或＜0．01）;喘息组急性期患儿血清IL-4／IFN-γ值明显高于非喘息组和对照组（ P ＜0．05或＜0．01）;喘息组急性期患儿尿LTE4水平明显高于对照组（P＜0．05）,与非喘息组比较差异无统计学意义（ P ＞0．05）;（2）喘息组恢复期患儿血清IL-4、尿LTE4水平明显低于急性期（ P ＜0．05）,但仍高于对照组（ P ＜0．05）;血清IFN-γ明显高于急性期（ P ＜0．05）,但仍低于对照组（ P ＜0．05）;喘息组恢复期患儿血清IL-4／IFN-γ值明显低于急性期（ P ＜0．05）,但仍高于对照组（ P ＜0．05）;（3）喘息组急性期患儿尿LTE4水平与血清IL-4水平呈线性正相关（ r ＝0．674, P ＜0．05）;与血清IFN-γ呈线性负相关（ r ＝－0．783, P ＜0．05）。结论 IL-4、IFN-γ及LTE4与婴幼儿喘息性疾病的发生发展具有一定关系,可能与Th1／Th2免疫失衡,气道炎性反应有关。     

支气管哮喘患者外周血单核细胞因子Th1/Th2失衡的检测

目的观察支气管哮喘患者在发病期是否存在Th1／Th2失衡。方法用酶联免疫吸附试验（ELISA）分别检测三组（哮喘发作组、哮喘缓解组及健康对照组，每组17例）外周血单核细胞（PBMC）产生的肿瘤坏死因子γ（IFN-γ）、白细胞介素4（IL-4）。结果与健康对照组比较哮喘急性发作组患者PBMC产生的IFN-γ[（139．6±13．0）pg／L]明显降低（P〈0．01），而IL-4[（114．7±20．8）pg／L]水平增高（P〈0．01），哮喘缓解组两种细胞因子水平与健康对照组差异无统计学意义。结论支气管哮喘急性发作期存在着Th1／Th2失衡。     

特应性皮炎患者单个核细胞Th1/Th2和IFN-γ及IL-4 mRNA表达

目的：探讨外周血单个核细胞Th1／Th2在特应性皮炎（AD）发病中的作用和IFN-γ及IL-4 mRNA表达的情况。方法：分别用流式细胞仪及RT—PCR方法检测97例AD患者（AD组）及20例健康人（对照组）外周血单个核细胞（PBMCs）Th1／Th2水平和IFN-γ、IL-4 mRNA表达。结果：AD组外周血Th1细胞百分比低于对照组（P〈0．01），而Th2百分比高于对照组（P〈0．01）；AD组PBMCs IFN-γ mRNA表达水平与对照组差异无统计学意义（P〉0．05），而IL-4 mRNA表达显著高于对照组（P〈0．01）。结论：AD患者体内存在Th1／Th2的失衡，并提示AD属Th2优势疾病。     

孟鲁司特对哮喘患儿外周血Th1/Th2平衡的调控作用及肺功能的影响

目的观察孟鲁司特对哮喘患儿外周血Th1／Th2平衡的调控作用及肺功能的影响。方法选择80倒哮喘急性发作期惠儿,随机均分为两组。治疗组40例在对照组40例常规吸入激素治疗的基础上,加用孟鲁司特钠片5mg／d,1次／d,睡前口服,连用3月。两组患儿均于治疗前和治疗3月后检测外周血白细胞介素4（IL-4）、干扰素-γ（IFN-γ）和免疫球蛋白E（IgE）水平及肺功能的变化。结果两组患儿治疗后外周血IL-4和IgE水平明显下降,IFN-γ水平明显上升（P〈0．05或P〈0．01）,肺功能指标均明显改善（P〈0．05）,且治疗组较对照组变化更明显（P〈0．05）,改善程度更高（P〈0．05）。结论孟鲁司特治疗哮喘的临床疗效确切,能明显改善患儿的肺功能,其作用机制可能是通过纠正Th1／Th2细胞因子平衡．使免疫反应由Th2型向Th1型逆转．抑制嗜酸性细胞聚集,减少IgE分泌．     

IL-4、IFN-γ和TGF-β_1与系统性红斑狼疮的关系

目的 探讨系统性红斑狼疮(SLE)与白细胞介素4(IL-4)、γ干扰素(IFN-γ)、生长转化因子β1(TGF-β1)的关系.方法 采用酶联免疫吸附试验(ELISA)测定36例SLE患者和17例健康对照组的外周血单个核细胞(PBMC)培养上清液中IL-4、IFN-γ、TGF-β1的含量.结果 Th1/Th2升高组的IFN-γ测值高(P＜0.05),IL-4与健康对照组相比无显著差异(P＞0.05);Th1/Th2降低组的IFN-γ测值低(P＜0.05),IL-4测值高(P＜0.05);Th1/Th2降低组的TGF-β1高于Th1/Th2升高组,但两组相比无显著差异(P＞0.05).结论 Th1和Th2细胞极化增强均参与了SLE的发病,TGF-β1可能与SLE患者的Th1、Th2细胞极化异常有关.     

川芎嗪对哮喘患儿外周血Th1/Th2平衡的调节作用

目的观察川芎嗪对哮喘患儿外周血Th1/Th2细胞因子的影响。方法选择80例哮喘急性发作期患儿,随机分为川芎嗪组和对照组。川芎嗪组在对照组常规治疗的基础上加用川芎嗪治疗10d。应用抗体夹心ELISA法检测两组患者治疗前后培养上清单个核细胞（PBMC）中白介素-4（IL-4）和γ-干扰素（IFN-γ）含量的变化。结果川芎嗪组患儿治疗后培养上清PBMC中IL-4水平较治疗前明显下降,IFN-γ水平明显上升（均P〈0.01）。而对照组治疗前后IL-4和IFN-γ水平比较无统计学差异（均P〉0.05）。川芎嗪组的临床显效率和有效率明显高于对照组（P〈0.05）。结论川芎嗪治疗哮喘的临床疗效确切,其作用机制与纠正Th1/Th2细胞因子平衡,使免疫反应由Th2型向Th1型逆转有关。     

骨风宁胶囊对强直性脊柱炎Th1／Th2类细胞因子表达影响的研究

目的：观察骨风宁胶囊对强直性脊柱炎（ankylosing spondylitis,AS）患者体内Th1／Th2类细胞因子的影响。方法：19例AS患者随机分为两组,分别给予骨风宁（9例）和磺胺柳氮吡啶（SSZ）（10例）,采用ELISA法测定其治疗前后外周血单个核细胞（peripheral blood monono—clear cells,PBMC）中细胞因子干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）的水平。结果：骨风宁治疗后AS患者PBMC中IFN-γ、IL-2的表达明显降低,与治疗前相比差异有显著性（P〈0．05）,IL-4的表达差异无显著性。SSZ治疗后AS患者PBMC中IFN-γ的表达水平明显降低（P〈0．05）,IL-4较治疗前明显升高（P〈0．05）,IL-2的表达无明显变化（P〉0．05）。结论：骨风宁胶囊能使IFN-γ、IL-2表达降低,促进AS患者的免疫应答从Th1型向Th2型转变,使病情缓解。SSZ可促使AS患者的免疫应答从Th1型向Th2型转变。     

哮喘患儿外周血Th1／Th2平衡的失调及川芎嗪的干预作用

且的探讨哮喘患儿外周血Th1/Th2平衡的失调及川芎嗪的干预作用。方法对45例惠性发作期哮喘患儿（治疗组）在常规治疗的基础上加用川芎嘻治疗10天。双抗体夹心ELISA法检测治疗前后外周血培养上清单个核细胞（PBMC）中白介素-4（IL-4）、γ-干扰素（IFN-γ）水平的变化和肺功能的变化,并以30例健康儿童作对照（对照组）。结果治疗组患儿治疗前培养上清PBMC中IL-4水平明显高于对照组,IFN-γ水平明显低于对照组．肺功能指标较对照组明显下降．经川芎嗪治疗10天后患儿IL-4水平较治疗前明显降低．IFN-γ水平较治疗前上升．肺功能指标明显改善。结论哮喘患儿存在着Th1／Th2平衡失调,免疫状态由Th1向Th2“克隆漂移”。而川芎嗪能改善哮喘患儿肺功能,调节Th1／Th2细胞因子平衡,使免疫反应由Th2型向Th1型逆转,从而达到治疗哮喘的目的。     

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.