来曲唑在子宫内膜异位症治疗中的作用

目的通过观察芳香化酶抑制剂-来曲唑作用于体外培养的子宫内膜异位症患者在位内膜细胞(Ectopic endometrial cells of women with endometriosis,EE)后芳香化酶及芳香化酶转录刺激因子-类固醇源性因子(SF-1)的表达情况,探讨来曲唑作为芳香化酶抑制剂对子宫内膜异位症(内异症)的作用。方法以0、0.1、1、10、100 nmol/L浓度的来曲唑对体外培养的子宫内膜异位症者的在位内膜细胞(EE)分别进行刺激。72 h后采用RT-PCR法从核酸水平检测Aromatase和SF-1的mRNA表达情况。结果不同浓度的来曲唑均可明显抑制细胞内Aromatasem RNA及SF-1mRNA表达,与空白组比较有显著性差异(P<0.05);且抑制作用呈浓度依赖性。结论芳香化酶抑制剂-来曲唑对内异症在位内膜细胞具有明显抑制EE细胞内芳香化酶及其转录调节因子SF-1的与mRNA表达。     

芳香化酶P450与环氧化酶-2在子宫内膜异位症和子宫腺肌病中的表达及意义

目的 研究细胞色素芳香化酶P450(P450arom)和环氧化酶-2(COX-2)在子官内膜异位症(EMs)和子宫腺肌病(AM)在位和异位内膜中的表达及相关性.方法 应用免疫组化Envision法和半定量逆转录聚合酶链反应(RT-PCR)技术检测正常子宫内膜、EMs及AM的在位和异位内膜中P450arom及COX-2的蛋白与mRNA的表达,并进行相关性分析.结果 P450arom和COX-2在正常子宫内膜中无表达或弱表达,二者在EMs和AM在位和异位内膜中的表达均高于正常子宫内膜,差异均有显著性意义(P<0.05).P450arom与COX-2在EMs和AM异位内膜中的表达均高于在位内膜,差异均有显著性意义(P<0.05).P450arom在EMs和AM增殖期和分泌期表达无差异(P>0.05).COX-2在正常子宫内膜、EMs分泌期表达高于增殖期,差异均有、显著性意义(P<0.05).在AM表达不随月经周期变化.P450arom mRNA与COX-2mRNA在EMs中的表达水平呈正相关(r=0.964,P<0.01);在AM中的表达水平亦呈正相关(r=0.813,P<0.01).结论 P450arom和COX-2在EMs和AM中呈过表达,与EMs和AM的发病相关.二者协同作用促进EMs和AM的发生发展.     

来曲唑对体外培养子宫内膜异位细胞增殖的影响

目的 探讨来曲唑对体外培养的子宫内膜异位症患者在位内膜细胞的增殖影响.方法 MTT比色法检测来曲唑对位内膜细胞(Eutopic Endometrium,EE)/正常内膜(normal endometrium NE)抑制情况,并采用蛋白印迹法与RT-PCR方法检测芳香化酶及其转录调节因子SF-1的蛋白与mRNA表达情况.结果 NE细胞用药组与对照组比较无显著性差异(P>0.05);EE细胞在来曲唑作用下呈现较强的抑制增殖效应,抑制作用随浓度增加而加强,细胞增殖活力明显降低,有显著性差异(P<0.01),不同浓度的来曲唑均可明显抑制细胞内芳香化酶及其转录调节因子SF-1的蛋白与mRNA表达,且呈剂量依赖性,有显著性差异(P<0.01).结论 芳香化酶抑制剂-来曲唑对内异症在位内膜细胞具有抑制其增殖作用,明显抑制EE细胞内芳乔化酶及其转录调节因子SF-1的蛋白与mRNA表达.     

异位子宫内膜芳香化酶P450A的表达及其意义

目的研究异位子宫内膜及在位内膜P450芳香化酶mRNA表达,探讨其在子宫内膜异位症发病中的作用和临床意义。方法采用逆转录聚合酶联反应(RT-PCR)技术检测45例卵巢异位子宫内膜、22例盆腹膜子宫内膜异位病灶、32例在位内膜和35例对照组子宫内膜中P450芳香化酶(P450A)mRNA的表达。结果67例异位内膜均有P450A mRNA的表达,在卵巢异位子宫内膜和盆腹膜异位子宫内膜组间其表达无显著性差异(P>0.05);异位子宫内膜P450A mRNA表达量均高于在位内膜(P<0.01);35例对照组子宫内膜几乎无表达。结论正常子宫内膜无P450A表达,但子宫内膜异位症患者的在位内膜有P450A,而异位子宫内膜则呈P450A高表达。提示异位子宫内膜局部存在异常雌激素合成;在位内膜本身的保护机制劣于正常内膜。     

COX-2在实验性子宫内膜异位症中的表达及意义

目的探讨环氧化酶COX-2在实验性子宫内膜异位症(EMs)在位及异位内膜中的表达及意义。方法利用大鼠内异症动物模型,采用免疫组化技术,检测手术对照组、内异症模型组、痛可舒治疗组在位及异位子宫内膜COX-2表达情况。结果手术对照组、内异症模型组、痛可舒治疗组在位及异位子宫内膜COX-2的表达不同,内异症异位子宫内膜的表达高于内异症在位子宫内膜,明显高于正常子宫内膜(P<0.01)。痛可舒治疗后异位子宫内膜COX-2的表达明显降低(P<0.01)。内异症异位子宫内膜COX-2表达在各时间点间差异有比较意义(P<0.01)。结论COX-2的高表达可能是导致子宫内膜异位症的发病机制之一,痛可舒可使其表达下降,对COX-2的深入研究将为子宫内膜异位症的治疗提供新的靶点。     

Toll样受体2在子宫内膜异位症病人异位和正常内膜组织中的表达及意义

目的 探讨 Toll样受体2(TLR2)在子宫内膜异位症(EMs)病人异位和正常内膜组织中的表达和意义.方法 选取2014年2月-2016年2月在昆山市中医医院妇科经病理证实为子宫内膜异位症病人的异位内膜39例(EMs异位内膜组)以及在位内膜32例(EMs在位内膜组),再选取30例未患有子宫内膜异位的女性在位内膜组织30例(正常对照组).采用RT-PCR法检测TLR2在EMs异位内膜、EMs在位内膜以及正常内膜组织中mRNA的表达情况.采用 Western blot法检测TLR2在各组中蛋白的表达情况.结果 EMs异位内膜组、EMs在位内膜组、正常对照组中TLR2 mRNA和蛋白表达有显著性差异(P﹤0.05),EMs异位内膜组和EMs在位内膜组TLR2 mRNA和蛋白表达显著高于正常对照组,EMs异位内膜组中的TLR2 mRNA和蛋白表达显著高于EMs在位内膜组.结论 TLR2 mRNA和蛋白的高表达,说明TLR2在EMs的发病和发展过程中可能起着重要作用.     

子宫内膜异位症血管生成相关分子分型的研究

目的:探讨子宫内膜异位症相关基因型的变化以及血管内皮生长因子(VEGF)和病程相关蛋白(PR蛋白)的表达情况,为子宫内膜异位症血管生成相关的分子分型提供有意义的线索。方法:用PCR、Northern blot及免疫组化技术检测30例卵巢内膜样囊肿患者的30份异位子宫内膜(异位内膜组)、30份在位子宫内膜(在位内膜组)以及25例非子宫内膜异位症患者的25份子宫内膜(对照组)中的VEGF和PR基因及蛋白的表达水平。结果:异位内膜组与在位内膜组的VEGF mRNA表达水平均显著高于对照组(P<0.05),而在位内膜组与异位内膜组的VEGF mRNA表达水平比较,差异无统计学意义(P>0.05);异位内膜组织中PRmRNA的表达显著低于在位内膜组和对照组(P<0.01),在位内膜组织中PR mRNA的表达与对照组比较,差异无统计学意义(P>0.05)。内膜异位组异位内膜中的PR阳性率显著低于在位内膜组和对照组(P<0.05),而在位内膜中的PR阳性率与对照组比较,差异无统计学意义(P>0.05);异位内膜与在位内膜的VEGR阳性率显著高于对照组(P<0.01),而异位内膜与在位内膜的VEGF阳性率比较,差异无统计学意义(P>0.05)。结论:子宫内膜异位症患者中VEGF mRNA的高表达和PR mRNA的低表达可能参与了子宫内膜异位症的发生发展过程。     

IL-18在子宫内膜异位症中临床研究

目的 研究子宫内膜异位症患者子宫在位内膜和异位内膜的IL-18表达,探讨IL-18在内异症发病机制中的意义.方法 用免疫组织化学方法检测正常人子宫内膜和内异症患者的子宫在位内膜与异位内膜的IL-18表达.结果 IL-18的免疫组化结果均有表达,主要表达于子宫的上皮细胞,基质细胞也有表达,但是较弱.IL-18对照组子宫内膜标本阳性的灰度值高于内异症子宫在位内膜组而内异症异位灶组织阳性的灰度值最低,和对照组以及内异症在位内膜组相比差异均有统计学意义(P<0.05).结论 IL-18在内异症患者在位和异位内膜的异常表达,可能是影响内异症形成和发展的重要因素之一.     

子宫内膜异位症中子宫内膜间质细胞侵袭、转移能力的研究

目的 检测子宫内膜异位症(EMs)患者子宫内膜间质细胞中环氧化酶-2(COX-2)、前列腺素E2(PGE2)、锌指转录因子(Snail)和E-钙黏蛋白(E-cadherin)m RNA表达情况,分析EMs中子宫内膜间质细胞的侵袭、转移能力。方法 收集EMs患者的在位及异位病灶子宫内膜组织和子宫肌瘤患者的在位内膜组织,原代消化培养子宫内膜细胞,取纯化的第4代子宫内膜间质细胞进行研究,RT-PCR法检测细胞COX-2、PGE2、Snail和E-cad-herin m RNA的表达。结果 EMs和子宫肌瘤患者分泌期在位子宫内膜间质细胞COX-2、PGE2、Snail和E-cadherinm RNA表达与增殖期比较差异均无统计学意义;EMs患者在位及异位的子宫内膜间质细胞COX-2、PGE2、Snailm RNA表达比肌瘤患者在位细胞均明显升高,而E-cadherin m RNA表达降低(P<0.05或P<0.01);EMs患者异位的子宫内膜间质细胞COX-2、PGE2、Snail m RNA表达比在位间质细胞升高,而E-cadherin m RNA表达降低(P<0.05或P<0.01)。结论 EMs患者的子宫内膜间质细胞侵袭、转移能力强于非EMs患者,且在EMs发病中异位病灶子宫内膜间质细胞的侵袭、转移能力更强。     

子宫内膜异位症痛经患者内膜组织中雌激素受体表达的相关研究

目的 检测内异症痛经患者内膜组织中雌激素受体的表达,分析其与疼痛及其程度的关系.方法 内异症组50例,其中在位内膜组40例,异位内膜组10例,对照组30例,在位内膜组患者术前均对痛经程度进行评分,采用免疫组化法测定雌激素受体的表达.结果 EMs组在位内膜ER蛋白的表达高于对照组,差异有显著性(P＜0.05);EMs疼痛组与无痛组的表达差异有显著性(P＜0.05);ER蛋白在EMs重度疼痛组组织中阳性灰度值最高,而在轻度疼痛组灰度值最低,三组间比较差异均有显著性(P＜0.05).结论 内异症病灶局部雌激素受体表达增加,可能与子宫内膜异位症疼痛的发生、发展密切相关.     

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.     

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。     

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.     

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。     

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。     

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.     

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.     

Chondroprotective Effects of Wogonin in Experimental Models of Osteoarthritis in vitro and in vivo

We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-1β (IL-1β)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-1β-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes.