COMT基因功能多态性对帕罗西汀治疗2型糖尿病伴抑郁患者疗效的相关性

目的探讨儿茶酚氧位甲基转移酶(COMT)基因功能多态性(Val/Val、Val/Met和Met/Met)对帕罗西汀治疗2型糖尿病合并抑郁焦虑患者的疗效的影响。方法对32例血糖控制不理想的2型糖尿病合并抑郁焦虑患者,在常规降糖治疗基础上加用帕罗西汀每晨1次,每次20mg,疗程4周,观察治疗前、后汉密尔顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)分数的改变。结果治疗后不同基因组患者抑郁情绪有改善,HAMD、HAMA与治疗前比较每周均有显著性差异(P<0.01),但三基因组间并无统计学意义(P>0.05)。结论对2型糖尿病合并抑郁焦虑患者,加用帕罗西汀治疗能有效改善抑郁症状及更好地控制血糖,COMT基因功能多态性与帕罗西汀疗效差异并不相关。     

儿茶酚氧位甲基转移酶基因功能多态性对帕罗西汀治疗2型糖尿病伴抑郁患者疗效的相关性

目的:探讨儿茶酚氧位甲基转移酶(COMT)基因功能多态性对帕罗西汀治疗2型糖尿病合并抑郁焦虑患者的疗效的影响。方法:对52例血糖控制不理想的2型糖尿病合并抑郁焦虑患者,治疗前抽取外周静脉血,提取DNA,用PCI技术检测研究对象的基因型,分成Val/Val、Val/Met和Met/Met 3组,在常规降糖治疗基础上加用帕罗西汀每晨一次,每次20 mg,疗程4周,观察治疗前、后汉密尔顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)分数、餐后2 h血糖(2hPBG)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、帕罗西汀血药浓度的改变。结果:治疗后不同基因组患者抑郁情绪有改善,HAMD、HAMA、2hPBG、FBG、HbA1c、血药浓度与治疗前比较均有显著性差异(P<0.01),但4周后3基因组间差异并无显著性(P>0.05)。结论:对2型糖尿病合并抑郁焦虑患者,加用帕罗西汀治疗能有效改善抑郁症状及更好地控制血糖,COMT基因功能多态性与帕罗西汀疗效差异可能并不相关。     

帕罗西汀单用及与阿普唑仑联用治疗糖尿病合并焦虑抑郁的对照研究

目的:比较帕罗西汀单用及与阿普唑仑联用治疗糖尿病合并焦虑抑郁的疗效及安全性。方法:选取糖尿病合并焦虑抑郁患者86例,随机均分为观察组和对照组。观察组患者服用帕罗西汀20 mg,qd,并服用阿普唑仑0.4 mg,tid;对照组患者单独服用帕罗西汀。两组患者疗程均为8周。比较两组患者治疗前后空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A1c)、皮质醇、促肾上腺皮质激素(ACTH)水平及汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评分,并观察不良反应情况。结果:治疗后,观察组患者FPG、2 h PG、Hb A1c、皮质醇、ACTH水平及HAMA、HAMD评分均显著低于对照组及本组治疗前,差异有统计学意义(P<0.05)。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论:帕罗西汀联用阿普唑仑治疗糖尿病合并焦虑抑郁相比单用帕罗西汀可更好地改善患者的血糖、内分泌水平及不良情绪,且安全性相当。     

帕罗西汀对躯体形式障碍的疗效观察

目的观察帕罗西汀对躯体形式障碍的疗效。方法将64例患者分成2组,分别为帕罗西汀组与多塞平组。在治疗前、治疗后第2、4、8周末各进行汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定。结果治疗2周后帕罗西汀组汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评分低于多塞平组,治疗后帕罗西汀组汉密尔顿焦虑量表（HAMA）-汉密尔顿躯体化量表（HA-MA-SOM）评分2、4、8周均低于多塞平组。结论帕罗西汀起效快,汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评分下降明显,不良反应少。     

阿普唑仑联合帕罗西汀治疗糖尿病焦虑抑郁的临床研究

目的比较单一使用帕罗西汀和阿普唑仑联合帕罗西汀治疗糖尿病焦虑抑郁的临床效果。方法将56例糖尿病并发焦虑抑郁的患者随即分为两组,实验组和对照组均为28例。两组患者均进行糖尿病常规治疗,同时实验组患者使用帕罗西汀联合阿普唑仑治疗患者的焦虑抑郁,对照组仅单一使用帕罗西汀治疗患者的焦虑抑郁。治疗持续2个月以后比较两组患者的血糖下降情况和焦虑抑郁的缓解情况。结果治疗前两组患者的焦虑自评量表(HAMA)和抑郁自评量表(HAMD)评分均高于国内常模,且差异具有统计学意义(P<0.05)。治疗结束后两组患者的HAMA和HAMD评分均显著下降(P<0.05),但实验组下降更为明显(P<0.05)。两组患者的因用药所引发的不良反应无明显差异(P>0.05)。结论阿普唑仑联合帕罗西汀治疗糖尿病焦虑抑郁的疗效更佳,起效迅速且无明显不良反应,有较好的临床应用效果。     

舒必利与奥氮平治疗神经性厌食症患者的对照研究

目的:比较舒必利联合帕罗西汀与奥氮平联合帕罗西汀治疗神经性厌食症的疗效与副反应差别。方法:分析57例(其中使用舒必利组25例,奥氮平组32例)住院神经性厌食症患者治疗8周前后的体重,体重指数,汉密尔顿焦虑量表(HAMA),汉密尔顿抑郁量表(HAMD)及副反应量表(TESS)的结果。结果:两组治疗8周后体重,体重指数及汉密尔顿焦虑量表、汉密尔顿抑郁量表总分均比入院时有明显改善。同时治疗8周后奥氮平组比舒必利组在改善体重及体重指数上要更加明显,两组间比较有统计学差异,而在HAMA、HAMD、TESS的比较上未见统计学差异。结论:舒必利联合帕罗西汀与奥氮平联合帕罗西汀均能有效改善神经性厌食症患者的临床症状,奥氮平联合帕罗西汀相对舒必利联合帕罗西汀而言改善体重及体重指数的效果更佳,两组在副反应上未见明显差异。     

帕罗西汀联合疏肝解郁胶囊对女性抑郁症伴焦虑症状疗效观察

目的 探讨帕罗西汀联合疏肝解郁胶囊对女性抑郁症伴焦虑症状患者疗效观察.方法 将64例女性抑郁症伴焦虑症状者随机分2组各32例,联合组予帕罗西汀联合疏肝解郁胶囊,对照组予帕罗西汀,疗程均6周,采用汉密尔顿抑郁量表HAMD和汉密尔顿焦虑量表HAMA评定疗效,并记录不良反应情况.结果 联合组总有效率高于对照组,差异有统计学意义(P<0.05).两组治疗后HAMD、HAMA评分较治疗前均明显降低,差异均有统计学意义(P<0.05),联合组在治疗后1周、2周的HAMD、HAMA与对照组比较,差异就有统计学意义(P<0.05).且联合组加用舒肝解郁胶囊后无明显增加不良反应.结论 帕罗西汀联合疏肝解郁胶囊治疗女性抑郁症伴焦虑症状患者具有协同作用,不但起效快,而且无明显增加不良反应.     

帕罗西汀联合阿普唑仑治疗糖尿病焦虑抑郁的疗效观察

目的比较帕罗西汀联合阿普唑仑和单用帕罗西汀治疗糖尿病焦虑抑郁的疗效。方法将48例糖尿病伴发焦虑抑郁障碍患者随机分为研究组与对照组,每组24例,均给予糖尿病常规治疗。研究组帕罗西汀和阿普唑仑治疗,对照组单用帕罗西汀治疗,疗程8周。观察血糖控制情况,采用焦虑自评量表（HAMA）,抑郁自评量表（HAMD）评定焦虑抑郁症状改善情况,并与国内常模进行对比分析。结果治疗前2组HAMD表,HAMA评分均显著高于国内常模（P〈0.05）,治疗8周末HAMD、HAMA评分均较治疗前显著下降（P〈0.05）,研究组较对照组下降更显著（P〈0.05）。研究组较对照组起效快,在第1周和第2周2组比较,差异均有统计学意义（P〈0.05）。2组不良反应多为轻、中度,多能耐受,差异无统计学意义（P〉0.05）。结论帕罗西汀联合阿普唑仑治疗糖尿病焦虑抑郁症起效快,不增加不良反应,因而在临床治疗上是可行的。     

奎硫平联用帕罗西汀治疗抑郁症的疗效

目的:探讨奎硫平联用帕罗西汀治疗抑郁症的效果。方法:将63例抑郁症患者随机分为两组,分别给予奎硫平联用帕罗西汀(联用组)与帕罗西汀(对照组)治疗8周,以汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)评定临床疗效,以副反应量表(TESS)和相关实验室检查评定副反应。结果:治疗结束时两组HAMD和HAMA的评分均显著降低,尤以联用组明显,TESS评分各周差异均不明显。结论:奎硫平联用帕罗西汀治疗抑郁症的疗效优于单纯使用帕罗西汀,且耐受性好。     

帕罗西汀麦普替林治疗脑卒中后抑郁的对照观察

目的比较帕罗西汀和麦普替林治疗脑卒中后抑郁的疗效和不良反应。方法把符合入组条件的68例患者随机分成帕罗西汀组和麦普替林组,分别给予相应药物治疗。研究共观察8周,在治疗前和治疗的第2、4、6、8周末应用汉密尓顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)评定疗效,记录治疗过程中的不良反应。结果治疗过程中脱落5例。治疗后两组患者HAMD、HAMA评分均较治疗前明显下降(P<0.01),两组间同期比较差异无统计学意义(P>0.05);帕罗西汀组有效率84.38%,麦普替林组有效率87.10%,二者差别无统计学意义(P>0.05);帕罗西汀组不良反应少于麦普替林组,在口干便秘、排难困难、嗜睡等方面两组间差别有统计学意义(P<0.05)。结论帕罗西汀治疗脑卒中后抑郁疗效与麦普替林相当,不良反应少。     

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。     

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.     

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.     

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.     

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.