Taurine inhibition of metal-stimulated catecholamine oxidation

Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cyto-protective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessedin vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50–500 μM)- and manganese (10 μM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO₄-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1–20 mM). Protein carbonyl formation induced by ferric iron (500 μM) and L-dopa (500 μM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 μM) and ferric chloride (75 μM) to LLC-PK₁ cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK₁ cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones.     

KNT009安全性药理学研究

目的:观察KNT009对小鼠神经系统、犬心血管系统及呼吸系统的影响。方法:实验均分高、中、低剂量组及空白对照和阳性对照共5个组,小鼠实验给药组分别单次慢速静脉注射(iv)KNT009 160、80和40 mg/kg,加替沙星80 mg/kg,观察动物的自发活动和爬杆能力;犬实验给药组分别单次慢速iv KNT009 40、20 和10 mg/kg,加替沙星20 mg/kg,观察药物对犬血压、ECG、呼吸频率及节律的影响。结果:单次慢速iv KNT009对小鼠自发活动和爬杆能力无明显影响。单次慢速iv KNT009可降低犬收缩压、舒张压、平均动脉压,减慢心率,延长QT间期,使犬呼吸频率减慢,呼吸幅度加大,且均存在量效关系,3 h后上述指标基本恢复正常,加替沙星也有类似变化。结论:KNT009对心血管和呼吸系统有一定的影响,可使血压下降,心率减慢,QT间期延长,呼吸频率减慢,呼吸幅度加大。     

拉呋替丁鼠伤寒沙门氏菌基因回复突变试验

目的　体外观察拉呋替丁能否诱发鼠伤寒沙门氏菌组氨酸营养缺陷型突变株的回复突变。方法　Ames试验用TA97、TA98、TA10 0、TA10 2菌株并分加与不加肝微粒体酶活化系统( +/ -S9)试验。结果　拉呋替丁对四个菌株各剂量组的回复菌落数都未超过自然回复菌落数,Ames试验结果为阴性。结论　未见拉呋替丁致突变性。     

西洛他唑降低链脲佐菌素诱发糖尿病大鼠肾脏VCAM-1表达

目的　探讨西洛他唑对高糖大鼠肾组织VCAM - 1的影响及对肾脏的可能保护作用。方法　雄性SD大鼠,链脲佐菌素(STZ)制备糖尿病大鼠模型。观察西洛他唑12周后对血糖、糖化血红蛋白、肾重/体重比值、肾脏VCAM - 1mRNA及蛋白表达的影响。结果　糖尿病对照组及各治疗组肾重/体重比值均明显增加(P <0 . 0 1);VCAM - 1mRNA表达在糖尿病组明显升高,药物治疗后有显著改善( P <0. 0 1);Westernblot各组均有VCAM - 1表达,糖尿病组较正常组表达增强,药物治疗后呈下降趋势。结论　STZ诱发的糖尿病大鼠肾脏VCAM - 1表达增加,西洛他唑降可低糖尿病大鼠肾组织VCAM - 1mRNA和蛋白表达,对糖尿病肾脏具有保护作用。     

408名社区吸毒人员操守保持的相关因素分析

目的:正确推断社区吸毒解教人员操守保持的相关因素,为制定有效的戒毒政策提供科学依据。方法:以408名长沙市芙蓉区登记在册的操守保持者为研究对象,96名复吸者为对照,比较两组吸毒解教人员的人口学、吸毒和社区帮教相关情况的差异,并进行Logistic逐步回归分析。结果:操守保持者与复吸组比较,平均年龄、首次吸毒年龄相对较大,吸毒时间相对较短,曾经使用过毒品的种类和方式相对较少,戒毒次数相对较少;而操守保持者的社会帮教率(95·6%)明显高于复吸者(53·1%),平均每年尿液毒品检测次数相对较多,低保申请率和就业安置率相对较高。多因素分析结果表明劳教戒毒次数、就业安置和年尿液检测次数是影响操守成败的主要因素。结论:社区帮教措施能够促进社区吸毒解教人员保持操守,是戒毒所戒毒工作的延续和宏观戒毒管理的一个重要方面。     

国产盐酸舍曲林胶囊和片剂的人体药物动力学及生物等效性

目的研究国产盐酸舍曲林胶囊及片剂的相对生物利用度、药物动力学特征及生物等效性.方法采用随机、开放、3×3拉丁方设计实验,18名男性健康受试者分别单剂量口服含舍曲林50 mg的试验片剂、胶囊及参比制剂.采用HPLC-MS/MS/MS法测定给药后不同时间的血药浓度,计算3者的药物动力学参数及评价其生物等效性.结果 18例健康志愿者口服参比制剂和试验制剂舍曲林胶囊及片剂后,参比制剂中舍曲林的主要药物动力学参数cmax为(10.14±3.43)μg·L-1;tmax为(4.44±1.10)h;AUC0～96为(262.82±100.66)μg·h·L-1;t1/2为(29.19±4.91)h.试验制剂片剂中舍曲林的主要药物动力学参数cmax为(10.16±3.22)μg·L-1;tmax为(4.33±1.85)h;AUC0～96为(269.71±107.47)μg·h·L-1;t1/2为(30.99±6.49)h.试验制剂胶囊中舍曲林的主要药物动力学参数cmax为(10.39±3.59)μg·L-1;tmax为(4.94±1.30)h;AUC0～96为(264.45±112.57)μg·h·L-1;t1/2为(29.68±5.25)h.试验制剂片剂和胶囊分别对参比制剂的相对生物利用度F为(103.4%±18.2%)、(99.8%±13.6%).结论经统计学分析,国产试验制剂胶囊剂和片剂与参比制剂具有生物等效性.     

Gender differences in limonin pharmacokinetics in rats.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.     

带锁滑动鹅头钉治疗粉碎性股骨转子间骨折的临床研究

为了总结分析运用自行研制的带锁滑动鹅头钉治疗粉碎性股骨转子间骨折的疗效,随机将69例Evan'sⅢ型、Ⅳ型的患者分为两组,一组采用自制带锁滑动鹅头钉治疗(观察组);一组采用DHS治疗(对照组).分别对两组患者的一般资料、手术资料及术后功能恢复情况进行评估比较.结果骨折平均愈合时间观察组为3.65±0.97个月,对照组为4.32±1.38个月,两组比较,术后9个月观察组患侧较健侧平均缩短0.82±0.36cm,对照组平均缩短1.08±0.51cm,两组比较差异有显著性意义(P＜0.05).观察组显效率91.1%,对照组显效率71.1%,两组比较,具有非常显著性差异(P＜0.01).提示带锁滑动鹅头钉治疗粉碎性股骨转子间骨折具有防止骨不连及各种畸形愈合.     

非骨水泥型假体周围早期骨密度变化临床观察

为观察非骨水泥型假体置换术后周围骨密度的变化,对25例非骨水泥型人工假体置换患者分别于术后1周、3个月及6个月应用双能X线骨密度仪,按Grune[1]分7个测量兴趣区测量假体周围骨密度.结果显示假体周围骨密度术后3个月平均丢失11.7%,6个月平均丢失17.77%.其中以1和7区明显,1区术后3、6个月分别减少21.25%、25.55%(P＜0.01),7区术手3、6个月分别减少22.80%、32.14%(P＜0.01).说明假体置换术后早期周围骨密度均有不同程度的减少,其中以假体近端(1、7区)明显,且骨量丢失以术后前3个月最为显著.     

复方苍术汤治疗老年肥胖或超重合并糖耐量异常32例临床观察

目的:观察复方苍术汤治疗老年肥胖或超重合并糖耐量异常(IGT)的疗效.方法:以复方苍术汤治疗老年肥胖或超重合并IGT患者32例,并与盐酸二甲双胍治疗30例作对照,对治疗前后患者体重、腰围、臀围、腰臀比(WHR)、糖耐量、空腹血清胰岛素水平、血脂的变化进行对比观察.结果:复方苍术汤组治疗后患者的体重、腰围、臀围及WHR、糖耐量试验的血糖水平、空腹血清胰岛素水平、血脂与治疗前比较明显降低(P＜0.01或P＜0.05),与对照组比较差异无显著性(P＞0.05).结论:复方苍术汤对肥胖或超重合并IGT患者的体重、腰围、臀围及WHR、血糖、空腹血清胰岛素水平、血脂有明显降低作用,可用于老年肥胖或超重合并IGT患者的减重及干预治疗.