Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.     

Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors

In this study, the behavioural response to dopamine D₁-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D₂-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC), SKF 77434 (0.1 mg/kg SC), quinpirole (0.1 and 0.25 mg/kg SC) or RU 24213 (0.3 mg/kg SC), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D₁-like agonist plus a D₂-like agonist [SKF 38393 (7.5 mg/kg SC) plus quinpirole (0.25 mg/kg SC), SKF 81297 (0.2 mg/kg SC) plus quinpirole (0.1 mg/kg SC), and SKF 77434 (0.1 mg/ kg SC) plus RU 24213 (0.3 mg/kg SC)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 μg/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D₁-like and D₂-like receptors, and that this effect is long-lasting. Received: 24 January 1997 /Final version: 5 March 1997     

überlebensverbesserung eines unizentrischen Gesamtkollektivs aus 20 Jahren

PURPOSE: The development of overall survival of a DOSAK (German-Austrian-Swiss Cooperative Group on tumours of the maxillofacial region) clinic's overall population comprising a time period of more than 20 years (1983-2004) should be assessed. At a cutoff date (January 1st, 1997), a change from a primarily surgically based to a consequent multi-modality treatment regimen was implemented. The periods of time before and after that change should be compared. METHODS AND PATIENTS: The data of the DOSAK registry entries on 1038 patients suffering from primary untreated oral and oropharyngeal carcinomas were updated with respect to follow-up and mortality data to achieve a 100% quality of follow-up. The end point (death) was reached in 67% of the overall population. Statistical analysis was carried out by the Trium Analysis Online corporation, Munich. RESULTS: The portion of female and older tumor patients increased, more than half of all tumor patients were clearly in stage IV of the disease at first referral. The portion of patients operated on persisted approximately (80%), the portion of additional treatment modalities could be increased considerably. The fact of a bony infiltration by the tumor and the operability remained highly significantly relevant for survival in multivariate analysis, despite of multi-modality treatment. The survival rate of the patients remained significantly dependent on the clinical stage of the disease in multivariate analysis but could be improved by 10% in the clinical stages II and III and in the patients who could not be operated on. All in all, the cutoff date was statistically relevant for survival in multivariate analysis, i.[Symbol: see text]e. the change in the treatment regimen had a verifiable positive effect on the survival of a unicentric overall population. CONCLUSION: Survival improvement in an overall population via change in treatment strategy is possible in relatively short time; the clinical stages II and III and the non-operable patients have the greatest benefit from a multi-modality treatment.     

D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族的遗传多态性

目的 调查D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族群体中的遗传分布规律。方法 采集308份血及唾液标本应用PCR技术，扩增产物用非变性聚丙酰胺凝胶电泳分离，银染显色分析。结果 两位点各群体基因型频率分布均符合Hardy-Weinberg平衡，每一位点等位基因频率分布在各群体间无显著差异；通过对10个汉族家系的遗传模式分析，证实了两位点等位基因传递遵循孟德尔遗传规律。结论 D4S1647、D6S2414基因座在中国汉族，蒙古族，藏族群体均具有高度遗传多态性。     

利培酮治疗与细胞色素P4502D6/C188T酶基因多态性的关联分析

目的　研究利培酮临床效应的个体差异与其代谢酶细胞色素P4 5 0 2D6 (cytochromeP4 5 02D6 ,CYP2D6 )酶基因多态性的相关性。方法　对 88例符合CCMD 3精神分裂症诊断标准的患者和 96例健康对照者作病例 -对照分析。精神分裂症患者给予利培酮治疗 8周 ,用阳性和阴性症状量表 (posi tiveandnegativesymptomscale ,PANSS)评分评价利培酮疗效。采用聚合酶链反应扩增及限制性片段长度多态性 (PCR RFLP)技术对CYP2D6exonⅠ的C188T位点突变进行检测 ,分析利培酮临床效应与其主要代谢酶CYP2D6 /C188T酶基因多态性的相关性。结果　中国上海地区人群的CYP2D6 /C188T突变率(弱代谢型 )为 36 .3% ,病例组和正常对照组间基因型频率总体分布比较无显著差异 (χ2 =1.15 ,df=2 ,P >0 .0 5 ) ,两组间的等位基因频率之间比较也无显著性差异 (χ2 =0 .78,df=1,P >0 .0 5 )。进行性别及有否家族史分组后分析 ,亦无差异存在 ,且CYP2D6 /C188T突变与利培酮临床效应之间并无相关性 (χ2 =1.12 ,df=2 ;χ2 =0 .0 3,df=1,P >0 .0 5 )。结论　未发现中国人CYP2D6 /C188T多态性与利培酮临床效应的个体差异有相关性。     

人血浆高敏感性C反应蛋白与代谢综合征相关性分析

目的:了解我国人群血浆高敏感性C反应蛋白(hs-CRP)水平与代谢综合征(MS)关系及其它影响hs-CRP水平的相关因素。方法:1198例血浆标本来自2006年3月~2006年11月在浙江省桐乡市第三人民医院体检人群。采用Beckm an LX20血生化全自动生化仪及其配套试剂,测定上述空腹血浆标本中血糖(FPG)、甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)和hs-CRP水平。MS诊断标准参照中华医学会推荐标准。采用SPSS13.0统计学软件,分析hs-CRP水平与MS关系及其它影响hs-CRP水平的相关因素。结果:男性hs-CRP水平(x±s=1.55±0.53)高于女性(x±s=1.32±0.56)(P<0.001)。15.3%被检者(183/1198)患有MS,其hs-CRP水平明显高于非MS者(P<0.001)。各MS判断指标中,分别有肥胖、高血压病、糖尿病、高TG、低HDL-c时,其hs-CRP水平也明显升高(P<0.001)。排除年龄、性别影响后,hs-CRP水平与MS显著相关(OR值2.18,P<0.001)。结论:hs-CRP水平与MS密切相关,hs-CRP水平增高可作为独立反映MS发生的标志性检测指标。     

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

不同起搏模式对病人生存质量影响的调查研究

[目的]探讨不同起搏模式对病人生存质量（QOL）的影响。[方法]以健康调查问卷（SF一36量表）对112例不同起搏模式病人进行问卷调查，比较3种起搏模式下病人的QOL水平。[结果]除机体疼痛、角色情绪2个维度外其余6个维度（生理功能、角色限制、活力、社会功能、精神健康、总体健康）3种起搏模式间比较差异有统计学意义（P〈0．05）。[结论]应用AAI型、DDD型起搏器的病人生存质量优于VVI型起搏。     

云南罗平医院员工对医院的认同度分析

通过问卷调查和访谈分析,调查了云南罗平医院194名员工对医院的认同度,调查对象包括行政、临床和后勤人员,从医院管理模式、医院绩效考核、医院薪酬待遇等方面用描述统计方法分析了数据,显示了医院员工的认同度情况及管理中存在的问题,并分析了不同因素对医院员工的认同度影响,为进一步改善医院管理状况,提高管理水平提供了参考。