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.     

气功对冠心病人CM_5ST段/心率斜率的影响

37名冠心病患者随机分为气功治疗组(22人)和对照组(15人)。气功治疗组接受12周动功治疗,对照组接受安慰剂治疗,治疗前后均测定CM_5 ST段/心率斜率。结果发现动功治疗组CM_5 ST段/心率斜率减少,而对照组不变或增大,两组有显著性差异,ST段下移及常规分级运动试验其它指标在两组间无显著差异。表明CM_5ST段/心率斜率是一个敏感的心肌缺血指标。     

Lack of effect of a single dose of hydrocortisone on serotonin(1A) receptors in recovered depressed patients measured by positron emission tomography with [11C]WAY-100635.

BACKGROUND: Elevated cortisol levels might account for the reduction in central serotonin 1A (5-hydroxytryptamine [5-HT](1A)) receptor binding and function observed in patients with major depression. We tested this hypothesis by studying the effect of acute administration of hydrocortisone on 5-HT(1A) receptor binding potential (BP) in subjects recovered from depression. METHODS: We studied 14 subjects (8 male, 6 female) who had recovered from at least two episodes of major depression and had been euthymic and drug free for at least 6 months. Serotonin 1A receptor BP was measured by [(11)C]WAY-100635 in conjunction with positron emission tomography. Subjects were tested on two occasions in a double-blind, random-order, crossover design after administration of either hydrocortisone (100 mg orally) or placebo 12 hours previously. Positron emission tomography scans were analyzed with a region of interest analysis. RESULTS: Hydrocortisone treatment did not decrease 5-HT(1A) receptor BP either in the hippocampus, which was our a priori hypothesis, or in other cortical 5-HT(1A) regions; however, female subjects had a higher 5-HT(1A) receptor BP in certain brain areas compared with male subjects. CONCLUSIONS: These data are consistent with an earlier study in healthy volunteers and do not support the proposal that decreased 5-HT(1A) receptor BP in patients with acute major depression is a consequence of cortisol hypersecretion.     

Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla.     

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。     

Lithium increases slow wave sleep: possible mediation by brain 5-HT2 receptors?

The effect of lithium on slow wave sleep (SWS) was studied in ten normal male volunteers using home based cassette sleep recording and automatic sleep stage analysis. Lithium increased SWS, an effect consisten with a reduction in brain 5-HT₂ receptor function.     

Synthesis of 14C‐labeled piperidines and application to synthesis of [14C]SCH 351125, a CCR5 receptor antagonist

1‐Benzyl‐4‐hydroxy[2‐¹⁴C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [¹⁴C]formaldehyde in high yield. The distribution pattern of ¹⁴C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [¹⁴C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐¹⁴C]piperidine in six steps. [¹⁴C]SCH 351125 is a mixture of four atropisomers. Preparation of [¹⁴C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.     

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。     

Effect of 5-Aminoisoquinolinone on the Adhesion of Colon Carcinoma

Objective： 5-Aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly （adenosine 5＇-diphosphate ribose） polymerase, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation by inhibiting the activity of poly （adenosine 5＇-diphosphate ribose） polymerase and the expression of cell adhesion molecules such as ICAM-1, P-selectin et al. But how about it in the tumor is not clear. The aim of the present study was to study the effects of 5-Aminoisoquinolinon on the adhesion of colon carcinoma line HT-29 cells to human umbilical vein endothelial cells; and the effects of 5-Aminoisoquinolinon on the expression of ICAM-1, P-selectin and the activity of poly （adenosine 5＇-diphosphate ribose） polymerase in colon carcinoma HT-29 cells. Methods： The adhesion of HT-29 cells to human umbilical vein endothelial cells was detected by adhesive experiment. Immunocytochemically Streptavidin-Peroxidase method was used to investigate the expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose）（ the product of poly （adenosine 5＇-diphosphate ribose） polymerase activation）. Results： the results of the adhesion assay of HT-29 cells to HUVEC showed that the OD570 value in each 5-AIQ-treated group was significant lower than that in the control group （5-AIQ-untreated） in a dose-dependent manner. The expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose） was significant lower in 5-Aminoisoquinolinone-treated HT-29 cell group than that in 5-Aminoisoquinolinoneuntreated groups. Conclusion： The data suggest that 5-Aminoisoquinolinone can inhibit the adhesion of HT-29 cells to human umbilical vein endothelial cells. 5-Aminoisoquinolinone also can inhibit poly （adenosine 5＇-diphosphate ribose） polymerase activation and the expressions of ICAM-1 and P-selectin in HT-29 cells. 5-Aminoisoquinolinone probably contributes to the prevention of tumor cell metastasis. Further study is needed.     

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。