细胞色素P450 2E1活性的测定方法

细胞色素P450(cytochmme P450)是主要的肝细胞Ⅰ相代谢酶之一,其亚家族细胞色素：P450 2E1(CYP2E1)在外来化学物的代谢活化中起重要作用,CYP2E1活性的高低与毒物对机体的最终毒性大小直接相关。多年来,体内CYP2E1活性的测定一直是国内外学者颇感棘手的问题。本文从体外、体内以及淋巴细胞中CYP2E1活性的测定等几方面对该问题进行综述。     

细胞色素P450 2E1基因多态性与小细胞肺癌相关性分析

小细胞肺癌在肺癌中恶性度极高。细胞色素P450 2El基因(CYP2E1)作为一种重要的I相代谢酶参与多种致癌物的代谢,其位点多态性可影响自身表达…。本研究采用病例对照研究方法,分析CYP2E1—1239位点多态性与小细胞肺癌发病风险的关系。     

细胞色素P450 2E1基因多态性与胃癌易患性

目的研究与前致癌物亚硝胺类代谢活化有关的细胞色素P450 2E1(cytochromeP450 2E1,CYP2E1)基因多态性与胃癌易患性的关系,探讨环境因素与遗传因素在胃癌发病中的作用.方法采用病例-对照分子流行病学方法,调查原发性胃癌患者和对照各48例,以聚合酶链反应-限制性片段长度多态(PCR-RFLP)检测被调查者的CYP2E1基因RsaⅠ位点的多态性,条件Logistic回归模型进行资料分析.结果 CYP2E1 A、B和C 3种基因型在病例组中的构成比分别为68.8%,29.2%和2.1%,对照组分别为45.83%,47.92%和6.25%,2组差异无统计学意义(x2=5.389,P=0.068).而病例和对照组CYP2E1基因Rsa Ⅰ位点等位基因c1和c2频率分别为83.3%,16.7%和69.8%,30.2%,差异有统计学意义(x2=5.241,P＜0.05).环境因素中食盐、香肠和熟食的过多摄入以及肿瘤家庭史和c1等位基因作为胃癌的危险因素进入回归模型,而经常喝茶作为保护性因子可能降低胃癌的发生危险.结论 CYP2E1基因Rsa Ⅰ位点等位基因c1与胃癌易感性相关联;某些饮食因素与胃癌的发生有关.     

细胞色素P450 2E1基因Rsa Ⅰ/Pst Ⅰ位点多态性与中国人肺癌易感性关系的Meta分析

肺癌是一种由环境与遗传因素相互作用引起的多因素疾病[1].暴露相同的环境因素,其结局不尽相同,说明不同个体对环境致癌物具有不同的易感性.代谢酶的多态性影响个体对肺癌的易感性,有报道称细胞色素P450 2E1(CYP 2E1)基因CYP2E1 Rsa Ⅰ/Pst Ⅰ变异对中国人肺癌发生起保护作用,携带c1/c2或c2/c2的个体发生肺癌的危险性与c1/c1个体相比明显降低[2-4].     

CYP2E1和GST基因多态性对二甲基甲酰胺代谢及毒性的影响

二甲基甲酰胺（DMF）是一种广泛应用的工业原料。DMF的毒性与其在体内的代谢过程有关。CYP2E1是DMF的主要Ⅰ相代谢酶,Ⅱ相代谢酶谷胱甘肽-S-转移酶（glutathione S-transferase,GST）则可能在DMF的解毒过程中起重要作用。代谢酶的基因多态性对毒物的代谢及毒作用有较大的影响。本文就CYP2E1和GST基因多态性与DMF的代谢及毒性的关系进行综述。     

白藜芦醇对细胞色素P450的影响

白藜芦醇是虎杖的活性成分之一,作为抗氧化剂具有多种复杂的作用机制,是近年来研究的热点课题。细胞色素P450是体内具有多种代谢底物的混合功能氧化酶,其作用底物多数是环境中常见的前致癌物和前毒物,细胞色素P450催化前致癌物和前毒物形成终致癌物,是癌症等多种疾病在机体发生发展的始动因素。乙醇是诱导其活性增加、进而引发酒精性肝病的因素之一,探索细胞色素P450致病机制、寻找抑制细胞色素P450的药物研究对于防治肿瘤和酒精性肝病等多种疾病的发生发展具有重要意义。     

GSTM1、GYP2E1和NQO1基因多态性与儿童白血病发病风险的初步研究

儿童白血病发病率近年呈上升趋势,其病因仍不清楚。研究表明毒物代谢酶谷胱甘肽硫转移酶(GSTM1)、细胞色素P4502E1(CYP2E1)和还原型辅酶Ⅰ醌类氧化还原酶(NQ01)的基因多态与多种肿瘤的发生有关,本研究针对GSTM1、CYP2E1和NQO1毒物代谢酶基因多态与儿童白血病发病风险进行了初步研究。     

CYP2E1基因多态性与慢性苯中毒

人类接触的化学物超过 70 0 0 0种 ,包括药物、食品添加剂、杀虫剂及工业溶剂等[1] 。许多化学物在人体的代谢存在两种路径 ,代谢活化和解毒。人体中有部分代谢酶能将脂溶性化学物转化为水溶性代谢物时 ,可使无毒化学物与细胞大分子 (如蛋白质 )及DNA相互作用 ,产生毒性。参与大多数的化合物、致癌物I相反应的代谢酶 ,主要包括细胞色素P4 5 0 (CYP)和微粒体环氧化水解酶。在所有物种中 ,应用cDNA克隆技术已经检测到 5 0 0多种P4 5 0酶基因 ,估计人类拥有 6 0种。在人类P4 5 0超家族中 ,主要有 3个基因家族(CYP1、CYP2、CYP3)在体内…     

四氯化碳对乙醇对3种细胞色素P450酶基因表达的影响

目的 探讨四氯化碳（carbon tetrachloride,CCl4)和乙醇（ethanol,EtOH)对人体淋巴细胞瘤细胞株（MCL－5）中3种细胞色素P450酶基因（CYP1A1，CYP2E1，CYP3A4）表达的影响，并研究剂量与效应的关系。方法 用常规的细胞培养方法，用DMSO，0.05,0,10,0.15,0.20mmol/L,CCl4和50，100，150，200mmol/L EtOh处理细胞48h，利用提纯RNA和合成cDNA的药盒，合成cDNA，然后通过逆转录聚合酶链反应（RT－PCR）表达3种CYP450酶基因,以β－Actin作为内对照，分析不同处理剂量时基因表达强度。结果 3种CYP450 MCL－5细胞株中都有基本表达，CYP2E1和CYP3A4表达在用0．05，0．10，0．15，0．20mmol/l CCl4和50，100，150，200mmol/L EtOH处理细胞48h后有被上调的趋势。结论 本研究结果提示，CCl4和EtOH对CYP450酶系统中的CYP2E1，CYP3A4基因有明显的诱导作用；这些基因被诱导后，可能会导致相对应酶活性的增加，同时加强对CCl,EtOH的代谢，使他们的毒性代谢产物增加。     

人细胞色素P450基因多态性与职业医学实践

癌症的发生大多与环境化学因素有关,就职业环境而言,从业人员长期暴露于一些较高浓度的外源化学物质环境中,这些物质在工作场所通过呼吸道、消化道、皮肤等途径进入机体,在大多数情况下,先经由细胞色素P450酶(cytochrome P450,CYP)催化的Ⅰ相反应活化后,由前致癌物转化为致癌物,与生物大分子发生加合,造成基因损伤,启动化学致癌过程.目前已知的环境化学物质至少达20万种以上,绝大部分是各种细胞色素P450的底物,有些还作为诱导物或阻抑物而起作用[1].     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.