饮用水有机提取物对大鼠肝脏CYP1A2与CYP2E1酶活性及蛋白表达的影响

[目的]探讨饮用水有机提取物对大鼠肝脏代谢酶CYP1A2与CYP2E1酶活性及蛋白表达的影响,为当地饮用水有机物污染的安全性评价及肝脏毒性机制的阐明提供依据。[方法]采用固相萃取法提取水样中有机污染物,40只SD大鼠随机分成4组,分别为对照组(玉米油)和低、中、高3个染毒组[剂量分别为5、20、80 L/(kg·d)],经口灌胃亚慢性染毒(12周)。荧光分光光度法和活性比色法分别测定CYP1A2与CYP2E1酶活性。采用Western blot法检测CYP1A2、CYP2E1的蛋白质表达水平。[结果]与对照组相比,高剂量组的CYP1A2酶活性明显升高,差异具有统计学意义(P<0.05);CYP2E1酶活性在中、高剂量组均明显升高(P<0.05)。随着染毒剂量的增加,CYP1A2的蛋白表达量在高剂量组升高(P<0.05);与对照组相比,CYP2E1的蛋白表达量在中、高剂量组均增加,差异具有统计学意义(P<0.05)。[结论]该地较高剂量的饮用水有机提取物可上调CYP1A2及CYP2E1的蛋白质表达,从而诱导CYP1A2和CYP2E1酶活性的增强。此可能为饮用水有机提取物肝脏毒性的重要机制之一。     

二氧化硫对大鼠肝和肺细胞色素P4502B1和2E1 mRNA表达及活性的影响

目的探讨二氧化硫(SO2)对肝、肺微粒体细胞色素P450两种亚型CYP2B1和CYP2E1mRNA表达及活性的影响。方法采用SO2动式染毒技术使雄性Wistar大鼠染毒7天,每天6h,SO2的染毒剂量分别为14、28和56mg/m3。采用分光光度法测定大鼠肝、肺微粒体CYP2E1活性,采用荧光分光光度法测定肝、肺微粒体CYP2B1活性,采用RT-PCR方法测定各组大鼠肝、肺组织中CYP2B1和CYP2E1mRNA表达水平。结果在肝中,较高剂量的SO2(28和56mg/m3)可使CYP2B1活性及mRNA水平降低,肝微粒体CYP2E1活性及mRNA在各剂量组均未发生显著改变。肺组织中CYP2B1活性在56mg/m3剂量组显著降低,但其mRNA水平在28及56mg/m3剂量组均显著降低;肺微粒体CYP2E1活性及mRNA水平在28及56mg/m3SO2处理组均降低显著。结论SO2可降低大鼠肝中CYP2B1和2E1及肺中CYP2B1和CYP2E1的活性及mRNA水平。     

不同价态砷对DNA和砷甲基转移酶的影响

目的观察不同价态、不同剂量砷染毒大鼠肝脏中DNA甲基转移酶和砷甲基转移酶mRNA的表达情况,寻找两者间的相关性及不同价态砷(iAs3+和iAs5+)体内甲基化间的差异。方法将35只健康清洁级Wistar雄性大鼠按体重随机分为7组,分别为正常对照(去离子水)组和低剂量(1/45 LD50,2.33 mg/kg)、中剂量(1/15 LD50,6.67 mg/kg)、高剂量(1/5LD50,20.00 mg/kg)砷酸氢钠(iAs5+)染毒组以及低剂量(2.33 mg/kg)、中剂量(6.67 mg/kg)、高剂量(20.00 mg/kg)亚砷酸钠(iAs3+)组,每组5只。采用自由饮水方式进行染毒,连续染毒90 d。采用实时荧光定量PCR法测定肝脏中DNA甲基转移酶(DNMT1、DNMT3A、DNMT3B)和砷甲基转移酶(As3MT)mRNA的表达情况。结果与对照组相比,各染毒组大鼠肝脏中As3MT mRNA的表达量较高,DNMT3A、DNMT3B mRNA的表达量较低,高、低剂量亚砷酸钠染毒组和高剂量砷酸氢钠染毒组DNMT1 mRNA的表达量均较高,中剂量亚砷酸钠染毒组和低剂量砷酸氢钠染毒组DNMT1 mRNA的表达量均较低,差异有统计学意义(P<0.05)。随着亚砷酸钠染毒剂量的升高,大鼠肝脏中As3MT mRNA的表达量呈上升趋势,DNMT3A、DNMT3B mRNA的表达量呈下降趋势;随着砷酸氢钠染毒剂量的升高,大鼠肝脏中As3MT mRNA的表达量呈下降趋势,DNMT3A、DNMT3B、DNMT1 mRNA的表达量呈上升趋势。As3MT的表达量与DNMT3A和DNMT3B表达量呈负相关(P<0.01);与DNMT1表达量无相关关系(P>0.01)。结论长期亚慢性暴露iAs3+和iAs5+均可促进As3MT的表达,抑制DNMT3A及DNMT3B的表达,但iAs3+和iAs5+间在剂量-效应关系上呈反向性;机体As3MT表达上调与DNMT3A和DNMT3B表达抑制间具有协同效应,并可导致基因低甲基化。     

1-溴丙烷亚急性吸入染毒对大鼠大脑NR2B和GluR2影响

目的 探讨1-溴丙烷(1-BP)对大鼠大脑离子型谷氨酸受体NR2B亚基和GluR2亚基的影响.方法 无特定病原体级成年雄性Wistar大鼠36只,随机分为对照组、低剂量组、中剂量组和高剂量组4组,于动式吸入染毒柜内分别暴露于质量浓度为0、1 250、2 500和5 000 mg/m3的1-BP气体,8 h/d,每周染毒5d,连续4周.实验结束后处死大鼠,分离脑组织,应用蛋白质印迹法和实时荧光定量聚合酶链式反应法测定NR2B和GluR2的蛋白和基因表达水平.结果 中、高剂量组大鼠大脑NR2B和GluR2的蛋白表达水平均高于对照组和低剂量组(P＜0.05或P＜0.01).与对照组相比,高剂量组大鼠大脑NR2B mRNA表达水平增加(P＜0.05),各剂量组大鼠大脑GluR2 mRNA表达水平均增加(P ＜0.05或P＜0.01).结论 一定水平的1-BP亚急性吸入染毒能增加大鼠大脑NR2B和GluR2的蛋白表达.     

染氟大鼠血清雌二醇水平与生精细胞端粒酶逆转录酶表达关系的研究

目的了解氟中毒大鼠雌激素水平与生精细胞端粒酶表达的关系。方法将30只雄性SD大鼠随机分为对照组、低剂量染毒组、高剂量染毒组,分别按0、10和20mg/kg体重的染毒剂量隔日腹腔注射氟化钠(NaF)溶液39天后,用放射免疫法测定大鼠血清中雌二醇含量,用原位杂交法检测端粒酶逆转录酶(TERT)表达情况。同时镜检成熟精子质量和睾丸组织病理学改变。结果染毒各组大鼠血清雌二醇含量低于对照组(P<0·05);且随着染毒剂量的增加,雌二醇含量逐渐降低。染毒各组大鼠生精细胞TERT阳性表达率分别低于对照组(P<0·05);且随着染毒剂量的增加,TERT阳性表达率逐渐降低。各染毒组大鼠精子数量和精子存活率低于对照组(P<0·05);精子畸形率高于对照组(P<0·05);随着染毒剂量的增加,精子数量、精子存活率降低(P<0·05),精子畸形率升高(P<0·05)。各染毒组大鼠血清雌二醇含量与生精细胞TERT表达率均呈正相关,低剂量染毒组r=0·941,P<0·01;高剂量染毒组r=0·929,P<0·01。结论NaF很可能是通过雌激素/雌激素受体-端粒酶逆转录酶-精子途径对生殖系统造成损害的,各染毒组大鼠血清雌激素含量与生精细胞TERT表达率呈显著正相关。     

氯乙烯致大鼠DNA损伤与肝代谢酶活性动态变化的研究

[目的]研究氯乙烯(VC)对大鼠肝细胞和外周血淋巴细胞DNA的损伤作用，及对VC代谢酶[谷胱甘肽硫转移酶(GST)、细胞色素P4502E1(CYP2E1)、乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)]活性的影响；探索VC所致损伤的早期敏感检测指标。[方法]大鼠染毒12周，分别在第3、6、9和12周处死动物，DNA损伤采用单细胞凝胶电泳(彗星试验)法，代谢酶活性测定采用分光光度法。[结果]彗星细胞数目随染毒剂量和染毒时间的增加而增加，肝细胞DNA损伤细胞百分率第12周中剂量组和高剂量组分别为12.38％和17.88％，外周血淋巴细胞DNA损伤细胞百分率第3周高剂量组为7．33％，第12周中剂量组和高剂量组分别为16．25％和28、25％，均显著高于相应对照组，彗星细胞发生率与VC染毒剂量间存在显著相关关系。ALDH和CYP2E1活性随染毒时间和染毒剂量的增加发生改变，差异具显著性。肝细胞DNA损伤与CYP2EI活性相关。[结论]VC可导致肝细胞和外周血淋巴细胞DNA发生损伤，且存在剂量．反应和时间一效应关系；VC致肝细胞DNA损伤与CYP2E1代谢酶活性相关。彗星细胞率可作为VC所致肝脏损伤的早期检测指标。     

脂易消对非酒精性脂肪肝CYP2E1基因表达的调控

目的 观察脂易消对非酒精性脂肪肝SD大鼠CYP2E1 mRNA的调控效果.方法 将60只大鼠随机分为正常组、模型组、易善复对照组、低剂量治疗组、中剂量治疗组、高剂量治疗组.正常组给予标准饲料喂养;低、中、高剂量治疗组均给予高脂饲料喂养,同时分别灌服低、中、高剂量脂易消;易善复对照组给予高脂饲料喂养,灌服易复善.结果 从肝组织CYP2E1相对表达量（V值）来看,模型组大鼠肝组织CYP2E1 mRNA表达水平较正常组明显增高（P〈0.01）;脂易消各剂量组和易善复组显著低于模型组（P〈0.01）,而各剂量组大鼠与易善复组比较差异无统计学意义（P〉0.05）.结论 脂易消能明显降低NAFL大鼠肝脏中CYP2E1 mRNA的表达.     

CYP2E1在1,2-二氯乙烷致脑氧化损伤中的作用

分别将昆明种小鼠随机分为对照组、单纯染毒组及低、中和高剂量二烯丙基硫化物(DAS)干预组。检测脑组织中CYP2E1蛋白和mRNA表达、MDA和GSH含量及SOD活性。单纯染毒组与对照组相比,小鼠脑组织中CYP2E1蛋白和mRNA表达及MDA含量显著升高,而GSH含量显著下降;DAS各干预组与单纯染毒组相比,CYP2E1蛋白和mRNA表达及MDA含量显著下降,GSH含量显著升高。提示1,2-DCE可诱导CYP2E1表达,导致脑组织氧化损伤。     

维生素Ｅ对1，2-二氯乙烷中毒性脑水肿保护作用的研究

目的探讨维生素E (vitamin E,Vit E)对1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)中毒性脑水肿的保护作用。方法将雌性昆明种小鼠随机分为空白对照组、Vit E对照组、1,2-DCE单纯染毒组及Vit E低、中和高剂量干预组。连续给予药物灌胃4 d后,采取静式吸入方式染毒3. 5 h/d,持续3 d。结果与空白对照组相比,单纯染毒组小鼠脑组织呈现明显脑水肿病理改变,脑含水量、脑组织中丙二醛(malondialdehyde,MDA)含量及细胞色素P450 2E1 (cytochrome P450 2E1,CYP2E1)蛋白和mRNA表达水平显著升高,脑组织中还原型谷胱甘肽(glutathione,GSH)含量、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase assay kit,CAT)活性、Occludin蛋白和mRNA及Claudin 5蛋白表达水平显著降低。与单纯染毒组相比,各干预组小鼠的脑含水量、脑组织MDA含量、CYP2E1蛋白和mRNA表达水平显著降低,GSH含量、Occludin蛋白及mRNA水平显著升高;中和高剂量干预组的小鼠脑组织中SOD和CAT活性及Claudin 5蛋白表达水平亦显著升高(P0. 05)。结论单纯1,2-DCE染毒可引起小鼠脑水肿,诱导脑组织中CYP2E1的表达,诱发脑组织氧化损伤,破坏紧密连接蛋白,并抑制Occludin和Claudin 5的表达;而Vit E干预可显著抑制CYP2E1的表达,缓解CYP2E1介导的氧化损伤,有效预防1,2-DCE引起的中毒性脑水肿。     

二硫化碳对大鼠视网膜组织诱导型一氧化氮合酶及细胞凋亡的影响

目的探讨二硫化碳（CS2）对大鼠视网膜组织诱导型一氧化氮合酶（iNOS）及细胞凋亡的影响。方法将24只SD雄性大鼠随机分为对照组、低剂量CS2染毒组和高剂量CS2染毒组，染毒结束后取视网膜组织制成切片，测量内视网膜厚度比率，还原型烟酰胺腺嘌呤二核苷酸黄递酶染色（NADPH-NDP）法检测iNOS活力，原位缺口末端标记法（TUNEL）检测细胞凋亡。结果（1）染毒组的内视网膜（包括内核层、内丛状层、节细胞层、神经纤维层和内界膜）厚度减小，与对照组相比，差异有统计学意义（P〈0．05）；高剂量染毒组与低剂量染毒组之间差异亦有统计学意义（P〈0．05）。（2）染毒组视网膜iNOS表达增加，与对照组相比，差异有统计学意义（P〈0．05或P〈0．01）；高剂量染毒组与低剂量染毒组之间差异亦有统计学意义（P〈0．05）。（3）染毒组视网膜出现细胞凋亡，凋亡指数与对照组相比，差异有统计学意义（P〈0．05或P〈0．01）；高剂量染毒组与低剂量染毒组之间差异亦有统计学意义（P〈0．05）。结论CS2能激活视网膜组织iNOS表达，由此产生的过量的NO可损伤视网膜细胞。同时，视网膜细胞凋亡也是CS2所致视网膜损害的机制之一。     

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.     

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.