体外染镉对大鼠卵巢孕激素合成的影响及其机制

目的 研究镉对孕激素合成过程中类同醇激素合成急性调节蛋白(StAR)、细胞色素P450胆固醇侧链裂解酶(P450scc)基因表达的影响及其与环磷腺苷(cAMP)的关系,为研究镉对孕激素合成影响的分子机制提供科学依据.方法 未成年Wistar大鼠皮下注射孕马血清促性腺激(PMSG)100U,48 h后取出卵巢颗粒细胞体外培养,备用.(1)取备用细胞随机分成4组,染镉剂量分别为0、10、20、40μmol/L,孵化30 min后,放射免疫方法测黄体酮、cAMP含量,用反转录-聚合酶链反应(RT-PCR)方法 测P450scc、StAR的mRNA表达水平.(2)再取备用细胞随机分为3组,分别为空白对照组、40μmol/L CdCl_2、l mmol/L 8-Br-cAMP(cAMP类似物)+40 μmol/L,CdCl_2,培养2 h后,测黄体酮含量及P450scc、StAR的mRNA表达水平.结果 (1)不同剂量染镉组卵巢颗粒细胞孵育液中黄体酮含量明显下降,差异有统计学意义(P<0.01);随着染镉剂量的增加,cAMP含量逐渐减少;各染镉剂量组StARmRNA和P450scc mRNA表达强度均低于对照组,差异有统计学意义(P<0.01).(2)加入1 mmol/L 8-Br-cAMP共同培养后,黄体酮含量增加,高于染镉(40 μmol/L)组和对照组.差异均有统计学意义(P<0.01);StAR mRNA和P450scc mRNA表达强度均高于40μmol/L染镉组,低于对照组,差异有统计学意义(P<0.05).结论 镉可通过直接和(或)间接途径影响孕激素合成过程StAR和P450scc的表达,进而干扰孕激素的合成;镉对细胞内cAMP的影响可能是其干扰StAR和P450scc基因表达的机制之一.     

铅对大鼠原代卵巢颗粒细胞分泌雌激素能力的影响

目的检测铅对大鼠卵巢颗粒细胞分泌功能的影响。方法分别以250、50、10mg/L终浓度的醋酸铅对体外培养的大鼠卵巢颗粒细胞进行24h染毒,测定细胞活性和细胞分泌产物(雌二醇和孕酮)含量。结果各染毒组与对照组比较,细胞活性未受影响,而雌二醇和孕酮水平均有所降低,高、中剂量组与对照组比较差异有显著性(P<0.01)。雌二醇含量与醋酸铅剂量的相关系数为-0.900(P<0.01);孕酮含量与醋酸铅剂量的相关系数为-0.908(P<0.01),提示在实验剂量下产生剂量-效应关系。结论铅对大鼠卵巢颗粒细胞分泌功能有抑制作用。     

N-乙酰半胱氨酸和caspase-3抑制剂对镉诱导293细胞凋亡的拮抗作用

目的研究N-乙酰半胱氨酸(-Nacetyl cysteine,NAC)和caspase-3抑制剂(Z-DEVD-fmk)对镉致293细胞凋亡的影响,探讨氧化损伤和caspase途径在镉致细胞凋亡中的作用。方法体外培养的转化人胚肾293细胞分别以0、20、40、80、120、200μmol/L的氯化镉(CdCl2)处理0、3、6、12、24 h,NAC和Z-DEVD-fmk预处理组分别在镉处理前以2.5、5.0、10.0 mmol/L的NAC和0.1、1.0、10μmol/L的Z-DEVD-fmk预处理24 h和1 h,然后再以40μmol/LCdCl2处理24 h,MTT法测细胞相对存活率,流式细胞术Annexin-V-PI双染法检测细胞凋亡百分率。结果随着镉处理浓度的增加,CdCl2对细胞活力的抑制作用增强,细胞的相对存活率明显降低,与0μmol/L镉处理组比较,40、80、120、200μmol/L镉处理组293细胞的凋亡百分率显著升高(P<0.01);200μmol/L镉处理组与120μmol/L CdCl2组比较293细胞的凋亡百分率显著下降(P<0.01)。与40μmol/L镉处理组比较,5.0 mmol/L和10 mmol/L NAC预处理组细胞凋亡百分率显著降低,0.1、1.0、10μmol/L Z-DEVD-fmk预处理可使镉致293细胞凋亡百分率显著降低。结论NAC和Z-DEMD-fmk对镉诱导293细胞凋亡有明显的抑制作用,镉诱导细胞凋亡与氧化损伤和caspase途径密切相关。     

N-乙酰半胱氨酸对镉致大鼠肝线粒体损伤的影响

目的研究 N-乙酰半胱氨酸(NAC)对镉致大鼠肝线粒体损伤的影响。方法取6只清洁级雄性 Wistar 大鼠肝脏,梯度离心得线粒体液。将所得线粒体液分为6组,分别为对照组、镉染毒组(CdCl_2的浓度分别为10、100、1000、10000μmol/L)和 NAC 预处理组(线粒体液先用500 μmol/L 的 NAC 预处理30min 后,加1000μmol/L 的 CdCl_2)。于培养箱内37℃孵育1 h 后,测定各组锰-超氧化物歧化酶(Mn-SOD)活力和还原型谷胱甘肽(GSH)、细胞色素 c(Cyt c)含量。结果与对照组相比,100、1000、10000μmol/L 镉染毒组 GSH 含量和 Mn-SOD 活力较低,差异均有统计学意义(P<0.05),且在10～10000μmol/L 范围内,随着 CdCl_2剂量的增加而呈降低趋势;1000、10000 μmol/L 镉染毒组 Cyt c 含量较高,差异均有统计学意义(P<0.05),且在0～10000μmol/L 范围内,随着 CdCl_2剂量的增加而呈升高趋势。与 NAC 预处理组相比,0、10、100、1000、10000 μmol/L 镉染毒组 GSH 含量和 Mn-SOD 活力以及0 μmol/L 镉染毒组 Cyt c 含量较低,1000、10000μmol/L 镉染毒组 Cyt c 含量较高,差异均有统计学意义(P<0.05)。结论镉可剂量依赖性地诱导大鼠肝线粒体氧化损伤,NAC 能有效预防镉所致大鼠肝线粒体氧化损伤。     

p38MAPK和ERK1／2对镉诱导NRK肾细胞c-myc与c-fos基因mRNA表达的影响

目的研究p38丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶（ERK）1／2抑制剂对镉染毒NRK肾细胞后原癌基因c—myc与c—fos表达的影响。方法用不同剂量CdCl2（0、2．5、5．0、10．0μmol／L）染毒大鼠NRK细胞12h,p38MAPK抑制剂SB20358010．0μmol／L和ERK1／2抑制剂PD9805910μmol／L预处理NRK细胞0．5h后,再加入10．0μmol／LCdCl2染毒细胞,用流式细胞技术检测细胞凋亡率,SYBRGreenI荧光定量PCR检测c-rnyc与c-fosmRNA表达。结果流式细胞仪检测NRK细胞染镉后细胞凋亡率随染毒剂量增加而增加;p38MAPK抑制剂SB203580＋10．0μmol／LCdCl2组与单独染镉组比较,细胞凋亡率显著下降;但ERK1／2抑制剂PD98058＋10．0μmol／LCdCl2组与单独染镉组比较,细胞凋亡率显著升高。实时荧光定量PCR检测NRK细胞染镉后c—myc和c—fosmRNA表达明显增强;单独用SB203580和PD98058刺激NRK细胞后c-myc和c—fosmRNA表达与对照组比较,差异无统计学意义,但SB203580和PD98058预处理NRK细胞0.5b后加入10．0μmol／LCdCl2与单纯10．0μmol／L染镉组比较,c—myc和c-fosmRNA表达显著降低。结论MAPK信号转导通路可能在镉诱导原癌基因c—myc和c—fos表达中发挥作用。     

冷暴露对大鼠黄体细胞与颗粒细胞功能的影响

目的探讨不同冷强度多次冷暴露对大鼠卵巢功能的影响。方法采用体外细胞培养法分离培养大鼠卵巢黄体、颗粒细胞,设37℃对照组与4、0℃冷暴露组,观察人绒毛膜促性腺激素(hCG)诱导黄体与颗粒细胞分泌孕酮及环磷酸腺苷(cAMP)的变化,采用放免分析方法测定孕酮与cAMP生成含量。结果与对照组比较,4℃重复3次冷暴露,黄体细胞与颗粒细胞的孕酮和cAMP生成量呈升高趋势,cAMP升高显著(P0.01);0℃第1次冷暴露,孕酮和cAMP生成量升高,cAMP升高显著(P0.01);第2次和第3次冷暴露,均显著下降(P0.05,P0.01)。结论冷暴露强度、次数对大鼠卵巢黄体细胞与颗粒细胞分泌孕酮及cAMP功能有影响。     

芹菜素对雌性大鼠下丘脑-腺垂体-卵巢轴调控作用

目的研究芹菜素(apigenin,Api)对雌性大鼠腺垂体、卵巢颗粒细胞分泌促卵泡激素(follicle stimulating hormone,FSH)、黄体生成素(luteinzing hormone,LH)、雌二醇(estradiol,E2)及孕酮(progesterone,P)的影响。方法应用细胞培养技术,放射免疫测定法及下丘脑-腺垂体-卵巢三级培养细胞顺序灌注法。采用下列顺序灌注法,Api浓度分别为10-4mol/L、10-5mol/L、10-6mol/L,(1)H-AP-O;(2)H-AP(Api)-O;(3)H-AP-O(Api),分别测定腺垂体和卵巢颗粒细胞培养液中FSH、LH、H2及P的含量。结果实验组(3、5、7组)分别与对照组(1组)比较差异有统计学意义(P<0.01),Api(10-4mol/L～10-6mol/L)以浓度依赖方式使培养的雌性动情前期大鼠卵巢颗粒细胞E2及P的含量也呈减少,且随着浓度的增加,E2及P的含量也呈减少趋势;Api组(10-4mol/L～10-6mol/L)动情前期雌性大鼠腺垂体细胞LH、FSH的分泌量与对照组比较差异无统计学意义(P>0.05)。结论 Api...     

邻苯二甲酸二辛酯对大鼠卵巢颗粒细胞分泌功能的影响

以邻苯二甲酸二辛酯(DOP)对大鼠卵巢颗粒细胞进行体外染毒、培养来研究DOP对卵巢颗粒细胞分泌功能的影响。提取未成年大鼠卵巢颗粒细胞进行体外培养,DOP染毒后测定细胞分泌产物(雌二醇和孕酮)含量。染毒组与对照组比较,雌二醇和孕酮水平均降低,差异有统计学意义(P<0.01)。雌二醇含量与DOP剂量的相关系数为-0.68(P<0.01);孕酮含量与DOP剂量的相关系数为-0.79(P<0.01),提示在实验剂量下产生剂量-反应关系。DOP对大鼠卵巢颗粒细胞分泌功能有抑制作用。     

大鼠卵巢细胞低温暴露后分泌功能的变化

目的 探讨不同冷强度多次低温暴露对大鼠卵巢功能的影响.方法 采用体外细胞培养法分离培养大鼠卵巢黄体、颗粒细胞,设37℃对照组与0、-10℃低温暴露组,观察人绒毛膜促性腺激素(hCG)诱导黄体与颗粒细胞分泌孕酮与环磷酸腺苷(cAMP)的变化,采用放免分析方法测定孕酮与cAMP生成含量.结果 0℃第1次低温暴露,孕酮和cAMP生成量升高,cAMP升高显著(P＜0.01),第2次和第3次低温暴露均显著下降(P＜0.05、P＜0.01);-10℃第1次低温暴露,孕酮生成量下降、cAMP生成量升高(P＜0.05),第2次和第3次低温暴露均显著下降(P＜0.01).结论 低温暴露强度、次数对大鼠卵巢黄体细胞与颗粒细胞分泌孕酮及cAMP功能有影响.     

沙棘油对镉致大鼠肝损伤的拮抗作用

目的 探讨沙棘油(SBO)对急性、亚慢性染镉致大鼠肝损伤的拮抗作用.方法 急性实验时,对照组和染镉组均灌胃0.9%NaCl,SBO干预组灌胃5 ml/kg SBO(纯度为95%).2 h后,对照组皮下注射0.9%NaCl,SBO干预组和染镉组皮下注射35 μmol/kg CdCl2.亚慢性实验时,染镉组和SBO干预组皮下注射6μmol/kg CdCl2,对照组皮下注射0.9%NaCl,连续6周.然后SBO干预组灌胃5 ml/kg SBO,对照组和染镉组灌胃0.9%NaCl,共2周.腹主动脉取血并取肝脏,测定急性、亚慢性染镉大鼠血清乳酸脱氢酶(LDH)、谷丙转氨酶(GPT)活力,肝丙二醛(MDA)、谷胱甘肽(GSH)含量及超氧化物歧化酶(SOD)活力.结果 急性、亚慢性镉染毒使大鼠血清LDH、GPT活力明显升高,肝MDA、GSH含量明显升高及SOD活力明显降低.SBO干预组可使急性染镉大鼠血清LDH、GPT活力,肝MDA、GSH含量分别降至单纯染镉组的71.5%(183.77,257.02)、58.3%(15.83,27.13)和74.8%(88.49,118.27)、64.9%(6.81,10.49),差异有统计学意义(P<0.01),肝SOD活力明显升高.亚慢性染镉时,SBO处理组血清GPT活力明显低于单纯染镉组,肝MDA、GSH含量明显下降,肝SOD活力明显升高,差异有显著性(P<0.01).结论 SBO对急性、亚慢性镉染毒致大鼠肝氧化损伤有一定的拮抗作用.     

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.