单甲脒盐酸盐原药的亚慢性毒性研究

目的研究85%单甲脒盐酸盐原药对大鼠的亚慢性经口毒性。方法分别用含625、125、25、0 mg/kg 85%单甲脒盐酸盐原药的饲料,给大鼠连续喂饲染毒3个月,观察一般表现、体重、进食量,实验结束时测定血常规7项、血生化11项、尿常规及生化8项,取脏器称重计算脏器质量系数并进行病理组织学检查。结果实验期间,对照组和低剂量组动物无异常发现;高、中剂量组动物活动减少,烦躁,眼鼻血性分泌物,会阴部污秽,皮肤破损或溃烂,体重、进食量下降,体重增长缓慢。实验结束时,高剂量组雌雄动物尿素氮(BUN)、碱性磷酸酶(ALP)升高,胆碱酯酶(ChE)降低;雄性动物天门冬氨酸氨基转移酶(AST)升高,总蛋白(TP)、白蛋白(ALB)、血糖(GLU)降低。中剂量组雌雄动物总蛋白(TP)、血糖(GLU)降低。高、中剂量组部分动物尿蛋白呈阳性。高剂量组动物脑、心、肝、肾、肾上腺及雄性睾丸脏器质量系数均高于对照组;中剂量组雌性动物脑、肾及雄性动物脑、肝及睾丸脏器重量系数均高于对照组。病理检查显示高剂量组部分动物可见肝细胞肿胀,细胞内有小圆形空泡,肝窦结构受压,中剂量组部分雌性动物周边性肝细胞内小圆形空泡。结论85%单甲脒盐酸盐原药影响动物食量、营养状况,引起行为改变、抗感染能力减低,体重和食物利用率下降,部分生化指标(TP、ALB、GLU、BUN、ALP、ChE)及部分脏器质量系数改变,且能造成部分动物肝脏损害。该药喂饲染毒最大无作用剂量,雌性大鼠为2.34 mg/kg,雄性大鼠为1.59 mg/kg。     

多效唑原药对SD大鼠慢性毒性与致癌性

目的探讨多效唑原药对SD大鼠的慢性毒性与致癌作用。方法无特定病原体级刚断乳SD大鼠按体质量随机分为对照组和低、中、高剂量组,每组120只,雌雄各半。采用饲喂法对大鼠进行为期2年的慢性毒性与致癌合并实验,4组雌性大鼠染毒剂量分别为0.0、11.7、48.5、193.9 mg·kg~(-1)·d~(-1),雄性大鼠染毒剂量分别为0.0、13.5、54.2、241.9 mg·kg~(-1)·d~(-1)。实验期间称量大鼠体质量;于染毒结束时进行血常规、血生化、脏器系数和组织病理学检查,计算大鼠死亡率和肿瘤发生率。结果 3个剂量组雌性、雄性大鼠分别在实验1、2周时即可观察到较同时间点同性别大鼠体质量下降(P0.05)的结果。实验结束时,3个剂量组雌性、雄性大鼠体质量均低于同性别对照组(P0.05);4组雌性或雄性大鼠死亡率分别比较,差异均无统计学意义(P0.05)。3个剂量组雌性大鼠脑脏器系数均高于对照组雌性大鼠(P0.05),高剂量组雌性大鼠肝脏、肾脏和卵巢脏器系数均高于对照组雌性大鼠(P0.05)。3个剂量组雄性大鼠总胆红素水平均低于对照组雄性大鼠(P0.05);中、高剂量组雄性大鼠脑和肺脏脏器系数均高于对照组雄性大鼠(P0.05),高剂量组雄性大鼠肝脏脏器系数高于对照组雄性大鼠(P0.05)。共有244只大鼠发生402个自发性肿瘤,肿瘤发生率为50.8%(244/480);对照组和低、中、高剂量组大鼠肿瘤发生率分别为61.7%(74/120)、42.5%(51/120)、50.0%(60/120)、49.2%(59/120),3个剂量组大鼠肿瘤发生率均无较对照组出现有统计学意义的升高。结论在本研究设计的染毒剂量条件下,多效唑原药对雌性和雄性SD大鼠慢性毒性的观察到最低有害作用剂量分别为11.7、13.5 mg·kg~(-1)·d~(-1);未见多效唑原药对SD大鼠具有致癌性。     

甲基磺草酮原药的毒性实验观察

目的了解受试样品甲基磺草酮原药的毒性特点和最大无作用剂量,为安全生产及慢性毒性实验提供剂量参考依据。方法依据GB15670-1995《农药登记毒理学试验方法》对其进行为期90天的毒性实验,依据《化妆品卫生规范》对其进行体外哺乳动物细胞染色体畸变试验和体外哺乳动物细胞基因突变试验。结果甲基磺草酮原药不诱发培养的哺乳动物细胞染色体畸变,体外哺乳动物细胞基因突变试验结果为阴性。在整个染毒期间,高剂量组雄性大鼠周平均体重从第4周开始至实验结束明显低于对照组(P0.01),中、高剂量组雄性大鼠WBC计数明显低于对照组(P0.01),高剂量组雌性大鼠的丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)活力明显高于对照组(P0.01),高剂量组雄、雌性大鼠的葡萄糖(GLU)明显高于对照组(P0.01),脏器系数测定结果表明,中、高剂量组雄性大鼠和高剂量组雌性大鼠肾脏系数明显高于对照组(P0.01),中、高剂量组雄、雌性大鼠肝脏系数明显高于对照组(P0.01、P0.05)。结论甲基磺草酮原药对中国仓鼠卵巢(CHO)细胞染色体畸变试验为无致畸变作用,对CHO细胞基因突变试验结果为无致突变作用。甲基磺草酮原药对雄、雌性大鼠经口染毒剂量为100.0mg/(kg.d)及以上时,对大鼠有毒性效应。甲基磺草酮原药对雄、雌性大鼠亚慢性经口毒性最大无作用剂量为25.0mg/(kg.d)。     

苯氧菌酯90天亚慢性毒性研究

[目的] 通过90 d亚慢性喂饲试验,提出农药杀菌剂-苯氧菌酯对大鼠的亚慢性无作用剂量,并探讨其毒作用特点.[方法] 苯氧菌酯对雄、雌大鼠的LD50均大于5 000 mg/kg体重.用清洁级Wistar大鼠,雄、雌各40只,体重为130～160 g.两种性别大鼠分别分为对照组和低、中、高3个剂量组.喂饲饲料中苯氧菌酯的含量雄、雌大鼠分别为0、560、1 110、2 770 mg/kg和0、625、1 249、3 117 mg/kg.相应的雄、雌大鼠每日染毒剂量分别为0、34.56、68.62、211.90 mg/kg和0、44.42、88.84、225.10 mg/kg.观察指标有日摄食量、体重、行为表现、血常规、血清生化、尿常规、脏器系数及病理学检查等.血清指标丙氨酸氨基转移酶活性(ALT)、天门冬氨酸氨基转移酶活性(AST)、碱性磷酸酶活性(ALP)、尿素氮含量(BUN)、肌酐含量(Cre)、胆固醇含量(CHO)、血糖含量(GLU)、总蛋白含量(TP)、白蛋白含量(ALB)、总胆红素含量(BIL)等.各项检测数据用OFFICE 97软件EXCEL中单因素方差分析检验各组间的差异.[结果] 动物的日平均摄食量各组大体一致,每只动物的日平均摄食量雄鼠为22.5～26.6 g,雌鼠为16～18.2 g.试验中,雄性大鼠高剂量组的体重增长在第4周和第6周开始出现明显降低,8周后体重持续到试验结束;而雌性高剂量组大鼠的体重增长则从染毒第2周即开始明显降低并直至试验结束(P＜0.01),雌性中剂量组从第6周后体重增长一直减少(P＜0.05或0.01).血常规检查未见有意义的改变.血清生化检测见雄性大鼠中、高剂量组的BUN、TP、ALB和BIL增加(P＜0.01);雌性大鼠高剂量组的GLU(P＜0.01)和ALB降低(P＜0.05).这些变化中,BUN的增加提示肾脏功能可能受到损害.尿常规检查各组未见有意义的改变.解剖检查各脏器未见异常改变.脏器系数测定结果表明雄性大鼠高剂量组心脏、肺脏、肝脏、肾脏、肾上腺和睾丸的脏器系数比对照组增高(P＜0.01);雄性大鼠高剂量组的心脏、肝脏、肾脏的脏器系数明显增高(P＜0.01).光镜病理检查见高剂量组雄鼠有1例脾窦扩张充血,雌鼠2例肝细胞浊肿.其他各组和其他脏器未见有毒理学意义的改变.[结论] 苯氧菌酯在达到中毒剂量时可影响多数脏器的血液循环而导致其脏器系数增大.雄鼠血中BUN含量增高与肾脏增重相联系,提示苯氧菌酯的毒作用靶点可能是肾脏.苯氧菌酯对雄、雌大鼠的无作用剂量分别为34.6和44.4 mg/kg*d-1.     

异丙隆原药慢性毒性研究

目的 为了解异丙隆原药的慢性毒性,提出其慢性最小有害作用剂量(LOAEL)和无害作用剂量(NOAEL).方法 480只SD种雄性和雌性大鼠(体重110～140 g)分为4组,3个染毒组分别喂饲染毒异丙隆原药50.0 mg/(kg·d)(高剂量组)、5.0 mg/(kg·d)(中剂量组)和0.5 mg/(kg·d)(低剂量组),对照组喂饲正常饲料,历时2 a;观察大鼠日常表现、检测体重和饲料消耗量;检查了解解剖、病理、血液学、血液生化和尿液等指标的改变.结果 高剂量组雌性和雄性大鼠的体重增长分别从试验第6周和第11个月开始减慢(P<0.01);高、中两剂量组雄性大鼠肝脏肿大,肝细胞水肿样变性和脂肪变性.结论 异丙隆原药对雌性和雄性大鼠慢性毒性的LOAEL分别为50.0 mg/(kg·d)和5.0 mg/(kg·d),而NAOEL为0.5 mg/(kg·d).     

精吡氟禾草灵原药的毒性研究

目的探讨精吡氟禾草灵原药致突变性及亚慢性毒性。方法按照GB15670-1995《农药登记毒理学试验方法》进行。结果精吡氟禾草灵原药致突变性的试验结果与对照组比较差异无统计学意义(P>0.05)。亚慢性毒性试验中:中、高剂量组雌鼠碱性磷酸酶(AKP)增高;雄鼠体重较对照组有明显减轻,肝脏和脑的脏器系数增高;高剂量组雄鼠肾脏脏器系数增高。结论本试验提示精吡氟禾草灵原药无明显致突变作用,对动物脑、肝、肾等脏器有损伤作用。SD大鼠亚慢性(90 d)经口毒性的最大无作用剂量雌、雄分别为6.8和8.4 mg/kg.d。     

除草剂特丁津亚慢性毒性阈值分析

目的　应用基准剂量法 (BMD)和无明显损害作用剂量 (NOAEL)法分析特丁津 (Terbutryn ,2 -特丁胺基 -4 -氨 -6-乙胺基 -均三氮苯 )原药亚慢性毒性阈值并进行比较。方法　特丁津亚慢性毒性试验 (90d)设对照、低、中、高剂量组 (0、167、5 0 0、15 0 0mg/kg饲料 ) ,基准剂量计算采用EPA(美国国家环保局 )的BMDS软件。结果　中、高剂量组雌雄性大鼠食物利用率低于对照组 ,肾脏体系数高于对照组 ,高剂量组雌雄性大鼠生化指标BUN高于对照组 ,差异有统计学意义。中高剂量组少数动物出现肝脏、肾脏炎症小灶 ;低剂量组雌雄性大鼠均未见明显异常。特丁津原药NOAEL值雄性大鼠为11 80mg/(kg·d) ,雌性大鼠为 12 84mg/(kg·d)。特丁津原药的BMDL(基准剂量的可信限下限值 )雌雄大鼠分别为 10 0 2、9 77mg/(kg·d) ,均小于相应的NOAEL。结论　选择的BMD值在低剂量组和中剂量组之间 ,即BMD值大于NOAEL。而BMD的可信性下限BMDL值除了雄性大鼠单指标计算的BMDL值外 ,均小于NOAEL。     

乙草胺原药的亚慢性毒性

按GB15670—1995《农药登记毒理学试验方法》,低、中、高剂量染毒组动物分别予含200、800、3200mg/kg96%乙草胺原药的饲料喂饲90d,阴性对照组动物喂饲标准饲料。结果显示,高剂量组动物各周体重明显低于对照组,肝脏、肾脏脏器系数及该组雄鼠睾丸脏器系数明显高于对照组;中、低剂量组动物各项指标与对照组比较差异无统计学或生物学意义。提示乙草胺原药对动物体重增长有抑制作用,其靶器官可能是肝脏、肾脏;雌、雄大鼠亚慢性经口毒性试验最大无作用剂量分别为65.1、59.6mg/(kg·d)。 更多还原     

杀虫磺原药大鼠亚慢性毒性研究

目的研究杀虫磺原药对大鼠亚慢性经口毒性,探讨其亚慢性毒性的阈作用剂量和最大无作用剂量。方法雌鼠剂量以135、67.50、22.50mg/kg,雄鼠剂量以157.5、78.752、6.25mg/kg,连续90d给予杀虫磺原药,观察动物的一般状况,体重增长及血液、生化指标并解剖进行病理检查。结果杀虫磺原药高剂量组动物,染毒8周后出现被毛蓬松、活动减少、体重减轻等症状;染毒结束后血清中谷草转氨酶（AST）升高,肝及雄鼠肾脏器系数增大,组织病理学检查显示：肝细胞明显浊肿,胞浆疏松,汇管区可见慢性炎细胞浸润。中剂量组动物染毒结束后谷草转氨酶（AST）显著升高,雄鼠肾脏器系数增大;肝细胞病变相同,但程度较轻。低剂量组动物一般行为、体重增长、尿常规、血液学、血液生化学、脏器重量、脏器系数及病理学检查均未见变化。结论本实验条件下,初步确定大鼠90d亚慢性经口最大无作用剂量,雌性为22.50mg/kg;雄性为26.25mg/kg。     

呋苯硫脲亚慢性经口毒性实验研究

目的研究呋苯硫脲亚慢性经口毒性,确定该农药最大无作用剂量和毒作用靶器官。方法分别用含25.00、5.00、1.00、0 g/kg呋苯硫脲原药的饲料,给80只大鼠连续喂饲染毒3个月,观察一般表现、体重、进食量,食物利用率、血常规7项、血生化11项、尿生化及常规8项,并进行脏器系数和脏器病理组织学检查。结果对照组和中低剂量组动物无异常发现;高剂量组动物自染毒第4周起活动减少,竖毛,被毛不洁、会阴部污秽,个别动物口眼鼻血性分泌物,体重增长速度缓慢,食物利用率减少。血液生化学检查结果显示雌鼠高中剂量组血糖(GLU)、高剂量组胆固醇(CHO)、中剂量组丙氨酸转氨酶(ALT)升高,高剂量组总胆红素(TB I)和总蛋白(TP)降低;雄鼠高剂量CHO升高,TP降低;尸解肉眼大体观察未见明显异常;脏器系数检查显示雌鼠高剂量组的肝/体、脑/体,雄鼠高中剂量的肝/体,高剂量的脑/体、睾丸/体均高于对照组;病理组织学检查可见高剂量组个别动物肝脏呈小片状肝细胞水肿。结论呋苯硫脲经口染毒最大无作用剂量在雌性大鼠为96.44 mg.kg-1.d-1,雄性大鼠为70.05 mg.kg-1.d-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 human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

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.     

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.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.