注射用环磷酰胺对大鼠致畸敏感期毒性研究

目的 观察环磷酰胺1次染毒或连续染毒对大鼠致畸敏感期的毒性反应.方法 选用SD大鼠,设对照组(生理氯化钠)、7.0、15.0 mg/kg染毒组,每组6只孕鼠.15.0 mg/kg组于孕第12天1次皮下注射染毒;7 mg/kg组于孕第11～13天连续皮下注射染毒3次.观察孕鼠体质量及一般健康状况,于妊娠第20天解剖并记录子宫连仔鼠质量、胎盘质量、仔鼠体质量、黄体数、死仔和活仔鼠数、仔鼠身长和尾长;检查仔鼠外观、骨骼和内脏.结果 ①2个染毒组的孕鼠染毒后均很快出现毒性反应,精神状态明显变差、活动减少、体质量减轻;②7.0和15.0 mg/kg染毒组死仔率分别为60.29%和18.37%,明显高于对照组的1.69%(P＜0.05);子宫连仔质量、胎盘质量、鼠仔体质量、身长、尾长均明显低于对照组(P＜0.05);③染毒组存活仔鼠普遍发生脑膜膨出,骨骼骨化不全,15.0 mg/kg组仔鼠大多数出现并趾、少趾、足外翻、短肋、缺肋等异常.结论 大鼠致畸敏感期1次(15.0 mg/kg)或连续3次(7.0 mg/kg)皮下注射环磷酰胺,均可导致明显的胚胎毒性反应,毒性反应的严重程度与染毒时间和剂量密切相关.     

ZNC-1大鼠生殖毒性试验

目的了解新药ZNC-1对大鼠生殖毒性的影响。方法按常规致畸试验方法,获取74只孕大鼠,分为5组:3个ZNC-1染毒组与阴性对照组,每组15只;阳性对照组,每组14只。在大鼠胚胎器官形成期6～15d,孕鼠连续经口给予ZNC-1,ZNC-1剂量为3000、1500、1000mg/kg。观察受试药物有无致畸作用。结果①ZNC-13000mg/kg剂量组孕鼠体重增长〔(140.73±37.24)g〕明显低于阴性对照组;②ZNC-13000mg/kg剂量组胎鼠身长〔(3.60±0.33)cm〕明显短于阴性对照组〔(3.88±0.19)cm〕;其他剂量组胎鼠的体重、身长、尾长与阴性对照组相比无明显差异。③ZNC-1各剂量对胎鼠骨骼内脏发育无影响,亦无明显外观畸形。结论在本试验条件下,ZNC-1在3000mg/kg剂量可引起母体毒性反应和胚胎毒性,但未见致畸作用;ZNC-11500mg/kg无胚胎毒性和致畸作用。     

甲醛对小鼠胚胎的发育毒性

目的 探讨甲醛对小鼠胚胎的体内发育毒性. 方法随机选择健康性成熟的昆明种小鼠,雌雄介笼产生孕鼠,孕鼠被随机分成5组,每组8只,分别在小鼠妊娠第6～15 d用5、10、20 mg/kg.d的甲醛进行灌胃染毒,每天一次,同时设生理盐水对照和环磷酰胺阳性对照.观察孕鼠的体重增长情况;于妊娠第18 d处死孕鼠取出胚胎,观察胚胎的生长发育状况、死胎和吸收胎鼠数及畸形发生情况. 结果与生理盐水组比较,中、高剂量甲醛染毒可降低孕鼠体重的增长率(P<0.05),高剂量甲醛染毒孕鼠能使胚胎吸收和死亡发生率增加(P<0.05),并可抑制胎盘和胎仔生长发育,中、高剂量甲醛染毒导致胎鼠畸形发生率增加(P<0.05),但对孕鼠和胎仔的毒作用影响均弱于环磷酰胺的毒性作用(P<0.05). 结论甲醛在体内对小鼠胚胎具有发育毒作用和致畸形作用.     

富右旋反式炔丙菊酯原药对大鼠的致畸作用

目的 观察富右旋反式炔丙菊酯对大鼠的致畸作用.方法 根据<农药登记毒理学试验方法>(GB15670-1995)进行试验.分别设4、20、100 mg/kg 3个富右旋反式炔丙菊酯原药染毒组,另设玉米油溶剂对照组和环磷酰胺阳性对照组.每组孕鼠12只.结果 与溶剂对照组比较,各染毒组孕鼠的黄体数、着床数、活胎率、死胎率和吸收胎率、染毒组胎鼠的体重、身长和尾长均未见明显改变,3个染毒组和溶剂对照组均未见外观畸形、内脏畸形和骨骼畸形;100 mg/kg组妊娠第16天和第20天孕鼠的体重分别为(339.7±13.1)g和(372.2±17.8)g,明显低于溶剂对照组[(356.2±19.3)g和(394.3±16.1)g].结论 在本实验条件下,富右旋反式炔丙菊酯原药对大鼠母体具有一定的毒性,无作用剂量为20 mg/kg;未发现胚胎毒性和致畸作用.     

3,4二呋咱基氧化呋咱对大鼠致畸性研究

目的 对新型高能量化合物3,4二呋咱基氧化呋咱(DNTF)的致畸性进行研究,为研究DNTF对人体健康影响和制订职业接触限值提供依据.方法 采用大鼠标准致畸试验,将受孕SD大鼠随机分为3个染毒组(剂量分别为5.0、15.8、50.0 mg/kg)、阴性对照组(植物油)和阳性对照组(环磷酰胺10.0 mg/kg),每组10～15只,对孕鼠于孕期7～12d每天灌胃染毒1次,共6d,妊娠第20天处死,检查孕鼠妊娠与胎鼠畸形情况.结果 与阴性对照组比较,3个染毒组的孕鼠体重、胎重、胎鼠生长发育、胎鼠畸形率、胎鼠骨骼和内脏畸形率的差异均无统计学意义(P＞0.05).结论 DNTF在5.0～50.0 mg/kg 染毒剂量范围内对大鼠无明显的母体毒性、胚胎毒性和致畸性.     

硫酸铟亚慢性毒性的实验研究

目的探讨硫酸铟的亚慢性毒性。方法选用60只健康Wistar大鼠,随机分成4个染毒组[硫酸铟染毒剂量分别为26.1,52.3,104.6,261.4 mg/kg(1/10~1/100 LD50)]和1个对照组。硫酸铟灌胃染毒,1次/d,实验期3个月。结果261.4 mg/kg染毒组大鼠体重增长缓慢,血红细胞、血小板计数降低,肝、肾明显肿大,肝细胞变性,肾小管细胞变性、溶解。4个染毒组大鼠血清尿素氮均明显增高。结论长期较低剂量硫酸铟染毒可对实验动物的生长发育、肾脏、肝脏及血液系统产生明显损害。肾脏可能是硫酸铟毒性作用的靶器官之一。大鼠经口硫酸铟染毒无可见有害作用水平(NOAEL)低于26.1 mg/kg。     

乙烷硒啉对大鼠致畸敏感期毒性试验研究

目的 观察乙烷硒啉对大鼠是否存在胚胎毒性和致畸毒性.方法 采用Wistat大鼠,每组妊娠鼠＞15只.试验设1 000 mg/kgbw、500 msg/kgbw、250 mg/kgbw和125 mg/kgbw 4个剂量组,同时设1个阳性对照组和1个溶剂对照组.在大鼠胚胎器官形成期连续灌胃给药10 d(孕6～15 d),在妊娠的第20天,处死妊娠鼠,计数黄体数、着床数、活胎数、早期死胎数(包括吸收胎)和晚期死胎数;观察胎仔性别、外观、称取胎重,并检查骨骼和内脏发育情况.结果 给药＞250 mg/kgbw剂量组的孕鼠体重增长缓慢,胎仔的活胎率降低到94.9%以下、吸收胎率增加到4.5%以上,与溶剂对照组比较差异均有统计学意义(P＜0.05或＜0.01);黄体数、着床数、死胎数、胎仔体重、身长、尾长和胎仔性别等与溶剂对照组基本一致.给药各剂量组未见明显的骨骼畸形和内脏器官畸形.结论 乙烷硒啉在＞250 mg/kgbw剂量时,对大鼠具有明显的母体毒性和胚胎毒性;在＜500 mg/kgbw剂量时,不存在骨骼、内脏器官的致畸毒性.     

菲醌对大鼠的致畸作用

目的 观察菲醌经口灌胃给药对大鼠的致畸作用。方法 菲醌以50、150、350mg/kg的剂量对Wistar大鼠经口灌胃给药进行致畸试验。结果 菲醌各剂量组胎鼠均未发现外观畸形,菲醌组内脏及骨骼畸形与阴性对照组比较差异无显著性。菲醌150mg/kg和350mg/kg组胚胎吸收明显增加。菲醌350mg/kg组,胎鼠平均体重和尾长小于阴性对照组,差异显著。结论 菲醌经口途径对孕鼠可引起脾大、体重减少、胚胎吸收率增高但对胎鼠的外观、内脏、骨骼无致畸作用。     

火麻仁蛋白对大鼠胚胎-胎仔发育的毒性效应研究

目的了解火麻仁蛋白对SD大鼠的胚胎、胎仔的致畸作用和毒性作用。方法将受孕的雌性大鼠随机分成火麻仁蛋白1.04、2.08和4.17g/kg·BW 3个剂量组及阴性对照组,在受孕的第7~16d每日经口给药1次。期间记录孕鼠体重及生长状况,于受孕第20d剖检母鼠,检查并记录胎仔的形态变化和窝仔、胎仔参数。结果在1.04~4.17g/kg体重剂量范围内,火麻仁蛋白各组孕鼠的生育力、胚胎发育、胎仔外观、内脏及骨骼发育情况与阴性对照组差异无统计学意义。结论在本研究条件下,未见火麻仁蛋白有胚胎-胎仔发育毒性作用、致畸作用与母体毒性作用。     

吡氟酰草胺对大鼠致畸毒性研究

选用8周龄的Wistar大鼠交配受孕,每组18~20只孕鼠。于妊娠第6~15天,染毒组以吡氟酰草胺灌胃染毒,剂量分别为100、300和1 000 mg/kg;阴性对照组用等量玉米油灌胃;阳性对照组于妊娠第12天腹腔注射环磷酰胺8 mg/kg。妊娠第20天处死孕鼠,记录黄体数、死胎数、活胎数、活胎重量等,并检查胎鼠外观、内脏、骨骼的畸形、变异及功能状况。结果表明,在试验剂量下吡氟酰草胺未对胚胎形成、胎鼠生长以及外观、内脏和骨骼造成影响。吡氟酰草胺对大鼠母体无明显毒性作用剂量为1 000 mg/(kg·d),且该剂量对子代亦不具有胚胎毒性和致畸作用。     

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.     

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.