大鼠急性经口1,1-二氨基-2,2-二硝基乙烯的毒代动力学研究

建立大鼠血液中1,1-二氨基-2,2-二硝基乙烯(FOX-7)的检测方法,将30只健康SPF级SD大鼠随机分为空白对照组、200和500 mg/kg FOX-7染毒组,每组10只。采用一次性经口灌胃方式染毒,染毒容量为1 ml/100 g。于染毒后第0.5、1、2、4、8、12、24 h对大鼠进行眼眶后静脉丛采血,使用紫外可见分光光度计检测血中FOX-7浓度。使用Phoenix WinNonlin 6.1软件进行血药浓度-时间数据分析与毒代参数计算。大鼠单次灌胃FOX-7 200和500 mg/kg后,药-时曲线下面积AUC_((0-24))分别为(27.01±1.94)μg/(h·L)和(29.26±3.31)μg/(h·L),AUC_((0-∞))分别为(42.01±2.18)μg/(h·L)和(41.51±3.66)μg/(h·L);达峰浓度C_(max)分别为(1.82±0.12)μg/ml和(2.33±0.20)μg/ml,达峰时间t_(max)为2 h;半衰期t_(1/2)分别为(10.83±2.77)h和(8.66±3.01)h。本研究为FOX-7毒代动力学模型的完善提供了科学依据。     

1,1-二氨基-2,2-二硝基乙烯对大鼠睾丸标志酶活力的影响

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对大鼠睾丸标志酶活力的影响,将40只健康7～12周龄SPF级雄性SD大鼠随机分为4组,分别为溶剂对照(4%淀粉溶液)组和49.8、99.6、199.1 mg/kg FOX-7染毒组,每组10只。采用经口灌胃方式进行染毒,每天1次,连续14 d。检测大鼠睾丸组织中的睾丸标志酶γ-谷氨酰转肽酶(γ-GT)、乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(AKP)的活力。结果显示,与溶剂对照组比较,99.6、199.1 mg/kg FOX-7染毒组大鼠睾丸组织中LDH的活力降低,各剂量FOX-7染毒组大鼠睾丸组织中AKP的活力降低,差异均有统计学意义(P0.05);而各剂量组大鼠睾丸组织中ACP、γ-GT的活力均无明显改变。提示FOX-7可能对雄性大鼠具有一定的生殖毒性。     

1,1-二氨基-2,2-二硝基乙烯急性染毒对小鼠初级精母细胞染色体畸变的影响

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对小鼠初级精母细胞染色体畸变的影响,将50只健康7-12周龄SPF级雄性昆明小鼠随机分为5组,分别为溶剂对照(4%淀粉溶液)组和348.22、139.29、69.64mg/kg FOX-7染毒组,另设阳性对照(40mg/kg环磷酰胺)组,每组10只。每日固定时间采用经口灌胃方式进行染毒,染毒容量为20ml/kg,连续5d。于首次染毒后第12天,观察染色体结构畸变率和单价体率。结果显示,与溶剂对照组比较,348.22mg/kg FOX-7染毒组小鼠初级精母细胞染色体结构畸变率较高,差异有统计学意义(P<0.05);而各剂量FOX-7染毒组小鼠初级精母细胞常染色体单价体和性染色体单件体率均无明显改变。提示FOX-7可能会引起小鼠初级精母细胞染色体发生结构畸形改变。     

小鼠急性经口暴露1，1-二氨基-2，2-二硝基乙烯的组织分布及代谢特征

为研究小鼠急性经口暴露1，1-二氨基-2，2-二硝基乙烯（FOX-7）的组织分布及代谢特征，将18只KM小鼠随机分为空白组和140、350 mg/kg FOX-7染毒组，单次经口灌胃染毒，采用生物发光成像技术分析发现，FOX-7于小鼠肾脏蓄积约4 h后经肾脏代谢，并较为清晰地展示出小鼠急性经口暴露FOX-7后的组织分布及代谢数据。     

1,1-二氨基-2,2-二硝基乙烯对大鼠亚急性经口毒性研究

为研究1,1-二氨基-2,2-二硝基乙烯(FOX-7)亚急性经口毒性作用,将40只健康成年SPF级SD大鼠随机分为按体重随机分为4组,分别为对照(4%淀粉溶液)组和35、70、140 mg/kg FOX-7染毒组,每组10只,雌雄各半。采用灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次,连续染毒28 d。观察动物的中毒表现,体重、食物利用率、尿常规、血常规、生化指标、主要脏器系数变化及病理学改变。结果显示,与对照组比较,70、140 mg/kg FOX-7染毒组大鼠体重增长及食物利用率均较低(P0.05),140 mg/kg FOX-7染毒组雄性大鼠尿中URO、FRO水平均较高(P0.01);70、140 mg/kg FOX-7染毒组雌性大鼠全血中RBC、HGB、PLT水平均较低(P0.01),血清TBIL、Cr、BUN均较高(P0.01);140 mg/kg FOX-7染毒组大鼠肝脏、脾脏的脏器系数均较高,140 mg/kg FOX-7染毒组雄性大鼠的睾丸系数较低。提示在本试验条件下,FOX-7对大鼠具有亚急性经口毒性作用,能抑制其生长发育,对肝脏、肾脏、脾脏、睾丸及血液有损伤作用。     

1.1⁃二氨基⁃2,2⁃二硝基乙烯对雄性大鼠性激素水平的影响

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对雄性大鼠性激素水平的影响,将受试物采用3个剂量(199.1、99.6、49.8 mg/kg)染毒,同时设溶剂对照组(4%淀粉溶液)。将40只健康SPF级雄性SD大鼠随机分为4组,每组10只,每日固定时间采用经口灌胃方式染毒,染毒容量为1 ml/100 g,连续14 d。于第0天、第7天、第14天称量大鼠体重,禁食12 h后,于第15天对大鼠进行腹主动脉采血,使用ELISA试剂盒检测雌二醇(E2)、促卵泡素(FSH)、黄体生成素(LH)、睾酮(T)、促性腺激素释放激素(GnRH)含量。结果显示,与溶剂对照组比较,FOX-7高剂量组大鼠第7天和第14天体重显著下降(P0.05),性激素T、FSH、LH、E2和GnRH含量均显著降低(P0.05)。提示高剂量的FOX-7可能会引起雄性大鼠性激素水平紊乱,生殖系统损伤。     

异丙酚对大鼠百草枯中毒的干预研究

目的探讨异丙酚对百草枯(Paraquat,PQ)中毒所致肺损伤的保护作用。方法128只雄性Wistar大鼠随机分为3组,对120只大鼠PQ 50 mg/kg一次性灌胃染毒,建立中毒大鼠肺损伤模型,异丙酚组(60只)于PQ染毒后1 h以二异丙酚腹腔注射10 mg/kg,2次/d,连续4d；染毒组(60只)于PQ染毒后1 h给予与异丙酚组等量的生理盐水；对照组(8只)1 ml/kg生理盐水一次性灌胃。于不同处理后1、3、7、14和28 d 5个时间点测定血浆、支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和肺组织匀浆中丙二醛(malondialdehyde,MDA)含量及肺组织匀浆中羟脯氨酸(hydroxyproline,HPY)含量,并观察3组大鼠中毒表现及肺组织病理改变。结果异丙酚组与染毒组比较,中毒表现明显减轻,血浆MDA含量1、3和7 d时分别为(4．31±0．94)、(4．04±0．87)、(3．24±1．14)nmol/ml,较对应染毒组[(10．15±3．15)、(6．97±1．65)、(5．44±0．66)nmol/ml]有明显降低,差异有统计学意义(P＜0．05或P＜0．01)；BALF中MDA含量1．3 d时分别为(3．47±1．09)、(2．79±1．11)nmol/ml,比染毒组[(5．58±1．19)、(4．86±1．89) nmol/ml]有明显降低,差异有统计学意义(P＜0．05或P＜0．01)；肺组织匀浆中MDA含量1、3 d时分别为(7．54±0．63)、(8．41±1．23)nmol/ml,较染毒组[(10．20±2．43)、(10．71±171)nmol/ml]有明显降低,差异有统计学意义(P＜0．06)。BALF中细胞计数1、3和7 d组明显低于染毒组,差异有统计学意义(P＜0．05)。病理观察异丙酚组肺组织水肿、充血及炎细胞浸润减轻。结论异丙酚能降低PQ中毒大鼠体内MDA含量,可能对PQ中毒大鼠肺损伤有保护作用。     

1,1-二氨基-2,2-二硝基乙烯对小鼠精子畸形的影响

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对小鼠精子畸形的影响,将小鼠随机分为6组,分别为阳性对照组、溶剂对照(4%淀粉溶液)组和34.82、69.64、139.29、348.22 mg/kg FOX-7染毒组及阳性对照(40 mg/kg环磷酰胺)组,每组12只。采用灌胃方式进行染毒,每日1次,连续染毒5 d。首次染毒35 d后,观察精子畸形情况。结果显示,与溶剂对照组比较,139.29、348.22 mg/kg FOX-7染毒组小鼠的精子畸形率均较高,差异有统计学意义(P0.05);且随着FOX-7染毒剂量的升高,小鼠的精子畸形率呈上升趋势。提示FOX-7可引起小鼠精子发生畸形。     

1，1-二氨基2，2-二硝基乙烯对哺乳动物细胞致突变性研究

在非代谢活化（-S9）和代谢活化（+S9）条件下，以1，1-二氨基-2，2-二硝基乙烯（FOX-7）处理小鼠淋巴瘤L5178Y细胞和中国仓鼠肺CHL细胞，进行体外哺乳动物细胞TK基因突变试验和染色体畸变试验。结果显示，分别以500、250、125 μg/ml浓度的FOX-7处理L5178Y细胞，各剂量组突变频率与溶剂对照组相比，差异有统计学意义（P<0.05），且具有剂量相关性；分别以300、200、100 μg/ml浓度FOX-7处理CHL细胞，各剂量组染色体畸变细胞率与溶剂对照组比较，差异无统计学意义（P>0.05）。提示FOX-7可能对小鼠淋巴瘤L5178Y细胞TK基因具有致突变性，对中国仓鼠肺CHL细胞染色体无致突变性。     

1,1-二氨基-2,2-二硝基乙烯对小鼠精原细胞染色体畸变的影响

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对小鼠精原细胞染色体畸变的影响,以348.22 mg/kg、139.29mg/kg、69.64 mg/kg剂量染毒小鼠,同时设阴性对照组(4%淀粉溶液)和阳性对照组(40 mg/kg的环磷酰胺),制备小鼠睾丸精原细胞染色体标本,观察染色体畸变类型和畸变率。结果显示阳性对照组、高剂量染毒组小鼠睾丸精原细胞染色体畸变率显著高于对照组(P0.05),提示高剂量的FOX-7可能会引起小鼠精原细胞染色体畸变。     

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.     

Die sogenannte Vinylchlorid-Krankheit—eine berufsbedingte Systemsklerose?

Zusammenfassung Es wurden 13 Arbeiter untersucht, die zwischen 1 3/4 und 18 Jahren in einem PVC-herstellenden Betrieb beschäftigt waren. 8 von ihnen wiesen sklerodermieartige Hautveränderungen (Abb. 2) auf, die histologisch charakterisiert sind durch Verbreiterung und Homogenisierung der kollagenen Faserbündel (Abb. 3 u. 4) sowie Fragmentation und Rarefizierung der elastischen Fasern (Abb. 5). Bei 7 Patienten bestanden trommelschlegelartige Auftreibungen einzelner Fingerendphalangen (Abb. 1). 11 Patienten zeigten Durchblutungsstörungen der Extremitäten (4 von diesen ein Raynaud-Syndrom) und 6 Patienten Acroosteolysen einzelner Fingerendphalangen (Abb. 6, Tabellen 1–3).Darüber hinaus bestand bei allen Patienten eine Thrombocytopenie, bei 12 Patienten eine Splenomegalie, bei 11 Patienten eine Einschränkung der Leberfunktion (erhöhte BSP-Retention). An der Leber ließ sich histologisch bei den 5 laparoskopierten Patienten eine deutliche Fibrosierung der Portalfelder nachweisen. Bei 4 Patienten bestanden Oesophagusvaricen (Tabellen 4 u. 5). 8 Patienten zeigten eine Partialinsuffizienz mit Hinweisen für vorwiegend restriktive Veränderungen.Die hier beschriebenen Veränderungen gehen weit über das bisher bekannte Acroosteolysesyndrom hinaus. Es wird der dringende Verdacht geäußert, daß langfristige Vinylchlorid-Exposition dieses komplexe Krankheitsbild verursacht. Daher wird für diese systemische Krankheit die Bezeichnung Vinylchlorid-Krankheit vorgeschlagen.Wir danken Frau E. Voigtländer für die Herstellung der klinischen und histologischen Abbildungen.     

Empathic processes: perception by medical students of patients'' anxiety and depression

Perceptions by medical students of patients' affective states were investigated, and the effect of the students' own emotions on such perceptions. One hundred and one fourth-year medical students rated the levels of anxiety and depression of three women patients presented on videotape, rated their own levels of anxiety and depression and completed a questionnaire on aspects of the rating process. Students had widely different and often inappropriate perceptions of patients' levels of anxiety and depression. Students who consistently overrated anxiety or depression in patients, compared to those who consistently underrated, were themselves significantly more anxious or depressed. These data suggest a need in medical education for systematic teaching of empathic skills and for recognition of potential bias in clinical decision-making arising from the clinician's own emotional state.     

The reported incidence of work-related ill-health in Scotland (2002-2003)

BACKGROUND: Although incidence data for work-related ill-health in the UK are available, more detailed information for smaller geographical areas has hitherto been unpublished. AIMS: To estimate the incidence of work-related ill-health reported by clinical specialists in Scotland, 2002-2003. METHODS: THOR (The Health and Occupation Reporting network) is a UK wide reporting scheme for work-related ill-health. In 2002-2003, 241 out of 2162 physicians in THOR were based in Scotland. We have summarized the reported cases and calculated incidence rates for categories of ill-health by age, gender and industry. The UK Labour Force Survey (2002) was used to provide denominator data, with comparisons made between rates for Scotland and the rest of the UK. RESULTS: In 2002-2003, 4043 estimated cases were reported from Scotland. Mental ill-health was most frequently reported (41%); followed by musculoskeletal disorders (31%), skin disorders (16%), respiratory disease (10%), hearing disorders (2%) and infection (1%). The reported average annual incidence rate per 100,000 employees for all work-related ill-health in Scotland was 86.0. The highest reported rate for mental ill-health was found for employees in public administration and defence (76.7 per 100,000), and health and social work (72.3 per 100,000). The construction industry had the highest reported rate of musculoskeletal disorders (41.6 per 100,000), while hairdressers appeared at most risk of developing occupational contact dermatitis (rate=86.4 per 100,000). CONCLUSIONS: Despite its limitations, THOR has indicated types of work-related ill-health and related industries for targeted disease prevention in Scotland.     

Function of the protein RPE65 in the visual cycle

A protein called RPE65 performs a key role in the trans-cis isomerization of retinol in the retinal pigment epithelium of the eye. The palmitoylation of RPE65 serves to switch off the visual cycle in darkness and to switch it on in the light.     

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.     

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.     

Acute symptoms following work with pesticides

BACKGROUND: Serious accidental poisoning by pesticides is rare in the UK, but more minor pesticide-related illness may be under-reported. Anecdotally, use of sheep dip has been linked with flu-like symptoms. AIM: To explore the frequency, nature and determinants of acute symptoms following work with pesticides. METHODS: A postal survey of men in three rural areas of England and Wales provided data on occupational use of five categories of pesticide, occurrence of 12 specified symptoms within 48 h of using pesticides and tendency to somatize. Risk factors for pesticide-related symptoms were assessed by modified Cox regression. RESULTS: Of 10 765 responders (response rate = 31%), 4108 had at some time used pesticides occupationally, including 935 (23%) who reported symptoms following such work on at least one occasion. In two areas, acute symptoms were most frequent following use of sheep dip (29 and 32% of users), but in the third area the rate was significantly lower (13% of users). The relative frequency of symptoms was similar for all five categories of pesticide, and flu-like symptoms did not cluster unusually among users of sheep dip. Risk of pesticide-related symptoms increased with somatizing tendency (prevalence ratio for highest versus lowest category 2.4, 95% confidence interval 2.0-3.0) and was higher in men who had used pesticides most often or handled concentrate. CONCLUSION: Acute symptoms are common following work with pesticides, but in many cases the illness may arise through psychological rather than toxic mechanisms.