石英对大鼠背根神经元高电压激活钙电流影响的探讨

[目的]通过分析石英作用后大鼠背根神经元(DRG)高电压激活(HVA)钙电流的变化,探讨石英对钙离子通道结构和功能的影响.[方法]原代培养DRG,分0、5、15、45、135μg/mL5个石英浓度组进行体外染尘,运用全细胞膜片钳记录技术记录不同染尘时间DRG HVA钙电流,每组记录约6个DRG.[结果]135μg/mL剂量组石英作用于DRG后HVA钙电流密度峰值为(-95.9±38.8)pA/pF,大干对照组和低剂量组,差异有统计学意义(P ＜0.05).HVA钙电流从30%升至70%的速率明显快于对照组和其他染尘组,差异有统计学意义(P＜0.01),但达峰时间差异无统计学意义(P＞0.05);135 μg/mL剂量组钙电流平均失活速率明显快于对照组和其他染尘组,差异有统计学意义(P=0.000),电流从峰值到记录结束时的下降率高于对照组和其他染尘组,差异有统计学意义(P＜0.05).45、135 μg/mL组的DRG膜电导值分别为(1 420.0±655.6)pS/μm2和(2257.4±454.2)pS/μm2,均高于对照组和低剂量染尘组,差异有统计学意义(P＜0.05).石英可使DRGHVA钙电流稳态激活曲线V1/2向正值方向移动约6.0～6.5mV,大于对照组,差异有统计学意义(P＜0.05),移动的幅度与染尘浓度关系不明显(P＞0.05);斜率k变化不明显(P＞0.05).石英作用后DRG HVA电流-电压(I-V)曲线形状改变不明显,对DRG HVA钙电流时间依赖性也没有明显影响.[结论]石英作用后DRG HVA钙通道结构和功能发生变化,使钙电流显著增大,呈激活快、失活也快的特征;另外,石英可使HVA钙通道在高刺激电压状况下(-10mV左右)更容易被激活.     

硒对镉诱导大鼠肝细胞端粒酶活力作用研究

目的 研究硒对镉诱导的大鼠肝细胞端粒酶活力、癌基因c-myc和p53表达的影响.方法 80只雄性SD大鼠随机分为16组,包括对照组,2.5、5.0和10.0 μmol/kg亚硒酸钠组,5.0、10.0和20.0μmol/kg氯化镉组,9个硒镉联合作用组.氯化镉采用腹腔注射染毒、亚硒酸钠采用灌胃染毒.用端粒重复序列扩增法(TRAP)检测端粒酶活力,用逆转录聚合酶链反应法检测c-myc和p53表达.结果 3个镉单独作用组的大鼠肝细胞端粒酶活力、c-myc和p53表达较对照组明显增高,差异有统计学意义(P＜0.05).硒镉联合作用组中,当2.5和5.0μmol/kg亚硒酸钠分别与5.0、10.0和20.0μmol/kg氯化镉联合作用时,大鼠肝细胞端粒酶活力、c-myc和p53 mRNA水平较相应剂量的镉单独作用组下降;当10.0 μmol/kg亚硒酸钠分别与5.0、10.0和20.0 μmol/kg氯化镉联合作用时,大鼠肝细胞端粒酶活力、c-myc和53 mRNA水平与相应剂量的镉单独作用组比较,差异无统计学意义(P＞0.05).结论 相对较低剂量的硒对镉引起的大鼠肝细胞端粒酶活力增高具有抑制作用,其抑制作用可能是通过降低c-myc和p53表达.     

纳米SiO2与标准SiO2致大鼠急性肺损伤的作用

目的观察并比较纳米SiO2与标准SiO2对大鼠的急性肺损伤作用.方法 42只SD大鼠按体重随机分成7组,用气管注入法一次性染尘,6组分别注入0.1、0.2、0.4 mg/ml的标准SiO2或纳米SiO2颗粒悬液1 ml,对照组注入等体积生理盐水.于染尘后第3天进行肺泡灌洗,测定2种粉尘染尘大鼠肺泡灌洗液(BALF)中的白细胞总数、总蛋白含量、乳酸脱氢酶(LDH)活力、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力等,比较2种粉尘的肺损伤作用.结果 0.4 mg纳米SiO2组白细胞总数(16.00×106)、LDH(914.29 U/L)均高于对照组(7.24×106,85.71 U/L),差异有统计学意义(P＜0.05或P＜0.01).染尘组的总蛋白含量与对照组比较无统计学意义.两种SiO2同一剂量组间比较,0.4mg纳米SiO2的白细胞总数(16.00×106)、LDH(914.29 U/L)均高于标准SiO2(9.09×106,476.19 U/L),差异有统计学意义(P＜0.05或P＜0.01).其他两剂量组间的差异无统计学意义.各染尘组MDA仅0.2 mg组标准SiO2(2.500 nmol/L)增高,与对照组(0.633 nmol/L)比较,差异有统计学意义(P＜0.05).两种SiO2各剂量组间MDA差异无统计学意义.0.2、0.4 mg纳米SiO2组以及0.2 mg标准SiO2组SOD分别为4.133、4.011、3.929 U/ml,明显低于对照组(6.088 U/ml),0.4 mg纳米SiO2组的SOD(4.011 U/ml)低于标准SiO2组(4.972 U/ml),差异均有统计学意义(P＜0.01或P＜0.05).结论纳米SiO2致急性肺损伤作用比标准SiO2强.     

氟化物对体外培养孕鼠子宫内膜上皮细胞的影响

目的研究氟化物对体外培养孕鼠子宫内膜上皮细胞的影响。方法选取20只清洁级昆明受孕小鼠,采用胰蛋白酶消化结合刮取法分离内膜上皮细胞,并测定细胞活力。设对照组和氟染毒组(F-浓度分别为2.5、5.0、10.0、20.0μg/ml)。细胞体外培养72h后,HE染色观察形态变化;并对首次传代的细胞染氟24h后,通过人工记数法测定细胞贴壁率;染氟72h后,采用四甲基偶氮噻唑蓝酶反应比色法(MTT法)检测细胞增殖能力。结果2.5、5.0μg/ml剂量组细胞无病理损伤,10.0μg/ml剂量组细胞出现颗粒变性、脂肪变性;20.0μg/ml剂量组细胞出现核溶解、死亡并脱壁。首次传代后对照组和各剂量组子宫内膜上皮细胞的贴壁率均在80%左右,差异无统计学意义(P>0.05)。与对照组相比,5.0、10.0、20.0μg/ml组吸光度值较低,差异均有统计学意义(P<0.05),表明子宫内膜上皮细胞增殖活力受到抑制。结论氟可引起体外培养的子宫内膜上皮细胞出现多种病理损伤,降低其体外增殖能力。     

瓷厂及钨矿生产性粉尘对血管内皮细胞的损伤效应

目的 评价瓷厂和钨矿生产性粉尘对血管内皮细胞的直接损伤作用,探讨粉尘引发心血管疾病的机制.方法 以人脐静脉内皮细胞(HUVEC)株HUV-EC-C为作用细胞,以瓷厂、钨矿作业点收集的生产性粉尘为实验粉尘,以中国标准石英为对照,将粉尘配制成25、50、100、200、400μg/ml浓度与HUVEC共培养24 h,测定细胞乳酸脱氢酶(LDH)活力、细胞的活力噻唑蓝(MTT)、一氧化氮(NO)和肿瘤坏死因子-α(TNF-α)的释放量.结果 瓷厂和钨矿作业点的生产性粉尘均能使HUVEC细胞培养液中LDH活力升高,释放NO及TNF-α水平升高,并随粉尘浓度升高呈现明确的剂量-反应关系.瓷厂和钨矿作业点生产性粉尘均能导致HUVEC细胞活力下降,呈剂量-反应关系.石英粉尘诱导HUVEC培养液中LDH活力升高的能力明显高于瓷厂和钨矿的生产性粉尘,差异有统计学意义(P＜0.05).瓷厂和钨矿生产性粉尘诱导HUVEC细胞活力下降及释放NO的能力相近且与标准石英相当.在较低剂量组(25、50、100μg/ml)时,瓷厂和钨矿生产性粉尘诱导TNF-α的释放量与标准石英相当,差异无统计学意义(P＞0.05),而在较高剂量组(200、400 μg/ml)时,标准石英诱导TNF-α的释放量明显高于瓷厂和钨矿生产性粉尘,差异有统计学意义(P＜0.05).结论 不同来源的生产性粉尘及标准石英均能损伤血管内皮细胞,诱导TNF-α释放,引起不同程度的生物学效应.     

氟化钠对体外培养大鼠成骨细胞增殖与分化的影响

为研究氟化钠对体外培养的大鼠成骨细胞增殖和分化的影响,用混合酶消化法分离24 h内新生清洁级SD大鼠颅盖骨成骨细胞,进行原代培养.采用倒置相差显微镜观察成骨细胞的形态,采用Gomori改良钙钴法对成骨细胞进行碱性磷酸酶(ALP)染色.向1×103个/孔成骨细胞中接种加入0.0、2.5、5.0、10.0、20.0、40.0、60.0、80.0、100.0、120.0mg/L的氟化钠,培养1～3 d,采用噻唑蓝(MTT)检测增殖活力.向1×103个/孔成骨细胞中接种加入0.0、2.5、5.0、10.0、20.0、40.0、60.0、80.0、100.0、120.0mg/L的氟化钠,培养3、5、7、9d时,采用PNPP法检测碱性磷酸酶活力.结果 显示,氟化钠作用于成骨细胞第2天时,2.5、5.0mg/L的氟化钠对成骨细胞增殖活力有明显的促进作用(P＜0.05);当氟化钠≥80.0mg/L时,可明显抑制成骨细胞的增殖(P＜0.05).染毒第9天,氟化钠≥40.0mg/L时对成骨细胞ALP活力有明显的抑制作用,差异均有统计学意义(P＜0.05).提示低剂量氟化钠有轻微促进成骨细胞增殖的作用,高剂量氟化钠则能抑制成骨细胞增殖和ALP的活力.     

氟对原代培养大鼠海马神经元氧化应激的影响与DNA损伤作用

目的研究氟对原代培养大鼠海马神经元氧化应激和DNA损伤的影响.方法 SD大鼠原代培养的海马神经元暴露于20、40、80μg/ml氟化钠24h后,检测海马神经元超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力,还原型谷胱甘肽(GSH)、丙二醛(MDA)的含量,细胞外乳酸脱氢酶(LDH)活力以及DNA损伤的情况.结果40、80μg/ml染毒组海马神经元内MDA含量高于对照组(P＜0.05),20、40、80 μg/ml染毒组GSH含量、GSH-Px活力低于对照组(P＜0.05),80μg/ml染毒组SOD活力低于对照组(P＜0.05).40、80μg/ml组细胞外LDH活力比对照组高(P＜0.05).彗星Olive尾矩升高(P＜0.01),相同剂量染氟组细胞内MDA含量与彗星Olive尾矩存在统计学的正相关关系(r=.895,P＜0.05).结论氟可引起大鼠海马神经元氧化应激和DNA损伤,氧化应激可能在氟致DNA损伤中起重要作用.     

氯化镍染毒对小鼠外周血网织红细胞微核形成的影响

目的研究氯化镍(NiCl2)诱导小鼠外周血网织红细胞微核形成的作用.方法将30只健康的成年雄性NIH小鼠随机分为6组,设生理盐水对照组、秋水仙素阳性对照组(剂量为0.75 mg/kg)、环磷酰胺阳性对照组(剂量为40.0mg/kg)和NiCl2染毒组(剂量分别为5.0、10.0、20.0 mg/kg),分2次腹腔注射染毒,间隔24 h,每次按0.1 ml/10 g体重腹腔注射.采用转铁蛋白受体荧光抗体和碘化丙碇染色,以疟原虫感染小鼠外周血红细胞为微核生物模型,调校流式细胞仪,检测秋水仙素、环磷酰胺和0、5.0、10.0、20.0 mg/kg NiCl2染毒后小鼠外周血含微核网织红细胞率的变化.结果秋水仙素和环磷酰胺染毒小鼠的外周血含微核网织红细胞率均明显高于对照组小鼠(P＜0.01),但不同剂量NiCl2染毒小鼠外周血含微核网织红细胞率均未见明显升高(P＞0.05).结论该研究条件下未观察到氯化镍有明显的诱导小鼠外周血网织红细胞微核形成的作用.     

硒对镉诱导的雄性SD大鼠肝细胞c-myc和p53蛋白表达及细胞凋亡的影响

目的 探讨不同剂量亚硒酸钠对氯化镉诱导的雄性SD大鼠肝细胞的凋亡率、c-Myc和P53蛋白表达的影响.方法 将65只健康SPF级SD雄性大鼠随机分为13组,分别设对照(生理盐水)组、氯化镉(5.0、10.0、20.0 μmol/kg)组及亚硒酸钠(2.5、5.0、10.0 μmol/kg)+氯化镉(5.0、10.0、20.0 μmol/kg)联合作用组,每组5只.氯化镉采用一次性腹腔注射染毒,亚硒酸钠采用一次性灌胃染毒.染毒后48 h,用流式细胞仪检测细胞凋亡率,免疫组化法测定c-Myc和P53蛋白的表达量.结果 与相同剂量氯化镉组相比,亚硒酸钠剂量为2.5 μmol/kg时,全部联合作用组的大鼠肝细胞凋亡率、c-Myc和P53蛋白表达均降低(P＜0.05或P＜0.01);而亚硒酸钠剂量为5.0、10.0 μmol/kg时,部分联合作用组的大鼠肝细胞凋亡率、c-Myc和P53蛋白表达降低(P＜0.05或P＜0.01).大鼠细胞凋亡率与c-Myc、P53蛋白表达量均呈正相关(P＜0.01).结论 2.5 μmol/kg的亚硒酸钠对氯化镉所诱导的大鼠肝细胞的凋亡及c-Myc和P53蛋白表达的升高具有一定的拮抗作用.     

Protective Effects of Vitamin E Succinate on Cisplatin1-Induced Nephrotoxicity in HEK293 Cells

目的 研究维生素E琥珀酸脂(Vitamin E succinate,VES)对顺铂(cis-diamminedichloroplatinum,CDDP)所致人胚肾293( HEK293)细胞毒性的保护作用.方法 体外培养人胚肾293细胞(HEK293),设空白对照组、VES(20 μg/ml)对照组、CDDP(25 μg/ml)单独染毒组以及低剂量CDDP( 25 μg/ml )+VES(5 μg/ml)联合处理组、中剂量CDDP(25 μg/ml)+VES( 10 μg/ml)联合处理组、高剂量CDDP( 25 μg/ml )+VES( 20 μg/ml)联合处理组,染毒12h.采用MTT法观察细胞增殖效应,测定细胞还原型谷胱甘肽(GSH)、丙二醛(MDA)含量和细胞培养液中乳酸脱氧酶(LDH)活力,采用荧光法检测DNA链间的交联情况.结果 与CDDP单独染毒组比较,各剂量CDDP+VES联合处理组HEK293细胞的存活率均升高,差异有统计学意义(P＜0.05,P＜0.01).VES能明显抑制CDDP所致HEK293细胞MDA含量和细胞培养液中LDH活力的升高,并能提高细胞GSH的含量(P＜0.05,P＜0.01).高剂量CDDP+VES联合处理组HEK293细胞的交联率低于CDDP单独染毒组,差异有统计学意义(P＜0.05).结论 VES能抑制CDDP所致HEK293细胞的细胞毒性,其机制可能与VES的抗氧化作用和对DNA损伤的防护作用有关.     

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.