牛磺酸对大鼠视网膜谷氨酸兴奋毒性的防护作用研究

目的:探明牛磺酸能否有效防护谷氨酸兴奋毒性引起的大鼠视网膜尤其是视网膜神经节细胞(retinalganglioncells,RGCs)损伤。方法:通过玻璃体注射谷氨酸建立大鼠视网膜谷氨酸兴奋毒性损伤模型,分为正常对照组,谷氨酸组,牛磺酸干预高、低剂量组,MK-801干预组(阳性对照组)和玻璃体注射PBS对照组。观察谷氨酸兴奋毒性对大鼠视网膜组织病理结构、超微结构、视网膜电图、RGCs数量的影响及牛磺酸的防护效应。结果:玻璃体注射谷氨酸使视网膜内层尤其是内网状层厚度变薄;内核层细胞:RGCs的超微结构发生变性改变;视网膜电图的a波、b波下降;神经节细胞层的细胞数显著减少(减少53%),以RGCs的减少为主(减少75%)。腹腔注射高剂量(25mg/kgbw)牛磺酸可有效防护谷氨酸所致上述损伤及RGCs数量的减少,而低剂量(5mg/kgbw)牛磺酸的作用不明显。结论:牛磺酸可有效防护谷氨酸兴奋毒性引起的视网膜尤其是RGCs损伤。     

牛磺酸对糖尿病大鼠视网膜超微结构的影响

目的 观察糖尿病大鼠视网膜早期病变，探讨牛磺酸对糖尿病大鼠视网膜超微结构的影响。方法 选择健康成年SD大鼠50只，随机分成正常对照组(CON)、糖尿病1月组(DM1)、牛磺酸干预的糖尿病1月组(DM1 T)、糖尿病3月组(DM3)、牛磺酸干预的糖尿病3月组(DM3 T)。一次性腹腔内注射链尿佐菌素(STZ)，建立糖尿病大鼠模型。在普通饲料中加入1.2％牛磺酸进行营养干预，对各组视网膜进行光镜HE染色及透射电镜观察。结果 视网膜HE染色显示，糖尿病组视网膜较正常对照组明显变薄，神经节细胞数明显减少。牛磺酸干预后视网膜厚度较糖尿病组增加，神经节细胞数相对增多。观察超微结构发现糖尿病大鼠感光细胞外段膜盘排列紊乱，膜盘间隙增大，严重者出现膜盘断裂、溶解；视杆内段线粒体等细胞器肿胀变性，内网状层轴突肿胀、空泡样变。牛磺酸干预后感光细胞外段膜盘排列明显变整齐，线粒体肿胀较轻，内网状层轴突肿胀较糖尿病组轻。结论 牛磺酸可明显改善糖尿病视网膜的超微结构改变。     

牛磺酸对糖尿病大鼠视网膜谷氨酸及γ-氨基丁酸的影响

目的探讨牛磺酸对糖尿病大鼠视网膜谷氨酸（Glu）及γ-氨基丁酸（GABA）的影响,旨在评价牛磺酸对糖尿病视网膜病变的保护作用。方法将SD大鼠随机分成3组,即正常对照组、糖尿病组、牛磺酸干预糖尿病组。一次性腹腔内注射链脲佐菌素（STZ）,建立糖尿病大鼠模型,在普通饲料中加入1．2％牛磺酸营养干预3个月后,用免疫组化及氨基酸分析法观察视网膜中Glu及GABA的浓度与表达。结果与正常对照组比较,糖尿病大鼠视网膜中牛磺酸浓度下降了6．8％,G1u和GABA的浓度分别增加了19．9％、81．6％（P〈0．01）,且免疫反应性增强。膳食补充牛磺酸后,与糖尿病组比较,大鼠视网膜中牛磺酸浓度增加了9．5％,而Glu和GABA的浓度分别降低了9．9％、29．2％（P〈0．01）,同时Glu及GABA的强阳性染色明显减弱。结论糖尿病大鼠,视网膜中Glu和GABA浓度增加,牛磺酸浓度下降。体外补充牛磺酸可能通过降低Glu和GABA浓度保护Mtiller细胞,从而减轻视网膜损伤.     

牛磺酸对甲基汞致大鼠脑氧化损伤的保护作用

[目的]探讨甲基汞致大鼠脑氧化损伤及牛磺酸对氧化损伤的保护作用。[方法]将24只健康清洁级Wistar大鼠按体质量随机分为4组,每组6只,分别为对照组、低剂量染汞组、高剂量染汞组和牛磺酸干预组。周一至周五每天进行染毒,对照组腹腔注射生理盐水,低剂量染汞组腹腔注射4μmol/kg氯化甲基汞,高剂量染汞组和牛磺酸干预组腹腔注射12μmol/kg氯化甲基汞;每周一、三、五染毒前2h进行预处理,对照组、低剂量染汞组和高剂量染汞组皮下注射生理盐水,牛磺酸干预组皮下注射1mmol/kg的牛磺酸;连续进行4周,最后一次染毒后,处死大鼠。取大脑皮质测定：活性氧（ROS）、巯基、羰基、丙二醛（MDA）的含量,超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-px）的活性及细胞凋亡率。[结果]与对照组比较,低、高汞组大鼠的体质量增长幅度降低（P〈0.05,P〈0.01）;ROS分别是其1.8和3.9倍（均P〈0.01）;SOD和GSH-px的活性均降低;巯基的含量降低;羰基的含量升高;MDA增加;细胞凋亡率分别升高3.4和10.0倍。牛磺酸干预组与高剂量染汞组比较,ROS的生成量降低了17%;SOD、GSH-px的活性有不同程度的升高;巯基、羰基和MDA的含量也有不同程度的改变;细胞凋亡率为高汞组的44%。[结论]甲基汞可导致脑氧化损伤,牛磺酸对甲基汞所致氧化损伤具有一定的保护作用。     

血小板生成素抑制阿霉素大鼠心肌细胞氧化损伤的实验研究

目的研究血小板生成素（TPO）对大鼠阿霉素（ADM）心肌细胞损伤的拮抗作用并探讨其机制。方法32只Wistar大鼠被随机分成4组,分别为对照组、ADM组、ADM＋TPOL组、ADM＋TPOH组。对照组给予生理盐水,其余各组给予ADM20mg／kg腹腔内注射,TPO干预组则加用不同剂量的TPO（10μg／kg或30μg/kg,隔天1次,共3次）。采用ELISA法测大鼠血清CK—MB及cTNI;观察电子显微镜下心肌细胞超微结构的变化;利用免疫组织化学染色观察心肌细胞组织学改变及DNA氧化损伤产物8-羟基脱氧乌苷（8-OHdG）表达情况,应用IPP6．0软件,计算累积光密度（IOD）及8-OHdG index。结果加用TPO干预后CK—MB、cTN1的活力较ADM组明显下降（P〈0．01）;电子显微镜下ADM组心肌细胞超微结构损害较TPO干预组严重;TPO干预组心肌组织病理损伤减轻,IOD、8-OHdG index值较其他各组明显降低（P〈0．01）上述指标在ADM＋TPOL组及ADM＋TPOH组间差异无统计学意义（P〉0．05）。结论TPO通过拮抗阿霉素对心肌的氧化损伤来发挥心脏保护作用。     

牛磺酸对大鼠视网膜光化学损伤c-fos表达影响

目的观察饲料中添加牛磺酸对光化学损伤后大鼠光感受器细胞凋亡的影响，并进一步从氧化应激基因c-fos表达变化角度探讨其防护机制。方法70只SD大鼠随机分为对照组、牛磺酸组。分别喂饲标准饲料或添加4％牛磺酸饲料喂饲15d后接受（3000±200）lx持续0，1，3，6，9，12，24h光照，凋亡细胞原位末端标记法（TUNEL）检测光感受器细胞凋亡情况并计算凋亡指数（AI）；RT．PCR法及免疫印迹法检测视网膜内c-fos mRNA以及蛋白表达水平。结果感光细胞凋亡指数随光照时间延长逐渐增加，牛磺酸组AI显著低于对照组（P〈0．05）。其中光照12h牛磺酸组与对照组AI分别为（12．3±4．7）％和（32．4±6．2）％；视网膜c-fos mRNA光照1h后一过性表达增高，牛磺酸组较对照组低（P〈0．05）；光照后视网膜c-fos蛋白表达逐渐升高。于3h达峰值。牛磺酸组显著低于对照组（P〈0．05）。结论在视网膜光化学损伤条件下，牛磺酸可能通过抑制视网膜c-fos的转录及表达。阻断光感受器细胞凋亡转导从而保护视网膜。     

小儿急性中毒143例分析

本研究拟通过观察谷氨酰胺合成酶（GS）、谷氨酰胺酶（PAG）、琥珀酸脱氢酶（SDH）和Na^＋-K^＋-ATPase活性的改变,探讨地卓西平（MK-801）和牛磺酸对锰致大鼠兴奋性毒性的影响。将大鼠按体重随机分成4组,第1组为对照组,皮下注射0．9％的氯化钠;第2组为单纯染锰组,皮下注射0．9％的氯化钠;第3、4组为预处理干预组,分别皮下注射0．3μmnol／kg的MK-801和1mmol／kg的牛磺酸,皮下注射2h后,第1组腹腔注射0．9％的氯化钠,第2-4组腹腔注射200μmol／kg的氯化锰,染锰25d,MK-801和牛磺酸隔日注射一次,共预处理13次。最后一次染毒后24h处死大鼠,切取大脑皮质和纹状体。测定大脑皮质SDH、Na^＋-K^＋-ATPase的活性;测定脑纹状体GS、PAG的活性。结果显示单纯染锰组与对照组比较,纹状体GS、脑皮质SDH和Na^＋-K^＋-ATPase的活性明显降低（P〈0．01）,纹状体PAG的活性升高。MK-801预处理干预组与单纯染锰组比较,纹状体GS和脑皮质Na^＋-K^＋-ATPase的活性明显升高,脑皮质SDH的活性升高,纹状体PAG的活性降低;牛磺酸预处理干预组纹状体CS和脑皮质SDH的活性明显升高,脑皮质的Na^＋．K^＋-ATPase活性升高。提示MK-801和牛磺酸对锰所致兴奋性毒性均有不同程变的拮抗作用。     

牛磺酸对镉致大鼠脑损伤组织中单胺类递质的影响

目的研究牛磺酸对镉致大鼠脑损伤组织中单胺类递质的影响。方法将40只大鼠按体重随机分为4组：正常对照组、模型组、高剂量组、低剂量组,每组10只。除正常对照组外,其余各组每周2次腹腔注射氯化镉（CdCl2）2．0ms／kg,正常对照组每周2次腹腔注射生理盐水（相同体积）。同时,高剂量组、低剂量组每日分别灌胃牛磺酸1000和750mg／kg,正常对照组和模型组每日灌胃蒸馏水。实验持续4周后处死动物,测定脑组织中乙酰胆碱酯酶（AchE）、胆碱乙酰转移酶（ChAT）活力及对脑组织病理形态学进行观察。结果牛磺酸高剂量组脑组织中AchE活力与模型组比较明显降低（P〈0．05）,ChAT活力明显增高（P〈0．05）;脑组织病理形态观察显示,模型对照组出现明显细胞核固缩,神经细胞数目减少,细胞排列层次减少;高剂量组海马神经细胞核固缩明显减少。结论牛磺酸可调节大鼠单胺类神经递质的释放水平,可显著改善镉致大鼠脑组织损伤。     

CS_2吸入染毒对雄性大鼠下丘脑-垂体-性腺轴超微结构的影响及NO干预作用

[目的]探讨二硫化碳（CS2）对雄性大鼠下丘脑-垂体-性腺轴超微结构的影响及一氧化氮（NO）的干预作用。[方法]将24只雄性SD大鼠按体重随机分为4组：对照组、CS2染毒组、硝普钠（sodium nitroprusside,SNP）干预组和N-甲基-L-精氨酸（L-NMMA）干预组。除对照组外,其余3组均以1250mg/m3CS2进行静式吸入染毒,2h/d,5d/周,共10周,SNP和L-NMMA干预组在动物染毒结束前10d开始分别腹腔注射SNP（5mg/kg）和L-NMMA（2mg/kg）,1次/d。染毒结束后,取下丘脑、垂体和睾丸组织,利用透射电子显微镜观察组织超微结构的改变。[结果]CS2染毒可造成下丘脑神经元、垂体促性腺激素细胞、生长激素细胞和睾丸支持细胞线粒体肿胀,内质网扩张,SNP对CS2引起的下丘脑、垂体、睾丸组织的损伤具有拮抗作用,而L-NMMA则进一步导致病变的发生。[结论]CS2可造成下丘脑、垂体和睾丸组织超微结构的改变,NO在此过程中发挥重要作用。     

α-硫辛酸对高糖诱导GK大鼠肝氧化损伤的影响

[目的]探讨α-硫辛酸（α-LA）对高糖诱导GK大鼠肝氧化损伤的影响。[方法]选用GK大鼠36只,分为6组,阴性对照组普通饮水、阳性对照组及4个干预组分别给予等量30％蔗糖饮水,干预组分别给予不同剂量的α-LA（25、50、75、100mg／kg）灌胃。干预9周后观察不同剂量的α-LA对高糖诱导下GK大鼠肝组织脂质过氧化水平、抗氧化酶活力以及肝线粒体活性氧（ROS）水平的影响。[结果]阳性对照组大鼠丙二醛（MDA）和线粒体ROS水平明显高于阴性对照组（P〈0．05）,而超氧化物歧化酶（SOD）及谷胱甘肽过氧化物酶（GSH-Px）水平明显低于阴性对照组（P〈0．05）,提示高糖饮水明显增加了GK大鼠肝脏的氧化应激水平。在高糖诱导情况下,各α-LA干预组与对照组比较,给予25mg／kg和50mg／kg剂量的α-LA干预可以有效降低肝组织MDA浓度,提高SOD、GSH-P活性以及降低肝线粒体ROS水平（P〈0．05）,其抗氧化损伤的效果好于75mg／kg和100mg／kg两个高剂量干预组。[结论]25mg／kg和50mg／kg剂量的α—LA对高糖诱导的GK大鼠肝组织的氧化损伤具有保护作用,但这种保护作用并未呈现明显的剂量作用关系,高剂量的α-LA（75—100mg／kg）保护作用不如低剂量组。     

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.