合欢花黄酮对慢性应激模型大鼠抗抑郁作用

目的 探讨合欢花黄酮对慢性应激抑郁模型大鼠行为和脑源性神经生长因子(BDNF)、凋亡诱导蛋白(Bax)表达及海马细胞凋亡影响.方法 取清洁级SD大鼠48只,根据1％蔗糖水偏嗜度和体重随机分成对照组、模型组、氟西汀组及合欢花20、40、80 mg/kg组6组;造模同时灌胃给药,每日1次,连续28 d,造模方法为慢性轻度不可预见性应激加孤养;观察大鼠行为改变,高效液相色谱法检测脑内去甲肾上腺素(NE)和五羟色胺(5-HT)含量,流式细胞技术检测海马细胞凋亡率,免疫蛋白印记技术检测大鼠海马BDNF、Bax表达.结果 与模型组比较,合欢花中高剂量组大鼠海马细胞凋亡率[(1.862±0.150)％、(1.516±0.167)％]均降低(P＜0.05),脑内5-HT[(611.0±115.8)、(760.7±112.3)ng/g]和NE[(371.0±152.4)、(430.0±153.1)ng/g]含量均升高(P＜0.01);慢性应激大鼠海马BDNF表达均减少,Bax表达增加,但合欢花各剂量组中大鼠海马BDNF表达有所增加,Bax表达减少(均P＜0.01).结论 合欢花能拮抗慢性应激模型大鼠抑郁症,其机制可能与增加脑内5-HT、NE含量与BDNF表达,降低Bax表达,减少海马细胞凋亡有关.     

bFGF对脑缺血大鼠海马及顶叶皮质c-Myc蛋白影响

目的 探讨碱性成纤维细胞生长因子(bFGF)对脑组织缺血再灌注神经元c-Myc蛋白表达影响及机制.方法 30只大鼠随机分为假手术组、缺血再灌注组、bFGF组,每组10只;应用线栓法制作大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞2 h再灌注损伤24 h,采用原位末端标记法(TUNEL)、免疫组织化学法检测海马及顶叶皮质内神经元凋亡和c-Myc蛋白表达.结果 假手术组大鼠海马及顶叶皮质偶见凋亡细胞,神经元内少见c-Myc蛋白阳性细胞;缺血再灌注组海马及顶叶皮质神经元凋亡增加,顶叶皮质及海马神经元内c-Myc蛋白表达灰度值为(88.16±2.43),(86.72±1.23),bFGF组神经元凋亡减少,神经元内c-Myc蛋白表达灰度值为(97.61±1.78),(95.35±2.34).结论 bFGF可减少缺血神经元凋亡,抑制脑缺血诱导的c-Myc蛋白的表达,对脑缺血再灌注海马及顶叶皮质神经元具有保护作用.     

脑源性神经营养因子对皮质酮诱导新生大鼠海马神经元凋亡的保护作用

目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)对皮质酮诱导新生大鼠海马神经元凋亡的保护作用。 方法 原代培养新生大鼠海马神经元,并分成对照组、皮质酮组、皮质酮+BDNF组,皮质酮造模浓度为100 μM,分别采用浓度为0.1、1、10、25、50、100 ng/ml的BDNF干预,造模及干预时间均为24 h。CCK8法测定细胞活力,分析BDNF的最佳作用浓度,流式细胞术和 Hoechst荧光染色检测细胞的凋亡情况,免疫印迹(Western-blotting)法检测细胞Caspase-3、Caspase-9的表达水平。 结果 与对照组比较,皮质酮组神经元凋亡率由(10.7±1.2)%上升为(33.9±3.5)%(t=18.707,P<0.01),胞体透亮,部分细胞核碎裂,凋亡特征明显,Caspase-3、Caspase-9表达显著上调(t₁=27.098,P₁＜0.01;t₂=24.311,P₂＜0.01);BDNF作用后,细胞活力显著上升,在浓度为1 ng/ml时与皮质酮组比较差异有统计学意义(t=3.562,P＜0.05),分析得出BDNF最佳浓度为48 ng/ml;BDNF(48 ng/ml)干预完成后,细胞凋亡率较皮质酮组下降至(18.7±2.1)%,差异有统计学意义(t=11.478,P＜0.01),细胞形态基本恢复正常,Caspase-3、Caspase-9表达明显下调(t₁=17.341,P₁=0.002;t₂=14.993,P₂=0.005)。 结论 BDNF能有效拮抗皮质酮诱导的海马神经元凋亡,保护神经元细胞。     

牛磺酸对锰致海马神经元损伤影响

目的 探讨牛磺酸对锰致海马神经元损伤的影响.方法 新生Wistar大鼠海马神经元细胞原代培养后随机分为空白组、牛磺酸组、低、中、高剂量锰组、牛磺酸+低、中、高剂量锰组,检测乳酸脱氢酶(LDH)活力、流式细胞仪定量凋亡率和观察神经元超微结构变化.结果 LDH活力低、中、高剂量锰组分别为(1 048.063 0±55.459 8)、(1 004.1233±65.339 4)、(1 405.303 3±163.311 5)U/L,明显高于空白组(895.203 3±53.228 6) U/L(F=31.802,P＜0.001),牛磺酸+低剂量锰组(834.595 0±173.445 5)U/L明显低于低剂量锰组(1 048.063±55.459 8) U/L(t=2.871,P=0.017);神经元凋亡率中、高剂量锰组分别为(44.6±4.0)％和(57.7±6.2)％,均明显高于空白组(17.5±2.5)％ (F=159.05,P＜0.001),牛磺酸+中剂量锰组(34.6±6.4)％明显低于中剂量锰组(44.6±4.0)％(t=3.813,P=0.019),牛磺酸+高剂量锰组(28.9±13.2)％明显低于高剂量锰组(57.7±6.2)％(t=3.709,P=0.021);电镜下观察,锰组神经元呈凋亡和坏死的形态学改变,牛磺酸+锰组与其比较有所改善.结论 锰在体外可剂量依赖性引起海马神经元死亡,牛磺酸可在一定程度上拮抗锰的神经毒性.     

持续低氧对海马神经元凋亡及蛋白表达影响

目的观察持续低氧致体外培养SD乳大鼠海马神经元细胞凋亡及c-jun、c-fos的表达情况。方法海马神经元原代细胞培养,取培养10 d的海马神经元,置于90%N2、5%O2、5%CO2混合气体培养箱中培养2,6,12,24h后,Hoechst 33258染色观察神经元细胞凋亡情况,并用蛋白印迹法检测c-jun、c-fos蛋白表达水平。结果随缺氧时间延长,凋亡细胞所占比例由(23.79±3.43)%上升至(74.36±5.58)%;c-jun、c-fos蛋白在缺氧2 h时表达增高,6 h时达高峰,之后逐渐降低,24 h时仍略高于正常对照。结论持续低氧可引起体外培养海马神经元c-jun、c-fos蛋白表达升高,这可能与神经细胞凋亡以及保护机制有关。     

EGCG对体外应激海马神经元的保护作用及其机制探讨

目的观察表没食子儿茶素没食子酸酯(EGCG)对体外应激海马神经元的保护作用,并探讨其相关作用机制。方法体外培养新生大鼠海马神经元,于原代培养D13时加入不同浓度的皮质酮,采用CCK8(cell counting kit-8)法检测对神经元存活率的影响;加入EGCG(0、0.1、1、5、10μmol/L)预处理24h后,加入皮质酮(CORT,1×10-5mol/L)建立应激损伤模型,采用CCK8法检测神经元的存活率;然后加入LY294002(PI3K/AKT特异性阻断剂)和U012(6ERK1/2特异性阻断剂),检测细胞存活率的改变,并以Hoechst33342核染色法检测细胞凋亡情况。结果皮质酮在10-6～10-4mol/L范围内对海马神经元的神经毒性作用呈现浓度-时间依赖性;0.1μmol/L EGCG处理对皮质酮造成的海马神经元损伤具有保护作用,能够增加细胞存活率,降低细胞凋亡的发生;而加入信号通路阻断剂LY294002(10 mol/L)和U0126(10 mol/L)后,此保护作用受到抑制,其能抑制EGCG对抗CORT引起的神经元细胞存活率下降,细胞凋亡增多。结论 EGCG处理对皮质酮造成的大鼠海马神经元损伤具有保护作用,其作用机制可能与EGCG调控PI3K/AKT、ERK1/2信号转导通路相关。     

邻苯二甲酸-单-乙基己基酯对原代培养新生大鼠海马神经元细胞活性和凋亡率的影响

目的探讨邻苯二甲酸-单-乙基己基酯[mono-(2-ethylhexyl)phthalate,MEHP]对新生大鼠海马神经元细胞活性和凋亡率的影响。方法取出生24 h内清洁级SD大鼠海马组织神经元原代培养8 d后,分别加入含终浓度0(溶剂对照)~100μmol/L MEHP的培养液暴露12、24 h。采用MTT法检测细胞活性,采用Hoechst 33258染色法检测神经元的凋亡情况。结果随着MEHP暴露剂量的升高,新生大鼠海马神经元的存活率、凋亡率均呈先上升后下降的趋势。结论 MEHP可抑制新生大鼠海马神经元细胞活性,促进神经元凋亡。提示MEHP对新生大鼠的海马神经元具有毒性作用。     

铝染毒致大鼠海马神经元凋亡与海马突触可塑性的关系研究

目的 探讨铝染毒对大鼠海马神经元凋亡的影响及其与海马突触可塑性的关系.方法 雄性SPF级SD大鼠40只,按体重随机分为对照组(0mg/kg)、高剂量组(90 mg/kg)、中剂量组(30 mg/kg)和低剂量组(10 mg/kg),每组10只.根据大鼠体重,染毒体积为10 ml/kg,每天乳酸铝灌胃1次,连续染毒30 d.对照组给予等体积的纯化水.染毒结束后,用电生理学方法检测大鼠场兴奋性突触后电位(fEPSP),用流式细胞术检测大鼠海马神经元的凋亡,用实时荧光定量PCR(real-time PCR)检测caspase-3、caspase-8、caspase-9基因的相对表达量.结果 与对照组比较,低、中、高剂量组在高频刺激后10、20、30、40、50和60 min的fEPSP平均波幅都有显著下降,差异有统计学意义(P＜0.05).与对照组比较,中、高剂量组海马神经元的凋亡率明显升高,差异有统计学意义(P＜0.05).与对照组比较,中、高剂量组海马的caspase-3基因相对表达量明显增加,差异有统计学意义;高剂量组海马的caspase-8基因相对表达量明显增加,差异有统计学意义(P＜0.05).结论 铝染毒可能通过促使大鼠神经元凋亡,影响海马的突触可塑性.     

虾青素对辛硫磷所致大鼠皮肤成纤维细胞氧化损伤的拮抗作用

目的 探讨虾青素对辛硫磷所致大鼠皮肤成纤维细胞氧化损伤及凋亡的拮抗作用.方法 取4只3日龄清洁级SD大鼠背部皮肤培养.取第4代成纤维细胞,正常对照组和辛硫磷氧化损伤组更换新鲜培养基,低、中、高剂量虾青素保护组分别更换含0.2、2、20 μg/L虾青素的培养基,于37℃、5％ CO2培养24h后,正常对照组更换新鲜培养基,辛硫磷氧化损伤组和各剂量虾青素保护组分别更换含10 μg/L辛硫磷的培养基,于37℃、5％ CO2培养24h.采用噻唑兰(MTT)比色法检测细胞存活率;采用流式细胞术检测细胞凋亡率;测定细胞超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活力和丙二醛(MDA)含量.结果 与对照组比较,辛硫磷染毒组和虾青素保护组大鼠皮肤成纤维细胞存活率和SOD、CAT活力下降,凋亡率和MDA含量升高.与辛硫磷染毒组比较,虾青素保护组大鼠皮肤成纤维细胞存活率和SOD、CAT活力较高,凋亡率和MDA含量下降;且随着虾青素剂量的升高,辛硫磷染毒大鼠皮肤成纤维细胞存活率和SOD、CAT活力呈上升趋势,凋亡率和MDA含量呈下降趋势.结论 虾青素对辛硫磷所致的大鼠皮肤成纤维细胞氧化损伤及凋亡具有明显的拮抗作用.     

母鼠慢性不可预见性应激后对子代大鼠海马脑源性神经营养因子表达的影响

【目的】探讨母鼠接受慢性不可预见性应激(chronic unpredictable stress,CUS)后短期内受孕对1月龄子代大鼠大脑海马中脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的影响。【方法】SD系成年雌性大鼠随机分为正常对照母鼠组(8只)和CUS母鼠组(12只)。采用11种刺激方法对CUS母鼠组进行21 d慢性不可预见性应激。于应激前、后,两组母鼠进行开场试验及蔗糖水消耗试验,分析CUS对母鼠自主行为的影响。用免疫组织化学染色和实时聚合酶链反应(Realtime Polymerase Chain Reaction,RT-PCR)法检测1周内受孕的CUS母鼠组所得子代大鼠(雌雄各30只)1月龄时海马中BDNF的表达情况,并与同期受孕的正常对照母鼠组所产子代大鼠进行同性别间的比较。【结果】CUS母鼠组应激后开场试验的总路程、周边路程、中央路程和蔗糖水消耗试验的蔗糖水消耗量明显少于应激前及正常对照母鼠组。子代大鼠海马中BDNF免疫反应阳性细胞的相对灰度值在正常雌性子代组为42.4±6.9,CUS雌性子代组为36.1±8.5(P0.05);在正常雄性子代组为43.7±6.4,CUS雄性子代组为39.6±8.4(P0.05)。子代大鼠海马中BDNF mRNA的表达量在正常雌性子代组为6.65±0.26,CUS雌性子代组为4.55±0.37(P0.05);在正常雄性子代组为6.77±0.20,CUS雄性子代组为4.75±0.30(P0.05)。【结论】母鼠接受慢性不可预见性应激后短期内受孕,会使子代大鼠海马中BDNF mRNA转录水平显著下降,而且这种改变与BDNF阳性细胞在海马中表达减少一致。     

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.