实验性矽肺肺泡巨噬细胞IGF—1表达水平研究

为观察胰岛素样生长因子－１（ＩＧＦ－１）的致纤维化作用,采用免疫组化技术观察了染尘后水同时期兔肺组织ＩＧＦ－１表达水平和支气管肺泡灌洗术（ＢＡＬ）对肺纤维化的影响。结果表明,染尘后１８０天组动物肺组织ＩＧＦ－１表达强度显著高于染尘后９０天组动物（Ｐ〈０．０１）,灌洗组动物肺组织ＩＧＦ－１表达强度及肺纤维化程度明显轻于未灌洗组动物。提示ＩＧＦ－１在矽肺纤维化形成和维持过程中发挥着重要作用。     

汉防己甲素抑制矽肺胶原mRNA表达的研究

在制备Ｐｒｏα１（Ｉ），Ｐｒｏα１（ＩＩＩ）胶原ｃＤＮＡ探针的基础上，采用斑点及原位分子杂交技术，观察汉防己甲素对矽组织中Ｉ，ＩＩＩ型胶原基因的ｍＲＮＡ的影响。结果表明染尘２，４个月的矽肺组织中Ｉ，ＩＩＩ型胶原ｍＲＮＡ的含量比正常肺组织明显增加（Ｐ＜０．０５），经汉防己甲素治疗后增高的Ｉ，ＩＩＩ型ｍＲＮＡ含量显著减少（Ｐ＜０．０５）。原位杂交显示，正常肺组织杂交颗粒主要分布于肺泡间隔的成纤维细胞中     

ＨＯ １、ＮＦ κＢ在矽肺纤维化中作用机制的实验研究

摘要：目的　观察血红素加氧酶 １ （ＨＯ １）及核转录因子ｋａｐｐａＢ （ＮＦ κＢ）在大鼠矽肺纤维化中的作用机
制及相互关系。方法　实验动物采用Ｗｉｓｔａｒ大鼠６０只,体重１８０～２２０ｇ,雌雄不拘,适应性饲养１周后,
随机分为４ 组, 分别为对照组（Ａ 组） 和染尘模型组（Ｂ 组）、染尘＋ ＨＯ １ 抑制剂组（Ｃ 组）、染尘＋
ＨＯ １诱导剂组（Ｄ 组）,每组１５只。采用气管暴露法滴注二氧化硅悬液制造大鼠矽肺模型。建模２８ｄ后
ＨＥ 染色观察各组大鼠肺组织病理结构,采用Ｗｅｓｔｅｒｎｂｌｏｔ法检测各组肺组织ＨＯ １ 和ＮＦ κＢ 蛋白含量,
采用荧光定量ＰＣＲ 法检测各组肺组织ＨＯ １ 和ＮＦ κＢ ｍＲＮＡ 的表达。结果　Ｗｅｓｔｅｒｎｂｌｏｔ检测结果显示
ＨＯ １、ＮＦ κＢ蛋白含量,对照组明显低于其他各组（犘＜０．０５）,Ｃ 组较Ｂ 组明显降低,而Ｄ 组较Ｂ 组表
达量明显升高（犘＜０．０５）。ＲＴ ＰＣＲ 检测各组ＨＯ １ ｍＲＮＡ 相对表达量分别为２．２５±０．３８、１．８１±０．７４、
７．７５±０．５６,Ｃ 组较Ｂ组表达明显降低,而Ｄ 组较Ｂ组表达显著升高（犘＜０．０５）;ＮＦ κＢｍＲＮＡ 相对表达
分别为３．０６±０．４２、６．１５±０．３７、１．３９±０．１４,Ｃ 组较Ｂ 组表达明显升高,而Ｄ 组较Ｂ 组表达显著降低
（犘＜０．０５）。结论　ＨＯ １、ＮＦ κＢ共同参与了大鼠矽肺纤维化的形成过程,通过对其干预可以改变大鼠矽
肺纤维化的程度,可为矽肺纤维化的诊断与治疗提供新途径。
关键词：血红素加氧酶 １;核转录因子 κＢ;矽肺纤维化;大鼠;锌原卟啉;钴原卟啉
中图分类号：Ｒ１３５．２　　文献标识码：Ａ　　文章编号：１００９ ６６３９ （２０１４）０５ ０４９０ ０５     

克矽平对矽肺大鼠Ⅰ、Ⅲ型胶原mRNA水平的影响

克矽平（Ｐｏｌｙｖｉｎｙｌｐｙｒｉｄｉｎｅ－Ｎ－ｏｘｉｄｅ，ＰＶＮＯ）是一种较为有效的抗矽肺药物。作者采用编码人Ⅰ、Ⅲ型胶原α１（Ⅰ）及α１（Ⅲ）链的ｃＤＮＡ探针，使用ｃＤＮＡ－ｍＲＮＡ斑点杂交技术，观察了染尘２个月、４个月及经克矽平治疗１、３个月的矽肺大鼠肺组织中Ⅰ、Ⅲ型胶原ｍＲＮＡ水平的改变情况。实验结果表明：大鼠染尘后２、４个月，肺组织中Ⅰ、Ⅲ型胶原ｍＲＮＡ水平较正常鼠肺组织有明显上升（Ｐ＜０．０５），经克矽平治疗后，Ⅰ、Ⅲ型胶原的ｍＲＮＡ水平显著下降。提示：克矽平对矽肺进程中胶原基因表达的增强有抑制作用。     

矽肺动物模型全肺灌洗治疗的病理观察

通过对动物模型实验治疗的病理观察，评价全肺大容量灌洗治疗矽肺的效果，并优选灌洗液。对４０只家兔和１０只幼猪经ＳｉＯ２染尘处理后，各随机分为药物组、盐水组和对照组。４～５周后施行全肺大容量灌洗。治疗后３～５个月处死各组动物，进行病理双盲检查。经统计学秩和检验，兔与猪各组肺矽结节纤维化级别分布的差异有非常显著意义（Ｐ＜０．００５）。经卡方检验，各灌洗组的纤维化程度与对照组相比，差异亦有非常显著意义（Ｐ＜０．０１）。灌洗液中药与盐水比，Ｐ＜０．０５；盐水与西药比，Ｐ＜０．０５。兔和猪矽肺各灌洗组的效果明显优于对照组。灌洗液中药优于盐水，盐水又优于西药     

支气管肺泡灌洗术排尘治疗矽肺的实验研究

通过观察染尘后不同时间矽肺大鼠支气管肺泡灌洗液（ＢＡＬＦ）中ＳｉＯ２含量、细胞总数、ＬＤＨ活性．蛋白和脂质过氧化物（ＬＰＯ）含量，结合矽肺病理变化情况，对支气管肺泡灌洗术（ＢＡＬ）治疗矽肺的可能性及有关机制进行初步探讨。实验结果表明：当染尘后不同时期ＢＡＬＦ中细胞总数、ＬＤＨ活性、总蛋白及ＬＰＯ含量均高于相应对照组，且差别有显著或非常显著意义（Ｐ＜０．０５或Ｐ＜０．０１）。随着染尘时间延长，ＢＡＬＦ中ＬＤＨ含量、细胞总数、ＬＤＨ活性和总蛋白含量呈下降趋势，而矽肺病变则逐渐加剧。提示：ＢＡＬ可以通过排出肺内部分粉尘、细胞和非细胞成份，对减少肺内纤维化机会，延缓矽肺病变的发生发展将有积极作用。且以早期或急性矽肺施行ＢＡＬ为宜。     

尘源性炎症反应与矽肺纤维化的关系

目的研究不同剂量石英粉尘所致的肺内炎症反应和纤维化病变间可能的联系。方法用不同剂量的石英粉尘染尘后,对１天组和４周组大鼠分别测定其支气管肺泡灌洗液（ＢＡＬＦ）中的细胞总数和分类计数,４周组大鼠还测定了ＢＡＬＦ细胞中羟脯氨酸量（ＨＯＰ）、血清铜蓝蛋白含量（ＣＰ）和全肺胶原蛋白量,并观察肺组织的病理变化。结果随着染尘剂量增加,１天组大鼠的细胞总数和中性粒细胞数增多,４周组大鼠的细胞总数和各分类计数增多,ＨＯＰ、ＣＰ和全肺胶原蛋白量增加;４周组大鼠的炎症和纤维化各指标间有良好的相关性。结论石英所致的肺内炎症反应可能与矽肺纤维化发生发展有关。     

大鼠矽肺气管肺泡灌洗液和肺组织磷脂谱的研究

本文报告了大姒矽肺支气管肺泡灌洗洗液和肺组织磷脂谱间变化的关系。实验分为正常对照组和石英组，在染尘后１５、４５、９０、１８０和２７０天分比剖检，测定其灌洗液和肺组织中总磷脂、ＤＰＰＣ、ＰＧ、ＰＥ含量。结果表明在实验期间石英组灌洗液和肺组织中总磷脂、ＤＰＰＣ、ＰＧ和ＰＥ含量升高趋势，且早期变化明显，但二者并不是呈简单的对应关系。     

延胡索酸二甲酯对大鼠醌还原酶和谷胱甘肽—S—转移酶的诱导作用

目的　探讨延胡索酸二甲酯（ＤＭＦ） 对大鼠主要脏器醌还原酶和谷胱甘肽Ｓ转移酶的诱导作用和意义。方法　雄性Ｗｉｓｔａｒ 大鼠饮食中补充０ ．２ ％ ＤＭＦ,于６ 、２４ 、７２ 小时、１ 和２ 周后取血并处死动物,用酶动力学法测定大鼠腺胃、肝、肺、肾和心脏中的醌还原酶（ＱＲ） 和谷胱甘肽Ｓ转移酶（ＧＳＴｓ） 活性,并按此法测定血清ＱＲ、ＧＰＴ和乳酸脱氢酶含量。结果　服用ＤＭＦ２４ 、７２ 小时、１ 和２ 周后可观察到腺胃、肝、肺、肾脏中ＱＲ 和ＧＳＴｓ 活性显著增高（ Ｐ＜ ０ ．０００ １ 或Ｐ＜ ０ ．０１） ,同时血清ＱＲ 活性也显著增高（ Ｐ＜ ０ ．０１ ,或Ｐ＜ ０ ．０００ １） 。ＤＭＦ对血清ＧＰＴ 和乳酸脱氢酶的活性则无影响。结论　ＤＭＦ对大鼠腺胃、肝、肺、肾和血清中的ＱＲ 和ＧＳＴｓ 活性具有诱导作用,ＤＭＦ有望成为人类抗氧化损伤的保护剂和解毒剂。     

矽肺相关蛋白的纯化,鉴定及其促成纤维细胞增殖作用

目的分离、鉴定与矽肺发生、发展过程相关的几种蛋白质,并测定其促成纤维细胞增殖的活性。方法采用高压液相色谱技术包括凝胶过滤柱层析、离子交换柱层析、反相Ｃ４高压液相色谱柱层析,分别对矽肺大鼠肺泡灌洗液（ＢＡＬＦ）、肺泡巨噬细胞冻融物（ＡＭＥ）及其条件培养液（ＡＭＣＭ）进行分离纯化,并通过Ｎ末端氨基酸序列的测定来鉴定这些蛋白质。结果（１）染尘２１天后,矽肺大鼠ＢＡＬＦ中白蛋白含量明显升高;（２）从ＢＡＬＦ、ＡＭＥ和ＡＭＣＭ中除纯化到相对分子质量为１５４００的溶菌酶外（其刺激成纤维细胞增殖的活性为１４０％）,还纯化到一种新的具有明显促成纤维细胞增殖的细胞因子（Ｆｉｂｒｏｂｌａｓｔｇｒｏｗｔｈｐｒｏｍｏｔｉｎｇｆａｃｔｏｒ,ＦＧＰＦ）,其最适作用浓度为２．０～６．０μｇ／ｍｌ。结论巨噬细胞分泌的ＦＧＰＦ和溶菌酶在矽肺纤维化过程中可能有重要作用。     

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.