1-溴丙烷神经毒性作用机制及生物标志研究进展

1-溴丙烷因其特有的化学性质成为可对臭氧层造成破坏的一类清洗剂的理想替代产品,广泛应用于精密仪器清洗等生产领域。1-溴丙烷具有神经毒性、生殖毒性和肝毒性,其中以神经毒性最为显著。本文从1-溴丙烷主要代谢酶、蛋白质组学技术和神经元损伤等几方面,分析了1-溴丙烷对神经系统毒性作用的可能机制及典型的生物标志。     

1-溴丙烷的神经毒性及作用机制研究进展

溴丙烷是臭氧层破坏物——氟利昂类物质的替代物,由于其固有的优点而得到广泛的使用。目前的研究表明,溴丙烷对人和动物具有潜在的神经毒性。本文就溴丙烷的神经毒性及其作用机制研究进展作一简要综述,并进一步探讨可行的防治方法。     

1-溴丙烷对两种雄性大鼠生殖毒性的研究

目的研究1-溴丙烷对两种雄性大鼠的生殖毒性。方法将18只Fischer344大鼠和18只Wistar大鼠分别随机分为两组,一组给予新鲜空气,一组给予1000ppm1-溴丙烷,每天8h,连续暴露4周。在显微镜下对附睾的精子活动率和形态进行评价;睾丸等生殖器官进行了病理学评价。结果1-溴丙烷的暴露可引起大鼠的体重及生殖器官重量的下降;附睾的精子数减少、活动率下降、形态异常的精子增多;睾丸病理切片观察到曲精小管的精子释放延迟以及附睾的病理变化。结论1-溴丙烷暴露对两种雄性大鼠的生殖系统产生毒性影响,提示1-溴丙烷也可能对男性工人生殖系统产生不良影响。     

1-溴丙烷吸入暴露对雄性大鼠生殖系统的影响

目的研究1-溴丙烷亚急性暴露对雄性大鼠的生殖毒性.方法将48只雄性大鼠分为对照组、1-溴丙烷1 000、2000、4000 mg/m3暴露组.暴露组给予7 d,每天8 h的吸入暴露.结果1-溴丙烷高浓度暴露组大鼠的体重、前列腺和精囊质量显著下降,附睾精子运动率降低,形态异常精子增多.血浆肌酸激酶活力和肌型肌酸激酶含量降低.睾丸病理切片观察到曲细精管的精子释放延迟.结论1-溴丙烷亚急性暴露对雄性大鼠的生殖系统产生毒性影响,附睾精子运动率的下降是本次实验的最敏感指标.     

4例疑似1-溴丙烷中毒病例临床分析

收集4例疑似1-溴丙烷中毒患者资料,对1-溴丙烷接触情况、发病过程、临床表现和神经-肌电图变化以及治疗经过进行分析。本组资料中3例以感觉性共济失调表现起病,神经-肌电图均显示不同程度和范围的运动和/或感觉神经的轴突变性和/或脱髓鞘变性。提示1-溴丙烷中毒可能侵犯脊髓中枢神经及远端末梢神经,表现为以感觉性共济失调为主的多发性周围神经病或脊髓病变。     

溴丙烷两种同分异构体对雄性大鼠生殖系统的影响

目的了解溴丙烷两种同分异构体对雄性大鼠的生殖毒性和初步的毒性机制。方法将18只SPF级SD大鼠随机分为对照组、1-溴丙烷组(1g/kg)和2-溴丙烷组(1g/kg),连续腹腔注射1周。对附睾的精子数量和形态进行评价;HE和PAS染色评价睾丸的病理变化;运用TUNEL染色法和caspase-3活性的免疫组化法评价睾丸的细胞凋亡损伤;利用化学比色法对谷胱甘肽(GSH)、丙二醛(MDA)和超氧化物歧化酶(SOD)等氧化应激指标进行测量。结果溴丙烷导致睾丸重量下降、精子数量减少和精子形态异常比例增加。与对照组比较,1-溴丙烷显著增加大鼠睾丸谷胱甘肽还原酶(GR)活性(7.42±2.98vs.4.25±1.18)、附睾的MDA含量(0.49±0.20vs.0.39±0.08)和SOD活性(91.87±3.93vs.80.59±9.92)(均P0.05);2-溴丙烷显著升高睾丸和附睾的MDA含量(0.42±0.07vs.0.24±0.11;0.48±0.08vs.0.39±0.08),降低GSH含量(6.35±1.86vs.10.89±3.69),以及附睾谷胱甘肽转移酶(GST)(53.21±9.60vs.61.98±10.41)及GR活性(2.48±1.21vs.7.75±8.56)(均P0.05)。1-溴丙烷的病理切片除观察到睾丸生精小管的精子释放延迟外,未见其他病理变化,而2-溴丙烷的暴露使生精小管出现萎缩和空泡,生殖细胞发生减少、坏死。伴随着2-溴丙烷引起的睾丸病理变化,TUNEL标记结果显示每小管睾丸凋亡细胞数、凋亡百分比和凋亡指数明显高于对照组(17.72±4.59vs.5.92±1.05,P0.05;0.34±0.14vs.0.10±0.02,P0.05;6.64±3.40vs.0.59±0.20,P0.01),与1-溴丙烷组相比,凋亡百分比(0.34±0.14vs.0.12±0.03)和凋亡指数(6.64±3.40vs.0.76±0.21)明显升高(P0.05)。2-溴丙烷暴露使caspase-3活性增强,与对照组和1-溴丙烷组相比,平均每生精小管的阳性细胞数和caspase-3阳性百分比有明显的升高(均P0.01)。结论溴丙烷的两种同分异构体对雄性大鼠有一定的毒性,两种同分异构体可能具有不同的毒性机制,2-溴丙烷的毒性可能高于1-溴丙烷。     

1-溴丙烷对两种雄性大鼠肝脏毒性的研究

目的研究1-溴丙烷对两种雄性大鼠的肝脏毒性及谷胱甘肽S-转移酶(GST)在肝脏解毒代谢中的作用。方法将18只Fischer344大鼠和18只Wistar大鼠分别随机分为两组,一组给予新鲜空气,一组给予1000ppm1-溴丙烷,每天8h,连续暴露4周。通过血浆的生化指标和病理切片对肝脏的功能和形态进行了评价。利用化学比色法和实时定量PCR法对肝脏中的GST的活力和基因表达水平进行测量。结果1-溴丙烷暴露可引起两种大鼠体重的下降及肝脏重量的上升;病理发现肝脏中央静脉周围的肝细胞出现空泡样改变,血浆中CK、ALT和TBIL和DBIL等指标上升明显;两种大鼠肝脏细胞胞浆的GST活力增强,Fischer344大鼠微粒体GST的活力也增强;肝脏组织的GSTmRNA表达水平升高。结论1-溴丙烷暴露对两种雄性大鼠具有肝脏毒性,GST在1-溴丙烷的肝脏解毒代谢中可能起到较重要作用。     

1-溴丙烷职业接触限值研究进展

1-溴丙烷是消耗臭氧层的化学物—氟利昂类物质的替代物,随着近年在工业上的广泛应用,不断出现职业中毒的个案报道。本文就1-溴丙烷的毒性以及国外对其职业接触限值的研究进展作一简要综述,为今后国内制定1-溴丙烷的职业接触限值提供参考。     

1-溴丙烷暴露生物标志研究进展

1-溴丙烷作为氟氯烃类化合物的替代物,其使用和生产量都在逐年增加。近几年,学者开展了多项职业流行病学研究,探讨1-溴丙烷暴露的有效生物标志。拟通过文献综述,对1-溴丙烷可能的暴露标志进行比较分析。     

二溴氯丙烷中毒一例

二溴氯丙烷 ,化学名 1,2 二溴 3氯丙烷 ,由氯丙烯、溴素反应而成 ,对线虫有良好的防治效果。山东省从 2 0世纪 70年代中期到 80年代初开始生产和广泛使用二溴氯丙烷 ,同时也对其毒性进行了深入细致的研究[1 ] 。我们将近期收治的 1例二溴氯丙烷急性中毒病例加以总结分析 ,介绍如下。患者男 ,4 0岁 ,农民 ,因“进食二溴氯丙烷处理过的花生后感恶心、乏力、右上腹痛 3d”就诊 ,门诊以“二溴氯丙烷中毒”收入院。患者 3d前进食由农药二溴氯丙烷处理过的花生后不久即出现恶心、乏力、上腹部不适、右上腹痛 ,1d后背部出现片状红斑 ,曾到当地医院…     

The Effects of α-Tocopherol on Bone: A Double-Edged Sword?

Recent studies have found conflicting evidence on the role of α-tocopherol (αTF) on bone health. This nonsystematic review aimed to summarize the current evidence on the effects of αTF on bone health from cell culture, animal, and human studies in order to clarify the role of αTF on bone health. Our review found that αTF exerted beneficial, harmful or null effects on bone formation cells. Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis. However, high-dose αTF was possibly detrimental to bone in normal animals. Human studies mostly demonstrated a positive relationship between αTF, as assessed using high performance liquid chromatography and/or dietary questionnaire, and bone health, as assessed using bone mineral density and/or fracture incidence. Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone, the blocking of the entry of other Vitamin E isomers beneficial to bone, and the role of αTF as a prooxidant. However, these adverse effects have not been shown in human studies. In conclusion, αTF may have a dual role in bone health, whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone.     

Risk factor modelling of the spatio-temporal patterns of highly pathogenic avian influenza (HPAIV) H5N1: a review

Highly pathogenic avian influenza virus (HPAIV) H5N1 continues to impact on smallholder livelihoods, to constrain development of the poultry production sector, and to cause occasional human fatalities. HPAI H5N1 outbreaks have occurred in a variety of ecological systems with economic, agricultural and environmental differences. This review aimed to identify common risk factors amongst spatial modelling studies conducted in these different agro-ecological systems, and to identify gaps in our understanding of the disease's spatial epidemiology. Three types of variables with similar statistical association with HPAI H5N1 presence across studies and regions were identified: domestic waterfowl, several anthropogenic variables (human population density, distance to roads) and indicators of water presence. Variables on socio-economic conditions, poultry trade, wild bird distribution and movements were comparatively rarely considered. Few studies have analysed the HPAI H5N1 distribution in countries such as Egypt and Indonesia, where HPAIV H5N1 continues to circulate extensively.     

Investigation of toxicity through human cases and animal experiments--study of bromopropanes

In 1995, workers in a Korean electronic factory exhibited oligospermia or amenorrhea. We investigated the toxicity of 2-bromopropane used as an alternative to chlorofluorocarbons in the factory in animal experiments, and clarified that exposure to 2-bromopropane depletes spermatogenic cells in male rats and oocytes in female rats. Subsequently, we investigated the neurotoxicity of 2-bromopropane on the basis of the reported neuropathy in the Korean workers exposed to 2-bromopropane. For comparison, we employed 1-bromopropane, which is now used as a new alternative to chlorofluorocarbons. The results showed that 1-bromopropane is more neurotoxic than 2-bromopropane, causing harm to reproductive organs by inhibiting spermiation in the testis and impairing follicular development in the ovary. Shortly after the initial investigation of 1-bromopropane in animals, human cases were reported in the United States. Neurologic abnormalities in Chinese workers exposed to 1-bromopropane were also reported, such as the elongation of distal latency and lowered sense of vibration in the lower limbs. Thus, these serial studies revealed that 1-bromopropane is neurotoxic, but its dose-response relationship in humans remains unknown. In the investigation of 2-bromopropane toxicity, initial animal studies were designed on the basis of human studies, while in research on 1-bromopropane, animal studies preceded human studies and contributed to the prediction of toxicity in humans. However, the use of animal model is limited in its ability to predict the toxicity of chemicals introduced depending on species differences. Further studies should focus more on the differences and commonality between animals and humans in response to toxic agents.     

Anti-major histocompatibility complex antibody responses in macaques via intradermal DNA immunizations

In simian immunodeficiency virus (SIV) models, immunization of macaques with uninfected human cells or human major histocompatibility complex (MHC) proteins can induce xenogeneic immune responses which can protect the animals from subsequent SIV challenges. These studies suggest that the induction of anti-MHC immune responses can be a viable vaccine strategy against human immunodeficiency virus type 1 (HIV-1). We have previously shown in mouse studies that DNA immunization with class I and class II MHC-encoding plasmids can elicit both xenogeneic and allogeneic antibody responses against conformationally intact MHC molecules (Vaccine 17 (1999) 2479-92). Here we take these observations one step closer to human applications and report that intradermal needle immunizations of non-human primates with plasmid DNA encoding human MHC alleles can safely elicit xenogeneic anti-MHC antibody responses. Moreover, injecting macaques with DNA encoding a specific macaque allogeneic MHC induced anti-allogeneic MHC antibodies production. These studies show that DNA immunization with MHC-encoding vectors can indeed be used to induce specific anti-human xenogeneic, as well as anti-macaque allogeneic MHC immunity in non-human primates. This strategy could thus be used to mobilize anti-MHC antibody response which may be useful as part of an anti-HIV-1 vaccination approach.     

Cinnamon: not suitable for the treatment of diabetes mellitus

OBJECTIVE: To identify published studies evaluating the effects of cinnamon on glycaemic control. DESIGN: Literature search. METHOD: The Medline database was searched using all possible combinations of the words and medical subject headings (MeSH) 'cinnamon', 'diabetes mellitus', 'HbA1C' and 'glucose'. All human or animal studies in which cinnamon was administered as intervention were included. RESULTS: Several animal studies and 5 randomized placebo-controlled trials in humans were found. Most of the animal studies described beneficial effects of cinnamon on glycaemic control. One placebo-controlled trial in patients with type 2 diabetes found that cinnamon intake was associated with favourable effects on fasting plasma glucose. None of the studies reported an improvement in HbA1C. A study in patients with type 1 diabetes found that cinnamon had no effect. CONCLUSION: Based on the currently available evidence, cinnamon should not be recommended for the improvement ofglycaemic control.     

Prospective study of avian influenza transmission to humans in egypt

Background  

The highly pathogenic avian influenza (HPAI) H5N1 virus remains a public health threat and continues to cause outbreaks among poultry as well as human infections. Since its appearance, the virus has spread to numerous geographic areas and is now considered endemic in Egypt and other countries. Most studies on human H5N1 cases were conducted to investigate outbreak situations and were not designed to address fundamental questions about the epidemiology of human infection with H5N1 viruses. Our objective for this study is to answer these questions by estimating the prevalence and incidence rates of human cases and determine associated risk and protective factors in areas where H5N1 viruses are endemic.     

Testing vitamin B as a home remedy against mosquitoes

Vitamin B is often recommended in the popular media as a systemic repellent against mosquitoes. This information is especially prevalent on the Web. The results of a small number of published studies suggested that vitamin B complex supplements are not effective as repellents, but these studies were limited by the use of very few human subjects and only 1 species of mosquito, Aedes aegypti. We extended this work with the use of larger samples of human subjects and with Anopheles stephensi as the test organism. We tested whether ingestion of vitamin B supplements under various regimens affected the attractiveness of volatile skin components transferred to glass vials. Although there was substantial and consistent individual variation in attractiveness, we found no effect of vitamin B supplementation.     

Workgroup report: Biomonitoring study design, interpretation, and communication--lessons learned and path forward

Human biomonitoring investigations have provided data on a wide array of chemicals in blood and urine and in other tissues and fluids such as hair and human milk. These data have prompted questions such as a) What is the relationship between levels of environmental chemicals in humans and external exposures? b) What is the baseline or "background" level against which individual levels should be compared? and c) How can internal levels be used to draw conclusions about individual and/or population health? An interdisciplinary panel was convened for a 1-day workshop in November 2004 with the charge of focusing on three specific aspects of biomonitoring: characteristics of scientifically robust biomonitoring studies, interpretation of human biomonitoring data for potential risks to human health, and communication of results, uncertainties, and limitations of biomonitoring studies. In this report we describe the recommendations of the panel.     

The German view: effects of nitrogen dioxide on human health--derivation of health-related short-term and long-term values

The presented overview concerning health relevant effects caused by nitrogen dioxide (NO2) resumes the current state of results from animal experiments and human studies (epidemiology and short-term chambers studies). NO2 concentrations applied in animal experiments were mostly considerably higher than in ambient air. Therefore, short- and long-term limit values were derived from human data. Experimental studies conducted with humans demonstrate effects after short-term exposure to concentrations at or above 400 microg NO2/m3. Effects on patients with light asthma could not be observed after short-term exposure to concentrations below 200 microg/m3. On basis of epidemiological long-term studies a threshold below which no effect on human health is expected could not be specified. Two short-term limit values have been proposed to protect public health: a 1-h value of 100 microg/m3 and a 24-h mean value of 50 microg/m3. Due to the limitations of epidemiological studies to disentangle effects of single pollutants, a long-term limit value cannot be easily derived. However, applying the precautionary principle, it is desirable to adopt an annual mean of 20 microg NO2/m3 as a long-term mean standard to protect public health.     

Antigenic relationships between type a influenza viruses of human, porcine, equine, and avian origin

This paper summarizes the available information on the relationship of two envelope antigens (haemagglutinin and neuraminidase) of influenzaviruses isolated from different hosts. The relationship of the haemagglutinin antigens was based on the results of haemagglutination inhibition tests with postinfection sera and that of the neuraminidase antigens on the results of neuraminidase inhibition and gel precipitation tests with hyperimmune and monospecific sera. On the basis of the antigenic specificity of the haemagglutinin, the influenzaviruses of human origin are divided into several subtypes (H0, H1, H2); viruses of equine origin could be divided into two subtypes (Heq1, Heq2). Porcine influenza strains are regarded as belonging to a single subtype, all of them being related to the prototype swine influenzavirus A (swine/Iowa/15/30). Within the avian influenzaviruses, 6 antigenic subtypes were described in earlier studies. Antigenic relationships between the haemagglutinin of strains from different hosts were infrequent but were demonstrated and confirmed between human A/Hong Kong/68 and equine viruses and between A/Hong Kong/68 and swine/Taiwan/69. The swine/Taiwan/69 virus also shared the related neuraminidase with A/Hong Kong/68 virus, and represents the only isolation from nonhuman sources of an influenzavirus identical with a human pandemic strain. The studies on the antigenic specificity of the neuraminidases demonstrated 8 antigenic varieties of neuraminidase among avian influenzaviruses and also that the neuraminidase grouping did not correspond with the antigenic grouping with regard to haemagglutinin. The relationships between human and nonhuman influenzaviruses are emphasized because of their significance to studies on the origin of influenza pandemics in man.