微囊藻毒素MC-LR对肝细胞毒性机理研究

目的：研究微囊藻毒类MC－LR的肝脏毒性机理。方法：采用四唑盐比色试验和流式细胞术检测微囊藻毒素MC－LR对原代培养的肝细胞和Hela细胞生长、细胞周期和凋亡的影响。结果：微囊藻毒素在极低浓度时表现为抑制细胞生长或细胞毒作用，高逍度时可促进细胞生长。MC－LR导致肝细胞发生典型的凋亡样变化和细胞周期G2／M期阻滞。提示微囊藻毒素可能具有影响肝细胞周期的作用，可诱导肝细胞增殖，同时又能诱导肝细胞凋亡。流式细胞术结果表明微囊藻毒素对Hela细胞周期有类似影响趋势，但其程度远不如对肝细胞的影响明显。结论：微囊藻毒素对肝细胞的特异性作用可能是其肝脏毒性的机理之一。     

微囊藻毒素-LR毒性的分子机制研究进展

本文回顾了微囊藻毒素-LR细胞毒性的分子机制研究进展,介绍了微囊藻毒素-LR通过抑制PP2A 活性调节细胞生命活动的主要毒性机制,简述了其与DNA 损伤、细胞骨架破坏的关系,印证了微囊藻毒素-LR的强细胞毒性.开展微囊藻毒素-LR毒性的研究对人类健康具有十分重要的意义.     

微囊藻毒素诱导细胞凋亡研究进展

由于工农业排污和生活排污日趋增多，水体污染日益严重。引发藻类水华频繁爆发，已成为全球广泛关注的环境问题。其中以铜绿微囊藻（Microcystin aeruginosa）、水花鱼腥藻（Anabaena flos-aquae）、颤藻（Oscilllation aeruginosa）等产生的有毒成分微囊藻毒素（microcystin．MC）对人体健康危害最为严重。近年来，对微囊藻毒素的毒性研究已受到关注并取得了初步成果，但具体的毒性机制尚未明确。研究认为，细胞凋亡是毒索发挥其毒性作用的关键所在，因而微囊藻毒素致细胞凋亡的研究是热点之一。本就相关研究进展作一综述。     

太湖微囊藻毒素对细胞染色体及DNA损伤效应

目的研究太湖蓝藻水华中提取的微囊藻毒素的遗传毒性，探讨其对人类健康的潜在危害。方法应用小鼠骨髓嗜多染红细胞微核试验和单细胞凝胶电泳技术观察太湖蓝藻水华中微囊藻毒素引起的细胞染色体及DNA损伤效应。结果太湖蓝藻水华中提取的微囊藻毒素可明显增强小鼠骨髓嗜多染红细胞的微核率，并呈一定的剂量-反应关系；单细胞凝胶电泳技术显示可诱导中国仓鼠(V79)细胞DNA单链断裂，DNA断裂分级及细胞损伤率明显高于对照组。结论太湖蓝藻水华中提取的微囊藻毒素具有明显的遗传毒性，对人类健康存在潜在的远期危害。     

微囊藻毒素的细胞毒性研究进展

微囊藻毒素是微囊藻等淡水藻类产生的一类具有生物活性的环状7肽物质,它能抑制蛋白磷酸酶1和蛋白磷酸酶2A的活性,打破细胞内蛋白磷酸化/脱磷酸化的平衡,引起细胞损伤甚至坏死,对多种细胞产生毒性作用。本文就微囊藻毒素对不同细胞的毒性作用和机制及相关研究进行综述。     

微囊藻毒素和水体有机污染物联合诱导SHE细胞转化及相关癌基因的变化

应用ＳＨＥ细胞体外二阶段转化实验和免疫组化方法，分析了上海淀山湖水体有机污染物和微囊藻毒素（ＭＣＹＳＴ）联合诱导ＳＨＥ细胞恶性转化的作用，发现微囊藻毒素单独作用不能诱发ＳＨＥ细胞转化，但可明显促进低剂量水体有机污染物启动的细胞恶性转化。在典型的Ⅲ型转化灶细胞中ｒａｓＰ２１蛋白表达明显增强。提示：微囊藻毒素具有促癌作用，二阶段诱导的转化细胞中ｒａｓ癌基因被激活。     

微囊藻毒素和黄曲霉毒素及伏马菌素联合毒性

目的研究微囊藻毒素、黄曲霉毒素、伏马菌素对Hep G2细胞的半数抑制浓度（IC50）,探讨3种毒素的联合毒性.方法选用3种毒素各自最具代表性的异构体微囊藻毒素LR、黄曲霉毒素B1和伏马菌素B1,用水溶性四氮唑（WST-1）比色法测定3种物质对Hep G2细胞存活率的影响,计算IC50,并根据等效曲面联合毒性分析模型判断联合作用类型.结果染毒24h,微囊藻毒素LR对Hep G2细胞的IC50〉100μmol/L;黄曲霉毒素B1、伏马菌素B1及3毒素混合物的IC50分别为1.0,399.2和172.0μmol/L.根据等效曲面法求得的相互作用指数α为0.95.结论微囊藻毒素LR、黄曲霉毒素B1和伏马菌素B1对Hep G2的联合毒作用类型为相加作用.     

谷胱甘肽耗竭与微囊藻毒素-LR细胞毒性的关系初探

目的探讨谷胱甘肽耗竭与微囊藻毒素-LR(MCLR)细胞毒性的关系。方法不同剂量的MCLR作用人肝癌细胞HepG2后,采用四甲基偶氮噻唑蓝法检测细胞毒性,并用二硫硝基苯甲酸法测定细胞内还原型谷胱甘肽(GSH)的含量。结果细胞存活率随处理剂量的增加而降低,抗氧化剂N-乙酰半胱氨酸明显减轻MCLR诱导的细胞毒性。细胞内GSH含量显著降低,处理剂量与GSH水平之间呈现剂量-反应和时间-反应关系。结论谷胱甘肽耗竭可能是微囊藻毒素-LR引起细胞毒性的原因之一。     

微囊藻毒素-LR对睾丸支持细胞活性及凋亡基因表达的影响

[目的]研究微囊藻毒素-LR对睾丸支持细胞活性的影响及其对细胞凋亡相关基因表达的影响. [方法]分离纯化大鼠睾丸支持细胞,用低剂量(0～500×10-3 μg/ml)和高剂量(1～20 μg/ml)微囊藻度素-LR染毒细胞,细胞培养24 h、48 h和72 h后,用四甲基偶氮唑蓝(MTT)实验和中性红吸收(NR)实验检测微囊藻毒素-LR对支持细胞活性的影响;将纯化后的部分睾丸支持细胞接种于6孔板中,给予不同剂量的微囊藻毒素-LR (0,1,10μg/ml),于24h和48 h后提取细胞总RNA,RT-PCR方法检测细胞中凋亡相关基因P53、bax和bcl-2表达水平.[结果]低剂量(0～500×10-3 μg/ml)微囊藻毒素-LR作用于支持细胞24、48、72 h,细胞活性增强.高剂量微囊藻毒素-LR(10和20μg/ml)作用24、48 h,细胞活性显著降低.时闻效应实验结果显示随着暴露时间的延长细胞活性降低.细胞暴露于1 μg/ml微囊藻毒素-LR后与对照组细胞相比较P53和bcl-2 mRNA水平相对表达量增加,bax表达量降低.暴露予10 μg/ml微囊藻毒素-LR后P53和bax mRNA水平相对表达增加,bcl-2表达降低.[结论]低剂量的微囊藻毒素-LR对 细胞具有兴奋效应,随着剂量的增高及暴露时间的延长微囊藻毒素-LR能够明显抑制细胞活性.同时微囊藻毒素-LR可通过P53、bax和bcl-2基因的表达影响睾丸支持细胞的凋亡.     

铜绿微囊藻毒素的肝细胞毒性及活性氧生成作用

目的探讨微囊藻毒素的肝细胞毒性及其预防措施。方法利用原代培养的大鼠肝细胞，对水华提取物微囊藻毒素进行了细胞毒性和活性氧类（ＲＯＳ）生成的研究。结果在微囊藻毒素处理的肝细胞中，可以引起明显的依赖时间和剂量的乳酸脱氢酶（ＬＤＨ）释放率的升高，同时还可以引起明显的时间依赖的ＲＯＳ的升高。在去铁敏（ＤＦＯ）的作用下，可以分别使微囊藻毒素处理的肝细胞的ＬＤＨ释放率和ＲＯＳ升成率降低。结论微囊藻毒素具有明显的肝细胞毒性，其所导致的ＲＯＳ的生成很有可能是其产生的肝细胞毒性的原因之一     

Cooperation and conflict in childbirth care: representations and practices of nurses and obstetricians

In Brazil, where birthing generally occurs in hospitals and under the care of obstetricians, the incorporation of nurses is a strategy that has been used recently in an attempt to improve obstetric care. This study, conducted in two maternity hospitals in Rio de Janeiro, focuses on representations of obstetricians and nurses regarding teamwork and analyzes how the dimensions of power, cooperation/conflict, and technical autonomy are permeated by dualistic conceptions which influence the quality of health care for women during childbirth. On the one hand, the results show a consensus regarding the advantages of professional cooperation in the improvement of health care, assuming the existence of a clear definition of professional roles. At the same time, conflicts regarding therapeutic conduct during the birth process reflect the professionals' perceptions of autonomy and the influence of professional hierarchies, in which obstetric care is seen to depend on the "objective observation" of the women giving birth. The degree of conflict is differentiated according to the institutional context and related to dualistic conceptions such as objective/subjective, rational/emotional, and male/female.     

Epistemological problems in assessing cancer risks at low radiation doses

Historically, biology has not been subjected to any epistemological analysis as has been the case with mathematics and physics. Our knowledge of the effects in biological systems of various stimuli proves to be dualistic in a complementary (although not mutually exclusive) way, which bears resemblance to the knowledge of phenomena in quantum physics. The dualistic "limbs" of biological knowledge are the action of stimuli and the response of the exposed, biological system. With regard to radiogenic cancer, this corresponds to the action of the ionizations and the response of the exposed mammal to that action, respectively. The following conclusions can be drawn from the present analysis: Predictions as to radiogenic cancer seem often if not always to have neglected the response variability (variations in radiosensitivity) in individuals or among individuals in populations, i.e. the predictions have been based exclusively on radiation doses and exposure conditions. The exposed individual or population, however, must be considered an "open statistical system", i.e. a system in which predictions as to the effect of an agent are only conditionally possible. The knowledge is inverse to the size of the dose or concentration of the active agent. On epistemological grounds, we can not gain knowledge about the carcinogenic capacity of very low (non-dominant) radiation doses. Based on the same principle, we can not predict cancer risks at very low (non-dominant) radiation doses merely on the basis of models, or otherwise interpolated or extrapolated high-dose effects, observed under special exposure conditions.     

Preliminary Studies on Model Development for Rodent Toxicity and Its Interspecies Correlation with Aquatic Toxicities of Pharmaceuticals

Environmental toxicity due to pharmaceuticals has been an issue of serious concern for long time. Development of chemometric models with reliable predictive power has been considered as an effective tool for the design of new drug agents with reduced or without ecotoxic potential. Considering a higher degree of similarity in genetic homology towards drug receptor with mammals, we have used a dataset of 194 compounds with reported rodent, fish, daphnia and algae toxicity data for extrapolation of their toxicity towards humans. Allowing for rodents as the most surrogate to human physiology, attempts have also been made to develop interspecies correlation models keeping rodent toxicity as dependent variable so that any drug without reported rodent toxicity can be predicted using fish, daphnia or algae toxicity data which can be consequently extrapolated to human toxicity. The developed models have been subjected to multiple validation strategies. Acceptable results have been obtained in both cases of direct and interspecies extrapolation quantitative structure–activity relationship models.     

Patterns and trends in sediment toxicity in the San Francisco Estuary

Widespread sediment toxicity has been documented throughout the San Francisco Estuary since the mid-1980s. Studies conducted in the early 1990s as part of the Bay Protection and Toxic Cleanup Program (BPTCP), and more recently as part of the Regional Monitoring Program (RMP) have continued to find sediment toxicity in the Estuary. Results of these studies have shown a number of sediment toxic hotspots located at selected sites in the margins of the Estuary. Recent RMP monitoring has indicated that the magnitude and frequency of sediment toxicity is greater in the winter wet season than in the summer dry season, which suggests stormwater inputs are associated with sediment toxicity. Additionally, spatial trends in sediment toxicity data indicate that toxic sediments are associated with inputs from urban creeks surrounding the Estuary, and from Central Valley rivers entering the northern Estuary via the Delta. Sediment toxicity has been correlated with a number of contaminants, including selected metals, PAHs and organochlorine pesticides. While toxicity identification evaluations (TIEs) suggest that metals are the primary cause of sediment toxicity to bivalve embryos; TIEs conducted with amphipods have been inconclusive.     

Activation of lipid peroxidation in the liver mitochondria and acute toxicity of chemical compounds

The effect of toxic substances on the functional state of liver mitochondria has been studied. It has been shown, that the contact of toxic substances with mitochondria lead to the reduction of the degree of association of oxidation with phosphorylation. EDTA in concentrations necessary to inhibit lipid peroxide oxidation prevents toxic effects. Preliminary antioxidant treatment of mitochondria prevents toxic damage of membranes. A close correlation has been established between chemical compounds toxicity and the concentration of antioxidants necessary for the prevention of toxic effects, as well as between chemical compounds toxicity and cumulation of malonic dialdehyde in mitochondria membranes.     

邻苯二甲酸二丁酯生殖发育毒性研究进展

邻苯二甲酸二丁酯(DBP)广泛存在于环境中,具有一定的生殖发育毒性。该文针对DBP对妊娠期动物进行染毒所表现出的毒性,综述了DBP生殖发育毒性作用的特点、毒性作用机制以及对人群健康产生的影响,为进一步研究DBP的毒性及提高人群的预防措施提供参考。     

A view of nursing epistemology through reciprocal interdependence: towards a reflexive way of knowing

Abstract  The discipline of nursing has experienced the movement from modernism to postmodernism through expressions ranging from dualistic and polarized discourse to contradicting pluralistic positions. For the purpose of this paper, these responses are described as ways of knowing and are examined for their impact on the evolution of the nursing discipline. Reciprocal interdependence is offered as an alternate way of knowing capable of incorporating differing world views into a coherent and comprehensive systemic whole. The reflexive and potentially transformational impact of reciprocal interdependence on the advancement of nursing knowledge is reviewed through a discussion of the value of polarity, as well as the contribution of complementary and dialectical perspectives to the maintenance of interactions between the whole and its constituents.     

Statistical significance of sediment toxicity test results: threshold values derived by the detectable significance approach

A number of methods have been employed to determine the statistical significance of sediment toxicity test results. To allow consistency among comparisons, regardless of among-replicate variability, a protocol-specific approach has been used that considers protocol performance over a large number of comparisons. Ninetieth-percentile minimum significant difference (MSD) values were calculated to determine a critical threshold for statistically significant sample toxicity. Significant toxicity threshold values (as a percentage of laboratory control values) are presented for six species and nine endpoints based on data from as many as 720 stations. These threshold values are useful for interpreting sediment toxicity data from large studies and in eliminating cases where statistical significance is assigned in individual cases because among-replicate variability is small.     

Lead exposure in ironworkers

In adults, lead toxicity is most commonly caused by occupation in a lead industry. Whereas lead toxicity has been described in workers who are involved in bridge rehabilitation, as of this date there has been no systematic evaluation published regarding the conditions responsible for lead toxicity in ironworkers. This is a report of a study designed to identify risk factors for elevated blood-lead levels in ironworkers. One hundred fifty members of a 2,400-member local ironworkers union volunteered to have their blood drawn for lead and zinc protoporphyrin analysis and to complete a questionnaire regarding demographics, health, and occupation. The relationships between these variables and blood-lead level were analyzed using student's t-test, chi-square, and logistic regression. Current work on a lead job, rivet busting as the predominant job task, and cigarette smoking were all found to be significantly associated with elevated blood-lead level. Whereas cigarette smoking and current work with lead have been previously identified as risk factors for toxicity, interventions to prevent lead toxicity in ironworkers should also focus on work practices during rivet busting. Am. J. Ind. Med. 32:540–543, 1997. © 1997 Wiley-Liss, Inc.     

Occupational therapy as an academic discipline in Finland

The aim of this short report is to outline the relation between Finnish educational policy and the dualistic educational structure of Finland, to describe the consequences of this system for education in occupational therapy at university level, and to speculate on the likely development and challenges facing academic occupational therapy education in the future. The authors have been involved in the development process. Copyright © 2000 Whurr Publishers Ltd.