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Chemical Stressors (chemical + stressor)
Selected AbstractsMethylenedioxymethamphetamine (MDMA, ,Ecstasy'): a stressor on the immune systemIMMUNOLOGY, Issue 4 2004Thomas J. Connor Summary Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ,Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin (IL)-1,, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ,chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed. [source] Altered gene expression in the brain and ovaries of zebrafish (Danio Rerio) exposed to the aromatase inhibitor fadrozole: Microarray analysis and hypothesis generation,,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2009Daniel L. Villeneuve Abstract As part of a research effort examining system-wide responses of the hypothalamic-pituitary-gonadal (HPG) axis in fish to endocrine-active chemicals (EACs) with different modes of action, zebrafish (Danio rerio) were exposed to 25 or 100 ,g/L of the aromatase inhibitor fadrozole for 24, 48, or 96 h. Global transcriptional response in brain and ovarian tissue of fish exposed to 25 ,g/L of fadrozole was compared to that in control fish using a commercially available, 22,000-gene oligonucleotide microarray. Transcripts altered in brain were functionally linked to differentiation, development, DNA replication, and cell cycle. Additionally, multiple genes associated with the one-carbon pool by folate pathway (KEGG 00670) were significantly up-regulated. Transcripts altered in ovary were functionally linked to cell-cell adhesion, extracellular matrix, vasculogenesis, and development. Promoter motif analysis identified GATA-binding factor 2, Ikaros 2, alcohol dehydrogenase gene regulator 1, myoblast-determining factor, and several heat shock factors as being associated with coexpressed gene clusters that were differentially expressed following exposure to fadrozole. Based on the transcriptional changes observed, it was hypothesized that fadrozole elicits neurodegenerative stress in brain tissue and that fish cope with this stress through proliferation of radial glial cells. Additionally, it was hypothesized that changes of gene expression in the ovary of fadrozole-exposed zebrafish reflect disruption of oocyte maturation and ovulation because of impaired vitellogenesis. These hypotheses and others derived from the microarray results provide a foundation for future studies aimed at understanding responses of the HPG axis to EACs and other chemical stressors. [source] An overview of the use of quantitative structure-activity relationships for ranking and prioritizing large chemical inventories for environmental risk assessmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2003Christine L. Russom Abstract Ecological risk assessments for chemical stressors are used to establish linkages between likely exposure concentrations and adverse effects to ecological receptors. At times, it is useful to conduct screening risk assessments to assist in prioritizing or ranking chemicals on the basis of potential hazard and exposure assessment parameters. Ranking of large chemical inventories can provide evidence for focusing research and/or cleanup efforts on specific chemicals of concern. Because of financial and time constraints, data gaps exist, and the risk assessor is left with decisions on which models to use to estimate the parameter of concern. In this review, several methods are presented for using quantitative structure-activity relationships (QSARs) in conducting hazard screening or screening-level risk assessments. The ranking methods described include those related to current regulatory issues associated with chemical inventories from Canada, Europe, and the United States and an example of a screening-level risk assessment conducted on chemicals associated with a watershed in the midwest region of the United States. [source] Methodology for the evaluation of cumulative episodic exposure to chemical stressors in aquatic risk assessment,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2000Michael G. Morton Abstract An ecological risk assessment method was developed to evaluate the magnitude, duration, and episodic nature of chemical stressors on aquatic communities. The percent of an ecosystem's species at risk from a designated chemical exposure scenario is generated. In effects assessment, probabilistic extrapolation methods are used to generate estimated safe concentrations (ESCs) for an ecosystem using laboratory toxicity test results. Fate and transport modeling is employed to generate temporal stressor concentration profiles. In risk characterization, area under the curve integration is performed on predicted exposure concentration profiles to calculate a cumulative exposure concentration (CEC) for the exposure event. A correction is made to account for the allowable exposure duration to the stressor ESC. Finally, the CEC is applied to the extrapolation model (curve) of the stressor to predict percent species at risk to the episodic exposure. The method may be used for either prospective or retrospective risk assessments. The results of a retrospective risk assessment performed on the Leadenwah Creek, South Carolina, USA, estuarine community are presented as a case study. The creek experienced periodic episodes of pesticide-contaminated agricultural runoff from 1986 through 1989. Although limited biological data were available for method validation, the risk estimates compared well with the Leadenwah Creek in situ bioassay results. [source] Sequential analysis of lines of evidence,an advanced weight-of-evidence approach for ecological risk assessmentINTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 4 2006Ruth N Hull Abstract Weight-of-evidence (WOE) approaches have been used in ecological risk assessment (ERA) for many years. The approaches integrate various types of data (e.g., from chemistry, bioassay, and field studies) to make an overall conclusion of risk. However, the current practice of WOE has several important difficulties, including a lack of transparency related to how each line of evidence is weighted or integrated into the overall weight-of-evidence conclusion. Therefore, a sequential analysis of lines of evidence (SALE) approach has been developed that advances the practice of WOE. It was developed for an ERA of chemical stressors but also can be used for nonchemical stressors and is equally applicable to the aquatic and terrestrial environments. The sequential aspect of the SALE process is a significant advancement and is based on 2 primary ideas. First, risks can be ruled out with the use of certain lines of evidence, including modeled hazard quotients (HQs) and comparisons of soil, water, or sediment quality with conservative soil, water or sediment quality guidelines. Thus, the SALE process recognizes that HQs are most useful in ruling out risk rather than predicting risk to ecological populations or communities. Second, the SALE process provides several opportunities to exit the risk assessment process, not only when risks are ruled out, but also when magnitude of effect is acceptable or when little or no evidence exists that associations between stressors and effects may be causal. Thus, the SALE approach explicitly includes interaction between assessors and managers. It illustrates to risk managers how risk management can go beyond the simple derivation of risk-based concentrations of chemicals of concern to risk management goals based on ecological metrics (e.g., species diversity). It also can be used to stimulate discussion of the limitations of the ERA science, and how scientists deal with uncertainty. It should assist risk managers by allowing their decisions to be based on a sequential, flexible, and transparent process that includes direct toxicity risks, indirect risks (via changes in habitat suitability), and the spatial and temporal factors that can influence the risk assessment. [source] The joint effects of larval density and 14C-cypermethrin on the life history and population growth rate of the midge Chironomus ripariusJOURNAL OF APPLIED ECOLOGY, Issue 6 2003Helen L. Hooper Summary 1Chemical effects on organisms are typically assessed using individual-level endpoints or sometimes population growth rate (PGR), but such measurements are generally made at low population densities. In contrast most natural populations are subject to density dependence and fluctuate around the environmental carrying capacity as a result of individual competition for resources. As ecotoxicology aims to make reliable population projections of chemical impacts in the field, an understanding of how high-density or resource-limited populations respond to environmental chemicals is essential. 2Our objective was to determine the joint effects of population density and chemical stress on the life history and PGR of an important ecotoxicological indicator species, Chironomus riparius, under controlled laboratory conditions. Populations were fed the same ration but initiated at different densities and exposed to a solvent control and three concentrations of 14C-cypermethrin in a sediment,water test system for 67 days at 20 ± 1 °C. 3Density had a negative effect on all the measured life-history traits, and PGR declined with increasing density in the controls. Exposure to 14C-cypermethrin had a direct negative effect on juvenile survival, presumably within the first 24 h because the chemical rapidly dissipated from the water column. Reductions in the initial larval densities resulted in an increase in the available resources for the survivors. Subsequently, exposed populations emerged sooner and started producing offspring earlier than the controls. 14C-cypermethrin had no effect on estimated fecundity and adult body weight but interacted with density to reduce the time to first emergence and first reproduction. As a result, PGR increased with cypermethrin concentration when populations were initiated at high densities. 4Synthesis and applications. The results showed that the effects of 14C-cypermethrin were buffered at high density, so that the joint effects of density and chemical stress on PGR were less than additive. Low levels of chemical stressors may increase carrying capacity by reducing juvenile competition for resources. More and perhaps fitter adults may be produced, similar to the effects of predators and culling; however, toxicant exposure may result in survivors that are less tolerant to changing conditions. If less than additive effects are typical in the field, standard regulatory tests carried out at low density may overestimate the effects of environmental chemicals. Further studies over a wide range of chemical stressors and organisms with contrasting life histories are needed to make general recommendations. [source] Altered gene expression in the brain and liver of female fathead minnows Pimephales promelas Rafinesque exposed to fadrozoleJOURNAL OF FISH BIOLOGY, Issue 9 2008D. L. Villeneuve The fathead minnow Pimephales promelas is a small fish species widely used for ecotoxicology research and regulatory testing in North America. This study used a 2000 gene oligonucleotide microarray to evaluate the effects of the aromatase inhibitor, fadrozole, on gene expression in the liver and brain tissue of exposed females. Reproductive measures, plasma vitellogenin and gene expression data for the brain isoform of aromatase (cytP19B), vitellogenin precursors and transferrin provided evidence supporting the efficacy of the fadrozole exposure. Unsupervised analysis of the microarray results identified 20 genes in brain and 41 in liver as significantly up-regulated and seven genes in brain and around 45 in liver as significantly down-regulated. Differentially expressed genes were associated with a broad spectrum of biological functions, many with no obvious relationship to aromatase inhibition. However, in brain, fadrozole exposure elicited significant up-regulation of several genes involved in the cholesterol synthesis, suggesting it as a potentially affected pathway. Gene ontology-based analysis of expression changes in liver suggested overall down-regulation of protein biosynthesis. While real-time polymerase chain reaction analyses supported some of the microarray responses, others could not be verified. Overall, results of this study provide a foundation for developing novel hypotheses regarding the system-wide effects of fadrozole, and other chemical stressors with similar modes of action, on fish biology. [source] Transgenic mouse and cell culture models demonstrate a lack of mechanistic connection between endoplasmic reticulum stress and tau dysfunctionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010M.L. Spatara Abstract In vivo aggregation of tau protein is a hallmark of many neurodegenerative disorders, including Alzheimer's disease (AD). Recent evidence has also demonstrated activation of the unfolded protein response (UPR), a cellular response to endoplasmic reticulum (ER) stress, in AD, although the role of the UPR in disease pathogenesis is not known. Here, three model systems were used to determine whether a direct mechanistic link could be demonstrated between tau aggregation and the UPR. The first model system used was SH-SY5Y cells, a neuronal cultured cell line that endogenously expresses tau. In this system, the UPR was activated using chemical stressors, tunicamycin and thapsigargin, but no changes in tau expression levels, solubility, or phosphorylation were observed. In the second model system, wild-type 4R tau and P301L tau, a variant with increased aggregation propensity, were heterologously overexpressed in HEK 293 cells. This overexpression did not activate the UPR. The last model system examined here was the PS19 transgenic mouse model. Although PS19 mice, which express the P301S variant of tau, display severe neurodegeneration and formation of tau aggregates, brain tissue samples did not show any activation of the UPR. Taken together, the results from these three model systems suggest that a direct mechanistic link does not exist between tau aggregation and the UPR. © 2010 Wiley-Liss, Inc. [source] | ||||||||||