Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review

PubMed Central

Lucero, Boris Andrés; Iglesias, Verónica Paz; Muñoz, María Pía; Cornejo, Claudia Alejandra; Achu, Eduardo; Baumert, Brittney; Hanchey, Arianna; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

2016-01-01

Background Previous studies have demonstrated that acute poisoning from exposure to organophosphate (OP) pesticides in agricultural workers causes adverse health effects. However, neuropsychological and cognitive effects of chronic occupational exposure to OP pesticides remain controversial. Objective To identify, evaluate, and systematize existing evidence regarding chronic exposure to OP pesticides and neuropsychological effects in farmworkers. Methods Using the PubMed search engine, a systematic review process was implemented and replicated according to the PRISMA statement. Eligibility criteria included workers over 18 years of age exposed to OP pesticides as well as assessment of neuropsychological and cognitive functioning. Search terms were in English and Spanish languages and included organophosphate and workers. Results Of the search results, 33 of 1,256 articles meet eligibility criteria. Twenty-four studies found an association between chronic occupational exposure to OP pesticides and low neuropsychological performance in workers. We classified nine of the studies to have study design limitations. Studies indicated occupational exposure to OP pesticides is linked to difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual–spatial functioning, and coordination. Nine studies find no relationship between OP pesticides exposure and neuropsychological performance. Conclusions Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected. PMID:27128815

Chronic Respiratory Symptoms and Lung Function in Agricultural Workers - Influence of Exposure Duration and Smoking.

PubMed

Stoleski, Saso; Minov, Jordan; Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka

2015-03-15

Job exposure in agricultural workers often leads to respiratory impairment. To assess the influence of exposure duration and smoking on chronic respiratory symptoms and ventilatory capacity in agricultural workers. A cross-sectional study covered 75 agricultural workers, compared with an equal number of office workers matched by age, exposure duration and smoking status. Standardized questionnaire was used to obtain data on chronic respiratory symptoms, job and smoking history. Lung functional testing was performed by spirometry. The prevalence of respiratory symptoms was higher in agricultural workers, with significant difference for cough (P = 0.034), and dyspnea (P = 0.028). Chronic respiratory symptoms among agricultural workers were significantly associated with duration of exposure (P < 0.05) and daily smoking (P < 0.01), as well as with daily smoking in controls (P < 0.01). The average values of spirometric parameters in exposed workers were significantly different for MEF50 (P = 0.002), MEF75 (P = 0.000), and MEF25-75 (P = 0.049). Obstructive changes in small airways in exposed workers were strongly related to exposure duration (P < 0.05) and smoking (P < 0.01). Agricultural workers with job exposure more than 15 years had more expressed adverse respiratory symptoms and lung function decline. The results confirmed the influence of agricultural exposure and daily smoking on chronic respiratory symptoms and airflow limitation, primarily targeting the small airways.

A case-control study of chronic neuropsychiatric disease and organic solvent exposure in automobile assembly plant workers.

PubMed Central

Nelson, N A; Robins, T G; White, R F; Garrison, R P

1994-01-01

A case-control study of chronic neurological and psychiatric disease and occupational exposure to solvents was carried out in eight automobile assembly plants. Cases included 299 subjects who were granted medical disability retirement in 1980-8. Two control groups were selected, the first from those granted retirement in the same period because of medical disability from causes unrelated to solvent exposure. The second included hourly employees from the plant population. In these facilities, solvent exposures tended to be short term and low level, although common: the average duration of exposure was 2.3 years; about 41% experienced at least one day of exposure. Of those exposed, 46% had less than one year of exposure. Results for all psychiatric disease combined (273 cases) suggested that cases had lower exposures than either control group, regardless of how exposure was expressed. Results could not be explained by conventional confounding exposures or characteristics or by usual manifestations of the healthy worker effect. By contrast, chronic neurological disease, and multiple sclerosis in particular, seemed to be associated with exposure, although few cases were identified and observed increases in risk were not statistically significant. PMID:8199679

Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

PubMed

Mathur, Priya; Guo, Su

2011-06-01

Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

PubMed

Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

1991-11-01

THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic normobaric hypoxic and hypercapnic exposure in rats: Prevention of experimental chronic mountain sickness by hypercapnia

NASA Astrophysics Data System (ADS)

Lincoln, B.; Bonkovsky, H. L.; Ou, Lo-Chang

1987-09-01

A syndrome of experimental chronic mountain sickness can be produced in the Hilltop strain of Sprague-Dawley rats by chronic hypobaric hypoxic exposure. This syndrome is characterized by polycythemia, plasma hemoglobinemia, pulmonary hypertension and right ventricular hypertrophy with eventual failure and death. It has generally been assumed that these changes are caused by chronic hypoxemia, not by hypobaric exposure per se. We have now confirmed this directly by showing that chronic normobaric hypoxic exposure (10.5% O2) produces similar hematologic and hemodynamic changes. Further, the addition of hypercapnic exposure to the hypoxic exposure blunted or prevented the effects of the hypoxic exposure probably by stimulating respiration, thus increasing the rate of oxygen delivery to the cells. Changes in the rate-controlling enzymes of hepatic heme metabolism, 5-aminolevulinate synthase and heme oxygenase, and in cytochrome(s) P-450, the major hepatic hemoprotein(s), were also measured in hypoxic and hypercapnic rats. Hypoxia decreased 5-aminolevulinate synthase and increased cytochrome(s) P-450, probably by increasing the size of a “regulatory” heme pool within hepatocytes. These changes were also prevented by the addition of hypercapnic to hypoxic exposure.

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

PubMed Central

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

Chronic and acute exposures to the world trade center disaster and lower respiratory symptoms: area residents and workers.

PubMed

Maslow, Carey B; Friedman, Stephen M; Pillai, Parul S; Reibman, Joan; Berger, Kenneth I; Goldring, Roberta; Stellman, Steven D; Farfel, Mark

2012-06-01

We assessed associations between new-onset (post-September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center-area residents and workers enrolled in the World Trade Center Health Registry. World Trade Center-area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects.

Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

PubMed

Stewart, Adam Michael; Grossman, Leah; Collier, Adam D; Echevarria, David J; Kalueff, Allan V

2015-12-01

Nicotine is one of the most widely used and abused legal drugs. Although its pharmacological profile has been extensively investigated in humans and rodents, nicotine CNS action remains poorly understood. The importance of finding evolutionarily conserved signaling pathways, and the need to apply high-throughput in vivo screens for CNS drug discovery, necessitate novel efficient experimental models for nicotine research. Zebrafish (Danio rerio) are rapidly emerging as an excellent organism for studying drug abuse, neuropharmacology and toxicology and have recently been applied to testing nicotine. Anxiolytic, rewarding and memory-modulating effects of acute nicotine treatment in zebrafish are consistently reported in the literature. However, while nicotine abuse is more relevant to long-term exposure models, little is known about chronic effects of nicotine on zebrafish behavior. In the present study, chronic 4-day exposure to 1-2mg/L nicotine mildly increased adult zebrafish shoaling but did not alter baseline cortisol levels. We also found that chronic exposure to nicotine evokes robust anxiogenic behavioral responses in zebrafish tested in the novel tank test paradigm. Generally paralleling clinical and rodent data on anxiogenic effects of chronic nicotine, our study supports the developing utility of zebrafish for nicotine research. Copyright © 2015 Elsevier Inc. All rights reserved.

Methamphetamine exposure and chronic illness in police officers

PubMed Central

Ross, Gerald H; Sternquist, Marie C

2012-01-01

Background: The medical literature reports health hazards for law enforcement personnel from repeated exposure to methamphetamine and related chemical compounds. Most effects appear transitory, but some Utah police officers with employment-related methamphetamine exposures developed chronic symptoms, some leading to disability. This report is of an uncontrolled retrospective medical chart evaluation of symptomatic officers treated with a sauna detoxification protocol designed to reduce the chronic symptoms and improve the quality of life. Methods: Sixty-nine officers consecutively entering the Utah Meth Cops Project were assessed before and after a treatment program involving gradual exercise, comprehensive nutritional support and physical sauna therapy. Evaluations included pre- and post-treatment scores of the Research and Development Corporation (RAND) 36-item Short Form Health Survey (SF-36) in comparison with RAND population norms, pre- and post-treatment symptom score intensities, neurotoxicity scores, Mini-Mental Status Examination, presenting symptom frequencies and a structured evaluation of treatment program safety. Results: Statistically significant health improvements were seen in the SF-36 evaluations, symptom scores and neurotoxicity scores. The detoxification protocol was well tolerated, with a 92.8% completion rate. Conclusions: This investigation strongly suggests that utilizing sauna and nutritional therapy may alleviate chronic symptoms appearing after chemical exposures associated with methamphetamine-related law enforcement activities. This report also has relevance to addressing the apparent ill effects of other complex chemical exposures. In view of the positive clinical outcomes in this group, broader investigation of this sauna-based treatment regimen appears warranted. PMID:22089658

Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease.

PubMed

Eisner, Mark D; Balmes, John; Katz, Patricia P; Trupin, Laura; Yelin, Edward H; Blanc, Paul D

2005-05-12

Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction. Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies. Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD. Participants were recruited from all 48 contiguous U.S. states by random digit dialing. Lifetime ETS exposure was ascertained by structured telephone interview. We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD. Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD. The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21). The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84). The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure. ETS exposure may be an important cause of COPD. Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure.

A safe strategy to decrease fetal lead exposure in a woman with chronic intoxication.

PubMed

Leiba, Adi; Hu, Howard; Zheng, Amin; Kales, Stefanos N

2010-08-01

During pregnancy skeletal lead is mobilized by maternal bone turnover and can threaten fetal development. The exact strategy suggested to women of childbearing age, who were chronically exposed to lead, and, thus, have high bone lead burden, is not well established. We describe 4 years of follow-up of a 29-year-old woman with chronic lead intoxication. We (a) advised her to delay conception until 'toxicological clearance', (b) treated her with multiple courses of lead chelator, DMSA, and (c) prescribed oral calcium. Patient had low blood lead and protoporphyrin level during pregnancy until delivery. Delaying conception, lead chelation, and calcium supplementation can decrease fetal exposure.

Bilateral Vestibular Dysfunction Associated With Chronic Exposure to Military Jet Propellant Type-Eight Jet Fuel.

PubMed

Fife, Terry D; Robb, Michael J A; Steenerson, Kristen K; Saha, Kamala C

2018-01-01

We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3-5 years' duration while working on or near the flight line. Exposure to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n -hexane in the blood of one of the cases. The presenting symptoms were dizziness, headache, fatigue, and imbalance. Rotational chair testing confirmed bilateral vestibular dysfunction in all the three patients. Vestibular function improved over time once the exposure was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon exposure in humans, but only recently has emphasis been placed specifically on the detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity. Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular therapy offer the best chance for improved balance. Bilateral vestibular impairment is under-recognized in those chronically exposed to all forms of jet fuel.

Chronic vs. Short-Term Acute O 3 Exposure Effects on Nocturnal Transpiration in Two Californian Oaks

Treesearch

Nancy Grulke; E. Paoletti; R. L. Heath

2007-01-01

We tested the effect of daytime chronic moderate ozone (O3) exposure, short-term acute exposure, and both chronic and acute O3 exposure combined on nocturnal transpiration in California black oak and blue oak seedlings. Chronic O3 exposure (70 ppb for 8 h/day) was implemented in open-top chambers for...

Chronic Exposure to Ambient Ozone and Asthma Hospital Admissions among Children

PubMed Central

Lin, Shao; Liu, Xiu; Le, Linh H.; Hwang, Syni-An

2008-01-01

Background The association between chronic exposure to air pollution and adverse health outcomes has not been well studied. Objective This project investigated the impact of chronic exposure to high ozone levels on childhood asthma admissions in New York State. Methods We followed a birth cohort born in New York State during 1995–1999 to first asthma admission or until 31 December 2000. We identified births and asthma admissions through the New York State Integrated Child Health Information System and linked these data with ambient ozone data (8-hr maximum) from the New York State Department of Environmental Conservation. We defined chronic ozone exposure using three indicators: mean concentration during the follow-up period, mean concentration during the ozone season, and proportion of follow-up days with ozone levels > 70 ppb. We performed logistic regression analysis to adjust for child’s age, sex, birth weight, and gestational age; maternal race/ethnicity, age, education, insurance status, smoking during pregnancy, and poverty level; and geographic region, temperature, and copollutants. Results Asthma admissions were significantly associated with increased ozone levels for all chronic exposure indicators (odds ratios, 1.16–1.68), with a positive dose–response relationship. We found stronger associations among younger children, low sociodemographic groups, and New York City residents as effect modifiers. Conclusion Chronic exposure to ambient ozone may increase the risk of asthma admissions among children. Younger children and those in low socioeconomic groups have a greater risk of asthma than do other children at the same ozone level. PMID:19079727

Excretion of lead and its biological activity several years after termination of exposure

PubMed Central

Přerovská, I.; Teisinger, J.

1970-01-01

Přerovská, and Teisinger, J. (1970).Brit. J. industr. Med.,27, 352-355. Excretion of lead and its biological activity several years after termination of exposure. A group of 27 persons who had been treated some years previously for chronic lead poisoning at our clinic, and who had not come into occupational contact with lead since, was examined. Half of them had had no occupational exposure to lead for 3 to 5 years and the others for 8 to 17 years. In most of these persons there is still an increased lead excretion, originating from an increased deposit in the bones. The mobilization test after calcium versenate (CaEDTA) injection was greater than 0·350 mg/24 hours. The values found for haemoglobin, punctate basophilia, coproporphyrin and ALA in urine were normal, but there was, in all cases, a decreased ALA-D activity. This finding suggests biological activity of such negligible lead flow many years after termination of exposure. PMID:5488694

Chronic and Acute Exposures to the World Trade Center Disaster and Lower Respiratory Symptoms: Area Residents and Workers

PubMed Central

Friedman, Stephen M.; Pillai, Parul S.; Reibman, Joan; Berger, Kenneth I.; Goldring, Roberta; Stellman, Steven D.; Farfel, Mark

2012-01-01

Objectives. We assessed associations between new-onset (post–September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center–area residents and workers enrolled in the World Trade Center Health Registry. Methods. World Trade Center–area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Results. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Conclusions. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects. PMID:22515865

Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium.

PubMed

Pearce, William A; Chen, Rui; Jain, Nieraj

2018-05-22

To describe the clinical features of a unique pigmentary maculopathy noted in the setting of chronic exposure to pentosan polysulfate sodium (PPS), a therapy for interstitial cystitis (IC). Retrospective case series. Six adult patients evaluated by a single clinician between May 1, 2015, and October 1, 2017. Patients were identified by query of the electronic medical record system. Local records were reviewed, including results of the clinical examination, retinal imaging, and visual function assessment with static perimetry and electroretinography. Molecular testing assessed for known macular dystrophy and mitochondrial cytopathy genotypes. Mean best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), median cumulative PPS exposure, subjective nature of the associated visual disturbance, qualitative examination and imaging features, and molecular testing results. The median age at presentation was 60 years (range, 37-62 years). All patients received PPS for a diagnosis of IC, with a median cumulative exposure of 2263 g (range, 1314-2774 g), over a median duration of exposure of 186 months (range, 144-240 months). Most patients (4 of 6) reported difficulty reading as the most bothersome symptom. Mean BCVA was 0.1±0.18 logarithm of the minimum angle of resolution. On fundus examination, nearly all eyes showed subtle paracentral hyperpigmentation at the level of the retinal pigment epithelium (RPE) with a surrounding array of vitelliform-like deposits. Four eyes of 2 patients showed paracentral RPE atrophy, and no eyes demonstrated choroidal neovascularization. Multimodal retinal imaging demonstrated abnormality of the RPE generally contained in a well-delineated area in the posterior pole. None of the 4 patients who underwent molecular testing of nuclear DNA returned a pathogenic mutation. Additionally, all 6 patients showed negative results for pathogenic variants in the mitochondrial gene MTTL1. We describe a novel and possibly

General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis.

PubMed

Maxfield, Alice Z; Korkmaz, Hakan; Gregorio, Luciano L; Busaba, Nicolas Y; Gray, Stacey T; Holbrook, Eric H; Guo, Rong; Bleier, Benjamin S

2017-02-01

Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis-related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. 3b. Laryngoscope, 2016 127:296-302, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The costs of chronic noise exposure for terrestrial organisms.

PubMed

Barber, Jesse R; Crooks, Kevin R; Fristrup, Kurt M

2010-03-01

Growth in transportation networks, resource extraction, motorized recreation and urban development is responsible for chronic noise exposure in most terrestrial areas, including remote wilderness sites. Increased noise levels reduce the distance and area over which acoustic signals can be perceived by animals. Here, we review a broad range of findings that indicate the potential severity of this threat to diverse taxa, and recent studies that document substantial changes in foraging and anti-predator behavior, reproductive success, density and community structure in response to noise. Effective management of protected areas must include noise assessment, and research is needed to further quantify the ecological consequences of chronic noise exposure in terrestrial environments.

Chronic obstructive pulmonary disease and occupational exposure to silica.

PubMed

Rushton, Lesley

2007-01-01

Prolonged exposure to high levels of silica has long been known to cause silicosis This paper evaluates the evidence for an increased risk of chronic obstructive pulmonary disease (COPD) in occupations and industries in which exposure to crystalline silica is the primary exposure, with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests consistently elevated risks of developing COPD associated with silica exposure in several occupations, including the construction industry; tunneling; cement industry; brick manufacturing; pottery and ceramic work; silica sand, granite and diatomaceous earth industries; gold mining; and iron and steel founding, with risk estimates being high in some, even after taking into account the effect of confounders like smoking. Average dust levels vary from about 0.5 mg.m3 to over 10 mg.m3 and average silica levels from 0.04 to over 5 mg.m3, often well above occupational standards. Factors influencing the variation from industry to industry in risks associated with exposure to silica-containing dusts include (a) the presence of other minerals in the dust, particularly when associated with clay minerals; (b) the size of the particles and percentage of quartz; (c) the physicochemical characteristics, such as whether the dust is freshly fractured. Longitudinal studies suggest that loss of lung function occurs with exposure to silica dust at concentrations of between 0.1 and 0.2 mg.m3, and that the effect of cumulative silica dust exposure on airflow obstruction is independent of silicosis. Nevertheless, a disabling loss of lung function in the absence of silicosis would not occur until between 30 and 40 years exposure.

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia.

PubMed

Zhu, Gaochun; Chen, Zhenying; Dai, Bo; Zheng, Chaoran; Jiang, Huaide; Xu, Yurong; Sheng, Xuan; Guo, Jingjing; Dan, Yu; Liang, Shangdong; Li, Guilin

2018-06-01

Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG). Rats were given lead acetate through drinking water freely at doses of 0 g/L (control group), 0.5 g/L (low lead group), and 2 g/L (high lead group) for 1 year. Our results demonstrated that lead exposure caused autonomic nervous dysfunction, including blood pressure and heart rate increased and heart rate variability (HRV) decreased. Western blotting results indicated that after lead exposure, the protein expression levels in the SG of P2X4 receptor, IL-1β and Cx43 were up-regulated, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was activated. Real-time PCR results showed that the mRNA expression of P2X4 receptor in the SG was higher in lead exposure group than that in the control group. Double-labeled immunofluorescence results showed that P2X4 receptor was co-expressed with glutamine synthetase (GS), the marker of satellite glial cells (SGCs). These changes were positively correlated with the dose of lead exposure. The up-regulated expression of P2X4 receptor in SGCs of the SG maybe enhance the sympathoexcitatory response induced by chronic lead exposure. © 2018 Wiley Periodicals, Inc.

Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.

PubMed

Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Williams, Timothy; Ting, Hua; Lee, Shin-Da

2014-06-01

Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.

Chronic effects on JP-8 jet fuel exposure on the lungs. Final technical report, 1 April 1991-31 March 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witten, M.L.

1994-06-02

There are four major findings from the three years of work devoted to the effects of chronic JP-8 jet fuel exposure on the lungs and secondary organs. These findings are the following chronic exposure to JP-8 jet fuel alters pulmonary function and lung structures with an acute response with as little as seven days of low dose, approximately 500 mg/m3, exposure to JP-8 jet fuel; chronic exposure to JP-8 jet fuel increased liver, spleen, and kidney weights compared to controls. Microscopic evaluation of liver sections were normal; however, kidney and spleen had histological changes consistent with organic solvent exposure. Theremore » is a correlation between JP-8 jet fuel exposure-induced decreases in lung Substance P levels and lung neutral endopeptidase levels. Chronic exposure to JP-8 jet fuel caused a decrease in lung Substance P levels with a corresponding increase in lung neutral endopeptidase levels; and, there is a recovery process in the 56 day low dose JP-8 jet fuel-exposed lungs as marked by a return to baseline and longitudinal control 99mTcDTPA values. The 99mTcDTPA data was very consistent with our pathologic findings of very little lung injury in the 56 day low dose JP-8 jet fuel-exposed rats. We speculate that this finding indicates that there is a 'threshold' level of JP-8 jet fuel exposure that the lungs' defense mechanism(s) can tolerate.« less

Occupational exposure and risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

PubMed

Alif, Sheikh M; Dharmage, Shyamali C; Bowatte, Gayan; Karahalios, Amalia; Benke, Geza; Dennekamp, Martine; Mehta, Amar J; Miedinger, David; Künzli, Nino; Probst-Hensch, Nicole; Matheson, Melanie C

2016-08-01

Due to contradictory literature we have performed a systematic review and meta-analyse of population-based studies that have used Job Exposure Matrices to assess occupational exposure and risk of Chronic Obstructive Pulmonary Disease (COPD). Two researchers independently searched databases for published articles using predefined inclusion criteria. Study quality was assessed, and results pooled for COPD and chronic bronchitis for exposure to biological dust, mineral dust, and gases/fumes using a fixed and random effect model. Five studies met predetermined inclusion criteria. The meta-analysis showed low exposure to mineral dust, and high exposure to gases/fumes were associated with an increased risk of COPD. We also found significantly increased the risk of chronic bronchitis for low and high exposure to biological dust and mineral dust. Expert commentary: The relationship between occupational exposure assessed by the JEM and the risk of COPD and chronic bronchitis shows significant association with occupational exposure. However, the heterogeneity of the meta-analyses suggests more wide population-based studies with older age groups and longitudinal phenotype assessment of COPD to clarify the role of occupational exposure to COPD risk.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

PubMed

Islam, Rafiqul; Khan, Ismail; Hassan, Sheikh Nazmul; McEvoy, Mark; D'Este, Catherine; Attia, John; Peel, Roseanne; Sultana, Munira; Akter, Shahnaz; Milton, Abul Hasnat

2012-06-07

Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: A cross sectional study in Bangladesh

PubMed Central

2012-01-01

Background Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. Methods This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. Results A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose–response pattern was also observed. Conclusions These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years. PMID:22676249

Chronic myelogenous leukemia (CML)

MedlinePlus

CML; Chronic myeloid leukemia; CGL; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

PubMed Central

Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

2014-01-01

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001

Chronic particulate exposure, mortality and cardiovascular outcomes in the nurses health study

EPA Science Inventory

Adverse health effects of exposures to acute air pollution have been well studied. Fewer studies have examined effects of chronic exposure. Previous studies used exposure estimates for narrow time periods and were limited by the geographic distribution of pollution monitors. This...

Non-smoking Chronic Obstructive Pulmonary Disease Attributed to Occupational Exposure to Silica Dust.

PubMed

Tsuchiya, Kazuo; Toyoshima, Mikio; Kamiya, Yosuke; Nakamura, Yutaro; Baba, Satoshi; Suda, Takafumi

2017-01-01

An 85-year-old, never-smoking man presented with exertional dyspnea. He had been exposed to silica dust in the work place. Chest computed tomography revealed bronchial wall thickening without emphysema. A pulmonary function test showed airflow obstruction without impaired gas transfer. Airway hyperresponsiveness and reversibility were not evident. A transbronchial lung biopsy showed findings suggestive of mineral dust exposure, such as fibrosis and slight pigmentation of bronchioles. He was diagnosed with non-smoking chronic obstructive pulmonary disease (COPD) due to occupational exposure to silica dust. His symptoms were improved using an inhaled long-acting bronchodilator. The clinical characteristics of non-smoking COPD are discussed in this report.

Violence exposure, a chronic psychosocial stressor, and childhood lung function

PubMed Central

Suglia, Shakira Franco; Ryan, Louise; Laden, Francine; Dockery, Douglas; Wright, Rosalind J

2011-01-01

Background Chronic psychosocial stressors, including violence, have been linked to neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects. Methods We examined the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children 6 and 7 years of age. Mothers reported on their child’s lifetime exposure to community violence (ETV) and interparental conflict in the home [Conflict Tactics Scale (CTS)] within one year of the lung function assessment. Results In linear regression analyses, adjusting for maternal education, child’s age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% CI: −9.6, −1.5) decrease in percent predicted FEV1 and a 5.4% (95% CI: −9.7, −1.1) decrease in FVC compared to girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI: −8.0, 1.1) lower FEV1 and 5.3% lower (95% CI: −10.2, −0.4) FVC compared to boys in the lowest tertile. The ETV score was not a significant predictor of girl’s lung function. Conclusions Interparental conflict, specifically verbal aggression, and exposure to community violence were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight and respiratory illness history. Gender differences were noted based on the type of violence exposure which may warrant further exploration. PMID:18158365

Welding fume exposure and chronic obstructive pulmonary disease in welders.

PubMed

Koh, D-H; Kim, J-I; Kim, K-H; Yoo, S-W

2015-01-01

Occupational exposure is estimated to contribute 15% to the burden of chronic obstructive pulmonary disease (COPD). Welding fumes are suspected to accelerate the decline of lung function and development of COPD. To examine the relationship between welding fume exposure and COPD in Korean shipyard welders. The study involved a group of male welders working at two shipyards who underwent an annual health examination in 2010. Subjects completed a questionnaire about smoking habits and occupational history and a pulmonary function test (PFT) was carried out with strict quality control measures. Welding fume exposure concentrations were estimated using 884 measurements taken between 2002 and 2009 in one of the shipyards. Multiple linear and logistic regression was employed to evaluate the association between cumulative fume exposure and lung function parameters, controlling for age, height and cigarette smoking. Two hundred and forty subjects participated, with a mean age of 48 and mean work duration of 15 years. The mean cumulative fume exposure was 7.7mg/m(3). The prevalence of COPD was 15%. FEV1 and FVC showed non-significant negative correlations with cumulative fume exposure. Odds ratios of COPD were significantly elevated for the middle (3.9; 95% CI 1.4-13.3) and high exposure groups (3.8; 95% CI 1.03-16.2) compared with the low fume exposure group. Our findings support an association between welding fume exposure and increased risk of COPD. Further prospective study is needed to investigate whether this is a causal relationship. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs): A cross-sectional study

PubMed Central

Peper, Martin; Klett, Martin; Morgenstern, Rudolf

2005-01-01

Background Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs) has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. Methods Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years). PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180). Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years) was identified and compared with 16 paired controls. Results Blood analyses indicated a moderate exposure effect size (d) relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4). A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5) and 101 (0.07 ± 0.09 μg/l; d = 0.7). Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state) as well as attenuated attentional performance (response shifting and alertness in a cued reaction task). Conclusion Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well-being and

Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

PubMed

Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

2011-08-01

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

PubMed Central

da Silva, Fernando B. R.; Cunha, Polyane A.; Ribera, Paula C.; Barros, Mayara A.; Cartágenes, Sabrina C.; Fernandes, Luanna M. P.; Teixeira, Francisco B.; Fontes-Júnior, Enéas A.; Prediger, Rui D.; Lima, Rafael R.; Maia, Cristiane S. F.

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats.

PubMed

da Silva, Fernando B R; Cunha, Polyane A; Ribera, Paula C; Barros, Mayara A; Cartágenes, Sabrina C; Fernandes, Luanna M P; Teixeira, Francisco B; Fontes-Júnior, Enéas A; Prediger, Rui D; Lima, Rafael R; Maia, Cristiane S F

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Chronic exposure of grandparents to poverty and body mass index trajectories of grandchildren: a prospective intergenerational study.

PubMed

Li, Miao

2015-02-01

In this study, I used the growth curve model to examine the association between grandparents' (first generation (G1)) life-course exposure to chronic poverty and grandchildren's (third generation (G3)) body mass index (BMI; weight (kg)/height (m)(2)) growth trajectories. This association was estimated separately for male and female grandchildren. Analyses were based on prospective data from a US longitudinal survey, the Panel Study of Income Dynamics (1968-2011), and 2 of its supplemental studies: the Child Development Supplement (1997-2011) and the Transition into Adulthood Study (1997-2011). A prospectively enrolled nationally representative cohort of 2,613 G3 youth (1,323 male, 1,290 female) sampled in the 2 supplemental studies was linked to 1,719 grandparents from the Panel Study of Income Dynamics core sample. Chronic exposure to poverty among grandparents was prospectively ascertained annually over a 30-year period prior to the collection of data on grandchildren. Findings suggested that grandparents' chronic poverty exposure was positively associated with the slope of the BMI trajectory among granddaughters (β = 0.10, 95% confidence interval: 0.03, 0.17) but not among grandsons (β = 0.02, 95% confidence interval: -0.04, 0.08). The association between grandparents' chronic poverty exposure and granddaughters' BMI growth slope remained even after controlling for parental (second generation (G2)) socioeconomic status and BMI. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chronic exposure to biomass fuel smoke and markers of endothelial inflammation

PubMed Central

Caravedo, Maria A; Herrera, Phabiola M; Mongilardi, Nicole; de Ferrari, Aldo; Davila-Roman, Victor G; Gilman, Robert H; Wise, Robert A; Miele, Catherine H; Miranda, J Jaime; Checkley, William

2016-01-01

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble ICAM-1 and VCAM-1, von Willebrand factor (VWF), and high sensitivity C-reactive protein (hs-CRP) in 228 biomass exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56 years (SD=13), average BMI was 26.5 kg/m2 (SD=4.4), 48% were male, 59.4% completed high school and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302 ng/mL; p<0.001), soluble VCAM-1 (403 vs. 362 ng/mL; p<0.001), and E-selectin (54.2 vs. 52.7 ng/mL; p=0.05) were increased in biomass exposed vs. non-exposed participants, respectively; whereas serum levels of vWF (1148 vs. 1311 mU/mL; p<0.001) and hs-CRP (2.56 vs. 3.12 mg/L; p<0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (p=0.03) and VCAM-1 (p=0.05) and E-selectin (p=0.05), and remained negatively associated with serum levels of vWF (p=0.02) and hs-CRP (p<0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed. PMID:26476302

Chronic radioisotope effects on residents of the Techa River (Russia) region: cytogenetic analysis more than 50 years after onset of exposure.

PubMed

Vozilova, A V; Shagina, N B; Degteva, M O; Akleyev, A V

2013-08-30

This paper presents the results of a cytogenetic study conducted among residents of the Techa Riverside communities (Southern Urals, Russia) exposed in the early 1950s as a result of releases of liquid radioactive wastes from the Mayak plutonium-production facility. The study was performed 50-60 years after the beginning of the exposure for those individuals who were predominantly exposed to strontium radioisotopes ((89,90)Sr) through drinking contaminated river water and consumption of local foodstuff. Standard cytogenetic methods were used for evaluation of the frequency of unstable chromosome aberrations in exposed persons as well as in persons from the control group who were of similar age and sex, living in similar socio-economic conditions in non-contaminated territories of the Southern Urals. The exposure doses were reconstructed for the studied donors using the Techa River Dosimetry System developed in 2009. The doses of internal exposure from ingested radionuclides were evaluated using individual or family in vivo measurements of (90)Sr-body burden. Individual cumulative absorbed doses in red bone marrow (RBM) in the studied persons varied in the range of 0.01-4.4Gy. A significantly higher level of unstable chromosome aberrations (UCA) in T-cells was observed in the group of exposed individuals as compared to control group. The highest UCA level was detected in the individuals who were suspected of having chronic radiation syndrome. Copyright © 2013 Elsevier B.V. All rights reserved.

Chronic Exposure to Zinc Chromate Induces Centrosome Amplification and Spindle Assembly Checkpoint Bypass in Human Lung Fibroblasts

PubMed Central

Holmes, Amie L.; Wise, Sandra S.; Pelsue, Stephen C.; Aboueissa, AbouEl-Makarim; Lingle, Wilma; Salisbury, Jeffery; Gallagher, Jamie; Wise, John Pierce

2010-01-01

Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen, however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 hour exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy and tetraploidy. Zinc chromate also induced centrosome amplification in a concentration- and time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Further, chronic exposure to zinc chromate induced concentration- and time-dependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division and premature anaphase. Lastly, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures. PMID:20030412

Development of a Novel Simulation Reactor for Chronic Exposure to Atmospheric Particulate Matter

NASA Astrophysics Data System (ADS)

Ye, Jianhuai; Salehi, Sepehr; North, Michelle L.; Portelli, Anjelica M.; Chow, Chung-Wai; Chan, Arthur W. H.

2017-02-01

Epidemiological studies have shown that air pollution is associated with the morbidity and mortality from cardiopulmonary diseases. Currently, limited experimental models are available to evaluate the physiological and cellular pathways activated by chronic multi-pollutant exposures. This manuscript describes an atmospheric simulation reactor (ASR) that was developed to investigate the health effects of air pollutants by permitting controlled chronic in vivo exposure of mice to combined particulate and gaseous pollutants. BALB/c mice were exposed for 1 hr/day for 3 consecutive days to secondary organic aerosol (SOA, a common particulate air pollutant) at 10-150 μg/m3, SOA (30 μg/m3) + ozone (65 ppb) or SOA + ozone (65 ppb) + nitrogen dioxide (NO2; 100 ppb). Daily exposure to SOA alone led to increased airway hyperresponsiveness (AHR) to methacholine with increasing SOA concentrations. Multi-pollutant exposure with ozone and/or NO2 in conjunction with a sub-toxic concentration of SOA resulted in additive effects on AHR to methacholine. Inflammatory cell recruitment to the airways was not observed in any of the exposure conditions. The ASR developed in this study allows us to evaluate the chronic health effects of relevant multi-pollutant exposures at ‘real-life’ levels under controlled conditions and permits repeated-exposure studies.

Chronic Organic Solvent Exposure Changes Visual Tracking in Men and Women.

PubMed

de Oliveira, Ana R; Campos Neto, Armindo de Arruda; Bezerra de Medeiros, Paloma C; de Andrade, Michael J O; Dos Santos, Natanael A

2017-01-01

Organic solvents can change CNS sensory and motor function. Eye-movement analyses can be important tools when investigating the neurotoxic changes that result from chronic organic solvent exposure. The current research measured the eye-movement patterns of men and women with and without histories of chronic organic solvent exposure. A total of 44 volunteers between 18 and 41 years old participated in this study; 22 were men (11 exposed and 11 controls), and 22 were women (11 exposed and 11 controls). Eye movement was evaluated using a 250-Hz High-Speed Video Eye Tracker Toolbox (Cambridge Research Systems) via an image of a maze. Specific body indices of exposed and non-exposed men and women were measured with an Inbody 720 to determine whether the differences in eye-movement patterns were associated with body composition. The data were analyzed using IBM SPSS Statistics version 20.0.0. The results indicated that exposed adults showed significantly more fixations ( t = 3.82; p = 0.001; r = 0.51) and longer fixations ( t = 4.27; p = 0.001, r = 0.54) than their non-exposed counterparts. Comparisons within men (e.g., exposed and non-exposed) showed significant differences in the number of fixations ( t = 2.21; p = 0.04; r = 0.20) and duration of fixations ( t = 3.29; p = 0.001; r = 0.35). The same was true for exposed vs. non-exposed women, who showed significant differences in the number of fixations ( t = 3.10; p = 0.001; r = 0.32) and fixation durations ( t = 2.76; p = 0.01; r = 0.28). However, the results did not show significant differences between exposed women and men in the number and duration of fixations. No correlations were found between eye-movement pattern and body composition measures ( p > 0.05). These results suggest that chronic organic solvent exposure affects eye movements, regardless of sex and body composition, and that eye tracking contributes to the investigation of the visual information processing disorders acquired by workers exposed to

Association between chronic arsenic exposure and nutritional status among the women of child bearing age: a case-control study in Bangladesh.

PubMed

Milton, Abul H; Shahidullah, S M; Smith, Wayne; Hossain, Kazi S; Hasan, Ziaul; Ahmed, Kazi T

2010-07-01

The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 microg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5) and 360 controls (BMI 18.5-24.99) were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant's age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 microg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1-3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20-45 years.

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure

PubMed Central

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-01-01

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N = 33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 µg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL × sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. PMID:25936521

Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

PubMed Central

Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

2014-01-01

Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism.

PubMed

Jin, Yuanxiang; Lin, Xiaojian; Miao, Wenyu; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

2014-03-21

We evaluated the effects of a 20-week chronic exposure of mice to a low dose of cypermethrin (CYP), atrazine (ATZ) and 17α-ethynyestradiol (EE2) on energy metabolism. Here, male mice were exposed to 50 μg/kg BW/day CYP, 100 μg/kg BW/day ATZ or 1 μg/kg BW/day EE2 supplied in their drinking water for 20 weeks. During the exposure, mice were fed a high energy diet (HD). The bodyweights were not significantly affected by chronic exposure to EDCs, while the serum-free fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG) contents increased significantly in the ATZ- and CYP-HD groups. To determine the mechanism involved, we determined the expression levels of the genes in the glucose and fat metabolism pathways in the liver and adipose tissue. The results showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number of key genes involved in both the de novo FFA synthesis pathway and the transport of FFA from blood. The increased amount of FFA was partially consumed as energy through β-oxidation in the mitochondria. Some of the FFA was used to synthesize TG in the liver by up-regulating primary genes, which resulted in increased TG levels and lipid accumulation. The results indicate that chronic exposure to EDCs has the potential to cause energy metabolic dysregulation and hepatotoxicity in mice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

PubMed Central

Claussen, Catherine M; Dafny, Nachum

2016-01-01

The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0 mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization were also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals was observed for the 2.5 and 10.0 mg/kg MPD exposed groups. For 2.5 mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0 mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0 mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure

Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study.

PubMed

Argos, Maria; Kalra, Tara; Rathouz, Paul J; Chen, Yu; Pierce, Brandon; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; van Geen, Alexander; Graziano, Joseph; Ahsan, Habibul

2010-07-24

Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure

Neovascularization and Angiogenic Gene Expression Following Chronic Arsenic Exposure in Mice

PubMed Central

Soucy, Nicole V.; Mayka, Debra; Klei, Linda R.; Nemec, Antonia A.; Bauer, John A.; Barchowsky, Aaron

2015-01-01

Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5–500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50–250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease. PMID:15738583

Acute and chronic cold exposure differentially affects the browning of porcine white adipose tissue.

PubMed

Gao, Y; Qimuge, N R; Qin, J; Cai, R; Li, X; Chu, G Y; Pang, W J; Yang, G S

2018-07-01

Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal's response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.

Bumblebee learning and memory is impaired by chronic exposure to a neonicotinoid pesticide

PubMed Central

Stanley, Dara A.; Smith, Karen E.; Raine, Nigel E.

2015-01-01

Bumblebees are exposed to pesticides applied for crop protection while foraging on treated plants, with increasing evidence suggesting that this sublethal exposure has implications for pollinator declines. The challenges of navigating and learning to manipulate many different flowers underline the critical role learning plays for the foraging success and survival of bees. We assessed the impacts of both acute and chronic exposure to field-realistic levels of a widely applied neonicotinoid insecticide, thiamethoxam, on bumblebee odour learning and memory. Although bees exposed to acute doses showed conditioned responses less frequently than controls, we found no difference in the number of individuals able to learn at field-realistic exposure levels. However, following chronic pesticide exposure, bees exposed to field-realistic levels learnt more slowly and their short-term memory was significantly impaired following exposure to 2.4 ppb pesticide. These results indicate that field-realistic pesticide exposure can have appreciable impacts on learning and memory, with potential implications for essential individual behaviour and colony fitness. PMID:26568480

Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review.

PubMed

Valcke, Mathieu; Levasseur, Marie-Eve; Soares da Silva, Agnes; Wesseling, Catharina

2017-05-23

The main causes of chronic kidney disease (CKD) globally are diabetes and hypertension but epidemics of chronic kidney disease of unknown etiology (CKDu) occur in Central America, Sri Lanka, India and beyond. Althoug also being observed in women, CKDu concentrates among men in agricultural sectors. Therefore, suspicions fell initially on pesticide exposure, but currently chronic heat stress and dehydration are considered key etiologic factors. Responding to persistent community and scientific concerns about the role of pesticides, we performed a systematic review of epidemiologic studies that addressed associations between any indicator of pesticide exposure and any outcome measure of CKD. Of the 21 analytical studies we identified, seven were categorized as with low, ten with medium and four with relatively high explanation value. Thirteen (62%) studies reported one or more positive associations, but four had a low explanation value and three presented equivocal results. The main limitations of both positive and negative studies were unspecific and unquantified exposure measurement ('pesticides'), the cross-sectional nature of most studies, confounding and selection bias. The four studies with stronger designs and better exposure assessment (from Sri Lanka, India and USA) all showed exposure-responses or clear associations, but for different pesticides in each study, and three of these studies were conducted in areas without CKDu epidemics. No study investigated interactions between pesticides and other concommittant exposures in agricultural occupations, in particular heat stress and dehydration. In conclusion, existing studies provide scarce evidence for an association between pesticides and regional CKDu epidemics but, given the poor pesticide exposure assessment in the majority, a role of nephrotoxic agrochemicals cannot be conclusively discarded. Future research should procure assessment of lifetime exposures to relevant specific pesticides and enough power

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure.

PubMed

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-07-02

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N=33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 μg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL×sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chronic and Acute Ozone Exposure in the Week Prior to Delivery Is Associated with the Risk of Stillbirth

PubMed Central

Ha, Sandie; Pollack, Anna Z.; Zhu, Yeyi; Seeni, Indulaxmi; Kim, Sung Soo; Sherman, Seth; Liu, Danping

2017-01-01

Chronic and acute air pollution has been studied in relation to stillbirth with inconsistent findings. We examined stillbirth risk in a retrospective cohort of 223,375 singleton deliveries from 12 clinical sites across the United States. Average criteria air pollutant exposure was calculated using modified Community Multiscale Air Quality models for the day of delivery and each of the seven days prior, whole pregnancy, and first trimester. Poisson regression models using generalized estimating equations estimated the relative risk (RR) of stillbirth and 95% confidence intervals (CI) in relation to an interquartile range increase in pollutant with adjustment for temperature, clinical, and demographic factors. Ozone (O3) was associated with a 13–22% increased risk of stillbirth on days 2, 3, and 5–7 prior to delivery in single pollutant models, and these findings persisted in multi-pollutant models for days 5 (RR = 1.22, CI = 1.07–1.38) and 6 (RR = 1.18, CI = 1.04–1.33). Whole pregnancy and first trimester O3 increased risk 18–39% in single pollutant models. Maternal asthma increased stillbirth risk associated with chronic PM2.5 and carbon monoxide exposures. Both chronic and acute O3 exposure consistently increased stillbirth risk, while the role of other pollutants varied. Approximately 8000 stillbirths per year in the US may be attributable to O3 exposure. PMID:28684711

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

EPA Science Inventory

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993.
...

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

PubMed

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M; Wilks, Martin F; Spandidos, Demetrios A; Fenga, Concettina

2016-10-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well‑designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review)

PubMed Central

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M.; Wilks, Martin F.; Spandidos, Demetrios A.; Fenga, Concettina

2016-01-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well-designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases. PMID:27600395

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

PubMed

Simpson, Norah S; Scott-Sutherland, Jennifer; Gautam, Shiva; Sethna, Navil; Haack, Monika

2017-09-01

Chronic pain conditions are highly co-morbid with insufficient sleep. While the mechanistic relationships between the two are not understood, chronic insufficient sleep may be one pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of three weeks of restricted sleep with limited recovery (five nights of 4-hour sleep/night followed by two nights of 8-hour sleep/night) was compared to three weeks of 8-hour sleep/night (control protocol). Seventeen healthy adults participated, with fourteen completing both three-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared to the control protocol, participants in the sleep-restriction/recovery protocol experienced mild increases in spontaneous pain (p<0.05). Heat-pain thresholds decreased following the first week of sleep restriction (p<0.05), but normalized with longer exposure to sleep restriction. In contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both p<0.05), although only in the last two weeks of the sleep restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Central nervous system effect of chronic exposure to organophosphate insecticides.

DOT National Transportation Integrated Search

1963-10-01

Two cases are reported in which persistent CNS changes were noted in aerial applicator pilots after chronic exposure to organophosphate insecticides. The synptomatology, the basis for these symptoms and EEG changes and their reversibility are discuss...

Effects of chronic exposure to clothianidin on the earthworm Lumbricus terrestris

PubMed Central

Goulson, Dave

2017-01-01

Although neonicotinoids are targeted at insects, their predominant use as a seed dressing and their long persistence in soils mean that non-target soil organisms such as earthworms are likely to be chronically exposed to them. Chronic exposure may pose risks that are not evaluated in most toxicity tests. We experimentally tested the effect of field-realistic concentrations of a commonly used neonicotinoid, clothianidin, on mortality, weight gain, and food consumption to assess the impacts of chronic exposure over four months on fitness of L. terrestris individuals. We undertook three separate experiments, each with different exposure routes: treated soil only (experiment A), treated food and soil combined (experiment B) and treated food only (experiment C). Mortality was negatively affected by exposure from treated soil only with greatest mortality observed in the groups exposed to the two highest concentrations (20 ppb and 100 ppb), but no clear effect on mortality was found in the other two experiments. When clothianidin was present in the food, an anti-feedant effect was present in months one and two which subsequently disappeared; if this occurs in the field, it could result in reduced rates of decomposition of treated crop foliage. We found no significant effects of any treatment on worm body mass. We cannot rule out stronger adverse effects if worms come into close proximity to treated seeds, or if other aspects of fitness were examined. Overall, our data suggest that field-realistic exposure to clothianidin has a significant but temporary effect on food consumption and can have weak but significant impacts on mortality of L. terrestris. PMID:28413730

Does war hurt? Effects of media exposure after missile attacks on chronic pain.

PubMed

Lerman, Sheera F; Rudich, Zvia; Shahar, Golan

2013-03-01

This study focused on the effects of exposure to terrorist missile attacks on the physical and mental well being of chronic pain patients. In this prospective and longitudinal design, 55 chronic pain patients treated at a specialty pain clinic completed self-report questionnaires regarding their pain, depression and anxiety pre- and post a three week missile attack on the southern region of Israel. In addition, levels of direct and indirect exposure to the attacks were measured. Results of regression analyses showed that exposure to the attacks through the media predicted an increase in pain intensity and in the sensory component of pain during the pre-post war period, but did not predict depression, anxiety or the affective component of pain. These findings contribute to the understanding of the effects of terrorism on physical and emotional distress and identify chronic pain patients as a vulnerable population requiring special attention during terrorism-related stress.

Asthma, chronic bronchitis, and exposure to irritant agents in occupational domestic cleaning: a nested case-control study.

PubMed

Medina-Ramón, M; Zock, J P; Kogevinas, M; Sunyer, J; Torralba, Y; Borrell, A; Burgos, F; Antó, J M

2005-09-01

Women employed in domestic cleaning are at increased risk for symptoms of obstructive lung disease, but the agents responsible are unknown. To investigate common tasks and products in occupational domestic cleaning in relation to respiratory morbidity. Case-control study in domestic cleaning women nested within a large population based survey of women aged 30-65 years; 160 domestic cleaning women with asthma symptoms, chronic bronchitis symptoms, or both and 386 without a history of respiratory symptoms were identified. Detailed exposures were evaluated for 40 cases who reported still having symptoms at the recruitment interview, and 155 controls who reported not having symptoms. All tasks performed and products used when cleaning houses were determined in a face-to-face interview. Lung function, methacholine challenge, and serum IgE testing were performed. Personal exposure measurements of airborne chlorine and ammonia were performed in a subsample. Associations between asthma, chronic bronchitis, and cleaning exposures were evaluated using multiple logistic regression analysis. Airborne chlorine (median level 0-0.4 ppm) and ammonia (0.6-6.4 ppm) were detectable during occupational domestic cleaning activities. Cases used bleach more frequently than controls; adjusted odds ratio (OR) for intermediate exposure was 3.3 (95% CI 0.9 to 11) and for high exposure 4.9 (1.5 to 15). Other independent associations included accidental inhalation of vapours and gases from cleaning agents and washing dishes. These associations were more pronounced for cases with asthma symptoms than for those with symptoms of chronic bronchitis, but were not related to sensitisation to common allergens. Asthma symptoms in domestic cleaning women are associated with exposure to bleach and possibly other irritant agents. The public health impact of the use of irritant cleaning products could be widespread since the use of these products is common both in the workplace and at home.

Chronic occupational stress exposure may increase the vulnerability to acoustic trauma in military professionals.

PubMed

Mălina, Ciumaşu-Rimbu

2015-01-01

Today little is known about the connection between chronic stress exposure and hearing loss. These effects cannot be explained by differences in HPA axis response but recent studies saying that chronic stress induced limbic system alterations spread to nonlimbic areas affecting auditory system might be the key. On the other hand we know that subjects exposed to chronic stress may prove hypersensitivity to novel stressors. The aim of this study is to confirm that occupational chronic stress (OCS) exposure determines vulnerability to acoustic trauma and to establish a method to identify individuals at risk prior to their exposure to high intensity acoustic stimulus. 60 military personnel with known acoustic trauma injury evidentiated through audiograms and occupational chronic stress exposure quantified through validated questionnaires were exposed to mild novel stressor: occupational medicine evaluation and clinically assessed for maladaptive cardiovascular response (MCVR). Employees were split in two groups, group 1 (MCVR) and group 2 (non MCVR). We found positive correlation between level of perceived OCS and level of hearing loss on entire group and between groups with values of parameters significantly higher in group 1. Subjects exposed to OCS with hypersensitivity to novel stressor evidentiated through maladaptive cardiovascular stress response may be more vulnerable to high intensity acoustic stimulus and consequently acoustic trauma. Establishing methods and biomarkers that help us indentify individuals at risk of developing acoustic trauma might decrease the high burden of hearing loss.

Lack of association between chronic exposure to biomass fuel smoke and markers of right ventricular pressure overload at high altitude

PubMed Central

Caravedo, Maria A.; Painschab, Matthew S.; Davila-Roman, Victor G.; De Ferrari, Aldo; Gilman, Robert H.; Vasquez-Villar, Angel D.; Pollard, Suzanne L.; Miranda, J. Jaime; Checkley, William

2014-01-01

Background Chronic exposure to biomass fuel smoke has been implicated in the development of pulmonary hypertension and right ventricular pressure/volume overload through activation of inflammation, increase in vascular resistance and endothelial dysfunction. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography-derived pulmonary artery systolic pressure (PASP) levels in a high-altitude population-based study in Peru with and without chronic exposure to biomass fuel smoke. Methods NT-pro-BNP levels were measured in 519 adults (275 with and 244 without chronic exposure to biomass fuel smoke). Participants answered sociodemographics and clinical history questionnaires, underwent a clinical examination and blood testing for cardiopulmonary biomarkers. PASP was measured in a subgroup of 153 (31%) subjects. Results The study group consisted of 280 men (54%) and 239 women (46%). Average age was 56 years and average body mass index was 27 kg/m2. In multivariable analysis, there was no association between chronic exposure to biomass fuel smoke and NT-pro-BNP (p=0.31) or PASP (p=0.31). In the subgroup in which both NT-pro-BNP levels and PASP were measured, there was strong evidence of an association between these two variables (ρ=0.24, 95% CI 0.09-0.39; p=0.003). We found that age, high sensitivity C-reactive protein, being male and systolic blood pressure were positively associated with NT-pro-BNP levels whereas body mass index, LDL/HDL ratio and HOMA-IR were negatively associated (all p<0.01). Conclusions In this population-based study in a high-altitude setting, neither NT-pro-BNP levels nor echocardiography-derived PASP were associated with chronic exposure to biomass fuel smoke. PMID:25440802

Chronic systemic pesticide exposure reproduces features of Parkinson's disease.

PubMed

Betarbet, R; Sherer, T B; MacKenzie, G; Garcia-Osuna, M; Panov, A V; Greenamyre, J T

2000-12-01

The cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity. Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.

Identification of a threshold for biomass exposure index for chronic bronchitis in rural women of Mysore district, Karnataka, India.

PubMed

Mahesh, P A; Jayaraj, B S; Prabhakar, A K; Chaya, S K; Vijaysimha, R

2013-01-01

Exposure to air pollution due to combustion of biomass fuels remains one of the significant risk factors for chronic respiratory diseases such as chronic bronchitis. There is a need to identify the minimum threshold level of biomass index that is significantly associated with chronic bronchitis. This study was undertaken to identify a threshold for biomass exposure index in a rural women population in Mysore district, south India. A cross-sectional survey was conducted in a representative population of Mysore and Nanjangud taluks. Eight villages each from Mysore and Nanjangud were randomly selected based on the list of villages from census 2001. A house-to-house survey was carried out by trained field workers using the Burden of Obstructive Diseases questionnaire, which evaluated the biomass smoke exposure and chronic bronchitis. All the women aged above 30 yr were included in the study. A total of 2011 women from Mysore and 1942 women from Nanjangud participated in the study. All women were non-smoking and used biomass fuels as the primary fuel for cooking. A threshold of biomass fuel exposure of 60 was identified on multivariate analysis in Mysore district after adjusting for age, passive smoking and working in a occupational exposure to dust, as the minimum required for a significant association with chronic bronchitis. One in every 20 women in Mysore district exposed to biomass fuel exposure index of 110 or more developed chronic bronchitis. The minimum threshold of biomass exposure index of 60 is necessary to have a significant risk of developing chronic bronchitis in women. The number needed to harm to develop chronic bronchitis reduces with increasing biomass exposure index and women residing in rural Nanjangud have a higher risk for developing chronic bronchitis as compared to women in Mysore.

Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2012-11-01

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

Retrospective dosimetry related to chronic environmental exposure

NASA Technical Reports Server (NTRS)

Degteva, M. O.; Kozheurov, V. P.; Tolstykh, E. I.; Neta, R. (Principal Investigator)

1998-01-01

Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.

Retrospective dosimetry related to chronic environmental exposure.

PubMed

Degteva, M O; Kozheurov, V P; Tolstykh, E I

1998-01-01

Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

PubMed

Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2 , known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

PubMed Central

Rompala, Gregory R.; Mounier, Anais; Wolfe, Cody M.; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E.

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of

The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans.

PubMed

Dobrakowski, M; Kasperczyk, A; Czuba, Z P; Machoń-Grecka, A; Szlacheta, Z; Kasperczyk, S

2017-06-01

This study was designed to determine the levels of prolactin, leptin, osteopontin, and follistatin in workers chronically and subacutely exposed to lead compounds. The examined population consisted of three groups. The first group was composed of 56 male workers who were chronically exposed to lead for 13.38 ± 10.38 years. The second group served as a control group and consisted of 24 male administrative workers, while the third group included 32 male workers exposed to lead for 40 ± 3 days. The levels of leptin, osteopontin, and prolactin were significantly lower in the group of workers chronically exposed to lead than in the control group by 42%, 26%, and 41%, respectively. The levels of follistatin did not differ between those groups. The levels of all measured hormones did not change after a short-term exposure to lead compared to baseline. Chronic lead exposure is associated with significantly decreased level of prolactin, leptin, and osteopontin. Lead-induced changes in the levels of these hormones may disturb many functions of the human body, including the immune response, metabolism, reproduction, and bone turnover.

Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ

PubMed Central

Xu, Mei; Wang, Siying; Ren, Zhenhua; Frank, Jacqueline A.; Yang, Xiuwei H.; Zhang, Zhuo; Ke, Zun-ji; Shi, Xianglin; Luo, Jia

2016-01-01

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the scattering of MCF7, BT20 and T47D cell colonies in a 3-dimension culture system. Chronic ethanol exposure also increased colony formation in an anchorage-independent condition and stimulated cell invasion/migration. Chronic ethanol exposure increased cancer stem-like cell (CSC) population by more than 20 folds. Breast cancer cells exposed to ethanol in vitro displayed a much higher growth rate and metastasis in mice. Ethanol selectively activated p38γ MAPK and RhoC but not p38α/β in a concentration-dependent manner. SP-MCF7 cells, a derivative of MCF7 cells which compose mainly CSC expressed high levels of phosphorylated p38γ MAPK. Knocking-down p38γ MAPK blocked ethanol-induced RhoC activation, cell scattering, invasion/migration and ethanol-increased CSC population. Furthermore, knocking-down p38γ MAPK mitigated ethanol-induced tumor growth and metastasis in mice. These results suggest that chronic ethanol exposure can enhance the aggressiveness of breast cancer by activating p38γ MAPK/RhoC pathway. PMID:26655092

Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.

PubMed

Rouas, Caroline; Souidi, Maâmar; Grandcolas, Line; Grison, Stephane; Baudelin, Cedric; Gourmelon, Patrick; Pallardy, Marc; Gueguen, Yann

2009-11-01

The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. Copyright © 2009 Elsevier B.V. All rights reserved.

[The remote effects of chronic exposure to ionizing radiation and electromagnetic fields with respect to hygienic standardization].

PubMed

Grigor'ev, Iu G; Shafirkin, A V; Nikitina, V N; Vasin, A L

2003-01-01

A variety and rate of non-cancer diseases occurred in humans as a result of chronic exposure to ionizing radiation or to electromagnetic radiation (EMR) of high and superhigh frequency have been compared. The intensity of EMR was slightly higher than a sanitary standard for population. A risk of health impairments in workers having occupational exposure to EMR was assessed on the basis of Selie's concept of development of non-specific reaction of the body to chronic stress factors (general adaptation syndrome), models of changes in the body compensatory reserves and calculations of radiation risk after severe and chronic exposure to ionizing radiation.

Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

PubMed

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.

Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

PubMed Central

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence. PMID:23300696

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

PubMed

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

[Chronic noise exposure and the cardiovascular system in aircraft pilots].

PubMed

Tomei, F; Papaleo, B; Baccolo, T P; Tomao, E; Alfi, P; Fantini, S

1996-01-01

The aim of this study was to assess whether pilots are exposed to any risk of effects on the cardiovascular apparatus, whether chronic exposure to noise can be a risk factor for this occupation, the importance of intensity, length and type of exposure to noise, and if any relationship exists between audiometric deficits and cardiovascular effects. The study comprised 416 pilots subdivided into two groups according to the different levels of chronic exposure to noise, and a group of 150 control subjects not exposed to noise. The results showed: a) a higher prevalence of hypertension, nearly always diastolic, and of ECG abnormalities in the group of pilots of turboprop aircraft compared to jet plane pilots and to controls (p < 0.005 and p < 0.01 respectively); b) a higher prevalence of orthostatic hypotension in the two groups of pilots than in the controls (p < 0.05); c) a higher prevalence of hypertension with audiometric deficit compared to hypertension without audiometric deficit both in the more heavily and in the less heavily exposed to noise (p < 0.05), and a higher prevalence of hypertension with audiometric deficit in subjects exposed to higher levels of noise compared to hypertension with deficit but in subjects with lower levels of exposure (p < 0.05); d) a higher prevalence of abnormalities of basal, maximum effort and recovery ECG in pilots exposed to higher noise intensity (p < 0.05); e) improved hypertensive response to ergometric test in pilots with basal hypertension; f) subjects with a maximal load up to 120 W belonged prevalently to the group exposed to more intense noise (p < 0.001), while those with maximal load up to 210 W (p < 0.001) belonged to the group exposed to less intense noise. Considering that pilots are comparable for traditional cardiovascular risk factors, including age, both within the group and with the controls, the results confirm 1) that pilots could be exposed to the risk of effects on the cardiovascular apparatus, 2) that

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures

USGS Publications Warehouse

Kunz, James L.; Ingersoll, Christopher G.; Smalling, Kelly; Elskus, Adria; Kuivila, Kathryn

2017-01-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubiaand L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. aztecareproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;9999:1–8. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures.

PubMed

Kunz, James L; Ingersoll, Chris G; Smalling, Kelly L; Elskus, Adria A; Kuivila, Kathryn M

2017-09-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubia and L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. azteca reproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;36:2308-2315. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 SETAC.

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: I. BIOMARKERS FOR ASSESSING EXPOSURE AND EFFECTS

EPA Science Inventory

Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: I. Biomarkers for Assessing Exposure and Effects

Judy L. Mumford, Ph.D., Mike Schmitt, M.S.P.H., Richard K. Kwok, M.S.P.H., Rebecca Calderon, Ph.D., National Health and Environmental Effect...

Chronic exposure to ELF fields may induce depression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, B.W.

Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pinealmore » gland, giving rise to what may be termed functional pinealectomy. If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders. 85 references.« less

Chronic bronchitis in farmers.

PubMed

Melbostad, E; Eduard, W; Magnus, P

1997-08-01

Chronic bronchitis was studied in relation to work time and years of exposure in farming, as well as to production type, dusty occupation outside farming, and the combination of work exposure and smoking, in a population of farmers. In 1989 a representative cohort of 10,792 farmers and spouses was selected from a government register and invited to participate in a cross-sectional study in 1991. The total response rate was 80%. There were 33% part-time farmers, and among the men 32% of the full-time and 42% of the part-time farmers had worked in dusty occupations outside farming. Bronchitis symptoms were recorded on a self-administered questionnaire, spirometric data were obtained, and internal reference equations were calculated for forced expiratory volume in 1 s (FEV1.0). The exposure factors of importance for chronic bronchitis were full-time farming versus part-time farming, livestock production types (poultry, dairy, swine, horse and combinations), and occupational dust exposure outside agriculture. The combinations of the work exposure factors were significant and showed a 2- to 3-fold increase in risk for chronic bronchitis. Combinations with smoking showed up to a 6-fold increase in risk. Over the age of 50 years, chronic bronchitis was a risk factor for airway obstruction defined as the standardized residuals for FEV1.0 less than -2 for both nonsmokers (OR 2.8, 95% CI 1.1-6.8) and smokers (OR 8.5, 95% CI 5.1-14.3). Work exposure factors in farming and other dusty occupations enhance the risk for chronic bronchitis from 2- to 3-fold for farmers. In combination with smoking the risk increases to up to 6-fold.

Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study.

PubMed

Hanevik, Kurt; Wensaas, Knut-Arne; Rortveit, Guri; Eide, Geir Egil; Mørch, Kristine; Langeland, Nina

2014-11-15

Functional gastrointestinal disorders and fatigue may follow acute infections. This study aimed to estimate the persistence, prevalence, and risk of irritable bowel syndrome and chronic fatigue 6 years after Giardia infection. We performed a controlled prospective study of a cohort of 1252 individuals who had laboratory-confirmed Giardia infection during a waterborne outbreak in 2004. In total, 748 cohort cases (exposed) and 878 matched controls responded to a postal questionnaire 6 years later (in 2010). Responses were compared to data from the same cohort 3 years before (in 2007). The prevalences of irritable bowel syndrome (39.4%) by Rome III criteria and chronic fatigue (30.8%) in the exposed group 6 years after giardiasis were significantly elevated compared with controls, with adjusted relative risks (RRs) of 3.4 (95% confidence interval [CI], 2.9-3.9) and 2.9 (95% CI, 2.3-3.4), respectively. In the exposed group, the prevalence of irritable bowel syndrome decreased by 6.7% (RR, 0.85 [95% CI, .77-.93]), whereas the prevalence of chronic fatigue decreased by 15.3% from 3 to 6 years after Giardia infection (RR, 0.69 [95% CI, .62-.77]). Giardia exposure was a significant risk factor for persistence of both conditions, and increasing age was a risk factor for persisting chronic fatigue. Giardia infection in a nonendemic setting is associated with an increased risk for irritable bowel syndrome and chronic fatigue 6 years later. The prevalences of both conditions decrease over time, indicating that this intestinal protozoan parasite may elicit very long-term, but slowly self-limiting, complications. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Mortality in the Medicare Population and Chronic Exposure to Fine Particulate Air Pollution in Urban Centers (2000–2005)

PubMed Central

Zeger, Scott L.; Dominici, Francesca; McDermott, Aidan; Samet, Jonathan M.

2008-01-01

Background Prospective cohort studies constitute the major source of evidence about the mortality effects of chronic exposure to particulate air pollution. Additional studies are needed to provide evidence on the health effects of chronic exposure to particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) because few studies have been carried out and the cohorts have not been representative. Objectives This study was designed to estimate the relative risk of death associated with long-term exposure to PM2.5 by region and age groups in a U.S. population of elderly, for the period 2000–2005. Methods By linking PM2.5 monitoring data to the Medicare billing claims by ZIP code of residence of the enrollees, we have developed a new retrospective cohort study, the Medicare Cohort Air Pollution Study. The study population comprises 13.2 million participants living in 4,568 ZIP codes having centroids within 6 miles of a PM2.5 monitor. We estimated relative risks adjusted by socioeconomic status and smoking by fitting log-linear regression models. Results In the eastern and central regions, a 10-μg/m3 increase in 6-year average of PM2.5 is associated with 6.8% [95% confidence interval (CI), 4.9–8.7%] and 13.2% (95% CI, 9.5–16.9) increases in mortality, respectively. We found no evidence of an association in the western region or for persons ≥ 85 years of age. Conclusions We established a cohort of Medicare participants for investigating air pollution and mortality on longer-term time frames. Chronic exposure to PM2.5 was associated with mortality in the eastern and central regions, but not in the western United States. PMID:19079710

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage in Caenorhabditis elegans.

PubMed

Li, Ping; Xu, Tiantian; Wu, Siyu; Lei, Lili; He, Defu

2017-10-01

Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100 mg l -1 GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub-lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene-based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle-frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat-4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene-based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene-based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene-based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Occupational exposures and chronic obstructive pulmonary disease (COPD): comparison of a COPD-specific job exposure matrix and expert-evaluated occupational exposures

PubMed Central

Kurth, Laura; Doney, Brent; Weinmann, Sheila

2017-01-01

Objectives To compare the occupational exposure levels assigned by our National Institute for Occupational Safety and Health chronic obstructive pulmonary disease-specific job exposure matrix (NIOSH COPD JEM) and by expert evaluation of detailed occupational information for various jobs held by members of an integrated health plan in the Northwest USA. Methods We analysed data from a prior study examining COPD and occupational exposures. Jobs were assigned exposure levels using 2 methods: (1) the COPD JEM and (2) expert evaluation. Agreement (Cohen’s κ coefficients), sensitivity and specificity were calculated to compare exposure levels assigned by the 2 methods for 8 exposure categories. Results κ indicated slight to moderate agreement (0.19–0.51) between the 2 methods and was highest for organic dust and overall exposure. Sensitivity of the matrix ranged from 33.9% to 68.5% and was highest for sensitisers, diesel exhaust and overall exposure. Specificity ranged from 74.7% to 97.1% and was highest for fumes, organic dust and mineral dust. Conclusions This COPD JEM was compared with exposures assigned by experts and offers a generalisable approach to assigning occupational exposure. PMID:27777373

Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

PubMed

Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

2015-01-02

Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of the effects of chronic biomass fuel smoke exposure on peripheral endothelial functions: an observational study.

PubMed

Buturak, Ali; Genç, Ahmet; Ulus, Ozden Sıla; Duygu, Egemen; Okmen, Arda Sanlı; Uyarel, Hüseyin

2011-09-01

To evaluate the effect of chronic biomass fuel (BMF) smoke exposure on peripheral endothelial functions. Forty-seven healthy subjects who have been exposed to BMF smoke since birth (mean age 31.6±6.8 years, 21 male) were enrolled in the present cross-sectional observational study. The control group consisted of 32 healthy subjects (mean age 27.9±4.4 years, 11 male). The carotid intima media thickness (CIMT), flow associated dilatation (FAD %) and endothelium independent vasodilatation (GTN %) were assessed in all subjects. The carotid CIMT was defined as the distance between the leading edge of the lumen-intima and the media-adventitia interfaces. FAD % was defined as the percentage change in the internal diameter of the brachial artery during reactive hyperemia related to the baseline. GTN % was defined as the change in diameter in response to the application of 400 µg of glyceril trinitrate relative to the baseline scan at the end of the fourth minute. Statistical analysis was performed using Student's t-test, Chi-square test and Spearman rank order correlation analysis. The average exposure time of the subjects to biomass fuel smoke was 31.7±6.6 years. They have been exposed to dung inhalation products meanly 8.3±1.8 months in a year seasonally. The average daily exposure time was 15.7±3.3 hours. CIMT values of the two groups were not statistically different from each other (0.47±0.09 vs. 0.49±0.06 mm, p=0.138). However, a markedly reduced FAD % was determined in the study group (5.06±4.95 vs. 10.7±4.64, p<0.001). And GTN % of the BMF exposed group was significantly lower than the control group (14.41±8.47 vs. 21.85±7.87, p<0.001). FAD % and GTN % are markedly reduced in the individuals who have been exposed to BMF smoke inhalation products. Therefore, chronic BMF smoke exposure may be a risk factor for the development of endothelial dysfunction.

Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice.

PubMed

Tamura, Haruka; Ohgami, Nobutaka; Yajima, Ichiro; Iida, Machiko; Ohgami, Kyoko; Fujii, Noriko; Itabe, Hiroyuki; Kusudo, Tastuya; Yamashita, Hitoshi; Kato, Masashi

2012-01-01

We are routinely exposed to low frequency noise (LFN; below 0.5 kHz) at moderate levels of 60-70 dB sound pressure level (SPL) generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz) and high frequency noise (HFN; 16 kHz) at 70 dB SPL at a distance of approximately 10-20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance.

Chronic Exposure to Low Frequency Noise at Moderate Levels Causes Impaired Balance in Mice

PubMed Central

Tamura, Haruka; Ohgami, Nobutaka; Yajima, Ichiro; Iida, Machiko; Ohgami, Kyoko; Fujii, Noriko; Itabe, Hiroyuki; Kusudo, Tastuya; Yamashita, Hitoshi; Kato, Masashi

2012-01-01

We are routinely exposed to low frequency noise (LFN; below 0.5 kHz) at moderate levels of 60–70 dB sound pressure level (SPL) generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz) and high frequency noise (HFN; 16 kHz) at 70 dB SPL at a distance of approximately 10–20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance. PMID:22768129

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

PubMed

Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

2013-06-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

PubMed Central

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

Influence of chronic exposure to cold environment on thyroid gland function in rabbits.

PubMed

Mustafa, S; Elgazzar, A

2014-07-01

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect. © Georg Thieme Verlag KG Stuttgart · New York.

Chronic Bronchitis and Chronic Obstructive Pulmonary Disease (COPD) Among Textile Workers in Karachi, Pakistan.

PubMed

Nafees, Asaad Ahmed; Fatmi, Zafar; Kadir, Muhammad Masood; Sathiakumar, Nalini

2016-05-01

To determine the frequency and predictors of chronic bronchitis and COPD among textile workers in Karachi, Pakistan. Cross-sectional survey. Karachi, Pakistan, from October to December 2009. Male textile workers from 15 mills of Karachi were inducted. Data was collected using American Thoracic Society respiratory questionnaire (ATS-DLD-78-a) and spirometry. Out of 372 participants, 29 (7.8%) workers had chronic bronchitis (4, 9.1% aged ≥40 years) and 25 (6.7%) had COPD (12, 27.2% aged ≥40 years). Workers with chronic bronchitis had significantly decreased lung function compared to the healthy workers. Those reporting severe self-perceived dust exposure at work, ≥ 10 pack years of smoking, uneducated, longer duration of work (≥11 years), and ever smokers were more likely to have chronic bronchitis or COPD. In the multivariate analyses, severe self-perceived dust exposure at work (AOR = 7.4; 95% CI: 1.9, 28.0), family history of respiratory illness/symptoms (AOR = 4.8; 95% CI: 1.1, 20.9) and lack of education (AOR = 4.2; 95% CI: 1.1, 16.9) were significant predictors of chronic bronchitis. Duration of work ≥11 years (AOR = 5.5; 95% CI: 1.5, 19.7) and pack years of smoking ≥10 years (AOR = 3.5; 95% CI: 1.1, 11.7) were strong predictors for COPD. There is a high frequency of chronic bronchitis and COPD among textile workers. Multiple important predictors for prevention are identified.

Chronic radiation exposure modifies temporal dynamics of cytogenetic but not reproductive indicators in Scots pine populations.

PubMed

Geras'kin, Stanislav; Oudalova, Alla; Kuzmenkov, Alexey; Vasiliyev, Denis

2018-04-18

Over a period of 13 years (2003-2015), reproductive and cytogenetic effects are investigated in Scots pine populations growing in the Bryansk region of Russia radioactively contaminated as a result of the Chernobyl accident. In reference populations, the frequencies of cytogenetic abnormalities are shown to change with time in a cyclic manner. In chronically exposed populations, the cyclic patterns in temporal dynamics of cytogenetic abnormalities appear to be disturbed. In addition, a tendency to decrease in the frequencies of cytogenetic abnormalities with time as well as an increase in their variability with dose rate is revealed. In contrast, no significant impact of chronic radiation exposure on the time dynamics of reproductive indexes is detected. Finally, long-term observations on chronically exposed Scots pine populations revealed qualitative differences in the temporal dynamics of reproductive and cytogenetic indicators. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

PubMed

Flores-Montoya, Mayra Gisel; Sobin, Christina

2015-07-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

PubMed Central

Flores-Montoya, Mayra Gisel; Sobin, Christina

2014-01-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

Production and standing crop of litter and humus in a forest exposed to chronic gamma irradiation for twelve years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armentano, T.V.; Woodwell, G.M.

Continuous exposure since 1961 of an oak-pine forest at Brookhaven National Laboratory to chronic gamma irradiation has shown: (1) progressive reduction in litter production from the first year through 1965; (2) greater litter production in 1973 compared to 1965 at exposure rates below 9 R/day primarily because of the prolific sprouting of the oaks, especially Quercus alba; (3) further reduction in litter production in intermediate zones (14-49 R/day) from 1965 to 1973 as a result of replacement of the forest by a Carex pensylvanica mat; (4) increased litter production in the high exposure zone (125 R/day) in 1973 as amore » result of colonization by adventive species; (5) reduction in the standing crop of litter by 1973 at the lowest exposure rate studied (3.5 R/day) although in 1965 there was no reduction at exposure rates up to 15 R/day; (6) decline in humus content at 4.6 R/day and above with the standing crop in the Carex zone exceeding that of the shrub and damaged forest zones of lower exposures. Both further losses and partial recovery in the production and storage of organic matter have occurred since 1965. These changes constitute a portion of the long-term response of the forest to chronic disturbance. The pattern of response is the result of ecosystem processes that are still not in equilibrium with the chronic disturbance and which were not predictable from short-term studies, even those spanning as much as 4 yr.« less

The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon.

PubMed

Axelrad, J C; Howard, C V; McLean, W G

2003-03-14

Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC(50) for each OP or formulation was calculated. The IC(50) values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC(50) for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents.

Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan

Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LCmore » cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the

Exposure to Chronic Community Violence: Resilience in African American Children

ERIC Educational Resources Information Center

Jones, Janine M.

2007-01-01

In many African American communities, violence and poverty are often part of daily living. As a result, children are at risk for difficulties in all aspect of their lives, particularly their emotional well-being. This study explored the relationship between exposure to chronic community violence and the development of complex post-traumatic stress…

Occupational exposures and chronic obstructive pulmonary disease (COPD): comparison of a COPD-specific job exposure matrix and expert-evaluated occupational exposures.

PubMed

Kurth, Laura; Doney, Brent; Weinmann, Sheila

2017-03-01

To compare the occupational exposure levels assigned by our National Institute for Occupational Safety and Health chronic obstructive pulmonary disease-specific job exposure matrix (NIOSH COPD JEM) and by expert evaluation of detailed occupational information for various jobs held by members of an integrated health plan in the Northwest USA. We analysed data from a prior study examining COPD and occupational exposures. Jobs were assigned exposure levels using 2 methods: (1) the COPD JEM and (2) expert evaluation. Agreement (Cohen's κ coefficients), sensitivity and specificity were calculated to compare exposure levels assigned by the 2 methods for 8 exposure categories. κ indicated slight to moderate agreement (0.19-0.51) between the 2 methods and was highest for organic dust and overall exposure. Sensitivity of the matrix ranged from 33.9% to 68.5% and was highest for sensitisers, diesel exhaust and overall exposure. Specificity ranged from 74.7% to 97.1% and was highest for fumes, organic dust and mineral dust. This COPD JEM was compared with exposures assigned by experts and offers a generalisable approach to assigning occupational exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders

PubMed Central

2013-01-01

Background Exposure to pollutants including metals and particulate air pollution can alter DNA methylation. Yet little is known about intra-individual changes in DNA methylation over time in relationship to environmental exposures. Therefore, we evaluated the effects of acute- and chronic metal-rich PM2.5 exposures on DNA methylation. Methods Thirty-eight male boilermaker welders participated in a panel study for a total of 54 person days. Whole blood was collected prior to any welding activities (pre-shift) and immediately after the exposure period (post-shift). The percentage of methylated cytosines (%mC) in LINE-1, Alu, and inducible nitric oxide synthase gene (iNOS) were quantified using pyrosequencing. Personal PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) was measured over the work-shift. A questionnaire assessed job history and years worked as a boilermaker. Linear mixed models with repeated measures evaluated associations between DNA methylation, PM2.5 concentration (acute exposure), and years worked as a boilermaker (chronic exposure). Results PM2.5 exposure was associated with increased methylation in the promoter region of the iNOS gene (β = 0.25, SE: 0.11, p-value = 0.04). Additionally, the number of years worked as a boilermaker was associated with increased iNOS methylation (β = 0.03, SE: 0.01, p-value = 0.03). No associations were observed for Alu or LINE-1. Conclusions Acute and chronic exposure to PM2.5 generated from welding activities was associated with a modest change in DNA methylation of the iNOS gene. Future studies are needed to confirm this association and determine if the observed small increase in iNOS methylation are associated with changes in NO production or any adverse health effect. PMID:23758843

Antinociception induced by chronic exposure of rats to cigarette smoke.

PubMed

Anderson, Kenton L; Pinkerton, Kent E; Uyeminami, Dale; Simons, Christopher T; Carstens, Mirela Iodi; Carstens, E

2004-08-05

To investigate if chronic exposure to cigarette smoke induces analgesia, rats were exposed to concentrated cigarette smoke in an environmental chamber over four successive 5-day blocks (6 h/day), with 2 smoke-free days between blocks. A control group was exposed to room air. Tail flick latencies increased significantly (analgesia) during each smoke exposure block, with a relative decline in analgesia across blocks (tolerance) and a return to control levels during the first three smoke-free interludes while remaining higher after the conclusion of the 4-week exposure period. Mechanical (von Frey) withdrawal thresholds declined over time in smoke-exposed and control groups, with the smoke-exposed group showing significantly lower thresholds. Plasma nicotine reached 95.4 +/- 32 (S.D.) ng/ml at the end of weekly smoke exposure and declined to 44.9 +/- 10.6 ng/ml 24 h after withdrawal. Rats lost weight during smoke exposure and quickly regained weight during smoke-free interludes and at the cessation of smoke exposure. Analgesia may contribute to the initiation of smoking, and rapid reversal of the analgesic effect following acute exposure may contribute to the difficulty in quitting smoking.

Responses of Hyalella azteca to acute and chronic microplastic exposures.

PubMed

Au, Sarah Y; Bruce, Terri F; Bridges, William C; Klaine, Stephen J

2015-11-01

Limited information is available on the presence of microplastics in freshwater systems, and even less is known about the toxicological implications of the exposure of aquatic organisms to plastic particles. The present study was conducted to evaluate the effects of microplastic ingestion on the freshwater amphipod, Hyalella azteca. Hyalella azteca was exposed to fluorescent polyethylene microplastic particles and polypropylene microplastic fibers in individual 250-mL chambers to determine 10-d mortality. In acute bioassays, polypropylene microplastic fibers were significantly more toxic than polyethylene microplastic particles; 10-d lethal concentration 50% values for polyethylene microplastic particles and polypropylene microplastic fibers were 4.64 × 10(4) microplastics/mL and 71.43 microplastics/mL, respectively. A 42-d chronic bioassay using polyethylene microplastic particles was conducted to quantify effects on reproduction, growth, and egestion. Chronic exposure to polyethylene microplastic particles significantly decreased growth and reproduction at the low and intermediate exposure concentrations. During acute exposures to polyethylene microplastic particles, the egestion times did not significantly differ from the egestion of normal food materials in the control; egestion times for polypropylene microplastic fibers were significantly slower than the egestion of food materials in the control. Amphipods exposed to polypropylene microplastic fibers also had significantly less growth. The greater toxicity of microplastic fibers than microplastic particles corresponded with longer residence times for the fibers in the gut. The difference in residence time might have affected the ability to process food, resulting in an energetic effect reflected in sublethal endpoints. © 2015 SETAC.

Chronic Stress Exposure and Generation Are Related to the P-Factor and Externalizing Specific Psychopathology in Youth.

PubMed

Snyder, Hannah R; Young, Jami F; Hankin, Benjamin L

2017-05-25

Psychopathology is posited to be transdiagnostically linked to chronic stress. Yet efforts to understand the specificity and directionality of these links have been sparse, and the ubiquitous comorbidity of psychopathology has made the seemingly nonspecific links between psychological disorders and chronic stress difficult to interpret. The current study used a latent dimensional bifactor model of psychopathology to account for comorbidity and a multiwave prospective design to disentangle temporal associations between psychopathology and chronic stress longitudinally during the critical adolescent period for psychopathology risk and stress reactivity. A community sample of 567 youth (55.5% female, age M = 11.8 at baseline, M = 15.1 at end of study) were followed prospectively for 3 years, with chronic stress assessed with the Youth Life Stress Interview and psychopathology symptoms assessed via both self and parent report. Exposure to chronic stress predicted what is common across forms of psychopathology (the p factor), which in turn predicted generation of chronic stress over time. After accounting for comorbidity via the p factor, externalizing behaviors also had specific transactional links to chronic stress, whereas links between internalizing psychopathology and chronic stress were completely accounted for by common psychopathology. The results provide the first direct evidence that chronic stress is transdiagnostically and reciprocally linked to psychopathology, during a critical youth period for psychopathology onset and stress reactivity.

Glucoregulatory responses of adult and aged rats after exposure to chronic stress.

PubMed

Odio, M R; Brodish, A

1990-01-01

Stress has been implicated as an environmental factor that may accelerate the process of biological aging. However, this proposal has remained largely anecdotal due to relatively few studies that directly tested this hypothesis. In the present experiments groups of 6-month-old and 20-month-old male F-344 rats were chronically stressed for a six-month period. After the last stress session, when the animals were 12 months of age (adult) and 26 months of age (old), control and chronically stressed rats were tested for their ability to: (a) elicit glucose and insulin responses to an acute, novel stressor; (b) remove a circulatory glucose load elicited either by acute stress exposure or by injection of d-glucose; and (c) raise insulin levels after a glucose challenge. In control rats, we observed a deficit in each of these parameters in old compared to adult rats. Exposure to chronic stress did not exacerbate deterioration of these response mechanisms in either adult or old rats. In fact, the data showed a modest improvement in glucose tolerance in chronically stressed compared to age-matched control rats. We conclude that chronic stress did not exacerbate age-dependent decline of glucoregulatory capacity. From these results and from our earlier work, we speculate that the decline during aging of the functional integrity of systems involved in the response to stress may be sustained by periodic challenges from the organism's external environment.

Micro RNA responses to chronic or acute exposures to low dose ionizing radiation

PubMed Central

Chaudhry, M. Ahmad; Omaruddin, Romaica A.; Kreger, Bridget; de Toledo, Sonia M.; Azzam, Edouard I.

2014-01-01

Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose c-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of 137Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate c-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation. PMID:22367372

A cross-sectional study of secondhand smoke exposure and respiratory symptoms in non-current smokers in the U.S. trucking industry: SHS exposure and respiratory symptoms.

PubMed

Laden, Francine; Chiu, Yueh-Hsiu; Garshick, Eric; Hammond, S Katharine; Hart, Jaime E

2013-02-01

Previous studies have suggested associations of adult exposures to secondhand smoke (SHS) with respiratory symptoms, but no study has focused on blue-collar industrial environments. We assessed the association between SHS and respiratory symptoms in 1,562 non-current smoking U.S. trucking industry workers. Information on SHS exposure and respiratory health was obtained by questionnaire. Multiple logistic regression analyses were used to assess the associations of recent and lifetime exposures to SHS with chronic phlegm, chronic cough, and any wheeze, defined by American Thoracic Society criteria. In analyses adjusted for age, gender, race, childhood SHS exposure, former smoking, pack-years of smoking and years since quitting, body mass index, job title, region of the country, and urban residence, recent exposures to SHS were associated with all three respiratory symptoms (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.00-2.13) for chronic cough, 1.55 (95% CI = 1.08-2.21) for chronic phlegm, and 1.76 (95% CI = 1.41-2.21) for any wheeze). Workplace exposure was the most important recent exposure. Childhood exposure to SHS was also associated with all three symptoms, but only statistically significantly for chronic phlegm (OR = 1.84; 95% CI = 1.24-2.75). Additional years of living with a smoker were associated with an increased risk, but there was no evidence of a dose-response, except for chronic phlegm. In this group of trucking industry workers, childhood and recent exposures to SHS were related to respiratory symptoms.

A cross-sectional study of secondhand smoke exposure and respiratory symptoms in non-current smokers in the U.S. trucking industry: SHS exposure and respiratory symptoms

PubMed Central

2013-01-01

Background Previous studies have suggested associations of adult exposures to secondhand smoke (SHS) with respiratory symptoms, but no study has focused on blue-collar industrial environments. We assessed the association between SHS and respiratory symptoms in 1,562 non-current smoking U.S. trucking industry workers. Methods Information on SHS exposure and respiratory health was obtained by questionnaire. Multiple logistic regression analyses were used to assess the associations of recent and lifetime exposures to SHS with chronic phlegm, chronic cough, and any wheeze, defined by American Thoracic Society criteria. Results In analyses adjusted for age, gender, race, childhood SHS exposure, former smoking, pack-years of smoking and years since quitting, body mass index, job title, region of the country, and urban residence, recent exposures to SHS were associated with all three respiratory symptoms (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.00-2.13) for chronic cough, 1.55 (95% CI = 1.08-2.21) for chronic phlegm, and 1.76 (95% CI = 1.41-2.21) for any wheeze). Workplace exposure was the most important recent exposure. Childhood exposure to SHS was also associated with all three symptoms, but only statistically significantly for chronic phlegm (OR = 1.84; 95% CI = 1.24-2.75). Additional years of living with a smoker were associated with an increased risk, but there was no evidence of a dose–response, except for chronic phlegm. Conclusions In this group of trucking industry workers, childhood and recent exposures to SHS were related to respiratory symptoms. PMID:23368999

Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

PubMed

Hillmer, Ansel T; Tudorascu, Dana L; Wooten, Dustin W; Lao, Patrick J; Barnhart, Todd E; Ahlers, Elizabeth O; Resch, Leslie M; Larson, Julie A; Converse, Alexander K; Moore, Colleen F; Schneider, Mary L; Christian, Bradley T

2014-05-01

The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impact of antigenic exposures and role of molecular blood grouping in enhancing transfusion safety in chronically transfused thalassemics.

PubMed

Makroo, Raj Nath; Agrawal, Soma; Bhatia, Aakanksha; Chowdhry, Mohit; Thakur, Uday Kumar

2016-01-01

Red cell alloimmunization is an acknowledged complication of blood transfusion. Current transfusion practices for thalassemia do not cater to this risk. Serological phenotyping is usually not reliable in these cases unless performed before the first transfusion. Under such circumstances, molecular blood grouping is an effective alternative. To perform molecular blood group genotyping in chronically transfused thalassemia patients and assess the risk of antigenic exposure and incidence of alloimmunization with current transfusion protocols. Molecular blood group genotyping was performed for 47 chronically transfused thalassemia patients. Their 1-year transfusion records were retrieved to assess the antigenic exposure and the frequency thereof. Of 47 patients, 6 were already alloimmunized (3 with anti-E and 3 with anti-K) and were receiving the corresponding antigen negative units. We observed that random selection of ABO and Rh D matched units resulted in 57.7% ±8.26% chance of Rh and Kell phenotype matching also. Forty-four patients had received one or more antigenic exposures at least once. The 6 already alloimmunized patients were further exposed to antigens other than the ones they were immunized to. During the study period, only one patient developed an alloantibody, anti-E with exposure to antigens C (92%) and/or E (32%) at each transfusion. Several factors apart from mere antigen exposure may influence the development of alloimmunization as most of our patients received antigenic exposures but not alloimmunized. Our data provide an impetus for future large-scale studies to understand the development of alloimmunization in such patients.

Increased risk of chronic obstructive pulmonary diseases in coke oven workers: interaction between occupational exposure and smoking

PubMed Central

Hu, Y; Chen, B; Yin, Z; Jia, L; Zhou, Y; Jin, T

2006-01-01

Background Coke oven workers are regularly exposed to coke oven emissions (COE) and may be at risk of developing lung diseases. There is limited evidence for the link between exposure to COE and chronic obstructive pulmonary diseases (COPD). The aim of this study was to explore the dose‐response relationship between COE exposure and COPD and to assess the interaction with cigarette smoking. Methods Seven hundred and twelve coke oven workers and 211 controls were investigated in southern China. Benzene soluble fraction (BSF) concentrations as a surrogate of COE were measured in representative personal samples and the individual cumulative COE exposure level was quantitatively estimated. Detailed information on smoking habits and respiratory symptoms was collected and spirometric tests were performed. Results The mean BSF levels at the top of two coking plants were 743.8 and 190.5 μg/m3, respectively, which exceed the OSHA standard (150 μg/m3). After adjusting for cigarette smoking and other risk factors, there was a significant dose‐dependent reduction in lung function and increased risks of chronic cough/phlegm and COPD in coke oven workers. The odds ratio for COPD was 5.80 (95% confidence interval 3.13 to 10.76) for high level cumulative COE exposure (⩾1714.0 μg/m3‐years) compared with controls. The interaction between COE exposure and smoking in COPD was significant. The risk of COPD in those with the highest cumulative exposure to COE and cigarette smoking was 58‐fold compared with non‐smokers not exposed to COE. Conclusion Long term exposure to COE increases the risk of an interaction between COPD and cigarette smoking. PMID:16467069

Behavioral and Immunohistochemical Study of the Effects of Subchronic and Chronic Exposure to Glyphosate in Mice

PubMed Central

Ait Bali, Yassine; Ba-Mhamed, Saadia; Bennis, Mohamed

2017-01-01

Many epidemiological studies have described an adolescent-related psychiatric illness and sensorimotor deficits after Glyphosate based herbicide (GBH) exposure. GBH exposure in animal models of various ages suggests that it may be neurotoxic and could impact brain development and subsequently, behavior in adulthood. However, its neurotoxic effects on adolescent brain remain unclear and the results are limited. The present study was conducted to evaluate the neurobehavioral effects of GBH following acute, subchronic (6 weeks) and chronic (12 weeks) exposure (250 or 500 mg/kg/day) in mice treated from juvenile age until adulthood. Mice were subjected to behavioral testing with the open field (OF), the elevated plus maze, the tail suspension and Splash tests (STs). Their behaviors related to exploratory activity, anxiety and depression-like were recorded. After completion of the behavioral testing, adult mice were sacrificed and the expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and serotonin (5-HT) in the dorsal raphe nucleus (DRN), the basolateral amygdala (BLA) and the ventral medial prefrontal cortex (mPFC) was evaluated using immunohistochemical procedure. Our results indicate that unlike acute exposure, both subchronic and chronic exposure to GBH induced a decrease in body weight gain and locomotor activity, and an increase of anxiety and depression-like behavior levels. In addition, the immunohistochemical findings showed that only the chronic treatment induced a reduction of TH-immunoreactivity. However, both subchronic and chronic exposure produced a reduction of 5-HT-immunoreactivity in the DRN, BLA and ventral mPFC. Taken together, our data suggest that exposure to GBH from juvenile age through adulthood in mice leads to neurobehavioral changes that stem from the impairment of neuronal developmental processes. PMID:28848410

Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?

PubMed Central

Bjork, J; Albin, M; Welinder, H; Tinnerberg, H; Mauritzson, N; Kauppinen, T; Stromberg, U; Johansson, B; Billstrom, R; Mikoczy, Z; Ahlgren, T; Nilsson, P; Mitelman, F; Hagmar, L

2001-01-01

OBJECTIVES—To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML).
METHODS—A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure—that is, the exposure proportion for each occupational title—was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated.
RESULTS—For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures.
CONCLUSIONS—Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.


Keywords: risk factors; epidemiology; case-control study PMID:11600728

Work-Related Noise Exposure in a Cohort of Patients with Chronic Tinnitus: Analysis of Demographic and Audiological Characteristics.

PubMed

Ralli, Massimo; Balla, Maria Paola; Greco, Antonio; Altissimi, Giancarlo; Ricci, Pasquale; Turchetta, Rosaria; de Virgilio, Armando; de Vincentiis, Marco; Ricci, Serafino; Cianfrone, Giancarlo

2017-09-08

Work-related noise exposure is one of the major factors contributing to the development of adult-onset hearing loss and tinnitus. The aim of this study was to analyze, in patients with chronic tinnitus and long-term occupational noise exposure, (A) characteristics of hearing loss, tinnitus, comorbidities, demographic characteristics and a history of work-related noise exposure and (B) differences among individuals employed in occupations with high and low risk of developing work-related noise-induced hearing loss (NIHL). One hundred thirty six patients with chronic tinnitus and at least a 10 year-long working history were divided into two groups based on the risk of their profession to induce NIHL. Individuals employed in jobs at high risk for NIHL were mostly males and exhibited a poorer hearing threshold, more evident in the left ear. Tinnitus was mostly bilateral; the next largest presentation was left-sided; patients described their tinnitus as buzzing or high-pitched. Correlation between age, length of tinnitus and worse hearing was found. Patients with a higher degree of hearing impairment were mostly males and were more likely to have a family history of hearing loss and at least one cardiovascular comorbidity. Our study shows some differences in individuals with tinnitus and a history of a profession associated with increased exposure to NIHL compared to those without such a history.

Work-Related Noise Exposure in a Cohort of Patients with Chronic Tinnitus: Analysis of Demographic and Audiological Characteristics

PubMed Central

Balla, Maria Paola; Greco, Antonio; Altissimi, Giancarlo; Ricci, Pasquale; Turchetta, Rosaria; de Virgilio, Armando; de Vincentiis, Marco; Ricci, Serafino; Cianfrone, Giancarlo

2017-01-01

Work-related noise exposure is one of the major factors contributing to the development of adult-onset hearing loss and tinnitus. The aim of this study was to analyze, in patients with chronic tinnitus and long-term occupational noise exposure, (A) characteristics of hearing loss, tinnitus, comorbidities, demographic characteristics and a history of work-related noise exposure and (B) differences among individuals employed in occupations with high and low risk of developing work-related noise-induced hearing loss (NIHL). One hundred thirty six patients with chronic tinnitus and at least a 10 year-long working history were divided into two groups based on the risk of their profession to induce NIHL. Individuals employed in jobs at high risk for NIHL were mostly males and exhibited a poorer hearing threshold, more evident in the left ear. Tinnitus was mostly bilateral; the next largest presentation was left-sided; patients described their tinnitus as buzzing or high-pitched. Correlation between age, length of tinnitus and worse hearing was found. Patients with a higher degree of hearing impairment were mostly males and were more likely to have a family history of hearing loss and at least one cardiovascular comorbidity. Our study shows some differences in individuals with tinnitus and a history of a profession associated with increased exposure to NIHL compared to those without such a history. PMID:28885581

The effect of chronic carbon-monoxide exposure on the peak expiratory flow values of grill-kebab chefs.

PubMed

Al, Behcet; Yildirim, Cuma; Zengin, Suat; Cavdar, Murat; Togun, Ismail

2009-06-01

To determine the effect of chronic carbon-monoxide (CO) exposure on blood carboxy-hemoglobin (COHb) values in grill-kebab chefs, and if there is any subsequent airway obstruction. The study was carried out in Sahinbey Hospital, Medical School of Gaziantep University, Gaziantep, Turkey, between March 2007 and November 2007. Forty male grill-kebab chefs, working in restaurants for at least 3 years, and 48 non-smoker, male healthy volunteers were gathered for this study. The ages, body mass indexes (BMI), blood pressure (BP), COHb, N-terminal pro brain natriuretic peptide (NT-proBNP), and peak expiratory flow (PEF) values of the grill-kebab chefs and controls was measured. Statistical analysis was carried out using the SSPS 13.0 software. The average age for the study group was 33.0 +/- 9.1, and for the control group was 34.7+/- 6.5 years. The average occupation time for the study group was 16.1+/-7.3 years. The clinical attributes, ages, BMI, BP, and NT-proBNP values of both groups were similar. The COHb (6.5+/-1.5/2.0+/-1.1%) values were higher in grill-kebab chefs compared with the control group. The NT-proBNP values were determined as normal (<60 microg/L) in both groups. A higher decrease in PEF speed (average: 65.1/7.1 L/min) was recorded in the grill-kebab chefs. Chronic exposure to CO decreases PEF, with narrowing of the airway in grill-kebab chefs.

Injury, intense dust exposure, and chronic disease among survivors of the World Trade Center terrorist attacks of September 11, 2001.

PubMed

Alper, Howard E; Yu, Shengchao; Stellman, Steven D; Brackbill, Robert M

2017-12-01

The World Trade Center attack of September 11, 2001 in New York City (9/11) exposed thousands of people to intense concentrations of hazardous materials that have resulted in reports of increased levels of asthma, heart disease, diabetes, and other chronic diseases along with psychological illnesses such as post-traumatic stress disorder (PTSD). Few studies have discriminated between health consequences of immediate (short-term or acute) intense exposures versus chronic residential or workplace exposures. We used proportional hazards methods to determine adjusted hazard ratios (AHRs) for associations between several components of acute exposures (e.g., injury, immersion in the dust cloud) and four chronic disease outcomes: asthma, other non-neoplastic lung diseases, cardiovascular disease, and diabetes, in 8701 persons free of those conditions prior to exposure and who were physically present during or immediately after the World Trade Center attacks. Participants were followed prospectively up to 11 years post-9/11. Heart disease exhibited a dose-response association with sustaining injury (1 injury type: AHR =2.0, 95% CI (Confidence Interval) 1.1-3.6; 2 injury types: AHR = 3.1, 95% CI 1.2-7.9; 3 or more injury types: AHR = 6.8, 95% CI 2.0-22.6), while asthma and other lung diseases were both significantly associated with dust cloud exposure (AHR = 1.3, 95% CI 1.0-1.6). Diabetes was not associated with any of the predictors assessed in this study. In this study we demonstrated that the acute exposures of injury and dust cloud that were sustained on 9/11/2001 had significant associations with later heart and respiratory diseases. Continued monitoring of 9/11 exposed persons' health by medical providers is warranted for the foreseeable future.

The Longitudinal Effects of Chronic Mediated Exposure to Political Violence on Ideological Beliefs About Political Conflicts Among Youths.

PubMed

Gvirsman, Shira Dvir; Huesmann, L Rowell; Dubow, Eric F; Landau, Simha F; Boxer, Paul; Shikaki, Khalil

This study examines the effects of chronic (i.e., repeated and cumulative) mediated exposure to political violence on ideological beliefs regarding political conflict. It centers on these effects on young viewers, from preadolescents to adolescents. Ideological beliefs refers here to support of war, perception of threat to one's nation, and normative beliefs concerning aggression toward the out-group. A longitudinal study was conducted on a sample of Israeli and Palestinian youths who experience the Israeli-Palestinian conflict firsthand ( N = 1,207). Two alternative hypotheses were tested: that chronic exposure via the media increases support for war and aggression and elevates feeling of threat, or that chronic exposure via the media strengthens preexisting beliefs. Results demonstrated that higher levels of exposure were longitudinally related to stronger support for war. Regarding normative beliefs about aggression and threat to one's nation, mediated exposure reinforced initial beliefs, rendering the youths more extreme in their attitudes. These results mostly support the conceptualization of the relation between media violence and behaviors as "reciprocally determined" or "reinforcing spirals." The results are also discussed in light of the differences found between the effect of exposure to political violence firsthand and exposure via the media.

Chronic hydrocarbon exposure of harlequin ducks in areas affected by the Selendang Ayu oil spill at Unalaska Island, Alaska

USGS Publications Warehouse

Flint, Paul L.; Schamber, J.L.; Trust, K.A.; Miles, A.K.; Henderson, J.D.; Wilson, B.W.

2012-01-01

We evaluated chronic exposure of harlequin ducks (Histrionicus histrionicus) to hydrocarbons associated with the 2004 M/V Selendang Ayu oil spill at Unalaska Island, Alaska. We measured levels of hepatic 7-ethoxyresorufin-O-deethylase activity (EROD) in liver biopsy samples as an indicator of hydrocarbon exposure in three oiled bays and one reference bay in 2005, 2006, and 2008. Median EROD activity in ducks from oiled bays was significantly higher than in the reference bay in seven of nine pairwise comparisons. These results indicated that harlequin ducks were exposed to lingering hydrocarbons more than three years after the spill.

Investigation of chronic toxicity of hydroxyapatite nanoparticles administered orally for one year in wistar rats.

PubMed

Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

2017-07-01

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (nano HA), a prospective nano biomaterial is extensively studied, its interaction on biological systems following chronic exposure is less exploited. In the present study, Wistar rats were given various concentrations of nano HA in the diet to determine the chronic toxicity and potential carcinogenicity. Altogether 140 rats were used for the study under various administration dosages along with control. The animals were sacrificed after 12months of controlled continuous dosing. All in-life parameters, including body weight, food consumption, clinical observations, survival, biochemical and hematology, were unaffected by the chronic exposure of nano HA orally. Similarly, gross and histopathological evaluation was also unchanged following exposure to nano HA. No evidence of nano HA-related lesions or Nano HA-induced neoplasia was suggested in this rodent bioassay study. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose.

PubMed

Martí; Armario

1997-05-01

The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

PubMed

Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

2016-11-01

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl 2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl 2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl 2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl 2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease.

PubMed

Paulin, Laura M; Diette, Gregory B; Blanc, Paul D; Putcha, Nirupama; Eisner, Mark D; Kanner, Richard E; Belli, Andrew J; Christenson, Stephanie; Tashkin, Donald P; Han, MeiLan; Barr, R Graham; Hansel, Nadia N

2015-03-01

Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. To determine the impact of occupational exposures on COPD morbidity. A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Paulin, Laura M.; Diette, Gregory B.; Blanc, Paul D.; Putcha, Nirupama; Eisner, Mark D.; Kanner, Richard E.; Belli, Andrew J.; Christenson, Stephanie; Tashkin, Donald P.; Han, MeiLan; Barr, R. Graham

2015-01-01

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. Objectives: To determine the impact of occupational exposures on COPD morbidity. Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may

The Effect of Chronic Arsenic Exposure in Zebrafish

PubMed Central

Hallauer, Janell; Geng, Xiangrong; Yang, Hung-Chi; Shen, Jian; Tsai, Kan-Jen

2016-01-01

Abstract Arsenic is a prevalent environmental toxin and a Group one human carcinogenic agent. Chronic arsenic exposure has been associated with many human diseases. The aim of this study is to evaluate zebrafish as an animal model to assess arsenic toxicity in elevated long-term arsenic exposure. With prolonged exposure (6 months) to various concentrations of arsenic from 50 ppb to 300 ppb, effects of arsenic accumulation in zebrafish tissues, and phenotypes were investigated. Results showed that there are no significant changes of arsenic retention in zebrafish tissues, and zebrafish did not exhibit any visible tumor formation under arsenic exposure conditions. However, the zebrafish demonstrate a dysfunction in their neurological system, which is reflected by a reduction of locomotive activity. Moreover, elevated levels of the superoxide dismutase (SOD2) protein were detected in the eye and liver, suggesting increased oxidative stress. In addition, the progenies of arsenic-treated parents displayed a smaller biomass (four-fold reduction in body weight) compared with those from their parental controls. This result indicates that arsenic may induce genetic or epigenetic changes that are then passed on to the next generation. Overall, this study demonstrates that zebrafish is a convenient vertebrate model with advantages in the evaluation of arsenic-associated neurological disorders as well as its influences on the offspring. PMID:27140519

Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus.

PubMed

Mulholland, Patrick J; Spencer, Kathryn B; Hu, Wei; Kroener, Sven; Chandler, L Judson

2015-06-01

Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites. The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca(2+) imaging, and western blot analyses in a well-characterized in vitro model of chronic alcohol exposure. Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K(+) currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca(2+) transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca(2+) transients induced by chronic alcohol exposure were not related to synaptic targeting of N-methyl-D-aspartate (NMDA) receptors or morphological adaptations in apical dendritic arborization. These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a downregulation of KChIP3 drive the elevated bAP-associated Ca(2+) transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function.

Enhanced corticobulbar excitability in chronic smokers during visual exposure to cigarette smoking cues

PubMed Central

Vicario, Carmelo M.; Komeilipoor, Naeem; Cesari, Paola; Rafal, Robert D.; Nitsche, Michael A.

2014-01-01

Background Neuroimaging studies of chronic smokers report altered activity of several neural regions involved in the processing of rewarding outcomes. Neuroanatomical evidence suggests that these regions are directly connected to the tongue muscle through the corticobulbar pathways. Accordingly, we examined whether corticobulbar excitability might be considered a somatic marker for nicotine craving. Methods We compared motor-evoked potential (MEP) amplitudes recorded from the tongue and the extensor carpi radialis (control muscle) of chronic smokers under drug withdrawal and intake conditions as well as a nonsmoker group. All participants were tested during passive exposure to pictures showing a smoking cue or a meaningless stimulus. In the intake condition, chronic smokers were asked to smoke a real cigarette (CSn: group 1) or a placebo (CSp: group 2). Results Results show that MEP amplitudes recorded from the tongues of participants in the CSn and CSp groups under the withdrawal condition were selectively enhanced during exposure to a smoking cue. However, this effect on tongue MEP amplitudes disappeared in the intake condition for both the CSn and CSp groups. Limitations Limitations include the fact that the study was conducted in 2 different laboratories, the small sample size, the absence of data on chronic smoker craving strength and the different tastes of the real and placebo cigarettes. Conclusion These results suggest that, in chronic smokers, tongue muscle MEP amplitudes are sensitive to neural processes active under the physiological status of nicotine craving. This finding implicates a possible functional link between neural excitability of the corticobulbar pathway and the reward system in chronic smokers. PMID:24485386

Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome.

PubMed

Hoyt, Laura R; Randall, Matthew J; Ather, Jennifer L; DePuccio, Daniel P; Landry, Christopher C; Qian, Xi; Janssen-Heininger, Yvonne M; van der Vliet, Albert; Dixon, Anne E; Amiel, Eyal; Poynter, Matthew E

2017-08-01

Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774) amplifies IL-1β secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells), effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K + efflux or Zn 2+ homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD + . Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH) mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1β hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1β hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation. Copyright © 2017. Published by Elsevier

Chronic lead exposure is epidemic in obligate scavenger populations in eastern North America.

PubMed

Behmke, Shannon; Fallon, Jesse; Duerr, Adam E; Lehner, Andreas; Buchweitz, John; Katzner, Todd

2015-06-01

Lead is a prominent and highly toxic contaminant with important impacts to wildlife. To understand the degree to which wildlife populations are chronically exposed, we quantified lead levels within American black vultures (Coragyps atratus; BLVU) and turkey vultures (Cathartes aura; TUVU), two species that are useful as environmental sentinels in eastern North America. Every individual sampled (n=108) had bone lead levels indicative of chronic exposure to anthropogenic lead (BLVU: x¯=36.99 ± 55.21 mg Pb/kg tissue (±SD); TUVU: x¯=23.02 ± 18.77 mg/kg). Only a few showed evidence of recent lead exposure (BLVU liver: x¯=0.78 ± 0.93 mg/kg; TUVU liver: x¯=0.55 ± 0.34 mg/kg). Isotopic ratios suggested multiple potential sources of lead including ammunition, gasoline, coal-fired power plants, and zinc smelting. Black and turkey vultures range across eastern North America, from Quebec to Florida and individuals may traverse thousands of kilometers annually. The extent to which vultures are exposed suggests that anthropogenic lead permeates eastern North American ecosystems to a previously unrecognized degree. Discovery of an epidemic of chronic lead exposure in such widespread and common species and the failure of soft-tissue sampling to diagnose this pattern has dramatic implications for understanding modern wildlife and human health concerns. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

PubMed

Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

2018-08-01

Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Lost productive life years caused by chronic conditions in Australians aged 45-64 years, 2010-2030.

PubMed

Schofield, Deborah J; Shrestha, Rupendra N; Cunich, Michelle; Tanton, Robert; Kelly, Simon; Passey, Megan E; Veerman, Lennert J

2015-09-21

To estimate (1) productive life years (PLYs) lost because of chronic conditions in Australians aged 45-64 years from 2010 to 2030, and (2) the impact of this loss on gross domestic product (GDP) over the same period. A microsimulation model, Health&WealthMOD2030, was used to project lost PLYs caused by chronic conditions from 2010 to 2030. The base population consisted of respondents aged 45-64 years to the Australian Bureau of Statistics Survey of Disability, Ageing and Carers 2003 and 2009. The national impact of lost PLYs was assessed with Treasury's GDP equation. Lost PLYs due to chronic disease at 2010, 2015, 2020, 2025 and 2030 (ie, whole life years lost because of chronic disease); the national impact of lost PLYs at the same time points (GDP loss caused by PLYs); the effects of population growth, labour force trends and chronic disease trends on lost PLYs and GDP at each time point. Using Health&WealthMOD2030, we estimated a loss of 347,000 PLYs in 2010; this was projected to increase to 459,000 in 2030 (32.28% increase over 20 years). The leading chronic conditions associated with premature exits from the labour force were back problems, arthritis and mental and behavioural problems. The percentage increase in the number of PLYs lost by those aged 45-64 years was greater than that of population growth for this age group (32.28% v 27.80%). The strongest driver of the increase in lost PLYs was population growth (accounting for 89.18% of the increase), followed by chronic condition trends (8.28%). Our study estimates an increase of 112 000 lost PLYs caused by chronic illness in older workers in Australia between 2010 and 2030, with the most rapid growth projected to occur in men aged 55-59 years and in women aged 60-64 years. The national impact of this lost labour force participation on GDP was estimated to be $37.79 billion in 2010, increasing to $63.73 billion in 2030.

New Insights into the Effects of Chronic Kidney Failure and Dialysate Exposure on the Peritoneum.

PubMed

Vlahu, Carmen A; Aten, Jan; de Graaff, Marijke; van Veen, Henk; Everts, Vincent; de Waart, Dirk R; Struijk, Dirk G; Krediet, Raymond T

♦ INTRODUCTION: Chronic uremia and the exposure to dialysis solutions during peritoneal dialysis (PD) induce peritoneal alterations. Using a long-term peritoneal exposure model, we compared the effects of chronic kidney failure (CKD) itself and exposure to either a 'conventional' or a 'biocompatible' dialysis solution on peritoneal morphology and function. ♦ METHODS: Wistar rats (Harlan, Zeist, the Netherlands) were grouped into: normal kidney function (NKF), CKD induced by 70% nephrectomy, CKD receiving daily peritoneal infusions with 3.86% glucose Dianeal (CKDD), or Physioneal (both solutions from Baxter Healthcare, Castlebar, Ireland) (CKDP). At 16 weeks, a peritoneal function test was performed, and histology, ultrastructure, and hydroxyproline content of peritoneal tissue were assessed. ♦ RESULTS: Comparing CKD with NKF, peritoneal transport rates were higher, mesothelial cells (MC) displayed increased number of microvilli, blood and lymph vasculature expanded, vascular basal lamina appeared thicker, with limited areas of duplication, and fibrosis had developed. All alterations, except lymphangiogenesis, were enhanced by exposure to both dialysis fluids. Distinct MC alterations were observed in CKDD and CKDP, the latter displaying prominent basolateral protrusions. In addition, CKDP was associated with a trend towards less fibrosis compared to CKDD. ♦ CONCLUSIONS: Chronic kidney failure itself induced peritoneal alterations, which were in part augmented by exposure to glucose-based dialysis solutions. Overall, the conventional and biocompatible solutions had similar long-term effects on the peritoneum. Importantly, the latter may attenuate the development of fibrosis. Copyright © 2016 International Society for Peritoneal Dialysis.

Bilateral Vestibular Dysfunction Associated With Chronic Exposure to Military Jet Propellant Type-Eight Jet Fuel

PubMed Central

Fife, Terry D.; Robb, Michael J. A.; Steenerson, Kristen K.; Saha, Kamala C.

2018-01-01

We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3–5 years’ duration while working on or near the flight line. Exposure to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n-hexane in the blood of one of the cases. The presenting symptoms were dizziness, headache, fatigue, and imbalance. Rotational chair testing confirmed bilateral vestibular dysfunction in all the three patients. Vestibular function improved over time once the exposure was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon exposure in humans, but only recently has emphasis been placed specifically on the detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity. Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular therapy offer the best chance for improved balance. Bilateral vestibular impairment is under-recognized in those chronically exposed to all forms of jet fuel. PMID:29867750

Association between Hypertension and Chronic Arsenic Exposure in Drinking Water: A Cross-Sectional Study in Bangladesh

PubMed Central

Islam, Mohammad Rafiqul; Khan, Ismail; Attia, John; Hassan, Sheikh Mohammad Nazmul; McEvoy, Mark; D’Este, Catherine; Azim, Syed; Akhter, Ayesha; Akter, Shahnaz; Shahidullah, Sheikh Mohammad; Milton, Abul Hasnat

2012-01-01

Chronic arsenic exposure and its association with hypertension in adults are inconclusive and this cross-sectional study investigated the association. The study was conducted between January and July 2009 among 1,004 participants from 1,682 eligible women and men aged ≥30 years living in rural Bangladesh who had continuously consumed arsenic-contaminated drinking water for at least 6 months. Hypertension was defined as systolic blood pressure ≥140 mmHg (systolic hypertension) and diastolic blood pressure ≥90 mmHg (diastolic hypertension). Pulse pressure was calculated by deducting diastolic from systolic pressure and considered to be increased when the difference was ≥55 mmHg. The prevalence of hypertension was 6.6% (95% CI: 5.1–8.3%). After adjustment for other factors, no excess risk of hypertension was observed for arsenic exposure >50μg/L or to that of arsenic exposure as quartiles or as duration. Arsenic concentration as quartiles and >50 μg/L did show a strong relationship with increased pulse pressure (adjusted OR: 3.54, 95% CI: 1.46–8.57), as did arsenic exposure for ≥10 years (adjusted OR: 5.25, 95% CI: 1.41–19.51). Arsenic as quartiles showed a dose response relationship with increased pulse pressure. Our study suggests an association between higher drinking water arsenic or duration and pulse pressure, but not hypertension. PMID:23222207

Association between hypertension and chronic arsenic exposure in drinking water: a cross-sectional study in Bangladesh.

PubMed

Islam, Mohammad Rafiqul; Khan, Ismail; Attia, John; Hassan, Sheikh Mohammad Nazmul; McEvoy, Mark; D'Este, Catherine; Azim, Syed; Akhter, Ayesha; Akter, Shahnaz; Shahidullah, Sheikh Mohammad; Milton, Abul Hasnat

2012-12-07

Chronic arsenic exposure and its association with hypertension in adults are inconclusive and this cross-sectional study investigated the association. The study was conducted between January and July 2009 among 1,004 participants from 1,682 eligible women and men aged ≥30 years living in rural Bangladesh who had continuously consumed arsenic-contaminated drinking water for at least 6 months. Hypertension was defined as systolic blood pressure ≥140 mmHg (systolic hypertension) and diastolic blood pressure ≥90 mmHg (diastolic hypertension). Pulse pressure was calculated by deducting diastolic from systolic pressure and considered to be increased when the difference was ≥55 mmHg. The prevalence of hypertension was 6.6% (95% CI: 5.1-8.3%). After adjustment for other factors, no excess risk of hypertension was observed for arsenic exposure >50 μg/L or to that of arsenic exposure as quartiles or as duration. Arsenic concentration as quartiles and >50 μg/L did show a strong relationship with increased pulse pressure (adjusted OR: 3.54, 95% CI: 1.46-8.57), as did arsenic exposure for ≥10 years (adjusted OR: 5.25, 95% CI: 1.41-19.51). Arsenic as quartiles showed a dose response relationship with increased pulse pressure. Our study suggests an association between higher drinking water arsenic or duration and pulse pressure, but not hypertension.

Chronic exposure to environmental levels of tribromophenol impairs zebrafish reproduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Jun; Graduate School of the Chinese Academy of Sciences, Beijing 100039; Liu Chunsheng

Tribromophenol (2,4,6-TBP) is ubiquitously found in aquatic environments and biota. In this study, we exposed zebrafish embryos (F{sub 0}; 2'''' days post-fertilization, dpf) to environmental concentration (0.3 mug/L) and a higher concentration (3.0 mug/L) of TBP and assessed the impact of chronic exposure (120 dpf) on reproduction. TBP exposure did not cause a significant increase in the malformation and reduction in the survival in the F{sub 0}-generation fish. After TBP exposure, the plasma testosterone and estradiol levels significantly increased in males and decreased in females. The transcription of steroidogenic genes (3beta-HSD, 17beta-HSD, CYP17, CYP19A, CYP19B) was significantly upregulated in themore » brain and testes in males and downregulated in the brain and ovary in females. TBP exposure significantly downregulated and upregulated the expression of VTG in the liver of female and male fish, respectively. Meanwhile, TBP exposure altered the sex ratio toward a male-dominant state. The F{sub 1}-generation larvae exhibited increased malformation, reduced survival, and retarded growth, suggesting that TBP in the aquatic environment has significant adverse effects on fish population.« less

The Longitudinal Effects of Chronic Mediated Exposure to Political Violence on Ideological Beliefs About Political Conflicts Among Youths

PubMed Central

Gvirsman, Shira Dvir; Huesmann, L. Rowell; Dubow, Eric F.; Landau, Simha F.; Boxer, Paul; Shikaki, Khalil

2015-01-01

This study examines the effects of chronic (i.e., repeated and cumulative) mediated exposure to political violence on ideological beliefs regarding political conflict. It centers on these effects on young viewers, from preadolescents to adolescents. Ideological beliefs refers here to support of war, perception of threat to one's nation, and normative beliefs concerning aggression toward the out-group. A longitudinal study was conducted on a sample of Israeli and Palestinian youths who experience the Israeli-Palestinian conflict firsthand (N = 1,207). Two alternative hypotheses were tested: that chronic exposure via the media increases support for war and aggression and elevates feeling of threat, or that chronic exposure via the media strengthens preexisting beliefs. Results demonstrated that higher levels of exposure were longitudinally related to stronger support for war. Regarding normative beliefs about aggression and threat to one's nation, mediated exposure reinforced initial beliefs, rendering the youths more extreme in their attitudes. These results mostly support the conceptualization of the relation between media violence and behaviors as “reciprocally determined” or “reinforcing spirals.” The results are also discussed in light of the differences found between the effect of exposure to political violence firsthand and exposure via the media. PMID:26997852

Persistent effects of prior chronic exposure to corticosterone on reward-related learning and motivation in rodents.

PubMed

Olausson, Peter; Kiraly, Drew D; Gourley, Shannon L; Taylor, Jane R

2013-02-01

Repeated or prolonged exposure to stress has profound effects on a wide spectrum of behavioral and neurobiological processes and has been associated with the pathophysiology of depression. The multifaceted nature of this disorder includes despair, anhedonia, diminished motivation, and disrupted cognition, and it has been proposed that depression is also associated with reduced reward-motivated learning. We have previously reported that prior chronic corticosterone exposure to mice produces a lasting depressive-like state that can be reversed by chronic antidepressant treatment. In the present study, we tested the effects of prior chronic exposure to corticosterone (50 μg/ml) administered to rats or to mice in drinking water for 14 days followed by dose-tapering over 9 days. The exposure to corticosterone produced lasting deficits in the acquisition of reward-related learning tested on a food-motivated instrumental task conducted 10-20 days after the last day of full dose corticosterone exposure. Rats exposed to corticosterone also displayed reduced responding on a progressive ratio schedule of reinforcement when tested on day 21 after exposure. Amitriptyline (200 mg/ml in drinking water) exposure for 14 days to mice produced the opposite effect, enhancing food-motivated instrumental acquisition and performance. Repeated treatment with amitriptyline (5 mg/kg, intraperitoneally; bid) subsequent to corticosterone exposure also prevented the corticosterone-induced deficits in rats. These results are consistent with aberrant reward-related learning and motivational processes in depressive states and provide new evidence that stress-induced neuroadaptive alterations in cortico-limbic-striatal brain circuits involved in learning and motivation may play a critical role in aspects of mood disorders.

Chronic Arsenic Exposure in Nanomolar Concentrations Compromises Wound Response and Intercellular Signaling in Airway Epithelial Cells

PubMed Central

Boitano, Scott

2013-01-01

Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions, including mucociliary clearance, bactericide production, and as an initiating signal in wound repair. We evaluated the effects of chronic low-dose arsenic relevant to U.S. drinking water standards (i.e., 10 ppb [130nM]) on airway epithelial cells. Immortalized human bronchial epithelial cells (16HBE14o-) were exposed to 0, 130, or 330nM arsenic (as Na-arsenite) for 4–5 weeks and examined for wound repair efficiency and ATP-mediated Ca2+ signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca2+ signaling. We further show that arsenic compromises ATP-mediated Ca2+ signaling by altering both Ca2+ release from intracellular stores (via metabotropic P2Y receptors) and Ca2+ influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca2+ signaling under conditions of natural exposure, we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na-arsenite supplemented drinking water for 4 weeks. Tracheal epithelial cells from arsenic-exposed mice displayed reduced ATP-mediated Ca2+ signaling dynamics similar to our in vitro chronic exposure. Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water (i.e., 10–50 ppb) alters cellular mechanisms critical to airway innate immunity. PMID:23204110

Controlled exposure of volunteers with chronic obstructive pulmonary disease to sulfur dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linn, W.S.; Fischer, D.A.; Shamoo, D.A.

1985-08-01

Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO/sub 2/) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposures, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO/sub 2/ exposure. Oldermore » adults with COPD seem less reactive to a given concentration of SO/sub 2/ than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO/sub 2/ dose rates) and/or to lower airway reactivity in the COPD group.« less

Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

PubMed Central

Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

2013-01-01

Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

Urbanization and Daily Exposure to Biomass Fuel Smoke Both Contribute to Chronic Bronchitis Risk in a Population with Low Prevalence of Daily Tobacco Smoking.

PubMed

Miele, Catherine H; Jaganath, Devan; Miranda, J Jaime; Bernabe-Ortiz, Antonio; Gilman, Robert H; Johnson, Caroline M; Diette, Gregory B; Wise, Robert A; Checkley, William

2016-01-01

Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude. We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis. Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis. We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays.

Tracking exposure to child poverty during the first 10 years of life in a Quebec birth cohort.

PubMed

Séguin, Louise; Nikiema, Beatrice; Gauvin, Lise; Lambert, Marie; Thanh Tu, Mai; Kakinami, Lisa; Paradis, Gilles

2012-04-27

Early childhood poverty is associated with adult chronic diseases. The objectives of this study were to examine patterns of exposure to poverty during the first 10 years of life in the Quebec Longitudinal Study of Child Development (QLSCD) cohort according to three measures of poverty and to explore family characteristics associated with different poverty exposures. Data from 1,334 participants from the QLSCD were collected annually at home from ages 5 months through 10 years. Household income (previous 12 months) and sources of income were recorded at each data round. Poverty status was operationalized as 1) living below the low income cut-off of Statistics Canada, 2) receiving social welfare and 3) being in the lowest quintile of socio-economic status. We plotted trends in the prevalence of child poverty over time. We used latent class growth modelling to identify subgroups with similar poverty trajectories. Duration of poverty according to each measure was computed separately for early childhood, middle childhood, and the entire 10 years of life. Four trajectories of poverty were identified: stable poor, decreasing likelihood, increasing likelihood, and never poor. The three measures of poverty do not cover the same population, yet the characteristics of those identified as poor are similar. Children of non-European, immigrant mothers were most likely to be poor, and there was a higher likelihood of children from single-parent families to live in chronic poverty during the first 10 years. A large proportion of children are exposed to poverty before 10 years of age. More effective public policies could reduce child poverty.

Physiological response of juvenile rainbow trout to chronic low level exposures of waterborne silver.

PubMed

Galvez, F; Hogstrand, C; Wood, C M

1998-02-01

The physiological effects of chronic exposure to AgNO3 in moderately hard freshwater were investigated in juvenile rainbow trout (Oncorhynchus mykiss Walbaum). Two separate 28-day exposures were performed at silver concentrations of 0.5 and 2.0 micrograms/L in flowing Hamilton dechlorinated tap water. Exposure to 0.5 microgram/L Ag resulted in a slight increase (approximately 14.9%) in food consumption, whereas growth rates remained unaltered. Both plasma Na+ and Cl- levels were significantly decreased by 11.8% and 9.3%, respectively at day 16 of the exposure. Hepatic Ag concentrations were elevated approximately 4-fold in 0.5 microgram/L Ag-exposed fish. However, no significant increases in liver metallothionein (MT) concentrations were noted. No mortalities were observed during this 28-day exposure. In comparison, chronic exposure to 2.0 micrograms/L Ag resulted in a 28.8% decrease in food consumption and a 43.0% reduction in growth rate. Plasma [Na+] was decreased by 18.3%, whereas plasma [Cl-] was reduced by 12.2% at day 7. At both concentrations of silver, plasma ion concentrations appeared to recover thereafter. Silver accumulated steadily in the liver up until day 15 when concentrations were 39.7 micrograms/g wet weight (285-fold increase) above control levels. In addition, MT levels were increased by 81.2% at day 7. Silver exposure at 2.0 micrograms/L resulted in approximately 15.0% mortality over the 28-day period.

Lack of physiological responses to hydrocarbon accumulation by Mytilus trossulus after 3-4 years chronic exposure to spilled Exxon Valdez crude oil in Prince William Sound.

PubMed

Thomas, R E; Brodersen, C; Carls, M G; Babcock, M; Rice, S D

1999-01-01

Mussels, Mytilus trossulus, were sampled in 1992 and 1993 from beaches in Prince William Sound that had been oiled by the Exxon Valdez spill of March, 1989. At some of the oiled beaches, mussels were collected from beds overlying oiled sediments, and from bedrock adjacent to these beds. Mussels were also collected from beaches within the Sound that had not been impacted by the spill. Polynuclear aromatic hydrocarbon (PAH) concentrations in mussel tissue, physiological responses (byssal thread production, condition index, clearance rate, and glycogen content), were determined for each group of mussels. Total PAH concentrations in mussel tissue ranged from 0 to 6 micrograms g-1, and were significantly greater in mussels from oiled beds than those from reference beds. No significant differences were noted in byssal thread production, condition index, clearance rate, or glycogen content between oiled sample sites and reference sites. The lack of physiological response was surprising because mussels in this study were chronically exposed to PAH for 3-4 years, and none of the physiological responses measured appeared to be affected by that exposure. The lack of a physiological response suggests that chronically exposed mussels may develop a physiological tolerance to PAH, but we recognize that these measures may not have been sensitive enough to discriminate response from background noise.

Environmental exposure as an independent risk factor of chronic bronchitis in northwest Russia

PubMed Central

Nieminen, Pentti; Panychev, Dmitry; Lyalyushkin, Sergei; Komarov, German; Nikanov, Alexander; Borisenko, Mark; Kinnula, Vuokko L.; Toljamo, Tuula

2013-01-01

Background In some parts of the northwest Russia, Murmansk region, high exposures to heavy mining and refining industrial air pollution, especially sulphur dioxide, have been documented. Objective Our aim was to evaluate whether living in the mining area would be an independent risk factor of the respiratory symptoms. Design A cross-sectional survey of 200 Murmansk region adult citizens was performed. The main outcome variable was prolonged cough with sputum production that fulfilled the criteria of chronic bronchitis. Results Of the 200 participants, 53 (26.5%) stated that they had experienced chronic cough with phlegm during the last 2 years. The prevalence was higher among those subjects living in the mining area with its high pollution compared to those living outside this region (35% vs. 18%). Multivariable regression model confirmed that the risk for the chronic cough with sputum production was elevated in a statistical significant manner in the mining and refining area (adjusted OR 2.16, 95% CI 1.07–4.35) after adjustment for smoking status, age and sex. Conclusions The increased level of sulphur dioxide emitted during nickel mining and refining may explain these adverse health effects. This information is important for medical authorities when they make recommendations and issue guidelines regarding the relationship between environmental pollution and health outcomes. PMID:23440671

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

USGS Publications Warehouse

Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

2016-01-01

The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

Effect of chronic exposure to welding light on Calabar welders.

PubMed

Davies, K G; Asanga, U; Nku, C O; Osim, E E

2007-01-01

It was generally observed that welders in Calabar, Nigeria did not always wear their protective goggles during welding. Since chronic exposure to welding light can impair vision this study was done to assess the effect of exposure to welding light on ocular function of welders in Calabar, Nigeria. There were 195 subjects comprising 110 welders (test) and 85 control subjects. Both groups were all male and had similar age range. The tests employed were clinical examination for ocular disorders, assessment of visual acuity, and opthalmoscopy. Test questionnaire was also used to record information on length of service, precautionary measures at work place, age and past ocular illnesses. The study also compared incidence of ocular disorders between the two groups of welders (arc and carbide welders). The mean ages of the welders and their control were not significantly different (27.53 +/- 10.0 vs 27.78 +/- 8.5 yrs respectively). There was a significantly [P < 0.01] higher incidence of pingueculum, cataract, allergic conjunctivitis, corneal opacity, and keratoconjunctivitis (arc eye) in welders than in their control subjects. However, visual acuity, incidence of pterygium and glaucoma were similar. Between the two groups of welders, the incidence of pterygium, corneal opacity and keratoconjunctivitis was significantly [P < 0.01] higher in arc welders than carbide welders. The incidence of pingueculum and glaucoma were however, similar. In conclusion, chronic exposure to welding light without adequate precaution may cause ocular disorders. Arc welding is more dangerous to ocular function than carbide welding. Length of service and age are predisposing factors to ocular disorders in the welding business.

Showing up Matters: Newark Chronic Absenteeism in the Early Years

ERIC Educational Resources Information Center

Chen, Peter; Rice, Cynthia

2016-01-01

Based on a 180-day school year, any student who misses 18 days or more per year--or about two days per month--is considered chronically absent. An alarming 4,328 Newark students in grades kindergarten through 3rd grade were chronically absent during the 2013-14 school year. When young students miss too much school, they will likely struggle…

Occupational solvent exposure and adult chronic lymphocytic leukemia: No risk in a population-based case-control study in four Nordic countries.

PubMed

Talibov, Madar; Auvinen, Anssi; Weiderpass, Elisabete; Hansen, Johnni; Martinsen, Jan-Ivar; Kjaerheim, Kristina; Tryggvadottir, Laufey; Pukkala, Eero

2017-09-15

The aim of this study was to assess the effect of occupational solvent exposure on the risk of adult chronic lymphocytic leukemia (CLL). The current case-control study was nested in the Nordic Occupational Cancer Study (NOCCA) cohort. 20,615 CLL cases diagnosed in 1961-2005 in Finland, Iceland, Norway, and Sweden, and 103,075 population-based controls matched by year of birth, sex, and country were included. Occupational histories for cases and controls were obtained from census records in 1960, 1970, 1980/1981, and 1990. Exposure to selected solvents was estimated by using the NOCCA job-exposure matrix (NOCCA-JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. Overall, nonsignificant CLL risk elevations were observed for methylene chloride, perchloroethylene, and 1,1,1-trichloroethane. Compared to unexposed, significantly increased risks were observed for cumulative perchloroethylene exposure ≤13.3 ppm-years (OR = 1.85, 95% CI 1.16-2.96) and average life-time perchloroethylene exposure ≤2.5 ppm (1.61, 95% CI 1.01-2.56) among women, and cumulative methylene chloride exposure ≤12.5 ppm-years (OR = 1.19, 95% CI 1.01-1.41) and 12.5-74.8 ppm-years (OR = 1.23, 95% CI 1.01-1.51) among men in an analysis with 5 years lag-time, though without dose-response pattern. Decreased CLL risk was observed for aliphatic and alicyclic hydrocarbon solvents and toluene. This study did not support associations for solvent exposure and CLL. Observed weak associations for methylene chloride, perchloroethylene, 1,1,1-trichloroethane exposures, aliphatic and alicyclic hydrocarbons and toluene were not consistent across sexes, and showed no gradient with amount of exposure. © 2017 UICC.

FEV1 decline in patients with chronic obstructive pulmonary disease associated with biomass exposure.

PubMed

Ramírez-Venegas, Alejandra; Sansores, Raul H; Quintana-Carrillo, Roger H; Velázquez-Uncal, Monica; Hernandez-Zenteno, Rafael J; Sánchez-Romero, Candelaria; Velazquez-Montero, Alejandra; Flores-Trujillo, Fernando

2014-11-01

Biomass exposure is an important risk factor for chronic obstructive pulmonary disease (COPD). However, the time-course behavior of FEV1 in subjects exposed to biomass is unknown. We undertook this study to determine the FEV1 rate decline in subjects exposed to biomass. Pulmonary function was assessed every year in a Mexican cohort of patients with COPD associated with biomass or tobacco during a 15-year follow-up period. The mean rate of decline was significantly lower for the biomass exposure COPD group (BE-COPD) than for the tobacco smoke COPD group (TS-COPD) (23 vs. 42 ml, respectively; P < 0.01). Of the TS-COPD group, 11% were rapid decliners, whereas only one rapid decliner was found in the BE-COPD group; 69 and 21% of smokers versus 17 and 83% of the BE-COPD group were slow decliners and sustainers, respectively. A higher FEV1 both as % predicted and milliliters was a predictive factor for decline for BE-COPD and TS-COPD, whereas reversibility to bronchodilator was a predictive factor for both groups when adjusted by FEV1% predicted and only for the TS-COPD group when adjusted by milliliters. In the biomass exposure COPD group the rate of FEV1 decline is slower and shows a more homogeneous rate of decline over time in comparison with smokers. The rapid rate of FEV1 decline is a rare feature of biomass-induced airflow limitation.

Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites

PubMed Central

Veeramachaneni, D. N. Rao; Walters, William A.; Lozupone, Catherine; Palmer, Jennifer; Hewage, M. K. Kurundu; Bhatnagar, Rohil; Amir, Amnon; Kennett, Mary J.; Knight, Rob

2017-01-01

ABSTRACT Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation. IMPORTANCE Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability—three common early biomarkers of inflammation

Chronic fluoride exposure exacerbates headkidney pathology and causes immune commotion in Clarias gariepinus.

PubMed

Singh, Rashmi; Hussain, Md Arafat; Kumar, Jai; Kumar, Manmohan; Kumari, Usha; Mazumder, Shibnath

2017-11-01

The current study was aimed to understand the effects of chronic fluoride exposure on fish immune system. African sharp tooth catfish (Clarias gariepinus) were exposed to 73.45mg/L of fluoride corresponding to 1/10 96h LC 50 for 30 d and the effects on general fish health and several immune parameters were studied. Chronic fluoride exposure led to significant alteration in serum biochemical parameters including alkaline phosphatase, alanine transaminase, aspartate transaminase, triglycerides, cholesterol and blood urea nitrogen levels revealing the detrimental effect of fluoride on general fish health. Upregulation in cytochrome P450 1A expression, both at mRNA and protein level suggested that fluoride activates the detoxification machinery in headkidney (HK) of C. gariepinus. Histopathological analysis of HK from exposed fish further revealed fluoride-induced hypertrophy, increase in melano-macrophage centers (MMCs) and the development of cell-depleted regions. Fluoride reduced headkidney somatic index (HKSI) and the phagocytic potential of headkidney macrophages (HKM). It induced caspase-3-dependent headkidney leukocyte (HKL) apoptosis, elevated superoxide generation and production of pro-inflammatory cytokine TNF-α besides suppressed T-cell proliferation in the exposed fish. We surmise the elevation in superoxide levels coupled with increased TNF-α production to be plausible causes of fluoride-induced HKL apoptosis. It is concluded that chronic fluoride exposure induces structure-function alterations in HK, the primary lymphoid organ in fish leading to impairment in immune responses. Copyright © 2017. Published by Elsevier B.V.

Spatio-temporal modeling of chronic PM 10 exposure for the Nurses' Health Study

NASA Astrophysics Data System (ADS)

Yanosky, Jeff D.; Paciorek, Christopher J.; Schwartz, Joel; Laden, Francine; Puett, Robin; Suh, Helen H.

2008-06-01

Chronic epidemiological studies of airborne particulate matter (PM) have typically characterized the chronic PM exposures of their study populations using city- or county-wide ambient concentrations, which limit the studies to areas where nearby monitoring data are available and which ignore within-city spatial gradients in ambient PM concentrations. To provide more spatially refined and precise chronic exposure measures, we used a Geographic Information System (GIS)-based spatial smoothing model to predict monthly outdoor PM10 concentrations in the northeastern and midwestern United States. This model included monthly smooth spatial terms and smooth regression terms of GIS-derived and meteorological predictors. Using cross-validation and other pre-specified selection criteria, terms for distance to road by road class, urban land use, block group and county population density, point- and area-source PM10 emissions, elevation, wind speed, and precipitation were found to be important determinants of PM10 concentrations and were included in the final model. Final model performance was strong (cross-validation R2=0.62), with little bias (-0.4 μg m-3) and high precision (6.4 μg m-3). The final model (with monthly spatial terms) performed better than a model with seasonal spatial terms (cross-validation R2=0.54). The addition of GIS-derived and meteorological predictors improved predictive performance over spatial smoothing (cross-validation R2=0.51) or inverse distance weighted interpolation (cross-validation R2=0.29) methods alone and increased the spatial resolution of predictions. The model performed well in both rural and urban areas, across seasons, and across the entire time period. The strong model performance demonstrates its suitability as a means to estimate individual-specific chronic PM10 exposures for large populations.

Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

PubMed Central

Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Olive Ngalame, Ntube N.; Waalkes, Michael P.

2013-01-01

Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell’s ability to adapt to chronic cadmium exposure. PMID:23811327

Vapor, Dust and Smoke Exposure in relation to adult-onset asthma and chronic respiratory symptoms: The Singapore Chinese Health Study

PubMed Central

LeVan, Tricia D.; Koh, Woon-Puay; Lee, Hin-Peng; Koh, David; Yu, Mimi C.; London, Stephanie J.

2006-01-01

Occupational factors contribute to a significant fraction of respiratory disease and symptoms. We evaluated the role of occupational exposures on asthma, chronic bronchitis, and respiratory symptoms in a population-based cohort, the Singapore Chinese Health Study. History of occupations, occupational exposures, and respiratory conditions were collected by interviews with 52,325 Singaporeans born 1918–1953. Exposure to dusts, from cotton, wood, metal, mineral and/or asbestos, was associated with non-chronic cough and/or phlegm (OR = 1.19, 95% CI = 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI = 1.01, 1.57) and adult-onset asthma (OR = 1.14, 95% CI = 1.00, 1.30). Cotton dust was the major component contributing to respiratory symptoms. Vapor exposure, from chemical solvents, dyes, cooling oils, paints, wood preservatives and/or pesticides, was associated with non-chronic cough or phlegm (OR = 1.14, 95% CI = 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI = 1.19, 2.01) and adult-onset asthma (OR = 1.34, 95% CI = 1.15, 1.56). Chemical solvents, cooling oils and pesticides were the major sources contributing to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. PMID:16707657

Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide.

PubMed

Nutter, Thomas J; Cooper, Brian Y

2014-06-15

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Nav1.8, but increased Kv7 mediated inhibitory currents 8weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Nav1.9 expressed in muscle and vascular nociceptors. During a 60day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Nav1.9, but significant increases in the amplitude of Nav1.9 were observed 8weeks after exposure. Cellular studies, at the 8week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22°C). Acute application of permethrin (10μM) also increased the amplitude of Nav1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Nav1.9 expressed in muscle and vascular nociceptors. The reported increases in Kv7 amplitude may have been an adaptive response to increased Nav1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Nav1.9 and Kv7 could release spontaneous discharge and produce chronic deep tissue pain. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Mild Chronic Intermittent Cold Exposure on Rat Organs

PubMed Central

Wang, Xiaohui; Che, Honglei; Zhang, Wenbin; Wang, Jiye; Ke, Tao; Cao, Rui; Meng, Shanshan; Li, Dan; Weiming, Ouyang; Chen, Jingyuan; Luo, Wenjing

2015-01-01

Cold adaptation is a body's protective response to cold stress. Mild chronic intermittent cold (CIC) exposure has been used to generate animal models for cold adaptation studies. However, the effects of mild CIC exposure on vital organs are not completely characterized. In the present study, we exposed rats to mild CIC for two weeks, and then measured the body weights, the weights of brown adipose tissue (BAT), the levels of ATP and reactive oxygen species (ROS) in the brains, livers, hearts, muscles and BATs. Rats formed cold adaptation after exposure to CIC for two weeks. Compared to rats of the control group that were hosted under ambient temperature, rats exposed to mild CIC showed a lower average body weight, but a higher weight of brown adipose tissue (BAT). Rats exposed to CIC for two weeks also exhibited higher levels of ATP and ROS in all examined organs as compared to those of the control group. In addition, we determined the expression levels of cold-inducible RNA binding protein (Cirbp) and thioredoxin (TRX) in rat tissues after 2 weeks of CIC exposure. Both Cirbp and TRX were increased, suggesting a role of these two proteins for establishment of cold adaptation. Together, this study reveals the effects of mild CIC exposure on vital organs of rats during CIC exposure. PMID:26327811

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

PubMed Central

Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

2015-01-01

The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

PubMed Central

Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2016-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes.

PubMed

Milton, Abul H; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A; Mitchell, Kane

2017-05-23

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low-moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes

PubMed Central

Milton, Abul H.; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A.; Mitchell, Kane

2017-01-01

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low–moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations. PMID:28545256

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

PubMed

Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

PubMed

Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

2015-01-01

Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study.

PubMed

Mocroft, Amanda; Lundgren, Jens D; Ross, Michael; Fux, Christoph A; Reiss, Peter; Moranne, Olivier; Morlat, Philippe; Monforte, Antonella d'Arminio; Kirk, Ole; Ryom, Lene

2016-01-01

Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate

Effects of omeprazole or anti-reflux surgery on lower oesophageal sphincter characteristics and oesophageal acid exposure over 10 years.

PubMed

Emken, Birgitte-Elise G; Lundell, Lars R; Wallin, Lene; Myrvold, Helge E; Engström, Cecilia; Montgomery, Madeleine; Malm, Anders R; Lind, Tore; Hatlebakk, Jan G

2017-01-01

To compare the effect of anti-reflux surgery (ARS) versus proton pump inhibitor therapy on lower oesophageal sphincter (LOS) function and oesophageal acid exposure in patients with chronic gastro-oesophageal reflux disease (GORD) over a decade of follow-up. In this randomised, prospective, multicentre study we compared LOS pressure profiles, as well as oesophageal exposure to acid, at baseline and at 1 and 10 years after randomisation to either open ARS (n = 137) or long-term treatment with omeprazole (OME) 20-60 mg daily (n = 108). Median LOS resting pressure and abdominal length increased significantly and remained elevated in patients operated on with ARS, as opposed to those on OME. The proportion of total time (%) with oesophageal pH <4.0 decreased significantly in both the surgical and medical groups, and was significantly lower after 1 year in patients treated with ARS versus OME. After 10 years, oesophageal acid exposure was normalised in both groups, with no significant differences, and bilirubin exposure was within normal limits. After 10 years, patients with or without Barrett's oesophagus did not differ in acid reflux control between the two treatment options. Open ARS and OME were both effective in normalising acid reflux into the oesophagus even when studied over a period of 10 years. Anatomically and functionally the LOS was repaired durably by surgery, with increased resting pressure and abdominal length.

Early histological and functional effects of chronic copper exposure in rat liver.

PubMed

Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

2005-10-01

Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

The risk of chronic traumatic brain injury in professional boxing: change in exposure variables over the past century

PubMed Central

Clausen, H; McCrory, P; Anderson, V; Fallon, K

2005-01-01

Objectives: To determine if boxing exposure has changed over time and hence if current professional boxers are at the same risk of developing chronic traumatic brain injury (CTBI) as historical controls. Design: Literature review of published studies and analysis of data of active professional boxers. Subjects: Professional boxers in the United Kingdom and Australia. Main outcome measures: Boxing history and participation in sparring and professional bouts. Results: Since the 1930s, the average duration of a professional boxer's career has dropped from 19 years to five years, and the mean number of career bouts has reduced from 336 to 13. This is despite no significant decline in participation rates from 1931 until 2002. Conclusions: The incidence of boxing related CTBI will diminish in the current era of professional boxing because of the reduction in exposure to repetitive head trauma and increasing medical monitoring of boxers, with preparticipation medical and neuroimaging assessments resulting in the detection of early and potentially pre-symptomatic cases of CTBI. PMID:16118306

The risk of chronic traumatic brain injury in professional boxing: change in exposure variables over the past century.

PubMed

Clausen, H; McCrory, P; Anderson, V

2005-09-01

To determine if boxing exposure has changed over time and hence if current professional boxers are at the same risk of developing chronic traumatic brain injury (CTBI) as historical controls. Literature review of published studies and analysis of data of active professional boxers. Professional boxers in the United Kingdom and Australia. Boxing history and participation in sparring and professional bouts. Since the 1930s, the average duration of a professional boxer's career has dropped from 19 years to five years, and the mean number of career bouts has reduced from 336 to 13. This is despite no significant decline in participation rates from 1931 until 2002. The incidence of boxing related CTBI will diminish in the current era of professional boxing because of the reduction in exposure to repetitive head trauma and increasing medical monitoring of boxers, with preparticipation medical and neuroimaging assessments resulting in the detection of early and potentially pre-symptomatic cases of CTBI.

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study.

PubMed

Mescher, Craig; Gilbertson, David; Randall, Nicole M; Tarchand, Gobind; Tomaska, Julie; Baumann Kreuziger, Lisa; Morrison, Vicki A

2018-06-01

Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001). This prolonged survival was in the subgroups of patients aged 60-69 years (p< .0001) and those with 11q deletion (p < .0001). Those exposed to AO were more likely to be treated with fludarabine, chlorambucil and rituximab (38 vs. 21%, p < .001) and bendamustine plus rituximab (25 vs. 18%, p = 0.039) as first line therapy. Exposure to AO was not associated with either poor prognostic factors or shortened overall survival in our large veteran population with CLL.

Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children

PubMed Central

Bouchard, Maryse F.; Chevrier, Jonathan; Harley, Kim G.; Kogut, Katherine; Vedar, Michelle; Calderon, Norma; Trujillo, Celina; Johnson, Caroline; Bradman, Asa; Barr, Dana Boyd

2011-01-01

Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development. Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores. Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population. PMID:21507776

Chronic Ketamine Exposure Causes White Matter Microstructural Abnormalities in Adolescent Cynomolgus Monkeys.

PubMed

Li, Qi; Shi, Lin; Lu, Gang; Yu, Hong-Luan; Yeung, Fu-Ki; Wong, Nai-Kei; Sun, Lin; Liu, Kai; Yew, David; Pan, Fang; Wang, De-Feng; Sham, Pak C

2017-01-01

Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys ( n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.

Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

PubMed

Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

2017-10-04

Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

PubMed

Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

2018-08-01

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1 H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, α synuclein aggregation, oxidative damage and behavioral changes

PubMed Central

2010-01-01

Background In recent years, several lines of evidence have shown an increase in Parkinson's disease prevalence in rural environments where pesticides are heavily used. Although, the underlying mechanism for neuronal degeneration in sporadic PD remains unknown, mitochondrial dysfunction, oxidative stress and proteasomal dysfunction are proposed as contributing factors. In this study rats were chronically and continuously exposed to the pesticide, dichlorvos to identify the molecular mechanism of nigrostaital neuronal degeneration. Result Chronic dichlorvos exposure (2.50 mg/kg b.wt.s.c/daily for 12 weeks) caused nigrostriatal dopaminergic degeneration. The degenerative changes were accompanied by a loss of 60-80% of the nigral dopamine neurons and 60-70% reduction in striatal dopamine and tyrosine hydroxylase levels. Dichlorvos exposed animals also showed α -synuclein and ubiquitin positive inclusions along with swollen, dystrophic neurites and mitochondrial abnormalities like decreased complex I&IV activities, increased mitochondrial size, axonal degeneration and presence of electron dense perinuclear cytoplasmic inclusions in the substantia nigra of rats. These animals also showed evidence of oxidative stress, including increased mitochondrial ROS levels, decreased MnSOD activity and increased lipid peroxidation. Measurable impairments in neurobehavioral indices were also observed. Notable exacerbations in motor impairments, open field and catalepsy were also evident in dichlorvos exposed animals. Conclusion All these findings taken together indicate that chronic dichlorvos exposure may cause nigrostaital neurodegenaration and significant behavioral impairments. PMID:21073741

Chronic Ethanol Exposure Produces Time- and Brain Region-Dependent Changes in Gene Coexpression Networks

PubMed Central

Osterndorff-Kahanek, Elizabeth A.; Becker, Howard C.; Lopez, Marcelo F.; Farris, Sean P.; Tiwari, Gayatri R.; Nunez, Yury O.; Harris, R. Adron; Mayfield, R. Dayne

2015-01-01

Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global ‘rewiring‘ of coexpression systems involving glial and immune signaling as well as neuronal genes. PMID:25803291

Chronic Pain Under Missile Attacks: Role of Pain Catastrophizing, Media, and Stress-Related Exposure.

PubMed

Noyman-Veksler, Gal; Shalev, Hadar; Brill, Silviu; Rudich, Zvia; Shahar, Golan

2017-10-09

We examined the effects of exposure to missile attacks on patients' pain and depressive symptoms, moderated by pain-related catastrophizing. One-hundred Israeli chronic pain patients were assessed both prior and subsequent to military operation "Protective Edge," during which thousands of missiles landed on populated areas across the country. Baseline assessment included pain, depression, and catastrophizing, and postwar assessment tapped exposure to missiles, pain, and depression. Media exposure predicted an increase in sensory pain under high levels of catastrophizing (1 SD above the mean; unstandardized simple slope = 0.57, p = .01), and depression in the entire sample (b = 0.61, p = .01). Perceived stress related to the missiles exhibited an expected effect, predicting an increase in depressive symptoms (b = 1.45, p = .03). Unexpectedly, perceived stress predicted a decrease in sensory pain under high levels of catastrophizing (unstandardized simple slope = -0.49, p = .02). Media exposure to acute stress may render chronic pain patients more vulnerable to experiencing pain and depressive symptoms, depending on their use of pain-based catastrophizing. High catastrophizers may attend more to outside threats, amplifying the sensory and affective aspects of pain they experience. Perceived stress also plays a significant role in eliciting depressive symptoms in this population. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Ping; Koenig, Rolf; Boor, Paul J.

2008-04-01

Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltrationmore » was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice.« less

Effects of bioaerosol exposure on respiratory health in compost workers: a 13-year follow-up study.

PubMed

van Kampen, V; Hoffmeyer, F; Deckert, A; Kendzia, B; Casjens, S; Neumann, H D; Buxtrup, M; Willer, E; Felten, C; Schöneich, R; Brüning, T; Raulf, M; Bünger, J

2016-12-01

To determine the risk of German compost workers developing chronic respiratory effects from long-term exposure to bioaerosols. Respiratory health was determined in 74 currently exposed compost workers and 37 non-exposed controls after 13 years of follow-up. In addition, 42 former compost workers (drop-outs) who left their work during the follow-up period were also examined. Respiratory symptoms and working conditions were assessed using identical questionnaires as at baseline. In addition, lung function was measured using the same spirometer as in the initial study. Sera from both surveys were tested for specific IgE and IgG antibodies to moulds and the risk of work-related symptoms was evaluated using regression approaches for prospective studies with binary data. In the follow-up period, the number of participants reporting cough significantly increased in compost workers and drop-outs compared to the controls. Working as a compost worker for at least 5 years increased the relative risk for cough (RR 1.28; 95% CI 1.2 to 1.4) and for cough with phlegm (RR 1.32; 95% CI 1.2 to 1.5). Current and former compost workers had slightly lower predicted percentage of forced expiratory volume in 1 s and predicted percentage of forced vital capacity than controls, but decrease in lung function during follow-up was not different among the 3 groups. In addition, no significant changes could be detected in antibody concentrations. Our results suggest that chronic exposure to bioaerosols in composting plants is related to a significantly higher risk for cough with phlegm, indicating chronic bronchitis. However, compost workers showed no higher incidence of deterioration of pulmonary function over the study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Sex differences in the behavioral sequelae of chronic ethanol exposure.

PubMed

Jury, Nicholas J; DiBerto, Jeffrey F; Kash, Thomas L; Holmes, Andrew

2017-02-01

Rates of alcohol use disorders (AUDs) differ between men and women, and there is also marked variation between sexes in the effects of acute and chronic alcohol. In parallel to observations in humans, prior studies in rodents have described male/female differences across a range of ethanol-related behaviors, including ethanol drinking. Nonetheless, there remain gaps in our knowledge of the role of sex in moderating the effects of ethanol, particularly in models of chronic ethanol exposure. The goal of the current study was to assess various behavioral sequelae of exposing female C57BL/6J mice to chronic intermittent ethanol (CIE) via ethanol vapors. Following four weeks of CIE exposure, adult male and female mice were compared for ethanol drinking in a two-bottle paradigm, for sensitivity to acute ethanol intoxication (via loss of righting reflex [LORR]) and for anxiety-like behaviors in the novelty-suppressed feeding and marble burying assays. Next, adult and adolescent females were tested on two different two-bottle drinking preparations (fixed or escalating ethanol concentration) after CIE. Results showed that males and females exhibited significantly blunted ethanol-induced LORR following CIE, whereas only males showed increased anxiety-like behavior after CIE. Increased ethanol drinking after CIE was also specific to males, but high baseline drinking in females may have occluded detection of a CIE-induced effect. The failure to observe elevated drinking in females in response to CIE was also seen in females exposed to CIE during adolescence, regardless of whether a fixed or escalating ethanol-concentration two-bottle procedure was employed. Collectively, these data add to the literature on sex differences in ethanol-related behaviors and provide a foundation for future studies examining how the neural consequences of CIE might differ between males and females. Published by Elsevier Inc.

Sex differences in the behavioral sequelae of chronic ethanol exposure

PubMed Central

Jury, Nicholas J.; DiBerto, Jeffrey F.; Kash, Thomas L.; Holmes, Andrew

2016-01-01

Rates of alcohol use disorders (AUDs) differ between men and women, and there is also marked variation between sexes in the effects of acute and chronic alcohol. In parallel to observations in humans, prior studies in rodents have described male/female differences across a range of ethanol-related behaviors, including ethanol drinking. Nonetheless, there remain gaps in our knowledge of the role of sex in moderating the effects of ethanol, particularly in models of chronic ethanol exposure. The goal of the current study was to assess various behavioral sequelae of exposing female C57BL/6J mice to chronic intermittent ethanol (CIE) via ethanol vapors. Following four weeks of CIE exposure, adult male and female mice were compared for ethanol drinking in a two-bottle paradigm, for sensitivity to acute ethanol intoxication (via loss of righting reflex [LORR]) and for anxiety-like behaviors in the novelty-suppressed feeding and marble burying assays. Next, adult and adolescent females were tested on two different two-bottle drinking preparations (fixed or escalating ethanol concentration) after CIE. Results showed that males and females exhibited significantly blunted ethanol-induced LORR following CIE, whereas only males showed increased anxiety-like behavior after CIE. Increased ethanol drinking after CIE was also specific to males, but high baseline drinking in females may have occluded detection of a CIE-induced effect. The failure to observe elevated drinking in females in response to CIE was also seen in females exposed to CIE during adolescence, regardless of whether a fixed or escalating ethanol-concentration two-bottle procedure was employed. Collectively, these data add to the literature on sex differences in ethanol-related behaviors and provide a foundation for future studies examining how the neural consequences of CIE might differ between males and females. PMID:27624846

Toxicity of methyl tertiary-butyl ether (MTBE) following exposure of Wistar Rats for 13 weeks or one year via drinking water.

PubMed

Bermudez, Edilberto; Willson, Gabrielle; Parkinson, Horace; Dodd, Darol

2012-09-01

Thirteen-week and one-year toxicity studies of methyl tertiary-butyl ether (MTBE) administered in drinking water to Wistar rats were conducted. Male and female rats were exposed to MTBE in drinking water at 0.5, 3, 7.5 and 15 mg ml(-1) for 13 weeks and at 0.5, 3 and 7.5 (males) or 0.5, 3 and 15 mg ml(-1) (females) for 1 year. Body weights were reduced only in males following 13 weeks of exposure. Reduced water consumption and urine output were observed in males and females exposed to MTBE. Kidney cell replication and α(2u)-globulin levels in males were increased at 1 and 4 weeks of MTBE exposure and tubular cell regeneration was increased in male kidneys exposed to MTBE concentrations of 7.5 mg ml(-1) or greater for 13 weeks. Wet weights of male kidneys were increased following 13 weeks, 6 months and 1 year of exposure to MTBE concentrations of 7.5 mg ml(-1) or greater. Kidney wet weights were increased in females at MTBE concentrations of 15 mg ml(-1) for 13 weeks. Tertiary-butyl alcohol blood levels increased linearly with dose in males and females following 1 year of exposure. Chronic progressive nephropathy (CPN), of minimal to mild severity, increased in males, but not females, with 1 year of MTBE exposure. In summary, exposure of Wistar rats to MTBE in the drinking water resulted in minimal exposure-related effects including limited renal changes in male rats suggestive of α(2u)-globulin nephropathy following 13 weeks of exposure and an exacerbation of CPN in males at the end of 1 year of exposure. Copyright © 2011 John Wiley & Sons, Ltd.

Depleted uranium contamination by inhalation exposure and its detection after approximately 20 years: implications for human health assessment.

PubMed

Parrish, Randall R; Horstwood, Matthew; Arnason, John G; Chenery, Simon; Brewer, Tim; Lloyd, Nicholas S; Carpenter, David O

2008-02-01

Inhaled depleted uranium (DU) aerosols are recognised as a distinct human health hazard and DU has been suggested to be responsible in part for illness in both military and civilian populations that may have been exposed. This study aimed to develop and use a testing procedure capable of detecting an individual's historic milligram-quantity aerosol exposure to DU up to 20 years after the event. This method was applied to individuals associated with or living proximal to a DU munitions plant in Colonie New York that were likely to have had a significant DU aerosol inhalation exposure, in order to improve DU-exposure screening reliability and gain insight into the residence time of DU in humans. We show using sensitive mass spectrometric techniques that when exposure to aerosol has been unambiguous and in sufficient quantity, urinary excretion of DU can be detected more than 20 years after primary DU inhalation contamination ceased, even when DU constitutes only approximately 1% of the total excreted uranium. It seems reasonable to conclude that a chronically DU-exposed population exists within the contamination 'footprint' of the munitions plant in Colonie, New York. The method allows even a modest DU exposure to be identified where other less sensitive methods would have failed entirely. This should allow better assessment of historical exposure incidence than currently exists.

Deer carcass decomposition and potential scavenger exposure to chronic wasting disease

USGS Publications Warehouse

Jennelle, C.S.; Samuel, M.D.; Nolden, C.A.; Berkley, E.A.

2009-01-01

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy afflicting the Cervidae family in North America, causing neurodegeneration and ultimately death. Although there are no reports of natural cross-species transmission of CWD to noncervids, infected deer carcasses pose a potential risk of CWD exposure for other animals. We placed 40 disease-free white-tailed deer (Odocoileus virginianus) carcasses and 10 gut piles in the CWD-affected area of Wisconsin (USA) from September to April in 2003 through 2005. We used photos from remotely operated cameras to characterize scavenger visitation and relative activity. To evaluate factors driving the rate of carcass removal (decomposition), we used KaplanMeier survival analysis and a generalized linear mixed model. We recorded 14 species of scavenging mammals (6 visiting species) and 14 species of scavenging birds (8 visiting species). Prominent scavengers included American crows (Corvus brachyrhynchos), raccoons (Procyon lotor), and Virginia opossums (Didelphis virginiana). We found no evidence that deer consumed conspecific remains, although they visited gut piles more often than carcasses relative to temporal availability in the environment. Domestic dogs, cats, and cows either scavenged or visited carcass sites, which could lead to human exposure to CWD. Deer carcasses persisted for 18 days to 101 days depending on the season and year, whereas gut piles lasted for 3 days. Habitat did not influence carcass decomposition, but mammalian and avian scavenger activity and higher temperatures were positively associated with faster removal. Infected deer carcasses or gut piles can serve as potential sources of CWD prions to a variety of scavengers. In areas where surveillance for CWD exposure is practical, management agencies should consider strategies for testing primary scavengers of deer carcass material.

Recent versus chronic exposure to particulate matter air pollution in association with neurobehavioral performance in a panel study of primary schoolchildren.

PubMed

Saenen, Nelly D; Provost, Eline B; Viaene, Mineke K; Vanpoucke, Charlotte; Lefebvre, Wouter; Vrijens, Karen; Roels, Harry A; Nawrot, Tim S

2016-10-01

Children's neuropsychological abilities are in a developmental stage. Recent air pollution exposure and neurobehavioral performance are scarcely studied. In a panel study, we repeatedly administered to each child the following neurobehavioral tests: Stroop Test (selective attention) and Continuous Performance Test (sustained attention), Digit Span Forward and Backward Tests (short-term memory), and Digit-Symbol and Pattern Comparison Tests (visual information processing speed). At school, recent inside classroom particulate matter ≤2.5 or 10μm exposure (PM2.5, PM10) was monitored on each examination day. At the child's residence, recent (same day up to 2days before) and chronic (365days before examination) exposures to PM2.5, PM10 and black carbon (BC) were modeled. Repeated neurobehavioral test performances (n=894) of the children (n=310) reflected slower Stroop Test (p=0.05) and Digit-Symbol Test (p=0.01) performances with increasing recent inside classroom PM2.5 exposure. An interquartile range (IQR) increment in recent residential outdoor PM2.5 exposure was associated with an increase in average latency of 0.087s (SE: ±0.034; p=0.01) in the Pattern Comparison Test. Regarding chronic exposure at residence, an IQR increment of PM2.5 exposure was associated with slower performances in the Continuous Performance (9.45±3.47msec; p=0.007) and Stroop Tests (59.9±26.5msec; p=0.02). Similar results were obtained for PM10 exposure. In essence, we showed differential neurobehavioral changes robustly and adversely associated with recent or chronic ambient exposure to PM air pollution at residence, i.e., with recent exposure for visual information processing speed (Pattern Comparison Test) and with chronic exposure for sustained and selective attention. Copyright © 2016. Published by Elsevier Ltd.

Acute and Chronic Ethanol Exposure Differentially Regulate CB1 Receptor Function at Glutamatergic Synapses in the Rat Basolateral Amygdala

PubMed Central

Robinson, Stacey L.; Alexander, Nancy J.; Bluett, Rebecca J.; Patel, Sachin; McCool, Brian A.

2016-01-01

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

Contrast Medium Exposure During Computed Tomography and Risk of Development of End-Stage Renal Disease in Patients With Chronic Kidney Disease

PubMed Central

Hsieh, Ming-Shun; Chiu, Chien-Shan; How, Chorng-Kuang; Chiang, Jen-Huai; Sheu, Meei-Ling; Chen, Wen-Chi; Lin, Hsuan-Jen; Hsieh, Vivian Chia-Rong; Hu, Sung-Yuan

2016-01-01

Abstract The aim of the study was to investigate the long-term association between contrast medium exposure during computed tomography (CT) and the subsequent development of end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database. A total of 7100 patients with nonadvanced CKD who underwent contrast medium-enhanced CT were identified and served as the study cohort. To avoid selection bias, we used the propensity score to match 7100 nonadvanced CKD patients, who underwent noncontrast medium-enhanced CT to serve as the comparison cohort. The age, sex, index year, and frequency of undergoing CTs were also matched between the study and comparison cohorts. Participants were followed until a new diagnosis of ESRD or December 31, 2011. Hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated using the Cox proportional hazards regression. Contrast medium exposure was not identified as a risk factor for developing ESRD in nonadvanced CKD patients after confounders adjustment (adjusted HR = 0.91; 95% CI, 0.66–1.26; P = 0.580). We further divided the patients who underwent CTs with contrast medium use into ≤1 exposure per year on average, >1 and <2 exposure per year on average, and ≥2 exposure per year on average. After adjusting for confounders, we identified a much higher risk for developing ESRD in the 2 groups of >1 and <2 exposure per year on average and ≥2 exposure per year on average (adjusted HR = 8.13; 95% CI, 5.57–11.87 and adjusted HR = 12.08; 95% CI, 7.39–19.75, respectively) compared with the patients who underwent CTs without contrast medium use. This long-term follow-up study demonstrated that contrast medium exposure was not associated with an increased risk of ESRD development in nonadvanced CKD patients. PMID:27100424

Occupational exposure to dust and lung disease among sheet metal workers.

PubMed Central

Hunting, K L; Welch, L S

1993-01-01

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was

Silica exposure and systemic vasculitis.

PubMed Central

Mulloy, Karen B

2003-01-01

Work in Department of Energy (DOE) facilities has exposed workers to multiple toxic agents leading to acute and chronic diseases. Many exposures were common to numerous work sites. Exposure to crystalline silica was primarily restricted to a few facilities. I present the case of a 63-year-old male who worked in DOE facilities for 30 years as a weapons testing technician. In addition to silica, other workplace exposures included beryllium, various solvents and heavy metals, depleted uranium, and ionizing radiation. In 1989 a painful macular skin lesion was biopsied and diagnosed as leukocytoclastic vasculitis. By 1992 he developed gross hematuria and dyspnea. Blood laboratory results revealed a serum creatinine concentration of 2.1 mg/dL, ethrythrocyte sedimentation rate of 61 mm/hr, negative cANCA (antineutrophil cytoplasmic antibody cytoplasmic pattern), positive pANCA (ANCA perinuclear pattern), and antiglomerular basement membrane negative. Renal biopsy showed proliferative (crescentric) and necrotizing glomerulonephritis. The patient's diagnoses included microscopic polyangiitis, systemic necrotizing vasculitis, leukocytoclastic vasculitis, and glomerulonephritis. Environmental triggers are thought to play a role in the development of an idiopathic expression of systemic autoimmune disease. Crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, rapidly progressive glomerulonephritis and some of the small vessel vasculitides. DOE workers are currently able to apply for compensation under the federal Energy Employees Occupational Illness Compensation Program (EEOICP). However, the only diseases covered by EEOICP are cancers related to radiation exposure, chronic beryllium disease, and chronic silicosis. PMID:14644669

Biomarkers for assessing potential carcinogenic effects of chronic arsenic exposure in Inner Mongolia, CHINA

EPA Science Inventory

Arsenic is ubiquitous in the environment. Chronic arsenic exposure via drinking water has been associated. with carcinogenic, cardiovascular, neurological and diabetic effects in humans and has been of great public health concern worldwide. In 2001, U.S. Environmental Protection ...

Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

PubMed Central

Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

2016-01-01

Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:28239613

THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

EPA Science Inventory

Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

SOURCES AND ESTIMATED LOAD OF BIOAVAILABLE NITROGEN ATTRIBUTED TO CHRONIC NITROGEN EXPOSURE AND CHANGED ECOSYSTEM STRUCTURE AND FUNCTION

EPA Science Inventory

Bioavailable nitrogen is a limiting nutrient throughout the Eastern United States. Research demonstrates that exposure to large doses of nitrogen leads to deleterious environmental impacts. However, effects of chronic exposure to lower doses of nitrogen are under-appreciated. ...

Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations.

PubMed

Ramlan, Nurul Farhana; Sata, Nurul Syafida Asma Mohd; Hassan, Siti Norhidayah; Bakar, Noraini Abu; Ahmad, Syahida; Zulkifli, Syaizwan Zahmir; Abdullah, Che Azurahanim Che; Ibrahim, Wan Norhamidah Wan

2017-08-14

Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system. Copyright © 2017

Effects of a Chronic Lower Range of Triclosan Exposure on a Stream Mesocosm Community

EPA Science Inventory

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicrobial found in consumer soaps and toothpaste. It is in treated wastewater effluents at low part per billion concentrations, representing a potentially chronic exposure condition for biota inhabiting receiving strea...

Chronic disease prevalence in women and air pollution--A 30-year longitudinal cohort study.

PubMed

To, Teresa; Zhu, Jingqin; Villeneuve, Paul J; Simatovic, Jacqueline; Feldman, Laura; Gao, Chenwei; Williams, Devon; Chen, Hong; Weichenthal, Scott; Wall, Claus; Miller, Anthony B

2015-07-01

Air pollution, such as fine particulate matter (PM2.5), can increase risk of adverse health events among people with heart disease, diabetes, asthma and chronic obstructive pulmonary disease (COPD) by aggravating these conditions. Identifying the influence of PM2.5 on prevalence of these conditions may help target interventions to reduce disease morbidity among high-risk populations. The objective of this study is to measure the association of exposure of PM2.5 with prevalence risk of various chronic diseases among a longitudinal cohort of women. Women from Ontario who enrolled in the Canadian National Breast Screening Study (CNBSS) from 1980 to 1985 (n = 29,549) were linked to provincial health administrative data from April 1, 1992 to March 31, 2013 to determine the prevalence of major chronic disease and conditions (heart disease, diabetes, asthma, COPD, acute myocardial infarction, angina, stroke and cancers). Exposure to PM2.5 was measured using satellite data collected from January 1, 1998 to December 31, 2006 and assigned to resident postal-code at time of entry into study. Poisson regression models were used to describe the relationship between exposure to ambient PM2.5 and chronic disease prevalence. Prevalence rate ratios (PRs) were estimated while adjusting for potential confounders: baseline age, smoking, BMI, marital status, education and occupation. Separate models were run for each chronic disease and condition. Congestive heart failure (PR = 1.31, 95% CI: 1.13, 1.51), diabetes (PR = 1.28, 95% CI: 1.16, 1.41), ischemic heart disease (PR = 1.22, 95% CI: 1.14, 1.30), and stroke (PR = 1.21, 95% CI: 1.09, 1.35) showed over a 20% increase in PRs per 10 μg/m(3) increase in PM2.5 after adjusting for risk factors. Risks were elevated in smokers and those with BMI greater than 30. This study estimated significant elevated prevalent rate ratios per unit increase in PM2.5 in nine of the ten chronic diseases studied. Copyright © 2015 Elsevier Ltd. All rights

Pulmonary toxicity of chronic exposure to tobacco and biomass smoke in rats.

PubMed

Dogan, Omer Tamer; Elagoz, Sahande; Ozsahin, Sefa Levent; Epozturk, Kursat; Tuncer, Ersin; Akkurt, Ibrahim

2011-01-01

The objective of this study was to examine the separate and combined effects of tobacco and biomass smoke exposure on pulmonary histopathology in rats. In addition to smoking, indoor pollution in developing countries contributes to the development of respiratory diseases. Twenty-eight adult rats were divided into four groups as follows: control group (Group I, no exposure to tobacco or biomass smoke), exposed to tobacco smoke (Group II), exposed to biomass smoke (Group III), and combined exposure to tobacco and biomass smoke (Group IV). After six months the rats in all four groups were sacrificed. Lung tissue samples were examined under light microscopy. The severity of pathological changes was scored. Group II differed from Group I in all histopathological alterations except intraparenchymal vascular thrombosis. There was no statistically significant difference in histopathological changes between the subjects exposed exclusively to tobacco smoke (Group II) and those with combined exposure to tobacco and biomass smoke (Group IV). The histopathological changes observed in Group IV were found to be more severe than those in subjects exposed exclusively to biomass smoke (Group III). Chronic exposure to tobacco and biomass smoke caused an increase in severity and types of lung injury. Exposure to cigarette smoke caused serious damage to the respiratory system, particularly with concomitant exposure to biomass smoke.

Human Physiological Responses to Acute and Chronic Cold Exposure

NASA Technical Reports Server (NTRS)

Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

2001-01-01

When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

The impact of exposure to radio frequency electromagnetic fields on chronic well-being in young people--a cross-sectional study based on personal dosimetry.

PubMed

Heinrich, Sabine; Thomas, Silke; Heumann, Christian; von Kries, Rüdiger; Radon, Katja

2011-01-01

A possible influence of radio frequency electromagnetic field (RF EMF) exposure on health outcomes was investigated in various studies. The main problem of previous studies was exposure assessment. The aim of our study was the investigation of a possible association between RF EMF and chronic well-being in young persons using personal dosimetry. 3022 children and adolescents were randomly selected from the population registries of four Bavarian cities in Germany (participation 52%). Personal interview data on chronic symptoms, socio-demographic characteristics and potential confounders were collected. A 24-h radio frequency exposure profile was generated using a personal dosimeter. Exposure levels over waking hours were expressed as mean percentage of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference level. Half of the children and nearly every adolescent owned a mobile phone which was used only for short durations per day. Measured exposure was far below the current ICNIRP reference levels. The most reported chronic symptom in children and adolescents was fatigue. No statistically significant association between measured exposure and chronic symptoms was observed. Our results do not indicate an association between measured exposure to RF EMF and chronic well-being in children and adolescents. Prospective studies investigating potential long-term effects of RF EMF are necessary to confirm our results. Copyright © 2010 Elsevier Ltd. All rights reserved.

Evaluation of the neurotoxic effects of chronic embryonic exposure with inorganic mercury on motor and anxiety-like responses in zebrafish (Danio rerio) larvae.

PubMed

Abu Bakar, Noraini; Mohd Sata, Nurul Syafida Asma'; Ramlan, Nurul Farhana; Wan Ibrahim, Wan Norhamidah; Zulkifli, Syaizwan Zahmir; Che Abdullah, Che Azurahanim; Ahmad, Syahida; Amal, Mohammad Noor Azmai

Chronic exposure to mercury (Hg) can lead to cumulative impairments in motor and cognitive functions including alteration in anxiety responses. Although several risk factors have been identified in recent year, little is known about the environmental factors that either due exposure toward low level of inorganic mercury that may led to the developmental disorders. The present study investigated the effects of embryonic exposure of mercury chloride on motor function and anxiety-like behavior. The embryo exposed to 6 different concentrations of HgCl 2 (7.5, 15, 30, 100, 125, 250nM) at 5hpf until hatching (72hpf) in a semi-static condition. The mortality rate increased in a dose dependent manner where the chronic embryonic exposure to 100nM decreased the number of tail coiling, heartbeat, and swimming activity. Aversive stimulus was used to examine the effects of 100nM interferes with the development of anxiety-related behavior. No elevation in both thigmotaxis and avoidance response of 6dpf larvae exposed with 100nM were found. Biochemical analysis showed HgCl 2 exposure affects proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. These results showed that implication of HgCl 2 on locomotor and biochemical defects affects motor performance and anxiety-like responses. Yet, the potential underlying mechanisms these responses need to be further investigated which is crucial to prevent potential hazards on the developing organism due to neurotoxicant exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

End-stage renal disease after occupational lead exposure: 20 years of follow-up.

PubMed

Evans, Marie; Discacciati, Andrea; Quershi, Abdul Rashid; Åkesson, Agneta; Elinder, Carl-Gustaf

2017-06-01

Whether low-level exposure to lead may give rise to chronic kidney disease or end-stage renal disease (ESRD) is debated. In this study, we aimed to specifically investigate if low-level occupational exposure to lead was associated with increased incidence of ESRD. The incidence of starting renal replacement therapy as a result of ESRD was examined in a cohort of10 303 lead-workers who had controlled blood lead concentrations due to a compulsory occupational health surveillance programme in Sweden during the time period 1977-1990. The ESRD incidence (obtained through register-linkage) among the lead-exposed workers was compared with the age, sex and calendar period-adjusted expected incidence based on data from the Swedish renal registry. Dose-response association was evaluated in external (general population) and internal (within the occupational cohort) comparisons by highest achieved blood lead level. There were 30 (0.29%) individuals in the cohort who developed ESRD during the median follow-up period of 26.3 years. The standardised incidence ratio (SIR) for ESRD incidence was 0.79 (95% CI 0.54 to 1.13). Among those who achieved the highest blood lead (>41.4 µg/dL), the SIR was 1.01 (0.44 to 1.99). There was no evidence of a dose-response relationship between the maximum achieved blood lead or the cumulative blood lead exposure and ESRD in external or internal comparisons. This study of workers with documented occupational lead exposures followed for 20 years shows no statistically significant association between lead exposure (following the current occupational recommendations for Sweden) and ESRD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Chronic arsenicism].

PubMed

Bourgeais, A M; Avenel-Audran, M; Le Bouil, A; Bouyx, C; Allain, P; Verret, J L

2001-04-01

Arsenic is an ubiquitous natural element. Chronic and low level ingestion or inhalation may result in chronic arsenicism first characterized by skin changes. A 75 year old man, non-insulin-dependent diabetic, presented a diffuse hyperpigmentation with scattered white spots on the trunk. He complained of asthenia. Clinical diagnosis of chronic arsenicism was confirmed by arsenic determination in urine, plasma and phaneres. Thorough investigations led to discover very high arsenic levels in the own wine of the patient. This was probably the result of a wrong use of sodium arsenite-based fungicide, for cultivating his vine yard. Chronic arsenicism has become rare but it should always be kept in mind. Clinical presentation, with particular cutaneous features and routes of exposure are reviewed. Treatment is symptomatic. As arsenic is known to be a strong carcinogenic agent, patients with chronic arsenicism have to be followed up during a long time.

SOURCES AND ESTIMATED LOAD OF BIOAVAILABLE NITROGEN ATTRIBUTABLE TO CHRONIC NITROGEN EXPOSURE AND CHANGED ECOSYSTEM STRUCTURE AND FUNCTION

EPA Science Inventory

Bioavailable nitrogen is a limiting nutrient throughout the Eastern United States. Research demonstrates that exposure to large doses of nitrogen leads to deleterious environmental impacts. However, effects of chronic exposure to lower doses of nitrogen are not well known. Since...

Airborne particulate matter exposure and urinary albumin excretion: the Multi-Ethnic Study of Atherosclerosis

PubMed Central

O’Neill, M S; Diez-Roux, A V; Auchincloss, A H; Franklin, T G; Jacobs, D R; Astor, B C; Dvonch, J T; Kaufman, J

2010-01-01

Objectives Understanding mechanistic pathways linking airborne particle exposure to cardiovascular health is important for causal inference and setting environmental standards. We evaluated whether urinary albumin excretion, a subclinical marker of microvascular function which predicts cardiovascular events, was associated with ambient particle exposure. Methods Urinary albumin and creatinine were measured among members of the Multi-Ethnic Study of Atherosclerosis at three visits during 2000–2004. Exposure to PM2.5 and PM10 (µg/m3) was estimated from ambient monitors for 1 month, 2 months and two decades before visit one. We regressed recent and chronic (20 year) particulate matter (PM) exposure on urinary albumin/creatinine ratio (UACR, mg/g) and microalbuminuria at first examination, controlling for age, race/ethnicity, sex, smoking, second-hand smoke exposure, body mass index and dietary protein (n = 3901). We also evaluated UACR changes and development of microalbuminuria between the first, and second and third visits which took place at 1.5- to 2-year intervals in relation to chronic PM exposure prior to baseline using mixed models. Results Chronic and recent particle exposures were not associated with current UACR or microalbuminuria (per 10 µg/m3 increment of chronic PM10 exposure, mean difference in log UACR = −0.02 (95% CI −0.07 to 0.03) and relative probability of having microalbuminuria = 0.92 (95% CI 0.77 to 1.08)) We found only weak evidence that albuminuria was accelerated among those chronically exposed to particles: each 10 µg/m3 increment in chronic PM10 exposure was associated with a 1.14 relative probability of developing microalbuminuria over 3–4 years, although 95% confidence intervals included the null (95% CI 0.96 to 1.36). Conclusions UACR is not a strong mechanistic marker for the possible influence of air pollution on cardiovascular health in this sample. PMID:18032533

Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

PubMed Central

Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

2016-01-01

Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and

The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

PubMed

van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

2018-01-11

Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

Nocturnal pituitary hormone and renin profiles during chronic heat exposure.

PubMed

Saini, J; Brandenberger, G; Libert, J P; Follenius, M

1993-07-01

To establish the principal endocrine systems involved in the initial adaptation to chronic passive heat exposure, responses of the hydromineral and pituitary systems were compared. Nocturnal plasma profiles of growth hormone, prolactin, thyrotropin, and plasma renin activity were determined during a period of prolonged heat exposure designed to simulate a hot climate. Two groups of six male subjects (G1 and G2) were kept for 11 days in a climatically controlled apartment. The G1 group was exposed to 20 degrees C throughout the study, and the G2 group was exposed to 20 degrees C for 5 days and to 35 degrees C for the following 6 days. Blood was collected continuously during the 1st and 10th nights from 2300 to 0700 h and was sampled in 10-min aliquots for hormone analysis. Heat exposure increased the nocturnal mean core temperature (P < 0.02) and stimulated plasma renin activity (P < 0.01) but had little effect on the pituitary hormones except for a small increase in prolactin (P < 0.05). For the G1 group there was no change in hormone profiles. These results demonstrate that the principal initial endocrine system involved in acclimatization to passive heat exposure is the renin-angiotensin system, reflecting counteractive measures against salt and water losses. In contrast, 5 days of continuous heat exposure does not provoke metabolic changes, indicated by the small effect on pituitary hormone profiles.

CHRONIC EXPOSURE OF RATS TO 100-MHZ (CW) RADIOFREQUENCY RADIATION: ASSESSMENT OF BIOLOGICAL EFFECTS

EPA Science Inventory

A multidisciplinary approach was employed to assess the possible biological effects of chronic exposure of rats to 100-MHz continuous wave (CW) radiofrequency (RF) radiation. A group of 20 time-bred rats were exposed in a transverse electronmagnetic mode (TEM) transmission line t...

Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-01-01

parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

SILAC-based quantitative proteomic analysis reveals widespread molecular alterations in human skin keratinocytes upon chronic arsenic exposure.

PubMed

Mir, Sartaj Ahmad; Pinto, Sneha M; Paul, Somnath; Raja, Remya; Nanjappa, Vishalakshi; Syed, Nazia; Advani, Jayshree; Renuse, Santosh; Sahasrabuddhe, Nandini A; Prasad, T S Keshava; Giri, Ashok K; Gowda, Harsha; Chatterjee, Aditi

2017-03-01

Chronic exposure to arsenic is associated with dermatological and nondermatological disorders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin. Epidemiological studies suggest the association of skin cancer upon arsenic exposure, however, the mechanism of arsenic-induced carcinogenesis is not completely understood. We developed a cell line based model to understand the molecular mechanisms involved in arsenic-mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT, was chronically exposed to 100 nM sodium arsenite over a period of 6 months. We observed an increase in basal ROS levels in arsenic-exposed cells. SILAC-based quantitative proteomics approach resulted in identification of 2111 proteins of which 42 proteins were found to be overexpressed and 54 downregulated (twofold) upon chronic arsenic exposure. Our analysis revealed arsenic-induced overexpression of aldo-keto reductase family 1 member C2 (AKR1C2), aldo-keto reductase family 1 member C3 (AKR1C3), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) among others. We observed downregulation of several members of the plakin family including periplakin (PPL), envoplakin (EVPL), and involucrin (IVL) that are essential for terminal differentiation of keratinocytes. MRM and Western blot analysis confirmed differential expression of several candidate proteins. Our study provides insights into molecular alterations upon chronic arsenic exposure on skin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

PubMed Central

Besheer, Joyce; Fisher, Kristen R.; Lindsay, Tessa G.; Cannady, Reginald

2013-01-01

Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5–0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

Long-term exposure to traffic-related air pollution and cancer among survivors of myocardial infarction: A 20-year follow-up study.

PubMed

Cohen, Gali; Levy, Ilan; Yuval; Kark, Jeremy D; Levin, Noam; Broday, David M; Steinberg, David M; Gerber, Yariv

2017-01-01

Previous studies suggested a carcinogenic effect of exposure to traffic-related air pollution. Recently, higher rates of cancer incidence were observed among myocardial infarction survivors compared with the general population. We examined the association between chronic exposure to nitrogen oxides, a proxy measure for traffic-related air pollution, and cancer incidence and mortality in a cohort of myocardial infarction patients. Patients aged ≤65 years admitted to hospital in central Israel with a first myocardial infarction in 1992-1993 were followed to 2013 for cancer incidence and cause-specific mortality. Data on sociodemographic and cancer risk factors were obtained, including time-varying information on smoking. Using land use regression models, annual averages of nitrogen oxides during follow-up were estimated individually according to home addresses. Cox proportional hazards models were constructed to study the relationships with cancer outcomes. During a mean follow-up of 16 (SD 7) years, 262 incident cancers and 105 cancer deaths were identified among 1393 cancer-free patients at baseline (mean age 54 years; 81% men). In adjusted models, a 10 ppb increase in mean nitrogen oxide exposure was associated with a hazard ratio (HR) of 1.06 (95% confidence interval (CI) 0.96-1.18) for cancer incidence and HR of 1.08 (95% CI 0.93-1.26) for cancer mortality. The association with lung, bladder, kidney or prostate cancer (previously linked to air pollution) was stronger (HR 1.16; 95% CI 1.00-1.33). Chronic exposure to traffic-related air pollution may constitute an environmental risk factor for cancer post-myocardial infarction. Variation in the strength of association between specific cancers needs to be explored further. © The European Society of Cardiology 2016.

Chronic inhalation exposure of hamsters to nickel-enriched fly ash

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wehner, A.P.; Dagle, G.E.; Milliman, E.M.

1981-10-01

Hamsters were chronically exposed to approx.70 ..mu..g/liter respirable nickel-enriched fly ash (NEFA) aerosol, approx.17 ..mu..g/liter NEFA, or approx.70 ..mu..g/liter fly ash (FA) for up to 20 months. A control group received sham exposures. The NEFA particles of respirable size contained approximately 6% nickel, compared to about 0.3% for FA. Five hamsters/group were sacrificed after 4, 8, 12, or 16 months of exposure. An additional five hamsters/group were withdrawn from exposure at the same intervals for lifelong observations. Exposures to NEFA had no significant effect on body weight and life span of the animals although heavy deposits of NEFA in themore » lungs were demonstrated. However, lung weights of the high NEFA- and of the FA-exposed animals were significantly higher than those of the low-NEFA group and the controls, and mean lung volumes were significantly larger for the high-NEFA grop and the FA group than for the low-NEFA group and the controls. Dust was deposited (anthracosis) in the lungs of all exposed hamsters. Incidence and severity of interstitial reaction and bronchiolization were significantly higher in the dust-exposed groups than in the sham-exposed controls. The severity of anthracosis, interstitial reaction, and bronchiolization was significantly lower in the low-NEFA group than in the high-NEFA and FA groups. While two malignant primary thorax tumors were found in two hamsters of the high-NEFA group, no statistically significant carcinogenesis was observed. Of the exposure-related changes, only anthracosis decreased after withdrawal from exposure. Pulmonary nickel burdens after 20 months of exposure suggest that the pulmonary clearance rate was slower in the high-NEFA group than in the low-NEFA group.« less

Prenatal drug exposure and teratological risk: one-year experience of an Italian Teratology Information Service.

PubMed

De Santis, Marco; Cesari, Elena; Ligato, Maria Serena; Nobili, Elena; Straface, Gianluca; Cavaliere, Annafranca; Caruso, Alessandro

2008-02-01

Concern about exposure to drugs, radiation, or infection during pregnancy occur often because pregnancy is not always planned. A teratology information service offers rapid scientific counseling to all those worried about prenatal exposure. The aim of this study is to present data on the most common pharmaceutical products responsible for teratogenic risk in the one-year experience of a teratology information service in Italy. The survey was conducted among 8664 callers who contacted our Teratology Information Service in Rome between January and December 2006. Data on maternal age, gravidity, parity, maternal health status, and details of exposure (dose and timing) were collected and stored in a specific data base. Scientific counseling on prenatal exposure was given to the caller by a specialized service operator, specifying the type of risk and suggesting appropriate tests for prenatal diagnosis. Most of the people called regarding drug exposure; increased risk was present in only 5% of the pregnant women calling during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) are the first category that are actually considered of increased risk to the fetus. The second category is represented by antiepileptic drugs. This experience confirms previous data that there is a high teratological risk perception among both women and physicians. The drugs estimated to present increased risk are medications used for chronic neurological diseases, mainly mood disorders and epilepsy. Preconceptional counseling for these women could be an effective strategy to prevent such exposure and to improve maternal and fetal outcome.

How Does Chronic Cigarette Smoke Exposure Affect Human Skin? A Global Proteomics Study in Primary Human Keratinocytes.

PubMed

Rajagopalan, Pavithra; Nanjappa, Vishalakshi; Raja, Remya; Jain, Ankit P; Mangalaparthi, Kiran K; Sathe, Gajanan J; Babu, Niraj; Patel, Krishna; Cavusoglu, Nükhet; Soeur, Jeremie; Pandey, Akhilesh; Roy, Nita; Breton, Lionel; Chatterjee, Aditi; Misra, Namita; Gowda, Harsha

2016-11-01

Cigarette smoking has been associated with multiple negative effects on human skin. Long-term physiological effects of cigarette smoke are through chronic and not acute exposure. Molecular alterations due to chronic exposure to cigarette smoke remain unclear. Primary human skin keratinocytes chronically exposed to cigarette smoke condensate (CSC) showed a decreased wound-healing capacity with an increased expression of NRF2 and MMP9. Using quantitative proteomics, we identified 4728 proteins, of which 105 proteins were overexpressed (≥2-fold) and 41 proteins were downregulated (≤2-fold) in primary skin keratinocytes chronically exposed to CSC. We observed an alteration in the expression of several proteins involved in maintenance of epithelial barrier integrity, including keratin 80 (5.3 fold, p value 2.5 × 10 -7 ), cystatin A (3.6-fold, p value 3.2 × 10 -3 ), and periplakin (2.4-fold, p value 1.2 × 10 -8 ). Increased expression of proteins associated with skin hydration, including caspase 14 (2.2-fold, p value 4.7 × 10 -2 ) and filaggrin (3.6-fold, p value 5.4 × 10 -7 ), was also observed. In addition, we report differential expression of several proteins, including adipogenesis regulatory factor (2.5-fold, p value 1.3 × 10 -3 ) and histone H1.0 (2.5-fold, p value 6.3 × 10 -3 ) that have not been reported earlier. Bioinformatics analyses demonstrated that proteins differentially expressed in response to CSC are largely related to oxidative stress, maintenance of skin integrity, and anti-inflammatory responses. Importantly, treatment with vitamin E, a widely used antioxidant, could partially rescue adverse effects of CSC exposure in primary skin keratinocytes. The utility of antioxidant-based new dermatological formulations in delaying or preventing skin aging and oxidative damages caused by chronic cigarette smoke exposure warrants further clinical investigations and multi-omics research.

Association between marijuana exposure and pulmonary function over 20 years.

PubMed

Pletcher, Mark J; Vittinghoff, Eric; Kalhan, Ravi; Richman, Joshua; Safford, Monika; Sidney, Stephen; Lin, Feng; Kertesz, Stefan

2012-01-11

Marijuana smoke contains many of the same constituents as tobacco smoke, but whether it has similar adverse effects on pulmonary function is unclear. To analyze associations between marijuana (both current and lifetime exposure) and pulmonary function. The Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal study collecting repeated measurements of pulmonary function and smoking over 20 years (March 26, 1985-August 19, 2006) in a cohort of 5115 men and women in 4 US cities. Mixed linear modeling was used to account for individual age-based trajectories of pulmonary function and other covariates including tobacco use, which was analyzed in parallel as a positive control. Lifetime exposure to marijuana joints was expressed in joint-years, with 1 joint-year of exposure equivalent to smoking 365 joints or filled pipe bowls. Forced expiratory volume in the first second of expiration (FEV(1)) and forced vital capacity (FVC). Marijuana exposure was nearly as common as tobacco exposure but was mostly light (median, 2-3 episodes per month). Tobacco exposure, both current and lifetime, was linearly associated with lower FEV(1) and FVC. In contrast, the association between marijuana exposure and pulmonary function was nonlinear (P < .001): at low levels of exposure, FEV(1) increased by 13 mL/joint-year (95% CI, 6.4 to 20; P < .001) and FVC by 20 mL/joint-year (95% CI, 12 to 27; P < .001), but at higher levels of exposure, these associations leveled or even reversed. The slope for FEV(1) was -2.2 mL/joint-year (95% CI, -4.6 to 0.3; P = .08) at more than 10 joint-years and -3.2 mL per marijuana smoking episode/mo (95% CI, -5.8 to -0.6; P = .02) at more than 20 episodes/mo. With very heavy marijuana use, the net association with FEV(1) was not significantly different from baseline, and the net association with FVC remained significantly greater than baseline (eg, at 20 joint-years, 76 mL [95% CI, 34 to 117]; P < .001). Occasional and low cumulative

Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease

PubMed Central

Garruto, Ralph M; Reiber, Chris; Alfonso, Marta P; Gastrich, Heidi; Needham, Kelsey; Sunderman, Sarah; Walker, Sarah; Weeks, Jennifer; DeRosa, Nicholas; Faisst, Eric; Dunn, John; Fanelli, Kenneth; Shilkret, Kenneth

2008-01-01

Background The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD. Methods Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years. Results Our results indicate two types of risks for those who attended the feast, a Feast Risk and a General Risk. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillance of feast participants exposed to CWD is ongoing. Conclusion The risk data from this study provide a relative scale for cumulative exposure to CWD-infected tissues and surfaces, and those in the upper tiers of cumulative risk may be most at risk if CWD is transmissible to humans. PMID:18577220

Occupational airborne exposure in relation to Chronic Obstructive Pulmonary Disease (COPD) and lung function in individuals without childhood wheezing illness: A 50-year cohort study.

PubMed

Tagiyeva, Nara; Sadhra, Steven; Mohammed, Nuredin; Fielding, Shona; Devereux, Graham; Teo, Ed; Ayres, Jon; Graham Douglas, J

2017-02-01

Evidence from longitudinal population-based studies relating occupational exposure to the full range of different forms of airborne pollutants and lung function and airway obstruction is limited. To relate self-reported COPD and lung function impairment to occupational exposure to different forms of airborne chemical pollutants in individuals who did not have childhood wheeze. A prospective cohort study was randomly selected in 1964 at age 10-15 years and followed up in 1989, 1995, 2001 and 2014 (aged 58-64) by spirometry and respiratory questionnaire. Occupational histories were recorded in 2014 and occupational exposures assigned using an airborne chemical job exposure matrix. The risk of COPD and lung function impairment was analyzed in subjects, who did not have childhood wheeze, using logistic and linear regression and linear mixed effects models. 237 subjects without childhood wheeze (mean age 60.6 years, 47% male) were analyzed. There was no association between any respiratory outcomes and exposure to gases, fibers, mists or mineral dusts and no consistent associations with exposure to fumes. Reduced FEV 1 was associated with longer duration (years) of exposure to any of the six main pollutant forms - vapors, gases, dusts, fumes, fibers and mists (VGDFFiM) with evidence of a dose-response relationship (p-trend=0.004). Exposure to biological dusts was associated with self-reported COPD and FEV 1 Exposure to vapors was associated with self-reported COPD and FEV 1 exposure to biological dusts or vapors. People with no history of childhood wheezing who have been occupationally exposed to biological dusts or vapors or

ANCA-associated vasculitis in Greek siblings with chronic exposure to silica.

PubMed

Brener, Z; Cohen, L; Goldberg, S J; Kaufman, A M

2001-11-01

We present the case of two siblings with similar environmental exposure to silica. Both of them developed perinuclear antineutrophil cytoplasmic antibody (p-ANCA)-associated vasculitis with pulmonary-renal syndrome. p-ANCAs were present with antimyeloperoxidase specificity on capture enzyme-linked immunosorbent assay. Treatment with corticosteroids and cyclophosphamide resulted in resolution of the clinical picture. Chronic exposure to silica is the leading environmental factor associated with ANCA-positive vasculitis. Several clusters of systemic vasculitis have been described. Positive and negative human leukocyte antigens (HLA) have been reported in systemic vasculitis. Affected brothers in our case shared one parental HLA haplotype. To the best of our knowledge, this is the first report of a family cluster of silica-induced, ANCA-associated systemic vasculitis with members sharing some of their HLA antigens.

Neuropsychological effects of exposure to naphtha among automotive workers.

PubMed Central

White, R F; Robins, T G; Proctor, S; Echeverria, D; Rocskay, A S

1994-01-01

The association between exposure to naphtha and neurobehavioural measures was examined prospectively over one year among workers employed at an automotive plant that used naphtha to calibrate fuel injectors. The neurobehavioural tests included those that assess mood, basic intelligence, and functioning of the cerebral frontal lobes and limbic system and were designed so that acute, reversible, and chronic effects of solvent exposure could be assessed. Participants were 248 workers in June 1988, and the testing was repeated on 185 of these workers in 1989. Concentrations of naphtha at the plant ranged from six to 709 mg/m3, although exposure was greater in 1988 than in 1989. Duration of exposure for individual subjects ranged from 0.8 to 7.3 years. Cross sectional data analyses showed significant associations between level of exposure to naphtha and slower timed scores on trails A, and greater reports of negative affective symptoms on profile of mood states scales in 1988 but not 1989. Threshold model analyses of the 1989 data showed an association between score on visual reproductions immediate recall and daily exposure to naphtha at or above 1050 h x mg/m3. Models of chronic exposure showed no associations between chronic exposure and negative neurobehavioural outcome. Results suggest that naphtha produces mild acute reversible effects on function of the central nervous system at or above daily exposures of 540 h x mg/m3 (approximately 90 ppm/h). PMID:8111457

TOWARDS RELIABLE AND COST-EFFECTIVE OZONE EXPOSURE ASSESSMENT: PARAMETER EVALUATION AND MODEL VALIDATION USING THE HARVARD SOUTHERN CALIFORNIA CHRONIC OZONE EXPOSURE STUDY DATA

EPA Science Inventory

Accurate assessment of chronic human exposure to atmospheric criteria pollutants, such as ozone, is critical for understanding human health risks associated with living in environments with elevated ambient pollutant concentrations. In this study, we analyzed a data set from a...

Chronic Exposure to Deoxynivalenol Has No Influence on the Oral Bioavailability of Fumonisin B1 in Broiler Chickens

PubMed Central

Antonissen, Gunther; Devreese, Mathias; Van Immerseel, Filip; De Baere, Siegrid; Hessenberger, Sabine; Martel, An; Croubels, Siska

2015-01-01

Both deoxynivalenol (DON) and fumonisin B1 (FB1) are common contaminants of feed. Fumonisins (FBs) in general have a very limited oral bioavailability in healthy animals. Previous studies have demonstrated that chronic exposure to DON impairs the intestinal barrier function and integrity, by affecting the intestinal surface area and function of the tight junctions. This might influence the oral bioavailability of FB1, and possibly lead to altered toxicity of this mycotoxin. A toxicokinetic study was performed with two groups of 6 broiler chickens, which were all administered an oral bolus of 2.5 mg FBs/kg BW after three-week exposure to either uncontaminated feed (group 1) or feed contaminated with 3.12 mg DON/kg feed (group 2). No significant differences in toxicokinetic parameters of FB1 could be demonstrated between the groups. Also, no increased or decreased body exposure to FB1 was observed, since the relative oral bioavailability of FB1 after chronic DON exposure was 92.2%. PMID:25690690

Biology Based Lung Cancer Model for Chronic Low Radon Exposures

NASA Astrophysics Data System (ADS)

TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

2008-08-01

Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

N-hexane exposure: a cause of small fiber neuropathy.

PubMed

Guimarães-Costa, Raquel; Schoindre, Yoland; Metlaine, Arnaud; Lefaucheur, Jean-Pascal; Camdessanché, Jean-Philippe; Maisonobe, Thierry; Léger, Jean-Marc

2018-06-01

A 59-year-old woman presented with progressive paresthesias of all of her limbs for 4 years, associated with neuropathic pain, tingling in the tongue and allodynia, consistent with small fiber neuropathy (SFN). Several systemic symptoms and signs were found on clinical examination and laboratory work-up. Neurological investigations including neurophysiologic test and skin biopsy supported the diagnosis of SFN. Chronic exposure to N-hexane was then disclosed and suspected to be the cause of the disease. Following the discontinuation of chronic N-hexane exposure, the patient had a progressive improvement of all signs and symptoms, reinforcing the correlation between exposure to N-hexane, and development of SFN. Exposure to N-hexane may be considered as a novel reversible cause of SFN, which underlines the need to look for toxic etiologies in the diagnosis of SFN. © 2018 Peripheral Nerve Society.

Investigation of Hydrogen Sulfide Exposure and Lung Function, Asthma and Chronic Obstructive Pulmonary Disease in a Geothermal Area of New Zealand

PubMed Central

Bates, Michael N.; Crane, Julian; Balmes, John R.; Garrett, Nick

2015-01-01

Background Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world’s largest population exposed to ambient H2S—from geothermal sources. Objectives We investigated associations of H2S with lung function, COPD and asthma in this population. Methods 1,204 of 1,639 study participants, aged 18–65 years during 2008–2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. Results None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. Conclusions The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung

Investigation of hydrogen sulfide exposure and lung function, asthma and chronic obstructive pulmonary disease in a geothermal area of New Zealand.

PubMed

Bates, Michael N; Crane, Julian; Balmes, John R; Garrett, Nick

2015-01-01

Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world's largest population exposed to ambient H2S-from geothermal sources. We investigated associations of H2S with lung function, COPD and asthma in this population. 1,204 of 1,639 study participants, aged 18-65 years during 2008-2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require

Comparison of graded exercise and graded exposure clinical outcomes for patients with chronic low back pain.

PubMed

George, Steven Z; Wittmer, Virgil T; Fillingim, Roger B; Robinson, Michael E

2010-11-01

Quasi-experimental clinical trial. This study compared outcomes from graded exercise and graded exposure activity prescriptions for patients participating in a multidisciplinary rehabilitation program for chronic low back pain. Our primary purpose was to investigate whether pain and disability outcomes differed based on treatment received (graded exercise or graded exposure). Our secondary purpose was to investigate if changes in selected psychological factors were associated with pain and disability outcomes. Behavioral interventions have been advocated for decreasing pain and disability from low back pain, yet relatively few comparative studies have been reported in the literature. Consecutive sample with chronic low back pain recruited over a 16-month period from an outpatient chronic pain clinic. Patients received physical therapy supplemented with either graded exercise (n=15) or graded exposure (n=18) principles. Graded exercise included general therapeutic activities and was progressed with a quota-based system. Graded exposure included specific activities that were feared due to back pain and was progressed with a hierarchical exposure paradigm. Psychological measures were pain-related fear (Fear-Avoidance Beliefs Questionnaire, Tampa Scale for Kinesiophobia, Fear of Pain Questionnaire), pain catastrophizing (Coping Strategies Questionnaire), and depressive symptoms (Beck Depression Inventory). Primary outcome measures were pain intensity (visual analog scale) and self-report of disability (modified Oswestry Disability Questionnaire). Statistically significant improvements (P<.01) were observed for pain intensity and disability at discharge. The rate of improvement did not differ based on behavioral intervention received (P>.05 for these comparisons). Overall, 50% of patients met criterion for minimally important change for pain intensity, while 30% met this criterion for disability. Change in depressive symptoms was associated with change in pain intensity

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

PubMed

Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2014-05-15

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

Memory Deficit Recovery after Chronic Vanadium Exposure in Mice.

PubMed

Folarin, Oluwabusayo; Olopade, Funmilayo; Onwuka, Silas; Olopade, James

2016-01-01

Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

NASA Astrophysics Data System (ADS)

Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

2016-10-01

The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

Chronic alcohol exposure affects the cell components involved in membrane traffic in neuronal dendrites.

PubMed

Romero, Ana M; Renau-Piqueras, Jaime; Marín, M Pilar; Esteban-Pretel, Guillermo

2015-01-01

The specific traffic of the membrane components in neurons is a major requirement to establish and maintain neuronal domains-the axonal and the somatodendritic domains-and their polarized morphology. Unlike axons, dendrites contain membranous organelles, which are involved in the secretory pathway, including the endoplasmic reticulum, the Golgi apparatus and post-Golgi apparatus carriers, the cytoskeleton, and plasma membrane. A variety of molecules and factors are also involved in this process. Previous studies have shown that chronic alcohol exposure negatively affects several of these cell components, such as the Golgi apparatus or cytoskeleton in neurons. Yet very little information is available on the possible effects of this exposure on the remaining cell elements involved in intracellular trafficking in neurons, particularly in dendrites. By qualitative and quantitative electron microscopy, immunofluorescence and immunoblotting, we herein show that chronic exposure to moderate levels (30 mM) of ethanol in cultured neurons reduces the volume and surface density of the rough endoplasmic reticulum, and increases the levels of GRP78, a chaperone involved in endoplasmic reticulum stress. Ethanol also significantly diminishes the proportion of neurons that show an extension of Golgi into dendrites and dendritic Golgi outposts, a structure present exclusively in longer, thicker apical dendrites. Both Golgi apparatus types were also fragmented into a large number of cells. We also investigated the effect of alcohol on the levels of microtubule-based motor proteins KIF5, KIF17, KIFC2, dynein, and myosin IIb, responsible for transporting different cargoes in dendrites. Of these, alcohol differently affects several of them by lowering dynein and raising KIF5, KIFC2, and myosin IIb. These results, together with other previously published ones, suggest that practically all the protein trafficking steps in dendrites are altered to a greater or lesser extent by chronic

IL-33 and Thymic Stromal Lymphopoietin Mediate Immune Pathology in Response to Chronic Airborne Allergen Exposure

PubMed Central

Iijima, Koji; Kobayashi, Takao; Hara, Kenichiro; Kephart, Gail M.; Ziegler, Steven F.; McKenzie, Andrew N.; Kita, Hirohito

2014-01-01

Humans are frequently exposed to various airborne allergens in the atmospheric environment. These allergens may trigger a complex network of immune responses in the airways, resulting in asthma and other chronic airway diseases. Here, we investigated the immunological mechanisms involved in the pathological changes induced by chronic exposure to multiple airborne allergens. Naïve mice were exposed intranasally to a combination of common airborne allergens, including the house dust mite, Alternaria, and Aspergillus, for up to 8 weeks. These allergens acted synergistically and induced robust eosinophilic airway inflammation, specific IgE antibody production, type 2 cytokine response and airway hyperreactivity (AHR) in 4 weeks, followed by airway remodeling in 8 weeks. Increased lung infiltration of T cells, B cells, and type 2 innate lymphoid cells (ILC2s) was observed. CD4+ T cells and ILC2s contributed to the sources of IL-5 and IL-13, suggesting involvement of both innate and adaptive immunity in this model. The lung levels of IL-33 increased quickly within several hours after allergen exposure and continued to rise throughout the chronic phase of inflammation. Mice deficient in IL-33 receptor (Il1rl1−/−) and TSLP receptor (Tslpr−/−) showed significant reduction in airway inflammation, IgE antibody levels and AHR. In contrast, mice deficient in IL-25 receptor or IL-1 receptor showed minimal differences as compared to wild-type animals. Thus, chronic exposure to natural airborne allergens triggers a network of innate and adaptive type 2 immune responses and airway pathology, and IL-33 and TSLP likely play key roles in this process. PMID:25015831

Chronic Obstructive Pulmonary Disease and Herbicide Exposure in Vietnam-Era U.S. Army Chemical Corps Veterans.

PubMed

Cypel, Yasmin; Hines, Stella E; Davey, Victoria J; Eber, Stephanie M; Schneiderman, Aaron I

2018-04-01

Past research demonstrates a possible association between herbicide exposure and respiratory health. Biologic plausibility and inhalation as a mode of exposure further support the contention that herbicides may act as adverse contributors to respiratory status, especially in military personnel who were responsible for chemical maintenance and distribution during the Vietnam War. This study examines the association between chronic obstructive pulmonary disease and herbicide exposure among Vietnam-era U.S. Army Chemical Corps veterans. A 2013 three-phase health study was conducted that included a survey (mail or telephone), in-home physical examinations, and medical record reviews/abstractions. Living, eligible veterans (n = 4,027) were identified using an existing cohort of men (n = 5,609) who either served in Vietnam (n = 2,872) or never served in Southeast Asia (n = 2,737). The health survey collected self-reported data on physician-diagnosed pulmonary conditions (chronic obstructive pulmonary disease, emphysema, and chronic bronchitis), service-related herbicide spraying history, cigarette smoking status, alcohol use, and demographics. Data from service personnel files confirmed chemical operations involvement and service status, whereas serum samples analyzed for 2,3,7,8-tetrachlorodibenzo-p-dioxin supported self-reported herbicide exposure. National Institute for Occupational Safety and Health quality-assured spirometry was performed during the physical examinations on a subset of survey respondents (n = 468 of 733 selected for participation and who provided consent) to determine mainly spirometric obstructive respiratory disease (forced expiratory volume in 1 second [FEV 1 ]/forced vital capacity [FVC] < lower limit of normal [LLN], FVC ≥ LLN, and FEV 1  < LLN; and FEV 1 /FVC < LLN and FEV 1  ≥ LLN). Associations between chronic obstructive pulmonary disease and veteran characteristics were examined (n = 403

Determinants of Chronic Respiratory Symptoms among Pharmaceutical Factory Workers

PubMed Central

Enquselassie, Fikre; Tefera, Yifokire; Gizaw, Muluken; Wakuma, Samson; Woldemariam, Messay

2018-01-01

Background Chronic respiratory symptoms including chronic cough, chronic phlegm, wheezing, shortness of breath, and chest pain are manifestations of respiratory problems which are mainly evolved as a result of occupational exposures. This study aims to assess determinants of chronic respiratory symptoms among pharmaceutical factory workers. Methods A case control study was carried out among 453 pharmaceutical factory workers with 151 cases and 302 controls. Data was collected using pretested and structured questionnaire. The data was analyzed using descriptive statistics and bivariate and multivariate analysis. Result Previous history of chronic respiratory diseases (AOR = 3.36, 95% CI = 1.85–6.12), family history of chronic respiratory diseases (AOR = 2.55, 95% CI = 1.51–4.32), previous dusty working environment (AOR = 2.26, 95% CI = 1.07–4.78), ever smoking (AOR = 3.66, 95% CI = 1.05–12.72), and service years (AOR = 1.86, 95% CI = 1.16–2.99) showed statistically significant association with chronic respiratory symptoms. Conclusion Previous history of respiratory diseases, family history of chronic respiratory diseases, previous dusty working environment, smoking, and service years were determinants of chronic respiratory symptoms. Public health endeavors to prevent the burden of chronic respiratory symptoms among pharmaceutical factory workers should target the reduction of adverse workplace exposures and discouragement of smoking. PMID:29666655

Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

NASA Technical Reports Server (NTRS)

Theriot, C. A.; Glass, A.; Lam, C-W.; James, J.; Zanello, S. B.

2014-01-01

Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10-week-old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger-NYU nose-only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4-week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe

Impact of Particulate Matter Exposure and Surrounding "Greenness" on Chronic Absenteeism in Massachusetts Public Schools.

PubMed

MacNaughton, Piers; Eitland, Erika; Kloog, Itai; Schwartz, Joel; Allen, Joseph

2017-02-20

Chronic absenteeism is associated with poorer academic performance and higher attrition in kindergarten to 12th grade (K-12) schools. In prior research, students who were chronically absent generally had fewer employment opportunities and worse health after graduation. We examined the impact that environmental factors surrounding schools have on chronic absenteeism. We estimated the greenness (Normalized Difference Vegetation Index (NDVI)) and fine particulate matter air pollution (PM 2.5 ) within 250 m and 1000 m respectively of each public school in Massachusetts during the 2012-2013 academic year using satellite-based data. We modeled chronic absenteeism rates in the same year as a function of PM 2.5 and NDVI, controlling for race and household income. Among the 1772 public schools in Massachusetts, a 0.15 increase in NDVI during the academic year was associated with a 2.6% ( p value < 0.0001) reduction in chronic absenteeism rates, and a 1 μg/m³ increase in PM 2.5 during the academic year was associated with a 1.58% ( p value < 0.0001) increase in chronic absenteeism rates. Based on these percentage changes in chronic absenteeism, a 0.15 increase in NDVI and 1 μg/m³ increase in PM 2.5 correspond to 25,837 fewer students and 15,852 more students chronically absent each year in Massachusetts respectively. These environmental impacts on absenteeism reinforce the need to protect green spaces and reduce air pollution around schools.

The physiological consequences of exposure to chronic, sublethal waterborne nickel in rainbow trout (Oncorhynchus mykiss): exercise vs resting physiology.

PubMed

Pane, Eric F; Haque, Aziz; Goss, Greg G; Wood, Chris M

2004-03-01

In rainbow trout (Oncorhynchus mykiss), following chronic (42 day) exposure to both 384 microg Ni l(-1) and 2034 microg Ni l(-1), Ni accumulation was greatest in the gill, kidney and plasma, with the plasma as the main sink for Ni. Indeed, trapped plasma analysis revealed that extensive loading of Ni in the plasma accounted for substantial percentages of accumulated Ni in several tissues including the liver and heart. Accumulated Ni in the gill and kidney was less dependent on plasma Ni concentration, suggesting a more intracellular accumulation of Ni in these tissues. We present evidence for a clear, persistent cost of acclimation to chronic, sublethal Ni exposure. Chronic (40-99 day) exposure to sublethal waterborne Ni (243-394 microg Ni l(-1); approximately 1% of the 96 h LC(50)) impaired the exercise physiology, but not the resting physiology, of rainbow trout. Ni acted as a limiting stressor, decreasing maximal rates of oxygen consumption (MO2,max) during strenuous exercise in trout exposed for 34 days to sublethal Ni. This drop in high-performance gas exchange was attributed mainly to a reduction in relative branchial diffusing capacity (D(rel)) caused by thickening of secondary lamellae. Morphometric analysis of the gills of chronically exposed fish revealed overall swelling of secondary lamellae, as well as hypertrophic respiratory epithelia within secondary lamellae. Additionally, contraction of the lamellar blood pillar system and narrowing of interlamellar water channels occurred, possibly contributing to decreased high-performance gas exchange. Decreased aerobic capacity persisted in fish previously exposed to nickel despite a clean-water exposure period of 38 days and an almost complete depuration of gill Ni, suggesting that extrabranchial mechanisms of chronic Ni toxicity may also be important. Chronic impairment of such a dynamically active and critical organ as the gill may depress the overall fitness of a fish by impairing predator avoidance, prey

The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases.

PubMed

Emad, A; Rezaian, G R

1997-09-01

To find out the late pulmonary sequelae of sulfur mustard gas inhalation in 197 veterans, 10 years after their exposure. Cross-sectional clinical study. University hospital. One hundred ninety-seven veterans with a single, heavy exposure to sulfur mustard gas in 1986 and 86 nonexposed veterans as their control group. Pulmonary function tests, carbon monoxide diffusion capacity, bronchoscopy, and high-resolution CT of the chest were performed in all patients. Transbronchial lung biopsy was done in 24 suspected cases of pulmonary fibrosis. Asthma was diagnosed in 21 (10.65%), chronic bronchitis in 116 (58.88%), bronchiectasis in 17 (8.62%), airway narrowing due to searing or granulation tissue in 19 (9.64%), and pulmonary fibrosis in 24 (12.18%) cases. None of these were found among the control group except for a single case of chronic bronchitis. Although the respiratory symptoms of an acute sulfur mustard gas inhalation are usually transient and nonspecific, it can lead to the development of a series of chronic destructive pulmonary sequelae in such cases.

Chronic warm exposure impairs growth performance and reduces thermal safety margins in the common triplefin fish (Forsterygion lapillum).

PubMed

McArley, Tristan J; Hickey, Anthony J R; Herbert, Neill A

2017-10-01

Intertidal fish species face gradual chronic changes in temperature and greater extremes of acute thermal exposure through climate-induced warming. As sea temperatures rise, it has been proposed that whole-animal performance will be impaired through oxygen and capacity limited thermal tolerance [OCLTT; reduced aerobic metabolic scope (MS)] and, on acute exposure to high temperatures, thermal safety margins may be reduced because of constrained acclimation capacity of upper thermal limits. Using the New Zealand triplefin fish ( Forsterygion lapillum ), this study addressed how performance in terms of growth and metabolism (MS) and upper thermal tolerance limits would be affected by chronic exposure to elevated temperature. Growth was measured in fish acclimated (12 weeks) to present and predicted future temperatures and metabolic rates were then determined in fish at acclimation temperatures and with acute thermal ramping. In agreement with the OCLTT hypothesis, chronic exposure to elevated temperature significantly reduced growth performance and MS. However, despite the prospect of impaired growth performance under warmer future summertime conditions, an annual growth model revealed that elevated temperatures may only shift the timing of high growth potential and not the overall annual growth rate. While the upper thermal tolerance (i.e. critical thermal maxima) increased with exposure to warmer temperatures and was associated with depressed metabolic rates during acute thermal ramping, upper thermal tolerance did not differ between present and predicted future summertime temperatures. This suggests that warming may progressively decrease thermal safety margins for hardy generalist species and could limit the available habitat range of intertidal populations. © 2017. Published by The Company of Biologists Ltd.

Chronic exposure to cocaine binging predisposes to an accelerated course of dilated cardiomyopathy in conscious dogs following rapid ventricular pacing.

PubMed

Parikh, Pratik; Nikolaidis, Lazaros A; Stolarski, Carol; Shen, You-Tang; Shannon, Richard P

2005-12-01

Despite extensive study, the extent to which cocaine use predisposes to cardiac injury remains unknown. We hypothesized that chronic cocaine binging would increase susceptibility to a subsequent cardiac insult, even in the absence of demonstrable effects on baseline hemodynamics. We studied progression of dilated cardiomyopathy (DCM) induced by rapid ventricular pacing (240 beats per minute) in five conscious, chronically instrumented dogs, after exposure to repetitive cocaine binging (COC) in the form of four consecutive 1 mg/kg i.v. boluses daily for 8 days, to simulate human cocaine abuse. We compared the results with nine control dogs (CON) undergoing the exact pacing protocol, without prior cocaine exposure. Baseline hemodynamics were not significantly altered by chronic cocaine exposure. Following 2 weeks of pacing, COC dogs exhibited accelerated progression to DCM, depressed plasma nitric oxide levels (CON, 17 +/- 2 microM; COC, 10 +/- 2 microM, p < 0.05), and a significantly greater increase in plasma epinephrine (CON, 33 +/- 6 pg/ml; COC, 104 +/- 24 pg/ml). After only 2 weeks of pacing, COC dogs demonstrated progressive DCM of a magnitude comparable with end-stage pacing-induced DCM. Chronic cocaine binging increases susceptibility to a subsequent myocardial insult and accelerates progression of DCM in conscious dogs following rapid pacing. These data suggest that although chronic cocaine use alone may not affect myocardial function, it predisposes to greater susceptibility to a superimposed insult.

Chronic bronchitis, work related respiratory symptoms, and pulmonary function in welders in New Zealand.

PubMed

Bradshaw, L M; Fishwick, D; Slater, T; Pearce, N

1998-03-01

A cross sectional study of respiratory symptoms and lung function in welders was performed at eight New Zealand welding sites: 62 current welders and 75 non-welders participated. A questionnaire was administered to record demographic data, smoking habit, and current respiratory symptoms. Current and previous welding exposures were recorded to calculate a total lifetime welding fume exposure index. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were measured before the start of the shift. There were no significant differences in ethnicity, smoking habits, or years of work experience between welders and non-welders. Symptoms of chronic bronchitis were more common in current welders (11.3%) than in non-welders (5.0%). Of those workers with a cumulative exposure index to welding fume > or = 10 years, 16.7% reported symptoms of chronic bronchitis compared with 4.7% of those with a cumulative exposure index < 4 years (odds ratio (OR) 4.1, 95% confidence interval (95% CI) 0.90 to 17.6). Workers with chronic bronchitis had significantly lower measures of baseline PEF (p = 0.008) and FEV/FVC ratio (p = 0.001) than workers without chronic bronchitis. Multivariate analysis showed that current smoking (OR 9.3, 1.0 to 86.9) and total exposure index to welding fumes > 10 years (OR 9.5, 1.3 to 71.9) were independent risk factors for chronic bronchitis. The report of any work related respiratory symptom was more prevalent in welders (30.7%) than non-welders (15.0%) and workers with these symptoms had significantly lower FEV, (p = 0.004) and FVC (p = 0.04) values. Multivariate analysis identified a high proportion of time spent welding in confined spaces as the main risk factor for reporting these symptoms (OR 2.8, 1.0 to 8.3). This study has documented a high prevalence of symptoms of chronic bronchitis and other work related respiratory symptoms in current welders. Also, workers with chronic bronchitis had reduced PEF

Dust exposure and chronic respiratory symptoms among coffee curing workers in Kilimanjaro: a cross sectional study.

PubMed

Sakwari, Gloria; Bråtveit, Magne; Mamuya, Simon H D; Moen, Bente E

2011-11-24

Coffee processing causes organic dust exposure which may lead to development of respiratory symptoms. Previous studies have mainly focused on workers involved in roasting coffee in importing countries. This study was carried out to determine total dust exposure and respiratory health of workers in Tanzanian primary coffee-processing factories. A cross sectional study was conducted among 79 workers in two coffee factories, and among 73 control workers in a beverage factory. Personal samples of total dust (n = 45 from the coffee factories and n = 19 from the control factory) were collected throughout the working shift from the breathing zone of the workers. A questionnaire with modified questions from the American Thoracic Society questionnaire was used to assess chronic respiratory symptoms. Differences between groups were tested by using independent t-tests and Chi square tests. Poisson Regression Model was used to estimate prevalence ratio, adjusting for age, smoking, presence of previous lung diseases and years worked in dusty factories. All participants were male. The coffee workers had a mean age of 40 years and were older than the controls (31 years). Personal total dust exposure in the coffee factories were significantly higher than in the control factory (geometric mean (GM) 1.23 mg/m3, geometric standard deviation (GSD) (0.8) vs. 0.21(2.4) mg/m3). Coffee workers had significantly higher prevalence than controls for cough with sputum (23% vs. 10%; Prevalence ratio (PR); 2.5, 95% CI 1.0-5.9) and chest tightness (27% vs. 13%; PR; 2.4, 95% CI 1.1-5.2). The prevalence of morning cough, cough with and without sputum for 4 days or more in a week was also higher among coffee workers than among controls. However, these differences were not statistically significant. Workers exposed to coffee dust reported more respiratory symptoms than did the controls. This might relate to their exposure to coffee dust. Interventions for reduction of dust levels and provision of

Dust exposure and chronic respiratory symptoms among coffee curing workers in Kilimanjaro: a cross sectional study

PubMed Central

2011-01-01

Background Coffee processing causes organic dust exposure which may lead to development of respiratory symptoms. Previous studies have mainly focused on workers involved in roasting coffee in importing countries. This study was carried out to determine total dust exposure and respiratory health of workers in Tanzanian primary coffee-processing factories. Methods A cross sectional study was conducted among 79 workers in two coffee factories, and among 73 control workers in a beverage factory. Personal samples of total dust (n = 45 from the coffee factories and n = 19 from the control factory) were collected throughout the working shift from the breathing zone of the workers. A questionnaire with modified questions from the American Thoracic Society questionnaire was used to assess chronic respiratory symptoms. Differences between groups were tested by using independent t-tests and Chi square tests. Poisson Regression Model was used to estimate prevalence ratio, adjusting for age, smoking, presence of previous lung diseases and years worked in dusty factories. Results All participants were male. The coffee workers had a mean age of 40 years and were older than the controls (31 years). Personal total dust exposure in the coffee factories were significantly higher than in the control factory (geometric mean (GM) 1.23 mg/m3, geometric standard deviation (GSD) (0.8) vs. 0.21(2.4) mg/m3). Coffee workers had significantly higher prevalence than controls for cough with sputum (23% vs. 10%; Prevalence ratio (PR); 2.5, 95% CI 1.0 - 5.9) and chest tightness (27% vs. 13%; PR; 2.4, 95% CI 1.1 - 5.2). The prevalence of morning cough, cough with and without sputum for 4 days or more in a week was also higher among coffee workers than among controls. However, these differences were not statistically significant. Conclusion Workers exposed to coffee dust reported more respiratory symptoms than did the controls. This might relate to their exposure to coffee dust. Interventions for

Impact of Chronic Neonicotinoid Exposure on Honeybee Colony Performance and Queen Supersedure

PubMed Central

Sandrock, Christoph; Tanadini, Matteo; Tanadini, Lorenzo G.; Fauser-Misslin, Aline; Potts, Simon G.; Neumann, Peter

2014-01-01

Background Honeybees provide economically and ecologically vital pollination services to crops and wild plants. During the last decade elevated colony losses have been documented in Europe and North America. Despite growing consensus on the involvement of multiple causal factors, the underlying interactions impacting on honeybee health and colony failure are not fully resolved. Parasites and pathogens are among the main candidates, but sublethal exposure to widespread agricultural pesticides may also affect bees. Methodology/Principal Findings To investigate effects of sublethal dietary neonicotinoid exposure on honeybee colony performance, a fully crossed experimental design was implemented using 24 colonies, including sister-queens from two different strains, and experimental in-hive pollen feeding with or without environmentally relevant concentrations of thiamethoxam and clothianidin. Honeybee colonies chronically exposed to both neonicotinoids over two brood cycles exhibited decreased performance in the short-term resulting in declining numbers of adult bees (−28%) and brood (−13%), as well as a reduction in honey production (−29%) and pollen collections (−19%), but colonies recovered in the medium-term and overwintered successfully. However, significantly decelerated growth of neonicotinoid-exposed colonies during the following spring was associated with queen failure, revealing previously undocumented long-term impacts of neonicotinoids: queen supersedure was observed for 60% of the neonicotinoid-exposed colonies within a one year period, but not for control colonies. Linked to this, neonicotinoid exposure was significantly associated with a reduced propensity to swarm during the next spring. Both short-term and long-term effects of neonicotinoids on colony performance were significantly influenced by the honeybees’ genetic background. Conclusions/Significance Sublethal neonicotinoid exposure did not provoke increased winter losses. Yet

Associations between chronic community noise exposure and blood pressure at rest and during acute noise and non-noise stressors among urban school children in India.

PubMed

Lepore, Stephen J; Shejwal, Bhaskar; Kim, Bang Hyun; Evans, Gary W

2010-09-01

The present study builds on prior research that has examined the association between children's chronic exposure to community noise and resting blood pressure and blood pressure dysregulation during exposure to acute stressors. A novel contribution of the study is that it examines how chronic noise exposure relates to blood pressure responses during exposure to both noise and non-noise acute stressors. The acute noise stressor was recorded street noise and the non-noise stressor was mental arithmetic. The sample consisted of 189 3rd and 6th grade children (51.9% percent boys; 52.9% 3rd graders) from a noisy (n = 95) or relatively quiet (n = 94) public school in the city of Pune, India. There were no statistically significant differences between chronic noise levels and resting blood pressure levels. However, relative to quiet-school children, noisy-school children had significantly lower increases in blood pressure when exposed to either an acute noise or non-noise stressor. This finding suggests that chronic noise exposure may result in hypo-reactivity to a variety of stressors and not just habituation to noise stressors.

Multiple system atrophy following chronic carbon disulfide exposure.

PubMed Central

Frumkin, H

1998-01-01

Carbon disulfide toxicity is well characterized. The principal target organ is the nervous system, although cardiovascular, reproductive, ophthalmologic, and other effects are also recognized. The neurotoxicity manifests in three ways: encephalopathy, peripheral and cranial nerve dysfunction, and movement abnormalities. This report describes a case of olivopontocerebellar atrophy, a form of multiple system atrophy, developing in an adult after over 30 years of occupational exposure to carbon disulfide. The patient presented with the insidious onset of balance problems, impotence, and irritability, without tremor, cogwheel rigidity, bradykinesia, or changes in facial expression. Over the next few years severe ataxia developed, and the clinical diagnosis was confirmed with computed tomography and magnetic resonance imaging scans. The patient experienced multiple medical complications and died approximately 9 years after diagnosis. This case is consistent with a large body of clinical and experimental literature, much of it 50 years old, showing that carbon disulfide can cause movement disorders. It also serves as a reminder that movement disorders, ranging from parkinsonism to dystonia, are associated with a variety of toxic exposures such as manganese, carbon monoxide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and medications. Images Figure 1 PMID:9721261

Exposure to waterpipe smoke induces renal functional and oxidative biomarkers variations in mice.

PubMed

Rababa'h, Abeer M; Sultan, Bilal B; Alzoubi, Karem H; Khabour, Omar F; Ababneh, Mera A

2016-09-01

Waterpipe smoking (WPS) has been known for over 400 years. It has been spread widely especially between youth because of the addition of pleasant flavor and because it was misconsidered to be less harmful than cigarette. In this study, we investigated the effect of waterpipe smoking on renal oxidative and functional parameters and compared that at acute and chronic exposure time in mice. Mice were divided into three groups, namely acute, chronic and fresh air control. Acute group was exposed to waterpipe smoke for one hour daily for six days using whole-body exposure system, while chronic group was exposed to waterpipe smoke for one hour daily for 30 days using whole-body exposure system. Exposure to waterpipe smoke has shown significant changes on the mice kidney functional parameters such as creatinine and blood urea nitrogen. Both exposures (acute and chronic) has shown a significant reduction in superoxide dismutase (SOD) activity (p < 0.05), whereas the activity of other antioxidant enzymes (catalase and GPx) reduced only with chronic exposure to waterpipe smoke (p < 0.05). Additionally, the level of thiobarbituric acid reactive substances (TBARS) in mice kidney homogenates has shown a significant elevation following chronic exposure to waterpipe smoke (p < 0.05). In conclusion, chronic waterpipe smoke affects the kidney parameter and antioxidant markers, therefore affecting its functionality of detoxifying and removal of poisonous material from the body.

Chronic repeated exposure to weather-related stimuli elicits few symptoms of chronic stress in captive molting and non-molting European starlings (Sturnus vulgaris).

PubMed

de Bruijn, Robert; Reed, J Michael; Romero, L Michael

2017-10-01

Repeated exposure to acute stressors causes dramatic changes in an animal's stress physiology and the cumulative effects are often called chronic stress. Recently we showed that short-term exposure to weather-related stimuli, such as temperature change, artificial precipitation, and food restriction, cause acute responses in captive European starlings (Sturnus vulgaris). Here, we examined the effect of repeated exposure to weather-related stressors on heart rate and corticosterone (CORT) of captive non-molting and molting European starlings. Four times every day for 3 weeks, birds were exposed to either 30 min of a subtle (3°C) decrease in temperature, a short bout of simulated rain, or 2 hr of food removal. The order and time of presentation were randomly assigned on each day. We found no differences in heart rate or heart rate variability. Furthermore, there were no changes in baseline CORT levels, CORT negative feedback efficacy, or maximal adrenal capacity. Mass increased across the experimental period only in molting birds. CORT responses to restraint were decreased in both groups following treatment, suggesting the birds had downregulated their responses to acute stress. Molting birds showed evidence of suppression of the HPA axis compared with non-molting birds, which is consistent with previous research. Overall, our data show that repeated exposure to weather-related stressors does not elicit most of the symptoms normally associated with chronic stress. © 2018 Wiley Periodicals, Inc.

Concussion in Chronic Traumatic Encephalopathy

PubMed Central

Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.

2015-01-01

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

PubMed

Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

2015-11-01

Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. Copyright © 2015 Elsevier B.V. All rights reserved.

Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine

PubMed Central

Ball, Kevin T.; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

2015-01-01

Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one’s drug use history. PMID:26241170

C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

PubMed

Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

2016-01-01

We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.

Chronic Effects of Fluoride Exposure on Growth, Metamorphosis, and Skeleton Development in Bufo gargarizans Larvae.

PubMed

Chai, Lihong; Wang, Hongyuan; Zhao, Hongfeng; Dong, Suiming

2017-04-01

Bufo gargarizans tadpoles were chronically exposed to waterborne fluoride at measured concentrations ranging from 0.4 to 61.2 mg F - /L for 70 days from Gosner stage 26 to completion of metamorphosis. The chronic exposure caused a concentration-dependent mortality in all tested fluoride concentrations. Total length, snout-to-vent length (SVL), body mass, and developmental stage of tadpoles were significantly inhibited at 42.6 mg F - /L. In addition, significant metamorphic delay and increase in size at completion of metamorphosis occurred after exposure to 19.8 mg F - /L. Moreover, 19.8 mg F - /L suppressed the bone mineralization of larvae at completion of metamorphosis. However, the bone mineralization could be enhanced by 4.1 mg F - /L. In conclusion, our results suggested that the presence of high concentrations of fluoride could increase mortality risk, delay metamorphosis, and suppress skeletal ossification in B. gargarizans larvae.

EXPOSURE ASSESSMENT OF PARTICULATE MATTER FOR SUSCEPTIBLE POPULATIONS IN SEATTLE

EPA Science Inventory

In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and as...

Effects of acute and chronic exposure to both 900 MHz and 2100 MHz electromagnetic radiation on glutamate receptor signaling pathway.

PubMed

Gökçek-Saraç, Çiğdem; Er, Hakan; Kencebay Manas, Ceren; Kantar Gok, Deniz; Özen, Şükrü; Derin, Narin

2017-09-01

To demonstrate the molecular effects of acute and chronic exposure to both 900 and 2100 MHz radiofrequency electromagnetic radiation (RF-EMR) on the hippocampal level/activity of some of the enzymes - including PKA, CaMKIIα, CREB, and p44/42 MAPK - from N-methyl-D-aspartate receptor (NMDAR)-related signaling pathways. Rats were divided into the following groups: sham rats, and rats exposed to 900 and 2100 MHz RF-EMR for 2 h/day for acute (1 week) or chronic (10 weeks), respectively. Western blotting and activity measurement assays were used to assess the level/activity of the selected enzymes. The obtained results revealed that the hippocampal level/activity of selected enzymes was significantly higher in the chronic groups as compared to the acute groups at both 900 and 2100 MHz RF-EMR exposure. In addition, hippocampal level/activity of selected enzymes was significantly higher at 2100 MHz RF-EMR than 900 MHz RF-EMR in both acute and chronic groups. The present study provides experimental evidence that both exposure duration (1 week versus 10 weeks) and different carrier frequencies (900 vs. 2100 MHz) had different effects on the protein expression of hippocampus in Wistar rats, which might encourage further research on protection against RF-EMR exposure.

Brainstem auditory evoked potentials in children with lead exposure.

PubMed

Alvarenga, Katia de Freitas; Morata, Thais Catalani; Lopes, Andrea Cintra; Feniman, Mariza Ribeiro; Corteletti, Lilian Cassia Bornia Jacob

2015-01-01

Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months). The mean time-integrated cumulative blood lead index was 12 μg/dL (SD ± 5.7, range: 2.433). All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Prenatal famine exposure and cognition at age 59 years

PubMed Central

Stein, Aryeh D; Jolles, Jelle; van Boxtel, Martin PJ; Blauw, Gerard-Jan; van de Bor, Margot; Lumey, LH

2011-01-01

Background Despite the perceived importance of early life nutrition for mental development, few studies have related gestational undernutrition to later-life cognitive functioning. We investigated the consequences of gestational exposure to the Dutch famine of 1944–45 for cognitive functioning at the age of 59 years. Methods We recruited men and women who were (i) born in birth clinics in Amsterdam, Rotterdam and Leiden, between January 1945 and March 1946, whose mothers experienced famine during or immediately preceding pregnancy (n = 354); (ii) born in the same three institutions during 1943 and 1947, whose mothers did not experience famine during this pregnancy (n = 292); or (iii) same-sex siblings of those in the first two categories (n = 311). We assessed cognitive performance at the age of 59 years by means of a comprehensive test battery. Results All cognitive functioning test scores were within normal ranges for this age group. There were no differences in cognitive performance at the age of 59 years between individuals exposed to gestational undernutrition and those without this exposure. For the general cognitive index, a summary measure across six functional domains (mean 100, standard deviation (SD) 15 points), famine exposure was associated with a decrease of 0.57 points [95% confidence interval (95% CI) −2.41 to 1.28] points. Individuals exposed to famine in gestational weeks 1–10 had a cognitive functioning index 4.36 (95% CI 8.04–0.67) points lower than those without this exposure. Within-sibling-pair analyses gave consistent results. Conclusion We found no overall association between maternal exposure to acute famine in pregnancy and cognitive performance of the offspring at the age of 59 years, but cannot rule out an association specific to early pregnancy exposure. PMID:21247885

Prenatal famine exposure and cognition at age 59 years.

PubMed

de Groot, Renate Hm; Stein, Aryeh D; Jolles, Jelle; van Boxtel, Martin Pj; Blauw, Gerard-Jan; van de Bor, Margot; Lumey, Lh

2011-04-01

Despite the perceived importance of early life nutrition for mental development, few studies have related gestational undernutrition to later-life cognitive functioning. We investigated the consequences of gestational exposure to the Dutch famine of 1944-45 for cognitive functioning at the age of 59 years. We recruited men and women who were (i) born in birth clinics in Amsterdam, Rotterdam and Leiden, between January 1945 and March 1946, whose mothers experienced famine during or immediately preceding pregnancy (n = 354); (ii) born in the same three institutions during 1943 and 1947, whose mothers did not experience famine during this pregnancy (n = 292); or (iii) same-sex siblings of those in the first two categories (n = 311). We assessed cognitive performance at the age of 59 years by means of a comprehensive test battery. All cognitive functioning test scores were within normal ranges for this age group. There were no differences in cognitive performance at the age of 59 years between individuals exposed to gestational undernutrition and those without this exposure. For the general cognitive index, a summary measure across six functional domains (mean 100, standard deviation (SD) 15 points), famine exposure was associated with a decrease of 0.57 points [95% confidence interval (95% CI) -2.41 to 1.28] points. Individuals exposed to famine in gestational weeks 1-10 had a cognitive functioning index 4.36 (95% CI 8.04-0.67) points lower than those without this exposure. Within-sibling-pair analyses gave consistent results. We found no overall association between maternal exposure to acute famine in pregnancy and cognitive performance of the offspring at the age of 59 years, but cannot rule out an association specific to early pregnancy exposure.

Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nutter, Thomas J., E-mail: tnutter@dental.ufl.edu; Cooper, Brian Y., E-mail: bcooper@dental.ufl.edu

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered musclemore » pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and

Memory Deficit Recovery after Chronic Vanadium Exposure in Mice

PubMed Central

Folarin, Oluwabusayo; Olopade, Funmilayo; Onwuka, Silas; Olopade, James

2016-01-01

Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal. PMID:26962395

Chronic pain in multiple sclerosis: A 10-year longitudinal study.

PubMed

Young, Jamie; Amatya, Bhasker; Galea, Mary P; Khan, Fary

2017-07-01

Pain is a common symptom associated with multiple sclerosis (MS), and has lasting effects on an individual's functional capacity and quality of life. A wide range of prevalence rates of pain (between 23% and 90%)have been reported in MS and this is mainly due to the methodological differences amongst the studies such as variability in patient sources, method of sampling and the definition of pain used. Chronic pain in MS, defined as pain lasting for greater than 3-6 months, can have a significant impact on their biopsychosocial health, including negative impact on activities of daily living, relationships and social participation. The long-term course of MS-related pain and its impact in an Australian cohort over a 7-year period has been investigated earlier. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. This was a prospective longitudinal study conducted at the Rehabilitation Department of Royal Melbourne Hospital (RMH), a tertiary referral hospital in Victoria and Australia. The source of participants was from the RMH MS database and contains detailed MS patient information including demographic data, diagnosis details (using McDonald's criteria), pain characteristics. Structured face-face interviews and validated measures were used, which include the visual analogue scale (VAS); chronic pain grade (CPG); the assessment of quality of life (AQoL) and the carer strain index (CSI). The mean age of the participants (n=70) was 55.3 years and majority (70%) were female. The mean age of the participants (n=70) was 55.3 years and majority (70%) were female. The findings show that over time (10 years), participants report having greater bilateral bodily pain and greater description of pain as 'worse

Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris)

PubMed Central

Moffat, Christopher; Pacheco, Joao Goncalves; Sharp, Sheila; Samson, Andrew J.; Bollan, Karen A.; Huang, Jeffrey; Buckland, Stephen T.; Connolly, Christopher N.

2015-01-01

The global decline in the abundance and diversity of insect pollinators could result from habitat loss, disease, and pesticide exposure. The contribution of the neonicotinoid insecticides (e.g., clothianidin and imidacloprid) to this decline is controversial, and key to understanding their risk is whether the astonishingly low levels found in the nectar and pollen of plants is sufficient to deliver neuroactive levels to their site of action: the bee brain. Here we show that bumblebees (Bombus terrestris audax) fed field levels [10 nM, 2.1 ppb (w/w)] of neonicotinoid accumulate between 4 and 10 nM in their brains within 3 days. Acute (minutes) exposure of cultured neurons to 10 nM clothianidin, but not imidacloprid, causes a nicotinic acetylcholine receptor-dependent rapid mitochondrial depolarization. However, a chronic (2 days) exposure to 1 nM imidacloprid leads to a receptor-dependent increased sensitivity to a normally innocuous level of acetylcholine, which now also causes rapid mitochondrial depolarization in neurons. Finally, colonies exposed to this level of imidacloprid show deficits in colony growth and nest condition compared with untreated colonies. These findings provide a mechanistic explanation for the poor navigation and foraging observed in neonicotinoid treated bumblebee colonies.—Moffat, C., Pacheco, J. G., Sharp, S., Samson, A. J., Bollan, K. A., Huang, J., Buckland, S. T., Connolly, C. N. Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris). PMID:25634958

Adaptation in Caco-2 human intestinal cell differentiation and phenolic transport with chronic exposure to phenolic-rich blackberry (Rubus sp.) extract

USDA-ARS?s Scientific Manuscript database

As evidence mounts for a health-protective role of dietary phenolics, the importance of understanding factors influencing bioavailability increases. Recent evidence has suggested chronic exposure may impact phenolic absorption and metabolism. To explore alterations occurring from chronic dietary e...

Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

PubMed

Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

2017-08-01

Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows.

PubMed

Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid; Svendsen, Susanne Wulff

2018-03-01

We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate if exposure to hand-arm vibration (HAV) is an independent risk factor. We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register-based occupational codes (1993-2007) to a general population job exposure matrix to obtain year-by-year exposure intensities on measurement scales for force, upper arm elevation >90° and repetition and expert rated intensities of exposure to HAV. For 10-year exposure time windows, we calculated the duration of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. We found indications of safe exposure intensities for repetition (median angular velocity <45°/s), while force exertion ≥10% of maximal voluntary electrical activity and upper arm elevation >90° >2 min/day implied an increased risk reaching ORs of 1.7 and 1.5 after 10 years at low intensities. No associations were found for HAV. We found indications of safe exposure intensities for repetition. Any intensities of force and upper arm elevation >90° above minimal implied an increased risk across 10-year exposure time windows. No independent associations were found for HAV. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.

Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomousmore » growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells

Carbon disulfide exposure estimate and prevalence of chronic diseases after carbon disulfide poisoning-related occupational diseases.

PubMed

Chung, Hweemin; Youn, Kanwoo; Kim, Kyuyeon; Park, Kyunggeun

2017-01-01

In Korea, Carbon disulfide (CS 2 ) toxicity was an important social problem from the late 1980s to the early 1990s but there have been few large-scale studies examining the prevalence of diseases after CS 2 exposure discontinuance. So we investigated past working exposure to CS 2 characteristics from surviving ex-workers of a rayon manufacturing plant including cumulative CS 2 exposure index. Furthermore, we studied the prevalence of their chronic diseases recently after many years. We interviewed 633 ex-workers identified as CS 2 poisoning-related occupational diseases to determine demographic and occupational characteristics and reviewed their medical records. The work environment measurement data from 1992 was used as a reference. Based on the interviews and foreign measurement documents, weights were assigned to the reference concentrations followed by calculation of individual exposure index, the sum of the portion of each time period multiplied by the concentrations of CS 2 during that period. The cumulative exposure index was 128.2 ppm on average. Workers from the spinning, electrical equipment repair, and motor repair departments were exposed to high concentrations of ≥10 ppm. Workers from the maintenance of the ejector, manufacturing of CS 2, post-process, refining, maintenance and manufacturing of viscose departments were exposed to low concentrations below 10 ppm. The prevalence for hypertension, coronary artery disease, cerebrovascular disease, diabetes, arrhythmia, psychoneurotic disorder, disorders of the nervous system and sensory organ were 69.2%, 13.9%, 24.8%, 24.5%, 1.3%, 65.7%, 72.4% respectively. We estimated the individual cumulative CS 2 exposure based on interviews and foreign measurement documents, and work environment measurement data. Comparing the work environment measurement data from 1992, these values were similar to them. After identified as CS 2 poisoning, there are subjects over 70 years of average age with disorders of the

Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

PubMed

Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

2013-12-01

The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

Impact of Particulate Matter Exposure and Surrounding “Greenness” on Chronic Absenteeism in Massachusetts Public Schools

PubMed Central

MacNaughton, Piers; Eitland, Erika; Kloog, Itai; Schwartz, Joel; Allen, Joseph

2017-01-01

Chronic absenteeism is associated with poorer academic performance and higher attrition in kindergarten to 12th grade (K-12) schools. In prior research, students who were chronically absent generally had fewer employment opportunities and worse health after graduation. We examined the impact that environmental factors surrounding schools have on chronic absenteeism. We estimated the greenness (Normalized Difference Vegetation Index (NDVI)) and fine particulate matter air pollution (PM2.5) within 250 m and 1000 m respectively of each public school in Massachusetts during the 2012–2013 academic year using satellite-based data. We modeled chronic absenteeism rates in the same year as a function of PM2.5 and NDVI, controlling for race and household income. Among the 1772 public schools in Massachusetts, a 0.15 increase in NDVI during the academic year was associated with a 2.6% (p value < 0.0001) reduction in chronic absenteeism rates, and a 1 μg/m3 increase in PM2.5 during the academic year was associated with a 1.58% (p value < 0.0001) increase in chronic absenteeism rates. Based on these percentage changes in chronic absenteeism, a 0.15 increase in NDVI and 1 μg/m3 increase in PM2.5 correspond to 25,837 fewer students and 15,852 more students chronically absent each year in Massachusetts respectively. These environmental impacts on absenteeism reinforce the need to protect green spaces and reduce air pollution around schools. PMID:28230752

Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia Infection.

PubMed

Litleskare, Sverre; Rortveit, Guri; Eide, Geir Egil; Hanevik, Kurt; Langeland, Nina; Wensaas, Knut-Arne

2018-03-06

Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time. We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls). Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations. The prevalence of IBS 10 years after the outbreak was 43% (n = 248) among 576 exposed individuals and 14% (n = 94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n = 153) among 587 exposed individuals and 11% (n = 73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22). However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90). The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward. IBS and chronic fatigue were

Chronic Exposure to Type-I IFN under Lymphopenic Conditions Alters CD4 T Cell Homeostasis

PubMed Central

Le Saout, Cecile; Hasley, Rebecca B.; Imamichi, Hiromi; Tcheung, Lueng; Hu, Zonghui; Luckey, Megan A.; Park, Jung-Hyun; Durum, Scott K.; Smith, Mindy; Rupert, Adam W.; Sneller, Michael C.; Lane, H. Clifford; Catalfamo, Marta

2014-01-01

HIV infection and the associated chronic immune activation alter T cell homeostasis leading to CD4 T cell depletion and CD8 T cell expansion. The mechanisms behind these outcomes are not totally defined and only partially explained by the direct cytopathic effect of the virus. In this manuscript, we addressed the impact of lymphopenia and chronic exposure to IFN-α on T cell homeostasis. In a lymphopenic murine model, this interaction led to decreased CD4 counts and CD8 T cell expansion in association with an increase in the Signal Transducer and Activator of Transcription 1 (STAT1) levels resulting in enhanced CD4 T cell responsiveness to IFN-α. Thus, in the setting of HIV infection, chronic stimulation of this pathway could be detrimental for CD4 T cell homeostasis. PMID:24603698

Acidic Mammalian Chitinase Negatively Affects Immune Responses during Acute and Chronic Aspergillus fumigatus Exposure.

PubMed

Garth, Jaleesa M; Mackel, Joseph J; Reeder, Kristen M; Blackburn, Jonathan P; Dunaway, Chad W; Yu, Zhihong; Matalon, Sadis; Fitz, Lori; Steele, Chad

2018-07-01

Chitin is a polysaccharide that provides structure and rigidity to the cell walls of fungi and insects. Mammals possess multiple chitinases, which function to degrade chitin, thereby supporting a role for chitinases in immune defense. However, chitin degradation has been implicated in the pathogenesis of asthma. Here, we determined the impact of acidic mammalian chitinase (AMCase) ( Chia ) deficiency on host defense during acute exposure to the fungal pathogen Aspergillus fumigatus as well as its contribution to A. fumigatus -associated allergic asthma. We demonstrate that chitin in the fungal cell wall was detected at low levels in A. fumigatus conidia, which emerged at the highest level during hyphal transition. In response to acute A. fumigatus challenge, Chia -/- mice unexpectedly demonstrated lower A. fumigatus lung burdens at 2 days postchallenge. The lower fungal burden correlated with decreased lung interleukin-33 (IL-33) levels yet increased IL-1β and prostaglandin E 2 (PGE 2 ) production, a phenotype that we reported previously to promote the induction of IL-17A and IL-22. During chronic A. fumigatus exposure, AMCase deficiency resulted in lower dynamic and airway lung resistance than in wild-type mice. Improved lung physiology correlated with attenuated levels of the proallergic chemokines CCL17 and CCL22. Surprisingly, examination of inflammatory responses during chronic exposure revealed attenuated IL-17A and IL-22 responses, but not type 2 responses, in the absence of AMCase. Collectively, these data suggest that AMCase functions as a negative regulator of immune responses during acute fungal exposure and is a contributor to fungal asthma severity, putatively via the induction of proinflammatory responses. Copyright © 2018 American Society for Microbiology.

Association between Household Air Pollution Exposure and Chronic Obstructive Pulmonary Disease Outcomes in 13 Low- and Middle-Income Country Settings.

PubMed

Siddharthan, Trishul; Grigsby, Matthew R; Goodman, Dina; Chowdhury, Muhammad; Rubinstein, Adolfo; Irazola, Vilma; Gutierrez, Laura; Miranda, J Jaime; Bernabe-Ortiz, Antonio; Alam, Dewan; Kirenga, Bruce; Jones, Rupert; van Gemert, Frederick; Wise, Robert A; Checkley, William

2018-03-01

Forty percent of households worldwide burn biomass fuels for energy, which may be the most important contributor to household air pollution. To examine the association between household air pollution exposure and chronic obstructive pulmonary disease (COPD) outcomes in 13 resource-poor settings. We analyzed data from 12,396 adult participants living in 13 resource-poor, population-based settings. Household air pollution exposure was defined as using biomass materials as the primary fuel source in the home. We used multivariable regressions to assess the relationship between household air pollution exposure and COPD outcomes, evaluated for interactions, and conducted sensitivity analyses to test the robustness of our findings. Average age was 54.9 years (44.2-59.6 yr across settings), 48.5% were women (38.3-54.5%), prevalence of household air pollution exposure was 38% (0.5-99.6%), and 8.8% (1.7-15.5%) had COPD. Participants with household air pollution exposure were 41% more likely to have COPD (adjusted odds ratio, 1.41; 95% confidence interval, 1.18-1.68) than those without the exposure, and 13.5% (6.4-20.6%) of COPD prevalence may be caused by household air pollution exposure, compared with 12.4% caused by cigarette smoking. The association between household air pollution exposure and COPD was stronger in women (1.70; 1.24-2.32) than in men (1.21; 0.92-1.58). Household air pollution exposure was associated with a higher prevalence of COPD, particularly among women, and it is likely a leading population-attributable risk factor for COPD in resource-poor settings.

Identification of the key molecules involved in chronic copper exposure-aggravated memory impairment in transgenic mice of Alzheimer's disease using proteomic analysis.

PubMed

Yu, Jun; Luo, Xiaobin; Xu, Hua; Ma, Quan; Yuan, Jianhui; Li, Xuling; Chang, Raymond Chuen-Chung; Qu, Zhongsen; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by a progressive impairment of cognitive functions including spatial learning and memory. Excess copper exposure accelerates the development of AD; however, the potential mechanisms by which copper exacerbates the symptoms of AD remain unknown. In this study, we explored the effects of chronic copper exposure on cognitive function by treating 6 month-old triple AD transgenic (3xTg-AD) mice with 250 ppm copper sulfate in drinking water for 6 months, and identified several potential key molecules involved in the effects of chronic copper exposure on memory by proteomic analysis. The behavioral test showed that chronic copper exposure aggravated memory impairment of 3xTg-AD mice. Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry revealed a total of 44 differentially expressed proteins (18 upregulated and 26 down-regulated) in hippocampus between the wild-type (WT) mice and non-exposed 3xTg-AD mice. A total of 40 differentially expressed proteins were revealed (20 upregulated and 20 down-regulated) in hippocampus between copper exposed and non-exposed 3xTg-AD mice. Among these differentially expressed proteins, complexin-1 and complexin-2, two memory associated proteins, were significantly decreased in hippocampus of 3xTg-AD mice compared with the WT mice. Furthermore, the expression of these two proteins was further down-regulated in 3xTg-AD mice when exposed to copper. The abnormal expression of complexin-1 and complexin-2 identified by proteomic analysis was verified by western blot analysis. Taken together, our data showed that chronic copper exposure accelerated memory impairment and altered the expression of proteins in hippocampus in 3xTg-AD mice. The functional analysis on the differentially expressed proteins suggested that complexin-1 and complexin-2 may be the key molecules involved in chronic copper exposure

Risk assessment of low-level chemical exposures from consumer products under the U.S. Consumer Product Safety Commission chronic hazard guidelines.

PubMed Central

Babich, M A

1998-01-01

The U.S. Consumer Product Safety Commission (CPSC) is an independent regulatory agency that was created in 1973. The CPSC has jurisdiction over more the 15,000 types of consumer products used in and around the home or by children, except items such as food, drugs, cosmetics, medical devices, pesticides, certain radioactive materials, products that emit radiation (e.g., microwave ovens), and automobiles. The CPSC has investigated many low-level exposures from consumer products, including formaldehyde emissions from urea-formaldehyde foam insulation and pressed wood products, CO and NO2 emmissions from combustion appliances, and dioxin in paper products. Many chemical hazards are addressed under the Federal Hazardous Substances Act (FHSA), which applies to acute and chronic health effects resulting from high- or low-level exposures. In 1992 the Commission issued guidelines for assessing chronic hazards under the FHSA, including carcinogenicity, neurotoxicity, reproductive/developmental toxicity, exposure, bioavailability, risk assessment, and acceptable risk. The chronic hazard guidelines describe a series of default assumptions, which are used in the absence of evidence to the contrary. However, the guidelines are intended to be sufficiently flexible to incorporate the latest scientific information. The use of alternative procedures is permissible, on a case-by-case basis, provided that the procedures used are scientifically defensible and supported by appropriate data. The application of the chronic hazard guidelines in assessing the risks from low-level exposures is discussed. PMID:9539035

Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

PubMed

Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

2017-01-01

Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na + and F - . Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F - ) concentration since the analysis with ion electrode analyzer revealed that F - concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

PubMed Central

Rushton, L; Schnatter, A R; Tang, G; Glass, D C

2014-01-01

Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case–control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone. PMID:24357793

Occupational Exposures and Chronic Kidney Disease: Possible associations with endotoxin and ultrafine particles

PubMed Central

Sponholtz, Todd R.; Sandler, Dale P.; Parks, Christine G.; Applebaum, Katie M.

2015-01-01

Background Chronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case-control study. Methods Newly diagnosed cases of CKD (n=547) and controls (n=508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results There was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions. Conclusions CKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed. PMID:26572099

Occupational exposures and chronic kidney disease: Possible associations with endotoxin and ultrafine particles.

PubMed

Sponholtz, Todd R; Sandler, Dale P; Parks, Christine G; Applebaum, Katie M

2016-01-01

Chronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case-control study. Newly diagnosed cases of CKD (n = 547) and controls (n = 508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). There was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions. CKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed. © 2015 Wiley Periodicals, Inc.

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: VI. DEVELOPMENTAL EFFECTS.

EPA Science Inventory

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA:
VI. DEVELOPMENTAL EFFECTS

Richard K. Kwok, M.S.P.H., Judy L. Mumford, Ph.D., Pauline Mendola, Ph.D. Epidemiology and Biomarkers Branch, NHEERL, US Environmental Protection Agency; Yajua...

Chronic Noise Exposure Acts Cumulatively to Exacerbate Alzheimer’s Disease-Like Amyloid-β Pathology and Neuroinflammation in the Rat Hippocampus

PubMed Central

Cui, Bo; Li, Kang; Gai, Zhihui; She, Xiaojun; Zhang, Na; Xu, Chuanxiang; Chen, Xuewei; An, Gaihong; Ma, Qiang; Wang, Rui

2015-01-01

A putative etiological association exists between noise exposure and Alzheimer’s disease (AD). Amyloid-β (Aβ) pathology is thought to be one of the primary initiating factors in AD. It has been further suggested that subsequent dysregulation of Aβ may play a mechanistic role in the AD-like pathophysiology associated with noise exposure. Here, we used ELISA, immunoblotting, cytokine arrays, and RT-PCR, to examine both hippocampal Aβ pathology and neuroinflammation in rats at different time points after noise exposure. We found that chronic noise exposure significantly accelerated the progressive overproduction of Aβ, which persisted for 7 to 14 days after the cessation of exposure. This effect was accompanied by up-regulated expression of amyloid precursor protein (APP) and its cleavage enzymes, β- and γ-secretases. Cytokine analysis revealed that chronic noise exposure increased levels of tumor necrosis factor-α and the receptor for advanced glycation end products, while decreasing the expression of activin A and platelet-derived growth factor- AA. Furthermore, we found persistent elevations of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 expression that closely corresponded to the noise-induced increases in Aβ and neuroinflammation. These studies suggest that lifelong environmental noise exposure may have cumulative effects on the onset and development of AD. PMID:26251361

Chronic intermittent ethanol exposure produces persistent anxiety in adolescent and adult rats.

PubMed

Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

2015-02-01

Ethanol (EtOH) dependence and tolerance in the adult are marked by increased function of NMDA receptors and decreased function of GABAA receptors, which coincide with altered receptor subunit expression in specific brain regions. Adolescents often use EtOH at levels greater than adults, yet the receptor subunit expression profiles following chronic intermittent EtOH (CIE) exposure in adolescents are not known. Persistent age-dependent changes in receptor subunit alterations coupled with withdrawal-related anxiety may help explain the increase in alcohol abuse following adolescent experimentation with the drug. Adolescent and adult rats received 10 intraperitoneal administrations of 4.0 g/kg EtOH or saline every 48 hours. At either 24 hours or 12 days after the final exposure, anxiety-like behavior was assessed on the elevated plus maze and tissue was collected. Western blotting was used to assess changes in selected NMDA and GABAA receptor subunits in whole cortex and bilateral hippocampus. CIE exposure yields a persistent increase in anxiety-like behavior in both age groups. However, selected NMDA and GABAA receptor subunits were not differentially altered by this CIE exposure paradigm in adolescents or adults. CIE exposure produced persistent anxiety-like behavior, which has important implications for alcohol cessation. Given the reported behavioral and neuropeptide expression changes in response to this dose of EtOH, it is important for future work to consider the circumstances under which these measures are altered by EtOH exposure. Copyright © 2015 by the Research Society on Alcoholism.

Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

PubMed

Ren, Xuefeng; Wu, Xin; Sui, Gang; Gong, Zhihong; Yawson, Emmanuel; Wu, Banghua; Lai, Guanchao; Ruan, Xiaolin; Gao, Hongbin; Zhou, Feng; Su, Bing; Olson, James R; Tang, Xiaojiang

2015-05-01

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones. Copyright © 2014 John Wiley & Sons, Ltd.

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

USGS Publications Warehouse

Wang, Ning; Mebane, Christopher A.; Kunz, James L.; Ingersoll, Christopher G.; Brumbaugh, William G.; Santore, Robert C.; Gorsuch, Joseph W.; Arnold, W. Ray

2011-01-01

Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO3, pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15–72 μg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25–267 μg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13–61 μg Cu/L for survival; 8.8–38 μg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13–215 μg Cu/L) for survival or approximately fourfold (12–42 μg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

Impact of a Disposable Sterile Radiation Shield on Operator Radiation Exposure During Percutaneous Coronary Intervention of Chronic Total Occlusions.

PubMed

Shorrock, Deborah; Christopoulos, Georgios; Wosik, Jedrek; Kotsia, Anna; Rangan, Bavana; Abdullah, Shuaib; Cipher, Daisha; Banerjee, Subhash; Brilakis, Emmanouil S

2015-07-01

Daily radiation exposure over many years can adversely impact the health of medical professionals. Operator radiation exposure was recorded for 124 percutaneous coronary interventions (PCIs) performed at our institution between August 2011 and May 2013: 69 were chronic total occlusion (CTO)-PCIs and 55 were non-CTO PCIs. A disposable radiation protection sterile drape (Radpad; Worldwide Innovations & Technologies, Inc) was used in all CTO-PCI cases vs none of the non-CTO PCI cases. Operator radiation exposure was compared between CTO and non-CTO PCIs. Mean age was 64.6 ± 6.2 years and 99.2% of the patients were men. Compared with non-CTO PCI, patients undergoing CTO-PCI were more likely to have congestive heart failure, to be current smokers, and to have longer lesions, and less likely to have prior PCI and a saphenous vein graft target lesion. CTO-PCI cases had longer procedural time (median: 123 minutes [IQR, 85-192 minutes] vs 27 minutes [IQR, 20-44 minutes]; P<.001), fluoroscopy time (35 minutes [IQR, 19-54 minutes] vs 8 minutes [IQR, 5-16 minutes]; P<.001), number of stents placed (2.4 ± 1.5 vs 1.7 ± 0.9; P<.001), and patient air kerma radiation exposure (3.92 Gray [IQR, 2.48-5.86 Gray] vs 1.22 Gray [IQR, 0.74-1.90 Gray]; P<.001), as well as dose area product (267 Gray•cm² [IQR, 163-4.25 Gray•cm²] vs 84 Gray•cm² [IQR, 48-138 Gray•cm²]; P<.001). In spite of higher patient radiation exposure, operator radiation exposure was similar between the two groups (20 μSv [IQR, 9.5-31 μSv] vs 15 μSv [IQR, 7-23 μSv]; P=.07). Operator radiation exposure during CTO-PCI can be reduced to levels similar to less complicated cases with the use of a disposable sterile radiation protection shield.

[Blastomogenic effect following single and chronic exposure to a mixture of cesium-137 and strontium-90].

PubMed

Danetskaia, E V; Lavrent'ev, L N; Zapol'skaia, N A

1976-01-01

The rate of tumor incidence in different rhythms of rat stomach exposure to cesium-137 and strontium-90 was analysed. The correlative values of the administered nucleids activity were selected by analogy with their content in global natural fall-out. In single exposure to the concentrations of 400 and 100 mc/per rat of cesium-137 and strontium-90 mixture accordingly, osteogenic osteosarcomas developed approximatley 4 times as frequently as in chronic administration of the same radionucleids in concentrations of 2 and 8 mc/per rat, correspondingly.

Chronic Kidney Disease and Exposure to Nephrotoxic Metals

PubMed Central

Orr, Sarah E.; Bridges, Christy C.

2017-01-01

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely. PMID:28498320

Effects of chronic exposure to electromagnetic waves on the auditory system.

PubMed

Özgür, Abdulkadir; Tümkaya, Levent; Terzi, Suat; Kalkan, Yıldıray; Erdivanlı, Özlem Çelebi; Dursun, Engin

2015-08-01

The results support that chronic electromagnetic field exposure may cause damage by leading to neuronal degeneration of the auditory system. Numerous researches have been done about the risks of exposure to the electromagnetic fields that occur during the use of these devices, especially the effects on hearing. The aim of this study is to evaluate the effects of the electromagnetic waves emitted by the mobile phones through the electrophysiological and histological methods. Twelve adult Wistar albino rats were included in the study. The rats were divided into two groups of six rats. The study group was exposed to the electromagnetic waves over a period of 30 days. The control group was not given any exposure to the electromagnetic fields. After the completion of the electromagnetic wave application, the auditory brainstem responses of both groups were recorded under anesthesia. The degeneration of cochlear nuclei was graded by two different histologists, both of whom were blinded to group information. The histopathologic and immunohistochemical analysis showed neuronal degeneration signs, such as increased vacuolization in the cochlear nucleus, pyknotic cell appearance, and edema in the group exposed to the electromagnetic fields compared to the control group. The average latency of wave in the ABR was similar in both groups (p > 0.05).

Caregiver Experience During Patients’ Advanced Chronic Illness and Last Year of Life

PubMed Central

Sautter, Jessica M.; Tulsky, James A.; Johnson, Kimberly S.; Olsen, Maren K.; Burton-Chase, Allison M.; Lindquist, Jennifer Hoff; Zimmerman, Sheryl; Steinhauser, Karen E.

2014-01-01

Background/Objectives Caregivers of patients with serious illness endure significant burden, yet it is not clear at what stage of advanced illness patient and caregiver needs are greatest. This study compared prevalence and predictors of caregiver esteem and burden during two different stages of patients’ illnesses – advanced chronic illness and the last year of life. Design Longitudinal, observational cohort study. Setting Community sample recruited from outpatient clinics at Duke University and Durham VA Medical Centers. Participants Patients living with advanced cancer, congestive heart failure, or chronic obstructive pulmonary disease and their primary caregiver, retrospectively coded as chronic-illness (n=62) or end-of-life (n=62) patient-caregiver dyads. Measurements We measured caregiver experience monthly with the Caregiver Reaction Assessment (CRA), which includes caregiver esteem and 4 domains of burden: schedule, health, family, and finances. Results During both chronic-illness and end-of-life, high caregiver esteem was almost universal (95%); health, family, and financial burden were endorsed by <25% of the sample. Schedule burden was the most prevalent form of burden and was experienced more frequently by end-of-life caregivers (58%) than the chronic-illness caregivers (32%). Caregiver esteem and all dimensions of burden were relatively stable over one year. Few factors were associated with burden. Conclusion Caregiver experience is relatively stable over one year and similar among caregivers of patients in the last year of life and those further upstream in advanced illness. Schedule burden stands out as most prevalent and variable among dimensions of experience. Because prevalence of burden is not specific to stage of illness and is relatively stable over time, multidisciplinary healthcare teams should assess caregiver burden and refer burdened caregivers to supportive resources early in the course of chronic illness. PMID:24803020

Chronic exposure to particulate chromate induces spindle assembly checkpoint bypass in human lung cells.

PubMed

Wise, Sandra S; Holmes, Amie L; Xie, Hong; Thompson, W Douglas; Wise, John Pierce

2006-11-01

One of the hallmarks of lung cancer is chromosome instability (CIN), particularly a tetraploid phenotype, which is normally prevented by the spindle assembly checkpoint. Hexavalent chromium Cr(VI) is an established human lung carcinogen, and Cr(VI) induces tumors at lung bifurcation sites where Cr(VI) particles impact and persist. However, the effects of Cr(VI) on the spindle assembly checkpoint are unknown and little is known about prolonged exposure to particulate Cr(VI). Accordingly, we investigated particulate Cr(VI)-induced bypass of the spindle assembly checkpoint after several days of exposure in WHTBF-6 cells. We found that lead chromate indeed induces spindle assembly checkpoint bypass in human lung cells, as 72, 96, and 120 h treatments with 0.5 or 1 microg/cm2 lead chromate induced significant increases in the percentage of cells with aberrant mitotic figures. For example, treatment with 1 microg/cm2 lead chromate for 96 h induced 11, 12.3, and 14% of cells with premature anaphase, centromere spreading and premature centromere division, respectively. In addition, we found a disruption of mitosis with more cells accumulating in anaphase; cells treated for 96 h increased from 18% in controls to 31% in cells treated with lead chromate. To confirm involvement of the spindle assembly checkpoint, Mad2 expression was used as a marker. Mad2 expression was decreased in cells exposed to chronic treatments of lead chromate, consistent with disruption of the checkpoint. We also found concentration- and time-dependent increases in tetraploid cells, which continued to grow and form colonies. When cells were treated with chronic lead alone there was no increase in aberrant mitotic cells or polyploidy; however, chronic exposure to a soluble Cr(VI) showed an increase in aberrant mitotic cells and polyploidy. These data suggest that lead chromate does induce CIN and may be one mechanism in the development of Cr(VI)-induced lung cancer.

Development and course of chronic pain over four years in the general population: The HUNT pain study.

PubMed

Landmark, Tormod; Dale, Ola; Romundstad, Pål; Woodhouse, Astrid; Kaasa, Stein; Borchgrevink, Petter C

2018-05-13

Epidemiological studies of chronic pain frequently report high prevalence estimates. However, there is little information about the development and natural course of chronic pain. We followed a random sample of participants from a population-based study (HUNT 3) with annual measures over four years. Among those without chronic pain at baseline, the probability of developing moderate to severe chronic pain (cumulative incidence) during the first year was 5%, a pain status that was maintained among 38% at the second follow-up. The probability of developing chronic pain diminished substantially for those who maintained a status of no chronic pain over several years. Subjects with moderate to severe chronic pain at baseline had an 8% probability of recovery into no chronic pain, a status that was maintained for 52% on the second follow-up. The probability of recovery diminished substantially as a status of chronic pain was prolonged for several years. Pain severity, widespread pain, pain catastrophizing, depression and sleep were significant predictors of future moderate to severe chronic pain, both among subjects with and without chronic pain at baseline. These findings suggest that the prognosis is fairly good after a new onset of chronic pain. When the pain has lasted for several years, the prognosis becomes poor. The same social and psychological factors predict new onset and the prognosis of chronic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

ERIC Educational Resources Information Center

Hunter, John A.

2010-01-01

Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

CHRONIC EXPOSURE TO ARSENITE IN DRINKING WATER IMPAIRS GLUCOSE TOLERANCE IN C57BL/6 MICE

EPA Science Inventory

Chronic exposures to inorganic arsenic (iAs) have been associated with increased prevalence of type 2 diabetes mellitus. This study examines in vivo diabetogenic effects of iAs in an animal model. Here, weanling male C57BL/6 mice received deionized water containing iAs(III) (25 ...

Marijuana Exposure Among Children Younger Than Six Years in the United States.

PubMed

Onders, Bridget; Casavant, Marcel J; Spiller, Henry A; Chounthirath, Thiphalak; Smith, Gary A

2016-05-01

This study investigates marijuana exposures among children <6 years old in the United States using data from the National Poison Data System. From 2000 through 2013, there were 1969 marijuana exposures among children <6 years old and an exposure rate of 5.90 per million children. The mean age of an exposed child was 1.81 years (median = 1.58 years). The majority of the children were exposed through ingestion (75.0%), and 18.5% of exposures required admission to a health care facility. The rate of marijuana exposure was significantly (2.82 times) higher in states where its use was legalized prior to 2000 compared with states where its use is not legal. Because more states are likely to pass legislation legalizing medical and recreational use of marijuana, increased efforts to establish child-focused safety requirements regarding packaging of commercially sold marijuana products are needed to help prevent more children from being exposed to this schedule I substance. © The Author(s) 2015.

The Association Between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan.

PubMed

DeBeer, Bryann B; Davidson, Dena; Meyer, Eric C; Kimbrel, Nathan A; Gulliver, Suzy B; Morissette, Sandra B

2017-01-01

The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of chronic multisymptom illness (CMI). Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans' health is needed.

Prepubertal gynecomastia and chronic lavender exposure: report of three cases.

PubMed

Diaz, Alejandro; Luque, Laura; Badar, Zain; Kornic, Steve; Danon, Marco

2016-01-01

Prepubertal gynecomastia is a rare condition characterized by the growth of breast tissue in males as a consequence of early exposure to sexual hormones. When this condition is present, pathological sources of testosterone/estrogen production, such as adrenal or gonadal tumors must be searched for. A few reports have described an association between gynecomastia and substances that produce stimulation of the estrogen receptor, such as lavender and tea tree oil. Here we describe the cases of three boys who presented with prepubertal gynecomastia and were chronically exposed to lavender. Two of these boys were exposed to a cologne, named agua de violetas, used by Hispanic communities in the US, and in their countries of origin. We studied a sample of the cologne used by one of the patients. Analysis of the chemical composition of the agua de violetas cologne was performed using high-performance liquid chromatography as well as off-line mass spectrometric detection. All these, combined with the physical appearance and the smell, determined that the cologne had lavender as an ingredient. Exposure to estrogenic substances, such as lavender, should be explored in children presenting with prepubertal gynecomastia/thelarche.

The effects of chronic acetaminophen exposure on the kidney, gill and liver in rainbow trout (Oncorhynchus mykiss).

PubMed

Choi, Eugene; Alsop, Derek; Wilson, Joanna Y

2018-05-01

In this study, we examined if rainbow trout chronically exposed to acetaminophen (10 and 30 μgL -1 ) showed histological changes that coincided with functional changes in the kidney, gill and liver. Histological changes in the kidney included movement and loss of nuclei, non-uniform nuclei size, non-uniform cytoplasmic staining, and loss of tubule integrity. Histological effects were more severe at the higher concentration and coincided with concentration dependent increases in urine flow rate and increased urinary concentrations of sodium, chloride, potassium, calcium, urea, ammonia, glucose, and protein. Yet, glomerular filtration rate was not altered with acetaminophen exposure. In the gill, filament end swelling, whole filament swelling, and swelling of the lamellae were observed in exposed fish. Lamellar spacing decreased in both exposure groups, but lamellar area decreased only with 30 μgL -1 exposure. At faster swimming speeds, oxygen consumption was limited in acetaminophen exposed fish, and critical swimming speed was also decreased in both exposure groups. The liver showed decreased perisinusoidal spaces at 10 and 30 μgL -1 acetaminophen, and decreased cytoplasmic vacuolation with 30 μgL -1 acetaminophen. A decrease in liver glycogen was also observed at 30 μgL -1 . There was no change in plasma concentrations of sodium, chloride, potassium, calcium, magnesium, and glucose with exposure, suggesting compensation for urinary loss. Indeed, an increase in Na + -K + -ATPase activity in the gills was found with 30 μgL -1 acetaminophen exposure. Chronic exposure of rainbow trout to the environmentally relevant pharmaceutical acetaminophen, alters both histology and function of organs responsible for ion and nutrient homeostasis. Copyright © 2018 Elsevier B.V. All rights reserved.

The architecture of the avian retina following exposure to chronic 2 G

NASA Technical Reports Server (NTRS)

Orlando, R. G.; Negulesco, J. A.

1980-01-01

Rhode Island Red female chicks at 2 weeks posthatch were subjected, for 7 d, to either earth gravity of 1 G or a 2-G hypergravity environment by chronic whole-body centrifugation. Animals were sacrificed at 3 weeks posthatch and the eyes were enucleated, fixed in 10% BNF, doubly embedded, sectioned at 7-8 microns and routinely processed with H & E for histological examination. Compared to normogravity controls, animal exposure for 1 week to the chronic effects of 2-G resulted in a significantly decreased mean width of the photoreceptor, inner nuclear, and inner plexiform retinal layers. The outer nuclear, outer plexiform, and ganglion cell layers of the retina appeared minimally affected by the hypergravity state since the mean width of these layers showed no noticeable differences from earth gravity control animals. The present anatomic findings suggest a reduction in the detection of motion or rapid changes in illumination by the avian retina when the animal is exposed at a 2-G environment.

Minimizing Exposure at Work

Science.gov Websites

; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure (chronic) exposure to certain pesticides may increase your risk of chronic health effects. Therefore, it is

CHRONIC PERCHLORATE EXPOSURE CAUSES MORPHOLOGICAL ABNORMALITIES IN DEVELOPING STICKLEBACK

PubMed Central

Bernhardt, Richard R.; Von Hippel, Frank A.; O’Hara, Todd M.

2011-01-01

Few studies have examined the effects of chronic perchlorate exposure during growth and development, and fewer still have analyzed the effects of perchlorate over multiple generations. We describe morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (G1,2003) and for their offspring (G2,2004) that were not directly treated with perchlorate. The G1,2003 displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G2,2004) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites PMID:21465539

Occupational exposure to respirable crystalline silica and chronic non-malignant renal disease: systematic review and meta-analysis.

PubMed

Möhner, Matthias; Pohrt, Anne; Gellissen, Johannes

2017-10-01

While occupational exposure to respirable silica is known to lead to lung disease, most notably silicosis, its association with chronic kidney disease is unclear. This review explores the association between occupational exposure to respirable silica and chronic non-malignant renal disease such as glomerulonephritis. The evidence has been collected and compiled. Possible sources of bias are thoroughly discussed. Cohort studies with silica exposure and case-control studies of renal disease were searched in PubMed until January 2015. Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. A meta-analysis was performed to evaluate the association to silica exposure. A total of 23 cohort and four case-control studies were included in the analysis. The meta-analysis of cohort studies yielded elevated overall SMRs for renal disease. Some studies, however, included dose-response analyses, most of which did not show a positive trend. The approaches and results of the case-control studies were very heterogeneous. While the studies of cohorts exposed to silica found elevated SMRs for renal disease, no clear evidence of a dose-response relationship emerged. The elevated risk may be attributed to diagnostic and methodological issues. In order to permit a reliable estimation of a possible causal link, exposed cohorts should be monitored for renal disease, as the information from mortality studies is hardly reliable in this field.

Mouse allergen exposure, wheeze and atopy in the first seven years of life

PubMed Central

Phipatanakul, W.; Celedón, J. C.; Hoffman, E. B.; Abdulkerim, H.; Ryan, L. M.; Gold, D. R.

2008-01-01

Background Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood. Objective To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life. Methods Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months. Results Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis. Conclusions Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life. PMID:18616677

The promise and challenge of virtual gaming technologies for chronic pain: the case of graded exposure for low back pain.

PubMed

Trost, Zina; Zielke, Marjorie; Guck, Adam; Nowlin, Liza; Zakhidov, Djanhangir; France, Christopher R; Keefe, Francis

2015-01-01

Virtual reality (VR) technologies have been successfully applied to acute pain interventions and recent reviews have suggested their potential utility in chronic pain. The current review highlights the specific relevance of VR interactive gaming technologies for pain-specific intervention, including their current use across a variety of physical conditions. Using the example of graded-exposure treatment for pain-related fear and disability in chronic low back pain, we discuss ways that VR gaming can be harnessed to optimize existing chronic pain therapies and examine the potential limitations of traditional VR interfaces in the context of chronic pain. We conclude by discussing directions for future research on VR-mediated applications in chronic pain.

Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor-9 in mice.

PubMed

Kaur, Sandeep; Mukhopadhyay, C S; Sethi, R S

2016-11-01

Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor 9 (TLR-9) in mice. In this study, healthy male Swiss albino mice (n=30) aging 8-10 weeks were used to evaluate TLR-9 expression in lungs of mice following indoxacarb exposure with and without lipopolysaccharide (LPS). Indoxacarb was administered orally dissolved in groundnut oil at 4 and 2 mg/kg/day for 90 days. On day 91, five animals from each group were challenged with LPS/normal saline solution at 80 µg/animal. The lung tissues were processed for real time and immunohistochemical studies. LPS resulted increase in fold change m-RNA expression level of TLR-9 as compare to control, while indoxacarb (4 mg/kg) alone and in combination with LPS resulted 16.21-fold change and 29.4-fold change increase in expression of TLR-9 m-RNA, respectively, as compared to control. Similarly, indoxacarb (2 mg/kg) alone or in combination with LPS also altered TLR-9 expression. Further at protein level control group showed minimal expression of TLR-9 in lungs as compare to other groups, however, LPS group showed intense positive staining in bronchial epithelium as well as in alveolar septal cells. Indoxacarb at both doses individually showed strong immuno-positive reaction as compare to control, however when combined with LPS resulted intense staining in airway epithelium as compare to control. Chronic oral administration of indoxacarb for 90 days (4 and 2 mg/kg) alters expression of TLR-9 at m-RNA and protein level and co-exposure with LPS exhibited synergistic effect.

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

PubMed

Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

2016-01-01

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

One-year follow-up of the phagocytic activity of leukocytes after exposure of rats to asbestos and basalt fibers.

PubMed Central

Hurbánková, M

1994-01-01

The phagocytic activity of leukocytes in peripheral blood was investigated after 2, 24, and 48 hr; 1, 2, 4, and 8 weeks; and 6 and 12 months following intraperitoneal administration of asbestos and basalt fibers to Wistar rats. Asbestos and basalt fibers differed in their effects on the parameters studied. Both granulocyte count and phagocytic activity of leukocytes during the 1-year dynamic follow-up in both dust-exposed groups of animals changed in two phases, characterized by the initial stimulation of the acute phase I, followed by the suppression of the parameters in the chronic phase II. Exposure to asbestos and basalt fibers led, in phase II, to impairment of the phagocytic activity of granulocytes. Asbestos fibers also significantly decreased phagocytic activity of monocytes. Exposure to basalt fibers did not affect the phagocytic activity of monocytes in phase II. Results suggest that the monocytic component of leukocytes plays an important role in the development of diseases caused by exposure to fibrous dusts, but basalt fibers have lesser biological effects than asbestos fibers. PMID:7882931

A cross-sectional study of determinants of indoor environmental exposures in households with and without chronic exposure to biomass fuel smoke.

PubMed

Pollard, Suzanne L; Williams, D'Ann L; Breysse, Patrick N; Baron, Patrick A; Grajeda, Laura M; Gilman, Robert H; Miranda, J Jaime; Checkley, William

2014-03-24

Burning biomass fuels indoors for cooking is associated with high concentrations of particulate matter (PM) and carbon monoxide (CO). More efficient biomass-burning stoves and chimneys for ventilation have been proposed as solutions to reduce indoor pollution. We sought to quantify indoor PM and CO exposures in urban and rural households and determine factors associated with higher exposures. A secondary objective was to identify chronic vs. acute changes in cardiopulmonary biomarkers associated with exposure to biomass smoke. We conducted a census survey followed by a cross-sectional study of indoor environmental exposures and cardiopulmonary biomarkers in the main household cook in Puno, Peru. We measured 24-hour indoor PM and CO concentrations in 86 households. We also measured PM2.5 and PM10 concentrations gravimetrically for 24 hours in urban households and during cook times in rural households, and generated a calibration equation using PM2.5 measurements. In a census of 4903 households, 93% vs. 16% of rural vs. urban households used an open-fire stove; 22% of rural households had a homemade chimney; and <3% of rural households participated in a national program encouraging installation of a chimney. Median 24-hour indoor PM2.5 and CO concentrations were 130 vs. 22 μg/m3 and 5.8 vs. 0.4 ppm (all p<0.001) in rural vs. urban households. Having a chimney did not significantly reduce median concentrations in 24-hour indoor PM2.5 (119 vs. 137 μg/m3; p=0.40) or CO (4.6 vs. 7.2 ppm; p=0.23) among rural households with and without chimneys. Having a chimney did not significantly reduce median cook-time PM2.5 (360 vs. 298 μg/m3, p=0.45) or cook-time CO concentrations (15.2 vs. 9.4 ppm, p=0.23). Having a thatched roof (p=0.007) and hours spent cooking (p=0.02) were associated with higher 24-hour average PM concentrations. Rural participants had higher median exhaled CO (10 vs. 6 ppm; p=0.01) and exhaled carboxyhemoglobin (1.6% vs. 1.0%; p=0.04) than urban

A cross-sectional study of determinants of indoor environmental exposures in households with and without chronic exposure to biomass fuel smoke

PubMed Central

2014-01-01

Background Burning biomass fuels indoors for cooking is associated with high concentrations of particulate matter (PM) and carbon monoxide (CO). More efficient biomass-burning stoves and chimneys for ventilation have been proposed as solutions to reduce indoor pollution. We sought to quantify indoor PM and CO exposures in urban and rural households and determine factors associated with higher exposures. A secondary objective was to identify chronic vs. acute changes in cardiopulmonary biomarkers associated with exposure to biomass smoke. Methods We conducted a census survey followed by a cross-sectional study of indoor environmental exposures and cardiopulmonary biomarkers in the main household cook in Puno, Peru. We measured 24-hour indoor PM and CO concentrations in 86 households. We also measured PM2.5 and PM10 concentrations gravimetrically for 24 hours in urban households and during cook times in rural households, and generated a calibration equation using PM2.5 measurements. Results In a census of 4903 households, 93% vs. 16% of rural vs. urban households used an open-fire stove; 22% of rural households had a homemade chimney; and <3% of rural households participated in a national program encouraging installation of a chimney. Median 24-hour indoor PM2.5 and CO concentrations were 130 vs. 22 μg/m3 and 5.8 vs. 0.4 ppm (all p<0.001) in rural vs. urban households. Having a chimney did not significantly reduce median concentrations in 24-hour indoor PM2.5 (119 vs. 137 μg/m3; p=0.40) or CO (4.6 vs. 7.2 ppm; p=0.23) among rural households with and without chimneys. Having a chimney did not significantly reduce median cook-time PM2.5 (360 vs. 298 μg/m3, p=0.45) or cook-time CO concentrations (15.2 vs. 9.4 ppm, p=0.23). Having a thatched roof (p=0.007) and hours spent cooking (p=0.02) were associated with higher 24-hour average PM concentrations. Rural participants had higher median exhaled CO (10 vs. 6 ppm; p=0.01) and exhaled carboxyhemoglobin (1.6% vs. 1.0%; p

Behavioral effects of D3 receptor inhibition and 5-HT4 receptor activation on animals undergoing chronic cannabinoid exposure during adolescence.

PubMed

Abboussi, Oualid; Said, Nadia; Fifel, Karim; Lakehayli, Sara; Tazi, Abdelouahhab; El Ganouni, Soumaya

2016-04-01

Chronic exposure to cannabinoids during adolescence results in long-lasting behavioral deficits that match some symptomatologic aspects of schizophrenia. The aim of this study was to investigate the reversibility of the emotional and the cognitive effects of chronic exposure to cannabinoids during adolescence, via subsequent modulation of the serotoninergic 5-HT4 and dopaminergic D3 receptors. RS67333 as a 5-HT4 agonist and U-99194A as a D3 antagonist were administered separately at 1 mg/kg and 20 mg/kg, and in combination at 0.5 mg/kg and 10 mg/kg to adult animals undergoing chronic treatment with the synthetic cannabinoid receptor agonist WIN55,212-2 (1 mg/kg) during adolescence. Animals were tested for anxiety-like behavior and episodic-like memory in the open field and novel object recognition tests respectively 30 minutes after the last drug administration. Chronic WIN55,212-2 treated animals exhibited a lasting disruption of episodic memory and increased anxiety levels. The effect on episodic-like memory were partially restored by acute administration of RS67333 and U-99194A and completely by administration of both drugs in combination at lower doses. However, only RS67333 (20 mg/kg) improved the anxiogenic-like effect of WIN55,212-2. These findings give further support that chronic exposure to cannabinoids during adolescence may be used as an animal model for schizophrenia, and highlight D3 and 5-HT4 receptors as potential targets for an enhanced treatment of the cognitive aspect of this disease.

The Association between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan

PubMed Central

DeBeer, Bryann B.; Davidson, Dena; Meyer, Eric C.; Kimbrel, Nathan A.; Gulliver, Suzy B.; Morissette, Sandra B.

2017-01-01

Objective The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of Chronic Multisymptom Illness (CMI). Methods Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Results Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. Conclusions These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans’ health is needed. PMID:28045798

GENE EXPRESSION PROFILING OF MOUSE SKIN AND PAPILLOMAS FOLLOWING CHRONIC EXPOSURE TO MONOMETHYLARSONOUS ACID IN K6/ODC TRANSGENIC MICE

EPA Science Inventory

Methylarsonous acid [MMA(III)], a common metabolite of inorganic arsenic metabolism, increases tumor frequency in the skin of K6/ODC transgenic mice following a chronic exposure. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcin...

The impact of exposure to biomass smoke versus cigarette smoke on inflammatory markers and pulmonary function parameters in patients with chronic respiratory failure.

PubMed

Ocakli, Birsen; Acarturk, Eylem; Aksoy, Emine; Gungor, Sinem; Ciyiltepe, Fulya; Oztas, Selahattin; Ozmen, Ipek; Agca, Meltem Coban; Salturk, Cuneyt; Adiguzel, Nalan; Karakurt, Zuhal

The aim of this study was to evaluate the impact of exposure to biomass smoke vs cigarette smoke on serum inflammatory markers and pulmonary function parameters in patients with chronic respiratory failure (CRF). A total of 106 patients with CRF divided into age and gender-matched groups of cigarette-smoke exposure (n=55, mean [SD] age: 71.0 [12.0] years, 92.7% were females) and biomass smoke exposure (n=51, mean [SD] age: 73.0 [11.0] years, 94.1% were females) were included in this retrospective study. Data on patient demographics (age and gender), inflammatory markers, including neutrophil-to-lymphocyte ratio, C-reactive protein, platelet/mean platelet volume ratio, arterial blood gas analysis, and pulmonary function test findings, including forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC were obtained from medical records. Carbon dioxide partial pressure levels were significantly higher in the biomass smoke exposure than in the cigarette smoke exposure group (mean [SD] 51.0 [8.0] vs 47.0 [8.0] mmHg, p =0.026, respectively). Spirometry revealed similarly low levels for FEV 1 (%) (38.0 [16.0] vs 40.0 [12.0]%) and FVC (%) (45.0 [19.0] vs 39.0 [19.0]%) in cigarette-smoke and biomass smoke exposure groups, whereas biomass smoke exposure was associated with significantly higher FEV 1 /FVC (75.0 [14.0] vs 58.0 [12.0]%, p =0.001), lower FVC (mL) (mean [SD] 744.0 [410.0] vs 1,063.0 [592.0] mL, p =0.035) and lower percentage of patients with FEV 1 /FVC <70% (36.8% vs 82.0%, p <0.001) than cigarette smoke exposure. Our findings indicate similarly increased inflammatory markers and abnormally low pulmonary function test findings in both biomass smoke exposure and cigarette smoke exposure groups, emphasizing the adverse effects of biomass smoke exposure on lungs to be as significant as cigarette smoke exposure. Association of biomass smoke exposure with higher likelihood of FEV 1 /FVC ratio of >70% and more prominent loss of vital

The influence of occupational chronic lead exposure on the levels of selected pro-inflammatory cytokines and angiogenic factors.

PubMed

Machoń-Grecka, A; Dobrakowski, M; Boroń, M; Lisowska, G; Kasperczyk, A; Kasperczyk, S

2017-05-01

The aim of the study was to determine the effect of occupational exposure to lead on the blood levels of pro-inflammatory cytokines and selected factors that influence angiogenesis. The study population was divided into two groups. The first group consisted of 56 male workers chronically exposed to lead. The second group (control) was comprised of 24 male administrative workers. The serum levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were significantly higher in the group of workers chronically exposed to lead compared to control values by 38%, 68%, and 57%, respectively. Similarly, the values of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and fibroblast growth factor-basic (FGF-basic) were higher by 19% and 63%, respectively. In the group of workers chronically exposed to lead, there were positive correlations between the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and angiogenic factors (VEGF, FGF-basic, sVEGFR-1, and soluble angiopoietin receptor). In the control group, there were no correlations between the levels of the abovementioned parameters. Results of the present study indicate that chronic occupational lead exposure promotes inflammatory processes via induction of pro-inflammatory cytokines, modulates angiogenesis, and elicits interdependencies between the immune response and angiogenic factors.

Chronic Exposure to Methamphetamine Disrupts Reinforcement-Based Decision Making in Rats.

PubMed

Groman, Stephanie M; Rich, Katherine M; Smith, Nathaniel J; Lee, Daeyeol; Taylor, Jane R

2018-03-01

The persistent use of psychostimulant drugs, despite the detrimental outcomes associated with continued drug use, may be because of disruptions in reinforcement-learning processes that enable behavior to remain flexible and goal directed in dynamic environments. To identify the reinforcement-learning processes that are affected by chronic exposure to the psychostimulant methamphetamine (MA), the current study sought to use computational and biochemical analyses to characterize decision-making processes, assessed by probabilistic reversal learning, in rats before and after they were exposed to an escalating dose regimen of MA (or saline control). The ability of rats to use flexible and adaptive decision-making strategies following changes in stimulus-reward contingencies was significantly impaired following exposure to MA. Computational analyses of parameters that track choice and outcome behavior indicated that exposure to MA significantly impaired the ability of rats to use negative outcomes effectively. These MA-induced changes in decision making were similar to those observed in rats following administration of a dopamine D2/3 receptor antagonist. These data use computational models to provide insight into drug-induced maladaptive decision making that may ultimately identify novel targets for the treatment of psychostimulant addiction. We suggest that the disruption in utilization of negative outcomes to adaptively guide dynamic decision making is a new behavioral mechanism by which MA rigidly biases choice behavior.

Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model

PubMed Central

Jansen, Chad; Speck, Mark; Greineisen, William E; Maaetoft-Udsen, Kristina; Cordasco, Edward; Shimoda, Lori MN; Stokes, Alexander J; Turner, Helen

2018-01-01

Objective Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional responses in mast cells. SG contains histamine and matrix-active proteases, while LB are reservoirs of arachidonic acid and its metabolites, precursors for rapid synthesis of eicosanoids such as LTC4. Both of these compartments can be dynamically or ontologically regulated, with metabolic and immunological stimuli altering lipid body content and granule numbers responding to contextual signals from tissue. We previously described that chronic in vitro or in vivo hyperinsulinemia expands the LB compartment with a concomitant loss of SG capacity, suggesting that this ratio is dynamically regulated. The objective of the current study is to determine if chronic insulin exposure initiates a transcriptional program that biases model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis. Methods We used a basophilic leukemic cell line with mucosal mast cell-like features as a model system. We tested the hypothesis that chronic insulin exposure initiates a transcriptional program that biases these model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis. Transcriptional arrays were used to map gene expression patterns. Biochemical, immunocytochemical and mediator release assays were used to evaluate organelle numbers and functional responses. Results In a mucosal mast cell model, the rat basophilic leukemia line RBL2H3, mast cell granularity and SG numbers are inversely correlated with LB numbers. Chronic insulin exposure appears to modulate gene networks involved in both lipid body biogenesis and secretory granule formation. Western blot analysis confirms upregulation of protein levels for LB proteins, and decreases in proteins that are markers for SG cargo. Conclusions The levels of insulin in the extracellular milieu may modify the phenotype of mast cell-like cells in vitro. PMID

Public health and chronic low chlordecone exposures in Guadeloupe; Part 2: Health impacts, and benefits of prevention.

PubMed

Nedellec, Vincent; Rabl, Ari; Dab, William

2016-07-19

Inhabitants of Guadeloupe are chronically exposed to low doses of chlordecone via local food due to its past use in banana plantations. The corresponding health impacts have not been quantified. We develop a quantitative method and present the results in two articles: 1. Hazard identification, exposure-response functions, and exposure, 2. Health impacts, and benefits of a program to reduce the exposure of the population. Here is the second article. The exposure-response functions derived in Part 1 (for liver and prostate cancer, renal dysfunction and cognitive development) are combined with the exposure data to calculate the impacts. The corresponding costs are calculated via DALY's and VOLY. A no-effect threshold is included via the marginal fraction of the collective exposure above the reference dose. The health benefits are the impacts in 2002 (before the exposure reduction program) minus the impacts in 2006 (since the program). They are compared to the costs, namely the public annual expenditures for reducing the population exposure. Without threshold, estimated annual cases of liver cancer, prostate cancer and renal dysfunction are respectively 5.4, 2.8, 0.10 in 2002; and 2.0, 1.0, 0.04 in 2006. Annual IQ points lost (cognitive development) are respectively: 1 173 and 1 003. The annual cost of total impacts is 38.3 Million Euros (M€) in 2002 and 23.7 M€ in 2006. Comparing the benefit of 14.6 M€ with the 3.25 M€ spent for prevention, the program appears well justified. With threshold, the costs of the impacts are lower, respectively: 26.5 M€ in 2002 and 12.8 M€ in 2006, but the benefit is not very different: 13.7 M€. This is the first study that quantified chronic non genotoxic effects of chlordecone exposures in Guadeloupe. According to our results, preventive actions should be focused on pregnant women because of the high social cost of development impairment and also because their exposures decreased less rapidly than others. Prevention

Spatial cognition and sexually dimorphic synaptic plasticity balance impairment in rats with chronic prenatal ethanol exposure.

PubMed

An, Lei; Zhang, Tao

2013-11-01

Prenatal ethanol exposure can lead to long-lasting impairments in the ability of rats to process spatial information, as well as produce long-lasting deficits in long-term potentiation (LTP), a biological model of learning and memory processing. The present study aimed to examine the sexually dimorphic effects of chronic prenatal ethanol exposure (CPEE) on behavior cognition and synaptic plasticity balance (SPB), and tried to understand a possible mechanism by evaluating the alternation of SPB. The animal model was produced by ethanol exposure throughout gestational period with 4 g/kg bodyweight. Offspring of both male and female were selected and studied on postnatal days 36. Subsequently, the data showed that chronic ethanol exposure resulted in birth weight reduction, losing bodyweight gain, microcephaly and hippocampus weight retardation. In Morris water maze (MWM) test, escape latencies were significantly higher in CPEE-treated rats than that in control ones. They also spent much less time in the target quadrant compared to that of control animals in the probe phase. In addition, it was found that there was a more severe impairment in females than that in males after CPEE treatment. Electrophysiological studies showed that CPEE considerably inhibited hippocampal LTP and facilitated depotentiation in males, while significantly enhanced LTP and suppressed depotentiation in females. A novel index, developed by us, showed that the action of CPEE on SPB was more sensitive in females than that in males, suggesting that it might be an effective index to distinguish the difference of SPB impairment between males and females. Copyright © 2013 Elsevier B.V. All rights reserved.

Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice☆

PubMed Central

Basgen, John M.; Sobin, Christina

2014-01-01

Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) μg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) μg/dL]. Higher-level lead exposed mice [14.68 (2.74) μg/dL] had no change in either glomerular volume or podocyte number. The increase in glomerular volume was explained by increases in glomerular capillary and mesangial volumes with no change in podocyte volume. Early chronic lead exposure yielding very low blood lead levels alters glomerular development in pre-adolescent animals. PMID:24300173

Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep

PubMed Central

Kallapur, Suhas G.; Kramer, Boris W.; Knox, Christine L.; Berry, Clare A.; Collins, Jennifer J.P; Kemp, Matthew W.; Nitsos, Ilias; Polglase, Graeme R.; Robinson, James; Hillman, Noah H.; Newnham, John P.; Chougnet, Claire; Jobe, Alan H.

2011-01-01

The chorioamnionitis associated with preterm delivery is often polymicrobial with ureaplasma being the most common isolate. To evaluate interactions between the different pro-inflammatory mediators, we hypothesized that ureaplasma exposure would increase fetal responsiveness to LPS. Fetal sheep were given intra-amniotic injections of media (control) or Ureaplasma parvum serovar 3 either 7d or 70d before preterm delivery. Another group received an intraamniotic injection of E.coli lipo-polysaccharide (LPS) 2d prior to delivery. To test for interactions, intraamniotic U. parvum exposed animals were challenged with intraamniotic LPS and delivered 2d later. All animals were delivered at 124±1d gestation (Term=150d). Compared to the 2d LPS exposure group, the U. parvum 70d+LPS group had: 1) decreased lung pro and anti-inflammatory cytokine expression 2) fewer CD3+ T-lymphocytes, CCL2+, myeloperoxidase+, and PU.1+ cells in the lung. Interestingly, exposure to U. parvum for 7d did not change responses to a subsequent intraamniotic LPS challenge, and exposure to intraamniotic U. parvum alone induced mild lung inflammation. Exposure to U. parvum increased pulmonary TGFβ1 expression but did not change mRNA expression of either the receptor TLR4 or some of the downstream mediators in the lung. Monocytes from fetal blood and lung isolated from U. parvum 70d+LPS but not U. parvum 7d+LPS animals had decreased in vitro responsiveness to LPS. These results are consistent with the novel finding of down-regulation of LPS responses by chronic but not acute fetal exposures to U. parvum. The findings increase our understanding of how chorioamnionitis exposed preterm infants may respond to lung injury and postnatal nosocomial infections. PMID:21784974

Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

PubMed

Renand, Amedee; Archila, Luis D; McGinty, John; Wambre, Erik; Robinson, David; Hales, Belinda J; Thomas, Wayne R; Kwok, William W

2015-12-01

In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood. We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced. Fel d 1-, Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation. In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

PubMed Central

Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

2012-01-01

Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a six month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. PMID:22521957

Hepatic and renal trace element concentrations in American alligators (Alligator mississippiensis) following chronic dietary exposure to coal fly ash contaminated prey.

PubMed

Tuberville, Tracey D; Scott, David E; Metts, Brian S; Finger, John W; Hamilton, Matthew T

2016-07-01

Little is known about the propensity of crocodilians to bioaccumulate trace elements as a result of chronic dietary exposure. We exposed 36 juvenile alligators (Alligator mississippiensis) to one of four dietary treatments that varied in the relative frequency of meals containing prey from coal combustion waste (CCW)-contaminated habitats vs. prey from uncontaminated sites, and evaluated tissue residues and growth rates after 12 mo and 25 mo of exposure. Hepatic and renal concentrations of arsenic (As), cadmium (Cd) and selenium (Se) varied significantly among dietary treatment groups in a dose-dependent manner and were higher in kidneys than in livers. Exposure period did not affect Se or As levels but Cd levels were significantly higher after 25 mo than 12 mo of exposure. Kidney As and Se levels were negatively correlated with body size but neither growth rates nor body condition varied significantly among dietary treatment groups. Our study is among the first to experimentally examine bioaccumulation of trace element contaminants in crocodilians as a result of chronic dietary exposure. A combination of field surveys and laboratory experiments will be required to understand the effects of different exposure scenarios on tissue residues, and ultimately link these concentrations with effects on individual health. Copyright © 2016 Elsevier Ltd. All rights reserved.

The impairment of learning and memory and synaptic loss in mouse after chronic nitrite exposure.

PubMed

Chen, Yongfang; Cui, Zhanjun; Wang, Lai; Liu, Hongliang; Fan, Wenjuan; Deng, Jinbo; Deng, Jiexin

2016-12-01

The objective of this study is to understand the impairment of learning and memory in mouse after chronic nitrite exposure. The animal model of nitrite exposure in mouse was created with the daily intubation of nitrite in adult healthy male mice for 3 months. Furthermore, the mouse's learning and memory abilities were tested with Morris water maze, and the expression of Synaptophysin and γ-Synuclein was visualized with immunocytochemistry and Western blot. Our results showed that nitrite exposure significantly prolonged the escape latency period (ELP) and decreased the values of the frequency across platform (FAP) as well as the accumulative time in target quadrant (ATITQ) compared to control, in dose-dependent manner. In addition, after nitrite exposure, synaptophysin (SYN) positive buttons in the visual cortex was reduced, in contrast the increase of γ-synuclein positive cells. The results above were supported by Western blot as well. We conclude that nitrite exposure could lead to a decline in mice's learning and memory. The overexpression of γ-synuclein contributed to the synaptic loss, which is most likely the cause of learning and memory impairment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1720-1730, 2016. © 2015 Wiley Periodicals, Inc.

Surgical treatment of chronic pancreatitis--a 14 years experience.

PubMed

Stroescu, C; Dima, S; Scarlat, A; Ivanov, B; Bouaru, O; Ionescu, M; Vasilescu, C; Popescu, I

2010-01-01

Operative treatment of chronic pancreatitis is indicated for patients with intractable pain after failed medical and endoscopic treatment, or in the presence of complications of the disease. This study evaluates a single-center experience with operative management of chronic pancreatitis over a period of time of 14 years, regarding indication, surgical technique, early and late results. The records of 265 consecutive patients who underwent surgery for chronic pancreatitis between 1995 and 2008 were retrospectively reviewed and analyzed. Long-term outcomes were assessed by patient survey, with a median follow-up of 40 months. 265 patients underwent 275 operations for chronic pancreatitis with the main indication abdominal pain (46.8%), followed by suspected malignancy in 24.8% and recurrent episodes of acute pancreatitis in 18.6%. Resection procedures 54.5% (150), drainage procedures 1.09% (3), bypass and denervation procedures 44.36% (122) and exploratory laparotomy 3.27% (9) were performed with an overall morbidity of 22% and an in-hospital mortality rate of 2.64%. After a median follow-up of 40 months survival information was available for 137 patients (51.69%) with a 5-and actuarial survival rate of 74.7% and quality of life improvement in most patients, especially in the resected group. Our results suggest that in chronic pancreatitis the type of surgery has to be individualized in each patient (resection VS drainage) and organ preserving operations are safe and effective in providing long-term pain relief and in treating CP-related complications

Effects of chronic ammonia exposure on ammonia metabolism and excretion in marine medaka Oryzias melastigma.

PubMed

Gao, Na; Zhu, Limei; Guo, Zhiqiang; Yi, Meisheng; Zhang, Li

2017-06-01

Ammonia is highly toxic to aquatic organisms, but whether ammonia excretion or ammonia metabolism to less toxic compounds is the major strategy for detoxification in marine fish against chronic ammonia exposure is unclear to date. In this study, we investigated the metabolism and excretion of ammonia in marine medaka Oryzias melastigma during chronic ammonia exposure. The fish were exposed to 0, 0.1, 0.3, 0.6, and 1.1 mmol l -1  NH 4 Cl spiked seawater for 8 weeks. Exposure of 0.3-1.1 mmol l -1  NH 4 Cl had deleterious effects on the fish, including significant reductions in growth, feed intake, and total protein content. However, the fish could take strategies to detoxify ammonia. The tissue ammonia (T Amm ) in the 0.3-1.1 mmol l -1  NH 4 Cl treatments was significantly higher than those in the 0 and 0.1 mmol l -1  NH 4 Cl treatments after 2 weeks of exposure, but it recovered with prolonged exposure time, ultimately reaching the control level after 8 weeks. The amino acid catabolic rate decreased to reduce the gross ammonia production with the increasing ambient ammonia concentration. The concentrations of most metabolites remained constant in the 0-0.6 mmol l -1  NH 4 Cl treatments, whereas 5 amino acids and 3 energy metabolism-related metabolites decreased in the 1.1 mmol l -1  NH 4 Cl treatment. J Amm steadily increased in ambient ammonia from 0 to 0.6 mmol l -1 and slightly decreased when the ambient ammonia concentration increased to 1.1 mmol l -1 . Overall, marine medaka cope with sublethal ammonia environment by regulating the tissue T Amm via reducing the ammonia production and increasing ammonia excretion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of chronic carbon monoxide exposure on fetal growth and development in mice

PubMed Central

2011-01-01

Background Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse. PMID:22168775

Modeling accumulations of particles in lung during chronic inhalation exposures that lead to impaired clearance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolff, R.K.; Griffith, W.C. Jr.; Cuddihy, R.G.

Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2more » h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people.« less

Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

NASA Technical Reports Server (NTRS)

Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

1998-01-01

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor-9 in mice

PubMed Central

Kaur, Sandeep; Mukhopadhyay, C. S.; Sethi, R. S.

2016-01-01

Aim: Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor 9 (TLR-9) in mice. Materials and Methods: In this study, healthy male Swiss albino mice (n=30) aging 8-10 weeks were used to evaluate TLR-9 expression in lungs of mice following indoxacarb exposure with and without lipopolysaccharide (LPS). Indoxacarb was administered orally dissolved in groundnut oil at 4 and 2 mg/kg/day for 90 days. On day 91, five animals from each group were challenged with LPS/normal saline solution at 80 µg/animal. The lung tissues were processed for real time and immunohistochemical studies. Results: LPS resulted increase in fold change m-RNA expression level of TLR-9 as compare to control, while indoxacarb (4 mg/kg) alone and in combination with LPS resulted 16.21-fold change and 29.4-fold change increase in expression of TLR-9 m-RNA, respectively, as compared to control. Similarly, indoxacarb (2 mg/kg) alone or in combination with LPS also altered TLR-9 expression. Further at protein level control group showed minimal expression of TLR-9 in lungs as compare to other groups, however, LPS group showed intense positive staining in bronchial epithelium as well as in alveolar septal cells. Indoxacarb at both doses individually showed strong immuno-positive reaction as compare to control, however when combined with LPS resulted intense staining in airway epithelium as compare to control. Conclusion: Chronic oral administration of indoxacarb for 90 days (4 and 2 mg/kg) alters expression of TLR-9 at m-RNA and protein level and co-exposure with LPS exhibited synergistic effect. PMID:27956782

Chronic inflammation as a determinant of future aging phenotypes.

PubMed

Akbaraly, Tasnime N; Hamer, Mark; Ferrie, Jane E; Lowe, Gordon; Batty, G David; Hagger-Johnson, Gareth; Singh-Manoux, Archana; Shipley, Martin J; Kivimäki, Mika

2013-11-05

The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women. We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study's baseline (1997-1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007-2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants). Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38-0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15-2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58-3.80). Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic

Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice.

PubMed

Correa-Netto, N F; Coelho, L S; Galfano, G S; Nishide, F; Tamura, F; Shimizu, M K; Santos, J G; Linardi, A

2017-06-05

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

PubMed

Manning, Elizabeth E; van den Buuse, Maarten

2016-05-15

Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

PubMed Central

Correa-Netto, N.F.; Coelho, L.S.; Galfano, G.S.; Nishide, F.; Tamura, F.; Shimizu, M.K.; Santos, J.G.; Linardi, A.

2017-01-01

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice. PMID:28591380

Prospective assessment of chronic multisymptom illness reporting possibly associated with open-air burn pit smoke exposure in Iraq.

PubMed

Powell, Teresa M; Smith, Tyler C; Jacobson, Isabel G; Boyko, Edward J; Hooper, Tomoko I; Gackstetter, Gary D; Phillips, Christopher J; Smith, Besa

2012-06-01

To investigate the relationship between chronic multisymptom illness (CMI) and possible exposure to an open-air burn pit at three selected bases among those deployed to operations in Iraq and Afghanistan. Chronic multisymptom illness (reporting at least one symptom in at least two of the following symptom constructs: general fatigue; mood and cognition problems; and musculoskeletal discomfort) was assessed, differentiating by potential burn pit exposure, among deployers who completed 2004 and 2007 Millennium Cohort questionnaires. More than 21,000 Cohort participants were deployed in support of the current operations, including more than 3000 participants with at least one deployment within a 3-mile radius of a documented burn pit. After adjusting for covariates, no elevated risk of CMI was observed among those exposed. There was no increase in CMI symptom reporting in those deployed to three selected bases with documented burn pits compared with other deployers.

Chronic exposure to iron oxide, chromium oxide, and nickel oxide fumes of metal dressers in a steelworks

PubMed Central

Jones, J. Graham; Warner, C. G.

1972-01-01

Graham Jones, J., and Warner, C. G. (1972).Brit. J. industr. Med.,29, 169-177. Chronic exposure to iron oxide, chromium oxide, and nickel oxide fumes of metal dressers in a steelworks. Occupational and medical histories, smoking habits, respiratory symptoms, chest radiographs, and ventilatory capacities were studied in 14 steelworkers employed as deseamers of steel ingots for periods of up to 16 years. The men were exposed for approximately five hours of each working shift to fume concentrations ranging from 1·3 to 294·1 mg/m3 made up mainly of iron oxide with varying proportions of chromium oxide and nickel oxide. Four of the men, with 14 to 16 years' exposure, showed radiological evidence of pneumoconiosis classified as ILO categories 2 or 3. Of these, two had pulmonary function within the normal range and two had measurable loss of function, moderate in one case and mild in the other. Many observers would diagnose these cases as siderosis but the authors consider that this term should be reserved for cases exposed to pure iron compounds. The correct diagnosis is mixed-dust pneumoconiosis and the loss of pulmonary function is caused by the effects of the mixture of metallic oxides. It is probable that inhalation of pure iron oxide does not cause fibrotic pulmonary changes, whereas the inhalation of iron oxide plus certain other substances obviously does. Images PMID:5021996

Incidence and prevalence of chronic bronchitis: impact of smoking and welding. The RHINE study.

PubMed

Holm, M; Kim, J-L; Lillienberg, L; Storaas, T; Jögi, R; Svanes, C; Schlünssen, V; Forsberg, B; Gíslason, T; Janson, C; Torén, K

2012-04-01

To investigate the prevalence and incidence rate of chronic bronchitis (CB) in relation to smoking habits and exposure to welding fumes in a general population sample. Subjects from Northern Europe born between 1945 and 1971 who participated in Stage 1 (1989-1994) of the European Community Respiratory Health Survey were mailed a respiratory questionnaire in 1999-2001 (the RHINE study); 15,909 answered the questionnaire and gave complete data on smoking. CB was defined as chronic productive cough of at least 3 months a year for 2 consecutive years. The questionnaire comprised an item about age when CB started and items about exposure to welding fumes. The incidence of CB was retrospectively assessed for the observation period 1980-2001. CB had a prevalence of 5.4%, and was associated with current smoking and welding exposure. The incidence rate of CB was 1.9 per 1000 person-years, and was increased in relation to welding exposure (low exposure HR 1.4, 95%CI 1.1-1.8; high exposure HR 2.0, 95%CI 1.6-2.7) and in relation to smoking (HR 2.1, 95%CI 1.8-2.5). Smoking and occupational exposure to welding fumes are both associated with an increased risk of CB.

Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model

PubMed Central

Laube, Beth L.; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

2017-01-01

Objective To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs. Methods C57BL/6 male mice (age 10.5 ±2.4 weeks) were exposed for 20min/day to E-cigarette aerosol generated by a Joyetech 510-T® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99mtechnetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG. Results MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6±5.2%, 7.5±2.8% and 11.2±5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ±8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ±4.6)% (p < .05). Serum cotinine levels were <0.5ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml. Conclusions In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine. PMID:28651446

Chronic ethanol exposure changes dopamine D2 receptor splicing during retinoic acid-induced differentiation of human SH-SY5Y cells.

PubMed

Wernicke, Catrin; Hellmann, Julian; Finckh, Ulrich; Rommelspacher, Hans

2010-01-01

There is evidence for ethanol-induced impairment of the dopaminergic system in the brain during development. The dopamine D2 receptor (DRD2) and the dopamine transporter (DAT) are decisively involved in dopaminergic signaling. Two splice variants of DRD2 are known, with the short one (DRD2s) representing the autoreceptor and the long one (DRD2l) the postsynaptic receptor. We searched for a model to investigate the impact of chronic ethanol exposure and withdrawal on the expression of these proteins during neuronal differentiation. RA-induced differentiation of human neuroblastoma SH-SY5Y cells seems to represent such a model. Our real-time RT-PCR, Western blot, and immunocytochemistry analyses of undifferentiated and RA-differentiated cells have demonstrated the enhanced expression of both splice variants of DRD2, with the short one being stronger enhanced than the long one under RA-treatment, and the DRD2 distribution on cell bodies and neurites under both conditions. In contrast, DAT was down-regulated by RA. The DAT is functional both in undifferentiated and RA-differentiated cells as demonstrated by [(3)H]dopamine uptake. Chronic ethanol exposure during differentiation for up to 4 weeks resulted in a delayed up-regulation of DRD2s. Ethanol withdrawal caused an increased expression of DRD2l and a normalization of DRD2s. Thus the DRD2s/DRD2l ratio was still disturbed. The dopamine level was increased by RA-differentiation compared to controls and was diminished under RA/ethanol treatment and ethanol withdrawal compared to RA-only treated cells. In conclusion, chronic ethanol exposure impairs differentiation-dependent adaptation of dopaminergic proteins, specifically of DRD2s. RA-differentiating SH-SY5Y cells are suited to study the impact of chronic ethanol exposure and withdrawal on expression of dopaminergic proteins during neuronal differentiation.

The effect of World Trade Center exposure on the latency of chronic rhinosinusitis diagnoses in New York City firefighters: 2001-2011.

PubMed

Weakley, Jessica; Hall, Charles B; Liu, Xiaoxue; Zeig-Owens, Rachel; Webber, Mayris P; Schwartz, Theresa; Prezant, David

2016-04-01

To assess how the effect of World Trade Center (WTC) exposure on physician-diagnosed chronic rhinosinusitis (CRS) in firefighters changed during the decade following the attack on 9/11 (11 September 2001 to 10 September 2011). We examined temporal effects on the relation between WTC exposure and the incidence of physician diagnosed CRS in firefighters changed during the decade following the attack on 9/11 (11 September 2001 to 10 September 2011). Exposure was grouped by time of arrival at the WTC site as follows: (high) morning 11 September 2001 (n=1623); (moderate) afternoon 11 September 2001 or 12 September 2001 (n=7025); or (low) 13-24 September 2001 (n=1200). Piecewise exponential survival models were used to estimate incidences by exposure group, with change points in the relative incidences estimated by maximum likelihood. Incidences dramatically increased after 2007 due to a programmatic change that provided free medical treatment, but increases were similar in all exposure groups. For this reason, we observed no change point during the study period, meaning the relative incidence by exposure group (high vs moderate vs low) of CRS disease did not significantly change over the study period. The relative rate of developing CRS was 1.99 (95% CI=1.64 to 2.41) for high versus low exposure, and 1.52 (95% CI=1.28 to 1.80) for moderate versus low exposure during the 10-year follow-up period. The risk of CRS in FDNY firefighters appears increased with WTC-exposure, and has not diminished by time since exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chronic Sinusitis

MedlinePlus

... connected to chronic sinusitis Aspirin sensitivity that causes respiratory symptoms An immune system disorder, such as HIV/AIDS or cystic fibrosis Hay fever or another allergic condition that affects your sinuses Regular exposure to pollutants such as cigarette smoke Complications Chronic ...

Chronic cyanide exposure: a clinical, radioisotope, and laboratory study.

PubMed Central

El Ghawabi, S H; Gaafar, M A; El-Saharti, A A; Ahmed, S H; Malash, K K; Fares, R

1975-01-01

The effect of chronic cyanide exposure in the electroplating sections of three factories employing 36 workers was studied and compared with a control group. The concentration of cyanides to which the workers were exposed was measured. The regression line showing the relationship between thiocyanates in urine and the concentration of cyanides in the air was plotted. Increased percentages of haemoglobin and lymphocyte count were present in all exposed workers, in addition to punctate basophilia in 28 workers. Cyanmethaemoglobin was found to be characteristic. Apart from other complaints, two men with psychosis similar to one case reported in therapeutic thiocyanate intoxication were found. Twenty of the workers had thyroid enlargements to a variable degree and consistency, in two of whom it resembled lymphadenoid goitre. Thyroid 131I uptakes at 4 and 24 hours were significantly higher than in the controls, while 131PBI was unchanged. The reason for this iodine deficiency-like action is discussed. PMID:1156569

Smoking, sun exposure, number of nevi and previous neoplasias are risk factors for melanoma in older patients (60 years and over).

PubMed

Nagore, E; Hueso, L; Botella-Estrada, R; Alfaro-Rubio, A; Serna, I; Guallar, Jp; González, I; Ribes, I; Guillen, C

2010-01-01

Malignant melanoma risk factors have been studied in different geographical area populations. However, no study has focused on risk factors which are more frequently associated to the over 60's age group. A case-control study was performed that included 160 patients age > or = 60 years diagnosed of cutaneous melanoma and 318 controls matched for age and sex. Both groups were assessed, by personal interview and physical examination, for different phenotype characteristics (hair and eye color, phototype), the presence of other cutaneous lesions (solar lentigines, actinic keratoses and nevi), degree and type of solar exposure and personal and family past history of cutaneous or non-cutaneous cancer. Differences were evaluated by contingency tables and univariate and multivariate logistic regression. Of 17 factors, those risk factors with a strong effect on the development of melanoma in the elderly were: fair eyes, severe sunburns, years of occupational sun exposure, smoking, > 50 melanocytic nevi and personal history of NMSC and other non-cutaneous neoplasias. Tobacco smoking is an independent risk factor for cutaneous melanoma in the elderly. Intense (both acute and chronic) sun exposure and constitutional features, such as tumor susceptibility (NMSC, non-cutaneous neoplasias, and multiple nevi) are also associated with melanoma risk. All these factors should help to better design educational campaigns in older people.

Chronic intermittent ethanol exposure and withdrawal leads to adaptations in nucleus accumbens core postsynaptic density proteome and dendritic spines.

PubMed

Uys, Joachim D; McGuier, Natalie S; Gass, Justin T; Griffin, William C; Ball, Lauren E; Mulholland, Patrick J

2016-05-01

Alcohol use disorder is a chronic relapsing brain disease characterized by the loss of ability to control alcohol (ethanol) intake despite knowledge of detrimental health or personal consequences. Clinical and pre-clinical models provide strong evidence for chronic ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the nucleus accumbens (NAc). However, the neural mechanisms that contribute to aberrant glutamatergic signaling in ethanol-dependent individuals in this critical brain structure remain unknown. Using an unbiased proteomic approach, we investigated the effects of chronic intermittent ethanol (CIE) exposure on neuroadaptations in postsynaptic density (PSD)-enriched proteins in the NAc of ethanol-dependent mice. Compared with controls, CIE exposure significantly changed expression levels of 50 proteins in the PSD-enriched fraction. Systems biology and functional annotation analyses demonstrated that the dysregulated proteins are expressed at tetrapartite synapses and critically regulate cellular morphology. To confirm this latter finding, the density and morphology of dendritic spines were examined in the NAc core of ethanol-dependent mice. We found that CIE exposure and withdrawal differentially altered dendrite diameter and dendritic spine density and morphology. Through the use of quantitative proteomics and functional annotation, these series of experiments demonstrate that ethanol dependence produces neuroadaptations in proteins that modify dendritic spine morphology. In addition, these studies identified novel PSD-related proteins that contribute to the neurobiological mechanisms of ethanol dependence that drive maladaptive structural plasticity of NAc neurons. © 2015 Society for the Study of Addiction.

Traffic-Related Air Pollution Exposure in the First Year of Life and Behavioral Scores at 7 Years of Age

PubMed Central

Ryan, Patrick; LeMasters, Grace; Levin, Linda; Bernstein, David; Hershey, Gurjit K. Khurana; Lockey, James E.; Villareal, Manuel; Reponen, Tiina; Grinshpun, Sergey; Sucharew, Heidi; Dietrich, Kim N.

2013-01-01