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Sample records for chronic uranium exposure

  1. Comparative sensitivity of three populations of the cladoceran Moinodaphnia macleayi to acute and chronic uranium exposure.

    Science.gov (United States)

    Semaan, M; Holdway, D A; van Dam, R A

    2001-10-01

    Assessment of differences in the response of three different populations of the tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The populations tested included a laboratory stock (maintained for 10 years), a wild population collected from Bowerbird Billabong (an uncontaminated environment), and a population collected from Djalkmara Billabong (a relatively contaminated environment with elevated levels of uranium), located on the Ranger uranium mine site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was determined for all three populations. The no-observed-effect-concentration (NOEC; reproduction) and lowest observed-effect-concentration (LOEC; reproduction) for uranium ranged between 8-31 micrograms L-1 and 20-49 micrograms L-1, respectively, for all three populations. The 48 h EC50 (immobilization-lethality) for uranium ranged between 160-390 micrograms L-1 for all three populations. There was little difference in the response of the three populations of M. macleayi to acute and chronic uranium exposure, although the response of the laboratory population to chronic uranium exposure appeared more variable than the "wild" populations. There was no apparent tolerance in the population of M. macleayi obtained from Djalkmara Billabong when exposed to elevated levels of uranium. M. macleayi was significantly more sensitive to uranium exposure than other species previously tested. It was concluded that the sensitivity of the laboratory population (to uranium) is still representative of natural M. macleayi populations. PMID:11594022

  2. Chronic uranium exposure dose-dependently induces glutathione in rats without any nephrotoxicity.

    Science.gov (United States)

    Poisson, C; Stefani, J; Manens, L; Delissen, O; Suhard, D; Tessier, C; Dublineau, I; Guéguen, Y

    2014-10-01

    Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects. Rats were contaminated for 3 or 9 months by uranium in drinking water at different concentrations (0, 1, 40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and bones was linear and proportional to uranium intake after 3 and 9 months of contamination; it reached 6 μg per gram of kidney tissues for the highest uranium level in drinking water. Nevertheless, no histological lesions of the kidney were observed, nor any modification of kidney biomarkers such as creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L concentration of uranium, lipid peroxidation levels decreased in plasma, liver, and kidneys. Glutathione concentration increased in the liver for the 600-mg/L group, in the kidney it increased dose dependently, up to 10-fold, after 9 months of contamination. Conversely, chronic uranium exposure irregularly modified gene expression of antioxidant enzymes and activities in the liver and kidneys. In conclusion, chronic uranium exposure did not induce nephrotoxic effects under our experimental conditions, but instead reinforced the antioxidant system, especially by increasing glutathione levels in the kidneys.

  3. Role of oxidative stress in liver and kidney in uranium toxicity after chronic exposure

    International Nuclear Information System (INIS)

    Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 μg.g-1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration. (author)

  4. Effects of depleted uranium chronic exposure on detoxification systems in vivo and in vitro

    International Nuclear Information System (INIS)

    Uranium (U) is a heavy metal naturally presents in the environment. The aim of this work is to study effects of a U exposure on organs involved in the detoxification: the kidney and the liver (and notably the xenobiotics metabolizing enzymes (XME)). In order to mimic population chronic exposure, rats were contaminated during 9 months through the drinking water (40 mg/L). In vivo results show that U, in our experimental conditions, does not induce neither nephrotoxicity nor sensitivity to increase a renal toxicity induced by gentamicin. In the liver, U provokes impairments on the XME gene expression, particularly CYP3A. Nevertheless, paracetamole metabolism is modified only if it is administrated at a hepatotoxic dose. The in vitro results suggest an indirect effect of uranium on the XME, probably dependant of body adaptation mechanisms. Besides, in vitro studies were underline cytotoxic properties of U as well as the localisation of its soluble and/or participated forms in cytoplasmic and nuclear compartment. (author)

  5. Immunological changes of chronic oral exposure to depleted uranium in mice.

    Science.gov (United States)

    Hao, Yuhui; Ren, Jiong; Liu, Jing; Yang, Zhangyou; Liu, Cong; Li, Rong; Su, Yongping

    2013-07-01

    Direct ingestion of contaminated soil by depleted uranium (DU) might lead to internal exposure to DU by local populations through hand contamination. The purpose of this study was to assess the immunological changes of long-term exposure to various doses of DU in mice. Three-week-old Kunming mice were divided into the following 4 groups based on the various feeding doses (containing DU): 0 (control group), 3 (DU3 group), 30 (DU30 group), and 300 mg/kg feed (DU300 group). After 4 months of exposure, in the DU300 group, the innate immune function decreased, manifesting as decreased secretion of nitric oxide, interleukin (IL)-1β, IL-18, and tumour necrosis factor (TNF)-α in the peritoneal macrophages, as well as reduced cytotoxicity of the splenic natural killer cells. Moreover, the cellular and humoral immune functions were abnormal, as manifested by decreased proliferation of the splenic T cells, proportion of the cluster of differentiation (CD) 3(+) cells, ratio of CD4(+)/CD8(+) cells and delayed-type hypersensitivity, and increased proliferation of the splenic B cells, total serum immunoglobin (Ig) G and IgE, and proportion of splenic mIgM(+)mIgD(+) cells. Through stimulation, the secretion levels of interferon (IFN)-γ and TNF-α in the splenic cells were reduced, and the levels of IL-4 and IL-10 were increased. By comparison, in the DU30 and DU3 groups, the effects were either minor or indiscernible. In conclusions, chronic intake of higher doses of DU (300 mg/kg) had a significant impact on the immune function, most likely due to an imbalance in T helper (Th) 1 and Th2 cytokines. PMID:23659960

  6. Uranium microdistribution in renal cortex of rats after chronic exposure: a study by secondary ion mass spectrometry microscopy.

    Science.gov (United States)

    Tessier, Christine; Suhard, David; Rebière, François; Souidi, Maâmar; Dublineau, Isabelle; Agarande, Michelle

    2012-02-01

    For a few years, the biological effects on ecosystems and the public of the bioaccumulation of radionuclides in situations of chronic exposures have been studied. This work, in keeping with the ENVIRHOM French research program, presents the uranium microdistribution by secondary ion mass spectrometry (SIMS) technique in the renal cortex of rats following chronic exposure to this low level element in the drinking water (40 mg/L) as a function to exposure duration (6, 9, 12, and 18 months). The SIMS mass spectra and 238U+ ion images produced with a SIMS CAMECA 4F-E7 show the kinetic of uranium accumulation in the different structures of the kidney. For the rats contaminated up to 12 months, the radioelement is mainly fixed in the proximal tubules; then after 18 exposure months, uranium is detected in all the segments of the nephron. This work has also shown that ion microscopy is an analytical method to detect trace elements and give elemental cartography at the micrometer scale. PMID:22217926

  7. Nuclear toxicology file: ecological consequences of a chronic exposure to uranium; Dossier toxicologie nucleaire: Consequences ecologiques d'une exposition chronique a l'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Adam, Ch.; Alonzo, F.; Bonzom, J.M.; Gilbin, R.; Garnier-Laplace, J.; Simon, O. [Institut de Radioprotection et de Surete Nucleaire (IRSN:DEI/SECRE), Service d' Etude du Comportement des Radionucleides dans les Ecosystemes, 13 - Saint-Paul-lez-Durance (France)

    2008-09-15

    This article presents the thought process and the current developments, based on the experimental acquisition of the answers of the alive organisms to the chronic low dose exposures of natural uranium in fresh water, to identify the consequences of this exposure on the populations composing the ecosystems. The results acquired on the zebra fish (Danio rerio) show an impact on the first steps of development. We note a delay of hatching upon 40 % from 20 {mu}g/l of uranium. This delay comes along with a decrease of the size and with a reduction of the growth of larvas as well as with an increase of their mortality for higher uranium concentration. For adults exposed to uranium a decrease of reproduction success is observed from a concentration of 20{mu}g/l. The consequences in term of fertility (total number of laid roes) are drastic, with a reduction of a factor 2 and 60, for the organisms exposed respectively to 20 and 250 {mu}g/l of uranium. A study was also made on several generations (populations of benthic invertebrates), it suggests an adaptation (genetic selection) but created a bigger fragility to a new environment even identical to their environment of origin with notably a decrease of the reproduction. (N.C.)

  8. A study assessing the genotoxicity in rats after chronic oral exposure to a low dose of depleted uranium

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the potential genotoxicity induced by chronic oral exposure to depleted uranium (DU). Weanling Wistar rats (F0), 50/sex/group, were exposed to DU in food at doses of 0, 4, or 40 mg kg-1 day-1 for four months. They were subsequently mated, resulting in the birth of F1 rats. Fifty F1 weanlings/sex/group were exposed for four months to the same dose levels as their parents. After four months, the uranium content in the tissues, the potential damage to the genetic material, and pathomorphological changes of the testicles were observed in both F0 and F1 rats. The genotoxicity of DU was evaluated by the following methods: sperm abnormality assessment, the bone-marrow micronucleus test, and the comet assay. Uranium content in F1 rats was significantly higher than that in F0 rats in both the kidney and ovary (p1 with F0 rats, significant differences were detected for most of the indicators, with F1 rats always exhibiting more damage (p1 rats. Genotoxicity may be induced in rats after chronic oral exposure to a low dose of DU. (author)

  9. An incident study about acute and chronic human exposure to uranium by high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS).

    Science.gov (United States)

    Krystek, Petra; Ritsema, Rob

    2009-01-01

    From the year 2003 to 2005 around 1700 Dutch soldiers made a part of the international stabilisation force in Iraq. An incident happened as a group of four Dutch soldiers found a 30mm bullet identified as containing depleted uranium (DU). The main pathway of the acute exposure is via inhalation of small uranium containing particles, e.g. from a bullet during its explosion. To develop a method for acute exposure investigations were carried out about finding an efficient and suitable way to sample nasal mucus as medium of inhalation. Generally, in human exposure studies with regard to natural uranium (NU) or DU, urine is the matrix for analysis. Uranium concentrations in urine are based on daily ingestion depending on the composition of drinking water and food. A second possibility is the acute exposure to uranium after an incident, either through inhalation or impact. Nevertheless, the results deliver only interpretations in respect to chronic/long-term exposure. For the acute exposure procedures like sniffling out into cleansing tissues and rinsing the nose were tested with real-life samples from four soldiers involved in an incident with possibly acute exposure to uranium. For the quantification of uranium high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS) was applied. PMID:18187363

  10. Uranium bone content as an indicator of chronic environmental exposure from drinking water

    International Nuclear Information System (INIS)

    Uranium (U) is an ubiquitous radioelement found in drinking water and food. As a consequence of its prevalence, most humans ingest a few micrograms (μg) of this element daily. It is incorporated in various organs and tissues. Several studies have demonstrated that ingested U is deposited mainly in bones. Therefore, U skeletal content could be considered as a prime indicator for low-level chronic intake. In this study, 71 archived vertebrae bone samples collected in seven Canadian cities were subjected to digestion and U analysis by inductively coupled plasma mass spectrometry. These results were correlated with U concentrations in municipal drinking water supplies, with the data originating from historical studies performed by Health Canada. A strong relationship (r2 = 0.97) was observed between the averaged U total skeletal content and averaged drinking water concentration, supporting the hypothesis that bones are indeed a good indicator of U intake. Using a PowerBASIC compiler to process an ICRP systemic model for U (ICRP, 1995a), U total skeletal content was estimated using two gastrointestinal tract absorption factors (f1 = 0.009 and 0.03). Comparisons between observed and modelled skeletal contents as a function of U intake from drinking water tend to demonstrate that neither of the f1 values can adequately estimate observed values. An f1value of 0.009 provides a realistic estimate for intake resulting from food consumption only (6.72 μg) compared to experimental data (7.4 ± 0.8 μg), whereas an f1value of 0.03 tends to better estimate U skeletal content at higher levels of U (1–10 μg L−1) in drinking water

  11. Chronic uranium exposure and growth toxicity for phytoplankton. Dose-effect relationship: first comparison of chemical and radiological toxicity

    International Nuclear Information System (INIS)

    The bioavailability of uranium for freshwater organisms, as for other dissolved metals, is closely linked to chemical speciation in solution (U aqueous speciation undergoes tremendous changes in the presence of ligands commonly found in natural waters e.g. carbonate, phosphate, hydroxide and natural organic matter). For the studied chemical domain, short-term uranium uptake experiments have already shown that the free uranyl ion concentration [UO22+] is a good predictor of uranium uptake by the green algae Chlamydomonas reinhardtii, as predicted by the Free Ion Activity Model. In agreement with these results, acidic pH and low ligands concentrations in water enhance uranium bioavailability and consequently its potential chronic effects on phytoplankton. Moreover, uranium is known to be both radio-toxic and chemo-toxic. The use of different isotopes of uranium allows to expose organisms to different radiological doses for the same molar concentration: e.g. for a given element concentration (chemical dose), replacing depleted U by U-233 obviously leads to an enhanced radiological delivered dose to organisms (x104). In this work we established relationships between uranium doses (depleted uranium and 233-U ) and effect on the growth rate of the green algae Chlamydomonas reinhardtii. Uranium bioaccumulation was also monitored. Growth rate was measured both in classical batch (0-72 hrs) and continuous (turbidostat) cultures, the latter protocol allowing medium renewal to diminish exudates accumulation and speciation changes in the medium. The differences in effects will be, if possible, related to the development of defence mechanisms against the formation of reactive oxygen species (forms of glutathione) and the production of phyto-chelatins (small peptides rich in cystein that play an important role in the homeostasis and the detoxication of metals in cells). (author)

  12. Chronic uranium exposure and growth toxicity for phytoplankton. Dose-effect relationship: first comparison of chemical and radiological toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Gilbin, R.; Pradines, C.; Garnier-Laplace, J. [CEA Cadarache (DEI/SECRE/LRE), Laboratory of Radioecology and Ecotoxicology, Institute for Radioprotection and Nuclear Safety, 13 - Saint-Paul-lez-Durance (France)

    2004-07-01

    The bioavailability of uranium for freshwater organisms, as for other dissolved metals, is closely linked to chemical speciation in solution (U aqueous speciation undergoes tremendous changes in the presence of ligands commonly found in natural waters e.g. carbonate, phosphate, hydroxide and natural organic matter). For the studied chemical domain, short-term uranium uptake experiments have already shown that the free uranyl ion concentration [UO{sub 2}{sup 2+}] is a good predictor of uranium uptake by the green algae Chlamydomonas reinhardtii, as predicted by the Free Ion Activity Model. In agreement with these results, acidic pH and low ligands concentrations in water enhance uranium bioavailability and consequently its potential chronic effects on phytoplankton. Moreover, uranium is known to be both radio-toxic and chemo-toxic. The use of different isotopes of uranium allows to expose organisms to different radiological doses for the same molar concentration: e.g. for a given element concentration (chemical dose), replacing depleted U by U-233 obviously leads to an enhanced radiological delivered dose to organisms (x10{sup 4}). In this work we established relationships between uranium doses (depleted uranium and 233-U ) and effect on the growth rate of the green algae Chlamydomonas reinhardtii. Uranium bioaccumulation was also monitored. Growth rate was measured both in classical batch (0-72 hrs) and continuous (turbidostat) cultures, the latter protocol allowing medium renewal to diminish exudates accumulation and speciation changes in the medium. The differences in effects will be, if possible, related to the development of defence mechanisms against the formation of reactive oxygen species (forms of glutathione) and the production of phyto-chelatins (small peptides rich in cystein that play an important role in the homeostasis and the detoxication of metals in cells). (author)

  13. Constitution of a group of Czech and French uranium miners in order to estimate lung cancer risk linked to low chronic exposure to radon decay products

    International Nuclear Information System (INIS)

    West Bohemian and French uranium miners are characterized by a long duration of exposure to radon and its decay products, in comparison to most of the other groups of miners, studied in the recent international joint analysis by the National Cancer Institute (NCI) in USA. This analysis has confirmed the linearly increasing risk of lung cancer by cumulative radon exposure, describing the different factors that may influence this dose-response relationship. One of the main factors presently discussed is the influence of the exposure-rate effect: in other words, has the same cumulated exposure spread over 10 years the same risk of lung cancer as if it is cumulated in 2 years? The implication of an inverse exposure-rate effect for low chronic exposures as well as some methodological approaches will be discussed and tested by using the data of the Czech and French cohorts. These two cohorts present annual exposures varying by a factor of 5 to 10, French exposure rates being close or even less than 0.1 Working Level during the last 20 years. The project is integrated in a larger European project on uranium miners, co-ordinated by IPSN. (author)

  14. Analysis of the murine renal transcriptoma in conditions of acute and chronic exposure to uranium; Analyse du transcriptome renal murin dans des conditions d'exposition aigue et chronique a l'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Taulan, M

    2004-06-01

    The principal objective of this work was to evaluate the molecular alterations induced by uranium. For this, were used classical approaches of toxicology and implementation of a global analysis technique: S.A.G.E. (serial analysis of gene expression). After acute contamination, was brought to the shore an alteration of the renal function and a catalogue of different transcripts representative of molecular events consecutive to uranium incorporation was defined. More than 14 000 transcripts have been identified, among which 224 genes that present a variation in gene expression. These last ones have been classified in different categories of cell processes as inflammation, oxidative stress, cell transporters, signal transduction, apoptosis, metabolism and catabolism. The same study was made for a chronic exposure. This study shows that the chronic uranium ingestion changes numerous cell processes as these ones previously noticed. The whole of these data has allowed to validate the use of the genomic approach S.A.G.E. in the field of toxicology, by establishing a profile of gene expression of events relative to an uranium intoxication. The analysis of molecular consequences should allow to find early markers of an uranium contamination, means more efficient of this actinide elimination and new therapies targets. (N.C.)

  15. Effects of chronic uranium exposure on life history and physiology of Daphnia magna over three successive generations

    Energy Technology Data Exchange (ETDEWEB)

    Massarin, Sandrine [Laboratoire de Modelisation Environnementale, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Alonzo, Frederic, E-mail: frederic.alonzo@irsn.fr [Laboratoire de Modelisation Environnementale, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Garcia-Sanchez, Laurent [Laboratoire de Modelisation Environnementale, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Gilbin, Rodolphe [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Garnier-Laplace, Jacqueline [Service d' Etude du Comportement des Radionucleides dans les Ecosystemes, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Poggiale, Jean-Christophe [Laboratoire de Microbiologie, Geochimie et Ecologie Marines (UMR CNRS 6117), Centre d' Oceanologie de Marseille, Universite de la Mediterranee, Campus de Luminy, Case 901, Marseille Cedex 9, 13288 (France)

    2010-09-01

    Daphnia magna was exposed to waterborne uranium (U) at concentrations ranging from 10 to 75 {mu}g L{sup -1} over three successive generations (F0, F1 and F2). Progeny was either exposed to the same concentration as mothers to test whether susceptibility to this radioelement might vary across generations or returned to a clean medium to examine their capacity to recover after parental exposure. Maximum body burdens of 17, 32 and 54 ng U daphnid{sup -1} were measured in the different exposure conditions and converted to corresponding internal alpha dose rates. Low values of 5, 12 and 20 {mu}Gy h{sup -1} suggested that radiotoxicity was negligible compared to chemotoxicity. An increasing sensitivity to toxicity was shown across exposed generations with significant effects observed on life history traits and physiology as low as 10 {mu}g L{sup -1} and a capacity to recover partially in a clean medium after parental exposure to {<=}25 {mu}g L{sup -1}. Using a {sup 14}C-labelled food technique, the study showed that uranium affected carbon assimilation in F0 at concentrations of 25 and 75 {mu}g L{sup -1} (34 and 80% reduction respectively) and as low as 10 {mu}g L{sup -1} in F1 and F2 (40 and 36% reduction respectively). Consequences were strong for both somatic growth and reproduction and increased in severity across generations. Maximum size was reduced by 12% at 75 {mu}g L{sup -1} in F0 and 23% at 25 {mu}g L{sup -1} in F2. Reduction in 21-day fecundity ranged from 27 to 48% respectively at 25 and 75 {mu}g L{sup -1} in F0 and from 43 to 71% respectively at 10 and 25 {mu}g L{sup -1} in F2. Growth retardation caused a delay in deposition of first brood of 1.3 days at 75 {mu}g L{sup -1} in F0, of 1.9 days at 25 {mu}g L{sup -1} in F1 and of 5 days at 25 {mu}g L{sup -1} in F2. Differences in respiration rates and egg dry mass between the control and exposed daphnids were mainly an indirect result of uranium effect on body size. The observed increase in toxic effects across

  16. Y-12 Uranium Exposure Study

    Energy Technology Data Exchange (ETDEWEB)

    Eckerman, K.F.; Kerr, G.D.

    1999-08-05

    Following the recent restart of operations at the Y-12 Plant, the Radiological Control Organization (RCO) observed that the enriched uranium exposures appeared to involve insoluble rather than soluble uranium that presumably characterized most earlier Y-12 operations. These observations necessitated changes in the bioassay program, particularly the need for routine fecal sampling. In addition, it was not reasonable to interpret the bioassay data using metabolic parameter values established during earlier Y-12 operations. Thus, the recent urinary and fecal bioassay data were interpreted using the default guidance in Publication 54 of the International Commission on Radiological Protection (ICRP); that is, inhalation of Class Y uranium with an activity median aerodynamic diameter (AMAD) of 1 {micro}m. Faced with apparently new workplace conditions, these actions were appropriate and ensured a cautionary approach to worker protection. As additional bioassay data were accumulated, it became apparent that the data were not consistent with Publication 54. Therefore, this study was undertaken to examine the situation.

  17. Effects of chronic exposure to environmentally relevant concentrations of waterborne depleted uranium on the digestive tract of zebrafish, Danio rerio

    International Nuclear Information System (INIS)

    Uranium is a naturally occurring element, but activities linked to the nuclear fuel cycle can increase background levels in the surrounding waters. For this reason it is important to understand how this affects organisms residing in the water column. The objective of this study was to assess histopathological effects of uranium on the gut wall of a widely used model organism: zebrafish, Danio rerio. To this end we exposed zebrafish to 84 and 420 nM depleted uranium for over a month and then examined the histology of intestines of exposed individuals compared to controls. The gut wall of individuals exposed to 84 and 420 nM of uranium had large regions of degraded mucosa. Using transmission electron microscopy (TEM) coupled to energy-dispersive X-ray spectroscopy microanalysis (EDX) we found that uranium induced a decrease in the amount of calcium containing mitochondrial matrix granules per mitochondria. This is suggestive of perturbations to cellular metabolism and more specifically to cellular calcium homeostasis. TEM-EDX of the gut wall tissue further showed that some uranium was internalized in the nucleus of epithelial cells in the 420 nM treatment. Fluorescent in situ hybridization using specific probes to detect all eubacteria was performed on frozen sections of 6 individual fish in the 84 nM and 420 nM treatments. Bacterial colonization of the gut of individuals in the 420 nM seemed to differ from that of the controls and 84 nM individuals. We suggest that host–microbiota interactions are potentially disturbed in response to uranium induced stress. The damage induced by waterborne uranium to the gut wall did not seem to depend on the concentration of uranium in the media. We measure whole body residues of uranium at the end of the experiment and compute the mean dose rate absorbed for each condition. We discuss why effects might be uncoupled from external concentration and highlight that it is not so much the external concentration but the dynamics

  18. Effects of chronic exposure to environmentally relevant concentrations of waterborne depleted uranium on the digestive tract of zebrafish, Danio rerio.

    Science.gov (United States)

    Augustine, Starrlight; Pereira, Sandrine; Floriani, Magali; Camilleri, Virginie; Kooijman, Sebastiaan A L M; Gagnaire, Béatrice; Adam-Guillermin, Christelle

    2015-04-01

    Uranium is a naturally occurring element, but activities linked to the nuclear fuel cycle can increase background levels in the surrounding waters. For this reason it is important to understand how this affects organisms residing in the water column. The objective of this study was to assess histopathological effects of uranium on the gut wall of a widely used model organism: zebrafish, Danio rerio. To this end we exposed zebrafish to 84 and 420 nM depleted uranium for over a month and then examined the histology of intestines of exposed individuals compared to controls. The gut wall of individuals exposed to 84 and 420 nM of uranium had large regions of degraded mucosa. Using transmission electron microscopy (TEM) coupled to energy-dispersive X-ray spectroscopy microanalysis (EDX) we found that uranium induced a decrease in the amount of calcium containing mitochondrial matrix granules per mitochondria. This is suggestive of perturbations to cellular metabolism and more specifically to cellular calcium homeostasis. TEM-EDX of the gut wall tissue further showed that some uranium was internalized in the nucleus of epithelial cells in the 420 nM treatment. Fluorescent in situ hybridization using specific probes to detect all eubacteria was performed on frozen sections of 6 individual fish in the 84 nM and 420 nM treatments. Bacterial colonization of the gut of individuals in the 420 nM seemed to differ from that of the controls and 84 nM individuals. We suggest that host-microbiota interactions are potentially disturbed in response to uranium induced stress. The damage induced by waterborne uranium to the gut wall did not seem to depend on the concentration of uranium in the media. We measure whole body residues of uranium at the end of the experiment and compute the mean dose rate absorbed for each condition. We discuss why effects might be uncoupled from external concentration and highlight that it is not so much the external concentration but the dynamics of

  19. Assessment of exposure to depleted uranium

    International Nuclear Information System (INIS)

    In most circumstances, measurement of uranium excreted in urine at known times after exposure is potentially the most sensitive method for determining the amount of depleted uranium (DU) incorporated. The problems associated with this approach are that natural uranium is always present in urine because of the ingestion of natural uranium in food and drink, and that the uncertainties in the intakes as assessed from excretion measurements can be quite large, because many assumptions concerning the exposure characteristics (time pattern of exposure, route of intake, chemical form, solubility, biokinetics within the body) must be made. Applying currently available methods and instruments for the measurement of uranium in urine samples, DU incorporations of levels relevant with respect to potential health hazards can be detected reliably, even a long time after exposure. (author)

  20. In Vivo Nanodetoxication for Acute Uranium Exposure

    Directory of Open Access Journals (Sweden)

    Luis Guzmán

    2015-06-01

    Full Text Available Accidental exposure to uranium is a matter of concern, as U(VI is nephrotoxic in both human and animal models, and its toxicity is associated to chemical toxicity instead of radioactivity. We synthesized different PAMAM G4 and G5 derivatives in order to prove their interaction with uranium and their effect on the viability of red blood cells in vitro. Furthermore, we prove the effectiveness of the selected dendrimers in an animal model of acute uranium intoxication. The dendrimer PAMAM G4-Lys-Fmoc-Cbz demonstrated the ability to chelate the uranyl ion in vivo, improving the biochemical and histopathologic features caused by acute intoxication with uranium.

  1. Chronic exposure to uranium compounds: medical surveillance problems related to their physico-chemical properties and their solubility: actual data and future prospects

    International Nuclear Information System (INIS)

    A method was developped to assess uranium exposure hazards at work stations based on industrial experience acquired in Comurhex Malvesi at Narbonne. Applied to uranium tetrafluoride (UF4), the method involves five steps: 1/ Characterization of the industrial compound, including physico-chemical properties (density, surface area, X-ray spectrum and uranium enrichment). 2/ In vitro biological solubility with different synthetic fluids like Gamble solution added with differents gaz or compounds (Oxygen or hydrogen peroxyde), in order to determine the solubility class D, W or Y. 3/ Assessment of work station concentration in Bq m-3 and particle size distribution (AMAD). 4/ Monitoring workers by routine urinary excretion completed, if necessary, by fecal excretion and γ spectrometry. 5/ Use of individual protection filters or masks. Results and actual data on UF4 are presented and future prospects of studies on calcinated uranates are dealed with

  2. Bringing together Scientific Disciplines to better understand the health effects of Occupational Exposure to uranium

    International Nuclear Information System (INIS)

    Knowledge regarding the effects of chronic exposure to uranium comes up against the limitations specific to each discipline that takes an interest. The CURE (Concerted Uranium Research in Europe) project offers a scientific approach combining epidemiology, biology, toxicology and dosimetry to go beyond these limitations. (author)

  3. Emergency exposure levels for natural uranium

    International Nuclear Information System (INIS)

    An attempt is made to identify the inhalation hazards associated with the over-exposure of workers and of the general public, following an accidental release of uranium hexafluoride. Maximum emergency concentrations are recommended for periods of 10, 30, and 60 minutes. The quantitative aspect of the assessment is considered in the context of the development of exposure standards for chemical substances and this facilitates the derivation of levels which are compatible with occupational and public health experience and attainable by management, and to which most workers and members of the general public may be exposed without adverse effect. The radiological implications are also considered. (author)

  4. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat

    International Nuclear Information System (INIS)

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

  5. Uranium chronic contamination effects on the cholinergic system: in vivo and in vitro approaches

    International Nuclear Information System (INIS)

    Uranium (U) is a heavy metal which occurs naturally in the environment. It is both a chemical and a radiological toxicant. The aim of this work was: (i) to assess the effects of U chronic exposure on the cholinergic system (biosynthesis and breakdown enzymes, receptors and on behaviour of adult, young or predisposed to neuro-degenerative illness (ApoE KO) rodents; (ii) to grasp the neurotoxic effects of U on human neuronal cells. In vivo, this work shows a structure- (cortex more sensitive than hippocampus), rodent model- (young more sensitive than adults), time- (sub-chronic exposure more harmful than chronic exposure), exposure level- and isotope-dependent effect of U. In vitro, the study underlined the neuro-cytotoxic U potential and the presence of uranium precipitates in cells. These results show the deleterious impact of U on neuronal cells, and demonstrate that U induces impairments on the cholinergic system and the behaviour of rodents. (author)

  6. Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions

    International Nuclear Information System (INIS)

    Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L-1 (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

  7. Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

    Science.gov (United States)

    Laurent, Olivier; Gomolka, Maria; Haylock, Richard; Blanchardon, Eric; Giussani, Augusto; Atkinson, Will; Baatout, Sarah; Bingham, Derek; Cardis, Elisabeth; Hall, Janet; Tomasek, Ladislav; Ancelet, Sophie; Badie, Christophe; Bethel, Gary; Bertho, Jean-Marc; Bouet, Ségolène; Bull, Richard; Challeton-de Vathaire, Cécile; Cockerill, Rupert; Davesne, Estelle; Ebrahimian, Teni; Engels, Hilde; Gillies, Michael; Grellier, James; Grison, Stephane; Gueguen, Yann; Hornhardt, Sabine; Ibanez, Chrystelle; Kabacik, Sylwia; Kotik, Lukas; Kreuzer, Michaela; Lebacq, Anne Laure; Marsh, James; Nosske, Dietmar; O'Hagan, Jackie; Pernot, Eileen; Puncher, Matthew; Rage, Estelle; Riddell, Tony; Roy, Laurence; Samson, Eric; Souidi, Maamar; Turner, Michelle C; Zhivin, Sergey; Laurier, Dominique

    2016-06-01

    The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation. PMID:27183135

  8. From cell to man: Evaluation of osteopontin as a possible bio-marker of uranium exposure

    International Nuclear Information System (INIS)

    Background: Ore workers are conventionally monitored for exposure by measuring the uranium in their urine, but specific bio-markers of kidney damage still remain to be discovered. A recent toxico-genomics study allowed us to focus on osteopontin (OSTP) normally excreted in human urine and linked to mineral metabolism. Objectives: We examined the association between osteopontin and uranium exposure both in vitro, in a human kidney cell model, and in the urine of exposed individuals. Methods: OSTP was measured in supernatants of uranium-exposed HK2 cells to establish a dose-response curve and a time course experiment. Its role was studied through a gene extinction experiment. Uranium and OSTP were then monitored in the urine of exposed nuclear fuel industry workers and a chronically exposed population. These levels were compared with those found in a non-exposed population. Results: The study of HK2 cells indicated that OSTP secretion decreased after uranium exposure in a concentration and time dependent manner, but its suppression does not affect cell sensitivity to uranium. In spite of wide inter-individual variability, this parameter decreases also in human urine when urinary uranium exceeds 30 μg/L after an acute exposure, a value considered to be critical for kidney damage. Conclusion: This study reports how toxico-genomics can highlight putative toxicity bio-markers in an easy to access biological fluid. The decrease of urinary osteopontin in response to uranium exposure suggests kidney damage and would thus be complementary to current markers. (authors)

  9. Occupational exposures to uranium: processes, hazards, and regulations

    International Nuclear Information System (INIS)

    The United States Uranium Registry (USUR) was formed in 1978 to investigate potential hazards from occupational exposure to uranium and to assess the need for special health-related studies of uranium workers. This report provides a summary of Registry work done to date. The history of the uranium industry is outlined first, and the current commercial uranium industry (mining, milling, conversion, enrichment, and fuel fabrication) is described. This description includes information on basic processes and areas of greatest potential radiological exposure. In addition, inactive commercial facilities and other uranium operations are discussed. Regulation of the commercial production industry for uranium fuel is reported, including the historic development of regulations and the current regulatory agencies and procedures for each phase of the industry. A review of radiological health practices in the industry - facility monitoring, exposure control, exposure evaluation, and record-keeping - is presented. A discussion of the nonradiological hazards of the industry is provided, and the final section describes the tissue program developed as part of the Registry

  10. Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

    Science.gov (United States)

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Eric; Banzet, Nathalie; Defoort, Catherine; Bott, Romain; Dublineau, Isabelle; Aigueperse, Jocelyne; Gourmelon, Patrick; Martin, Jean-Charles; Souidi, Maâmar

    2013-01-01

    Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC-MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure.

  11. Internal exposure to uranium in a pooled cohort of gaseous diffusion plant workers

    International Nuclear Information System (INIS)

    Intakes and absorbed organ doses were estimated for 29 303 workers employed at three former US gaseous diffusion plants as part of a study of cause-specific mortality and cancer incidence in uranium enrichment workers. Uranium urinalysis data (>600 000 urine samples) were available for 58 % of the pooled cohort. Facility records provided uranium gravimetric and radioactivity concentration data and allowed estimation of enrichment levels of uranium to which workers may have been exposed. Urine data were generally recorded with facility department numbers, which were also available in study subjects' work histories. Bioassay data were imputed for study subjects with no recorded sample results (33 % of pooled cohort) by assigning department average urine uranium concentration. Gravimetric data were converted to 24-h uranium activity excretion using department average specific activities. Intakes and organ doses were calculated assuming chronic exposure by inhalation to a 5-μm activity median aerodynamic diameter aerosol of soluble uranium. Median intakes varied between 0.31 and 0.74 Bq d-1 for the three facilities. Median organ doses for the three facilities varied between 0.019 and 0.051, 0.68 and 1.8, 0.078 and 0.22, 0.28 and 0.74, and 0.094 and 0.25 mGy for lung, bone surface, red bone marrow, kidneys, and liver, respectively. Estimated intakes and organ doses for study subjects with imputed bioassay data were similar in magnitude. (authors)

  12. Monitoring genotoxic exposure in uranium mines

    International Nuclear Information System (INIS)

    Recent data from deep uranium mines in Czechoslovakia indicated that miners are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B1 and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold strains isolated from mines and throat swabs were investigated for mutagenic activity by the SOS chromotest and Salmonella assay with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic activation in citro. These data suggest that mycotoxins produced by molds in uranium mines are a new genotoxic factor im uranium miners. 17 refs., 4 tabs

  13. Monitoring genotoxic exposure in uranium mines

    Energy Technology Data Exchange (ETDEWEB)

    Sram, R.J.; Vesela, D.; Vesely, D. [Institute of Experimental Medicine, Prague (Czech Republic)] [and others

    1993-10-01

    Recent data from deep uranium mines in Czechoslovakia indicated that miners are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B{sub 1} and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold strains isolated from mines and throat swabs were investigated for mutagenic activity by the SOS chromotest and Salmonella assay with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic activation in citro. These data suggest that mycotoxins produced by molds in uranium mines are a new genotoxic factor im uranium miners. 17 refs., 4 tabs.

  14. Internal distribution of uranium and associated genotoxic damages in the chronically exposed bivalve Corbicula fluminea

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Olivier, E-mail: olivier.simon@irsn.fr [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France); Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Adam, Christelle; Gilbin, Rodolphe; Garnier-Laplace, Jacqueline [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France)

    2011-08-15

    Uranium (U) internal distribution and involved effects in the bivalve Corbicula fluminea have been studied after direct chronic exposure (90 d, 10 {mu}g.L-1). U distribution was assessed at the subcellular level (Metal Rich Granules -MRG-, pellets and cytosol fractions) in two main organs of the bivalve (gills and visceral mass). Micro-localisation was investigated by TEM-EDX analysis in the gills epithelium. DNA damage in gill and hemolymph samples was measured by the Comet assay. The 90-d exposure period led to a significant increase of U concentration in gills over time (x5) and a large U quantity in subcellular granules in gills. Finally, a significant increase (x2) in DNA damage was noted in exposed gills and haemocytes. This study shows that the accumulation levels and consequently the potential toxicity cannot be successfully predicted only on the basis of concentration in water or in tissues and subcellular fractions after chronic exposure. - Highlights: > Relevant information concerning the chronic impact of uranium on biota is scarce. > We study its biological speciation to explain bioavailability, accumulation, toxicity. > 80% of U accumulated was measured in the pellet fraction (organelles + granules/MRG). > Chronic exposure to U induced genetic damage in gill and haemolymph cells of the bivalve.

  15. Monitoring genotoxic exposure in uranium mines.

    OpenAIRE

    Srám, R J; Dobiás, L; Rössner, P; Veselá, D; Veselý, D; Rakusová, R; V. Rericha

    1993-01-01

    Recent data from deep uranium mines in Czechoslovakia indicated that mines are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B1 and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold...

  16. Depleted uranium exposure and health effects in Gulf War veterans

    OpenAIRE

    Squibb, Katherine S.; McDiarmid, Melissa A.

    2006-01-01

    Health effects stemming from depleted uranium (DU) exposure in a cohort of Gulf War veterans who were in or on US Army vehicles hit by friendly fire involving DU munitions are being carefully monitored through the Baltimore Veterans Affairs (VA) DU Follow-Up Program initiated in 1993. DU exposure in this cohort has been directly measured using inductively coupled plasma-mass spectrometer (ICP-MS) isotopic analysis for DU in urine specimens. Soldiers with embedded DU fragments continue to excr...

  17. Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions; Effets chimique et radiologique d'une ingestion chronique d'uranium sur le cerveau du rat. Effets sur les neurotransmissions dopaminergique, serotoninergique et cholinergique

    Energy Technology Data Exchange (ETDEWEB)

    Bussy, C

    2005-09-15

    Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L{sup -1} (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

  18. Occupational Exposures and Chronic Airflow Limitation

    Directory of Open Access Journals (Sweden)

    Helen Dimich-Ward

    1996-01-01

    Full Text Available The recent literature was reviewed to evaluate whether chronic airflow limitation is associated with occupational exposures to dusts. Only those studies that controlled for the effects of smoking were included. There is compelling evidence that exposure to inorganic dusts, such as from coal and hardrock mining or asbestos, are associated with the development of chronic airflow limitation, independently of pneumoconiosis. Nonsmoking gold miners are particularly at high risk of airflow obstruction and emphysema. Findings from studies of organic dusts, such as exposures to wood, cotton, grain or other agricultural dusts, or to mixed dust exposures, were less consistent but tended to show positive dose-response associations. In the majority of studies, no statistical interaction was shown between dust exposures and smoking; however, the effects of the dust exposures were often more pronounced. An occupational history should be considered, in addition to a smoking history, as an integral part of an investigation of chronic airflow limitation in a patient.

  19. Biological consequences of exposure to soluble forms of natural uranium

    International Nuclear Information System (INIS)

    Depending on dose, route of administration and chemical form of the administered uranium, exposure to uranium compounds can produce effects in a variety of organs. Of these, the kidney is the most sensitive, and is considered to be a critical target organ for hazard assessment. Although dose-effect relationships differ among species, injury and necrosis of the terminal segments of the renal proximal tubule is characteristic in all mammalian species that have been studied. Glomerular injury has also been reported. The critical occupational health issues is thus, ''To what extent can laboratory animal models be useful for predicting human health hazards to uranium?''. While direct quantitative extrapolations of dose-effect relationships in laboratory animals to humans is not a reality at present, it is possible, nevertheless, to explore in laboratory animal models certain specific questions regarding the biological effects of uranium in kidney that are relevant to hazard assessment. Indeed, a complete understanding of the laboratory animal model is critical for establishing valid extrapolations to humans. Issues relating to mechanisms of renal injury, dose-effect relationships and biological monitoring for uranium-induced nephrotoxicity are considered in this review. (author)

  20. Agricultural versus uranium industry regarding the exposure to natural radiation

    International Nuclear Information System (INIS)

    The potential exposure of the critical group is to be evaluated against national and international recommendation regarding the impact of general nuclear facilities. In Brazil, an agricultural industry together with uranium mining and milling facilities take place at an elevated natural radioactivity region. It was performed a dose and risk assessment to the local and remote population due to these two man made activities. This paper will present some data on dose and radiological risk to the local population (rural workers and their families) living at that region for occupational reasons. The non significant increase on the radiation dose exposure to a critical group due to the uranium industry will be pointed out. Problems associated in applying the ICRP dose limitation system to such situations will be discussed. (author)

  1. Military use of depleted uranium: assessment of prolonged population exposure

    OpenAIRE

    Giannardi, C.; Dominici, D.

    2001-01-01

    This work is an exposure assessment for a population living in an area contaminated by use of depleted uranium (DU) weapons. RESRAD 5.91 code is used to evaluate the average effective dose delivered from 1, 10, 20 cm depths of contaminated soil, in a residential farmer scenario. Critical pathway and group are identified in soil inhalation or ingestion and children playing with the soil, respectively. From available information on DU released on targeted sites, both critical and average exposu...

  2. Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect.

    Science.gov (United States)

    Petitot, F; Frelon, S; Chambon, C; Paquet, F; Guipaud, O

    2016-08-22

    The civilian and military use of uranium results in an increased risk of human exposure. The toxicity of uranium results from both its chemical and radiological properties that vary with isotopic composition. Validated biomarkers of health effects associated with exposure to uranium are neither sensitive nor specific to uranium radiotoxicity and/or radiological effect. This study aimed at investigating if serum proteins could be useful as biomarkers of both uranium exposure and radiological effect. Male Sprague-Dawley rats were chronically exposed through drinking water to low levels (40mg/L, corresponding to 1mg of uranium per animal per day) of either 4% (235)U-enriched uranium (EU) or 12% EU during 6 weeks. A proteomics approach based on two-dimensional electrophoresis (2D-DIGE) and mass spectrometry (MS) was used to establish protein expression profiles that could be relevant for discriminating between groups, and to identify some differentially expressed proteins following uranium ingestion. It demonstrated that the expressions of 174 protein spots over 1045 quantified spots were altered after uranium exposure (pproteins find that acute phase, inflammatory and immune responses as well as oxidative stress are likely involved in the response to contamination, suggesting a physiological perturbation, but that does not necessarily lead to a toxic effect. PMID:27267564

  3. Military use of depleted uranium assessment of prolonged population exposure

    CERN Document Server

    Giannardi, C

    2001-01-01

    This work is an exposure assessment for a population living in an area contaminated by use of depleted uranium (DU) weapons. RESRAD 5.91 code is used to evaluate the average effective dose delivered from 1, 10, 20 cm depths of contaminated soil, in a residential farmer scenario. Critical pathway and group are identified in soil inhalation or ingestion and children playing with the soil, respectively. From available information on DU released on targeted sites, both critical and average exposure can leave to toxicological hazards; annual dose limit for population can be exceeded on short-term period (years) for soil inhalation. As a consequence, in targeted sites cleaning up must be planned on the basis of measured concentration, when available, while special cautions have to be adopted altogether to reduce unaware exposures, taking into account the amount of the avertable dose.

  4. Risk of lung cancer from radon exposure: contribution of recently published studies of uranium miners

    International Nuclear Information System (INIS)

    The International Commission on Radiological Protection (ICRP) recently estimated the risk of lung cancer associated with radon exposure, and a statement was issued in ICRP Publication 115. This was based on recent epidemiological studies and the results from a joint analysis of cohorts of Czech, French, and German uranium miners, and indicated that the excess relative risk of lung cancer per unit of exposure should be expressed with consideration of chronic exposure over more than 10 years, by modelling time since median exposure, age attained or age at exposure, and taking in account, if possible, interaction between radon and tobacco. The lifetime excess absolute risk (LEAR) calculated from occupational exposure studies is close to 5 × 10−4 per working level month (WLM) (14 × 10−5 per hm J/m3). LEAR values estimated using risk models derived from both miners and domestic exposure studies are in good agreement after accounting for factors such as sex, attained age, and exposure scenario. A sensitivity analysis highlighted the high dependence of background mortality rates on LEAR estimates. Using lung cancer rates among Euro-American males instead of the ICRP reference rates (males and females, and Euro-American and Asian populations), the estimated LEAR is close to 7 × 10−4 per WLM (20 × 10−5 per hm J/m3).

  5. Epi-genetics modifications induced by a depleted uranium exposure in the zebra fish

    Energy Technology Data Exchange (ETDEWEB)

    Gombeau, K.; Pereira, S.; Adam-Guillermin, C. [IRSN/PRP-ENV/SERIS/LECO (France); Bourdineaud, J.P. [UMR CNRS 5805 EPOC (France); Ravanat, J.L. [INAC/Scib UMR E3 CEA-UJF (France)

    2014-07-01

    The work presented here integrates in the general framework of assessment of effects of chronic exposure to low doses of radionuclides. This evaluation necessarily involves the study of the mechanisms of toxic action at the cellular or subcellular level, in order to better understand the processes of propagation of effects to the level of the populations or ecosystems. As such, the question of the mechanisms underlying the trans-generational effects and the adaptive capacity of organisms is central, both in humans and in animal species. Epigenetic refer to changes in gene function that do not involve changes in DNA sequence, and which are transmitted in a hereditary manner by mitosis or meiosis. The latter plays a key role in these trans-generational effects. Among these changes, DNA-methylation is one of the most studied epigenetic parameters. This work is part of a PhD, included in the European COMET project (Euratom 7. Framework Program), and focuses on epigenetic modifications induced in zebra fish after a chronic exposure to radionuclides. Male and female fishes were exposed to 2 and 20 μg.L{sup -1} of depleted uranium for 24 days. After 7 and 24 days of exposure, brain, gonads, and eyes were collected in order to study changes in DNA methylation. In addition, genotoxicity was measured by the γH2AX assay. The overall changes in DNA methylation were studied by AFLP-MS and HPLC-MS, in order to know if the exposure to depleted uranium changes the global status of DNA methylation. We have found a decrease in the global level of methylation in the eyes of males after 24 days of exposure, the diminution being much more important and significant at the higher concentration of exposure (11.79 ± 3.62 against 52.43 ± 3.01 for controls) This study will be refined by analyzing the methylation of specific regions of the genome, because it represent the sequences of genes involved in major physiological functions and that may be subject to variations in the methylation

  6. Study of the biological effects of uranium exposure on zebra fish (D. rerio). Impact on life stages

    International Nuclear Information System (INIS)

    This work is part of an ongoing project (ENVIRHOM) started at IRSN in 2000, which consists in studying the environmental effects of radioactive substances at chronic low level of exposure. In this general frame, our aim was two fold: (i) to identify sensitivity of different critical life stages of zebra fish (fish of fresh water frequently used for tests standards in ecotoxicology) to uranium exposure and (ii) to evaluate underlying mechanisms. Experiments were conducted with eggs, larvae and genitors exposed to uranium at environmentally relevant concentrations (from 20 to 500 μg/L) in order to study survival, hatching of eggs, growth of larvae and reproduction of genitors. Bio-markers of exposure (i.e. U bioaccumulation) and bio-markers of effects at molecular level (i.e. genotoxic effects, reproductive-toxicity) were also measured. Sensitivity of fish to uranium was dependent of the life stage of development with the early life stage being the most sensitive to U either directly or maternally exposed. It underlines the relevance of including pro-larval stages for toxicity assessments in fish. Moreover drastic effects of uranium on reproductive success and DNA damages in the germ cells foretell a strong impact on the population for low concentration of exposure (20 μg/L). As it is increasingly recognized that population-level effects of toxic substances are more relevant in terms of ecological risk assessment, this study points out the need to include different life stages of organisms in eco-toxicological studies, especially the sensitive early stages. Moreover, it appears, through the comparative study of the radiological effects or by another isotope of the uranium of stronger radioactivity (233U or by an irradiation with 137Cs), that the effects of the uranium are due to its chemo-toxicity. (author)

  7. Estimating the lung burden from exposure to aerosols of depleted uranium

    International Nuclear Information System (INIS)

    Following exposure to aerosols of depleted uranium (DU), biological samples show the presence of a synthetic mixture of natural uranium and DU. By partitioning the uranium in the 24-h urine sample along the isotopic fractions of natural uranium and DU, one can study the kinetics of these subpopulations independently. A linear model is developed to estimate the lung burden of DU from measurements of DU in 24-h urine samples, years after inhalational exposure to aerosols of DU. This model takes into account the intracellular dissolution of the retained particles and the precipitation of a significant fraction of the dissolved DU as insoluble uranyl phosphates. (authors)

  8. Effects in Plant Populations Resulting from Chronic Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, Stanislav A.; Volkova, Polina Yu.; Vasiliyev, Denis V.; Dikareva, Nina S.; Oudalova, Alla A. [Russian Institute of Agricultural Radiology and Agroecology, 249032, Obninsk (Russian Federation)

    2014-07-01

    Human industrial activities have left behind a legacy of ecosystems strongly impacted by a wide range of contaminants, including radionuclides. Phyto-toxic effects of acute impact are well known, but the consequences of long-term chronic exposure to low pollutant concentrations is neither well understood nor adequately included in risk assessments. To understand effects of real-world contaminant exposure properly we must pay attention to what is actually going on in the field. However, for many wildlife groups and endpoints, there are no, or very few, studies that link accumulation, chronic exposure and biological effects in natural settings. To fill the gaps, results of field studies carried out on different plant species (winter rye and wheat, spring barley, oats, Scots pine, wild vetch, crested hair-grass) in various radioecological situations (nuclear weapon testing, the Chernobyl accident, uranium and radium processing) to investigate effects of long-term chronic exposure to radionuclides are discussed. Because each impacted site developed in its own way due to a unique history of events, the experience from one case study is rarely directly applicable to another situation. In spite of high heterogeneity in response, we have detected several general patterns. Plant populations growing in areas with relatively low levels of pollution are characterized by the increased level of both cytogenetic alterations and genetic diversity. Accumulation of cellular alterations may afterward influence biological parameters important for populations such as health and reproduction. Presented data provide evidence that in plant populations inhabiting heavily contaminated territories cytogenetic damage were accompanied by decrease in reproductive ability. In less contaminated sites, because of the scarcity of data available, it is impossible to establish exactly the relationship between cytogenetic effects and reproductive ability. Radioactive contamination of the plants

  9. Epidemiological study of workers at risk of internal exposure to uranium

    International Nuclear Information System (INIS)

    This work is a pilot-study among nuclear fuel cycle workers potentially exposed to alpha radiation. Internal exposure from inhalation of uranium compounds during uranium conversion and enrichment operations was estimated at the AREVA NC Pierrelatte plant. A plant specific semi-quantitative job exposure matrix (JEM) was elaborated for 2709 workers employed at this plant between 1960 and 2006. The JEM has permitted to estimate the exposure to uranium and 16 other categories of pollutants and to calculate individual cumulative exposure score. Numerous correlations were detected between uranium compounds exposure and exposure to other pollutants, such as asbestos, ceramic refractive fibers, TCE and so on. 1968-2005 mortality follow-up showed an increasing risk of mortality from pleural cancer, rectal cancer and lymphoma on the basis of national mortality rates. Analyses of association between cancer mortality and uranium exposure suggested an increase in mortality due to lung cancer among workers exposed to slowly soluble uranium compounds derived from natural and reprocessed uranium. However these results are not statistically significant and based on a small number of observed deaths. These results are concordant with previously reported results from other cohorts of workers potentially exposed to uranium. Experimental studies of biokinetic and action mechanism of slowly soluble uranium oxides bear the biological plausibility of the observed results. Influence of bias was reduced by taking into account of possible confounding including co-exposure to other carcinogenic pollutants and tobacco consumption in the study. Nevertheless, at this stage statistical power of analyses is too limited to obtain more conclusive results. This pilot study shows the interest and feasibility of an epidemiological investigation among workers at risk of internal exposure to uranium and other alpha emitters at the national level. It demonstrates the importance of exposure assessment for

  10. Induction of oxidative stress related responses in Arabidopsis thaliana following uranium exposure

    OpenAIRE

    Vanhoudt, Nathalie; Vandenhove, H.; Opdenakker, Kelly; Remans, Tony; Smeets, Karen; MARTINEZ BELLO, Daniel; van Hees, M.; Wannijn, J.; Vangronsveld, Jaco; Cuypers, Ann

    2009-01-01

    The reactive oxygen species (ROS)-signaling pathway is very important in heavy metal toxicity. Induction of the antioxidative defense mechanism, comprising ROS-scavenging enzymes and metabolites, in plants after environmental uranium contamination has been insufficiently studied in the past. This study aimed to analyze oxidative stress related responses in Arabidopsis thaliana after uranium exposure. Seventeen-day-old seedlings were exposed to 0, 0.1, 1, 10 and 100 μM uranium for 3 days. Afte...

  11. Uranium bioaccumulation and biological disorders induced in zebrafish (Danio rerio) after a depleted uranium waterborne exposure

    Energy Technology Data Exchange (ETDEWEB)

    Barillet, Sabrina, E-mail: sabrina.barillet@free.f [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.f [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Palluel, Olivier, E-mail: olivier.palluel@ineris.f [Ecotoxicological Risk Assessment Unit, INERIS (National Institute for Industrial Environment and Risks), Parc technologique ALATA, 60 550 Verneuil-en-Halatte (France); Porcher, Jean-Marc, E-mail: jean-marc.porcher@ineris.f [Ecotoxicological Risk Assessment Unit, INERIS (National Institute for Industrial Environment and Risks), Parc technologique ALATA, 60 550 Verneuil-en-Halatte (France); Devaux, Alain, E-mail: alain.devaux@entpe.f [Universite de Lyon, INRA, EFPA-SA, Environmental Science Laboratory (LSE), ENTPE, 69518 Vaulx en Velin cedex (France)

    2011-02-15

    Because of its toxicity and its ubiquity within aquatic compartments, uranium (U) represents a significant hazard to aquatic species such as fish. In a previous study, we investigated some biological responses in zebrafish either exposed to depleted or to enriched U (i.e., to different radiological activities). However, results required further experiments to better understand biological responses. Moreover, we failed to clearly demonstrate a significant relationship between biological effects and U radiological activity. We therefore chose to herein examine U bioaccumulation and induced effects in zebrafish according to a chemical dose-response approach. Results showed that U is highly bioconcentrated in fish, according to a time- and concentration-dependent model. Additionally, hepatic antioxidant defenses, red blood cells DNA integrity and brain acetylcholinesterase activity were found to be significantly altered. Generally, the higher the U concentration, the sooner and/or the greater the effect, suggesting a close relationship between accumulation and effect. - Research highlights: Depleted U bioconcentration factor is of about 1000 in zebrafish exposed to 20 {mu}g/L. Hepatic antioxidant disorders are noticed as soon as the first hours of exposure. DNA damage is induced in red blood cells after 20 d of exposure to 500 {mu}g DU/L. The brain cholinergic system (AChE activity) is impacted. - This study demonstrates that U is highly bioaccumulated in fish, resulting in biological disorders such as hepatic oxidative stress as well as genotoxic and neurotoxic events.

  12. Uranium bioaccumulation and biological disorders induced in zebrafish (Danio rerio) after a depleted uranium waterborne exposure

    International Nuclear Information System (INIS)

    Because of its toxicity and its ubiquity within aquatic compartments, uranium (U) represents a significant hazard to aquatic species such as fish. In a previous study, we investigated some biological responses in zebrafish either exposed to depleted or to enriched U (i.e., to different radiological activities). However, results required further experiments to better understand biological responses. Moreover, we failed to clearly demonstrate a significant relationship between biological effects and U radiological activity. We therefore chose to herein examine U bioaccumulation and induced effects in zebrafish according to a chemical dose-response approach. Results showed that U is highly bioconcentrated in fish, according to a time- and concentration-dependent model. Additionally, hepatic antioxidant defenses, red blood cells DNA integrity and brain acetylcholinesterase activity were found to be significantly altered. Generally, the higher the U concentration, the sooner and/or the greater the effect, suggesting a close relationship between accumulation and effect. - Research highlights: → Depleted U bioconcentration factor is of about 1000 in zebrafish exposed to 20 μg/L. → Hepatic antioxidant disorders are noticed as soon as the first hours of exposure. → DNA damage is induced in red blood cells after 20 d of exposure to 500 μg DU/L. → The brain cholinergic system (AChE activity) is impacted. - This study demonstrates that U is highly bioaccumulated in fish, resulting in biological disorders such as hepatic oxidative stress as well as genotoxic and neurotoxic events.

  13. Chronic fatigue syndrome following a toxic exposure.

    Science.gov (United States)

    Racciatti, D; Vecchiet, J; Ceccomancini, A; Ricci, F; Pizzigallo, E

    2001-04-10

    Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS. PMID:11327394

  14. The Toxicity of Depleted Uranium

    OpenAIRE

    Wayne Briner

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a c...

  15. Uranium

    International Nuclear Information System (INIS)

    The article includes a historical preface about uranium, discovery of portability of sequential fission of uranium, uranium existence, basic raw materials, secondary raw materials, uranium's physical and chemical properties, uranium extraction, nuclear fuel cycle, logistics and estimation of the amount of uranium reserves, producing countries of concentrated uranium oxides and percentage of the world's total production, civilian and military uses of uranium. The use of depleted uranium in the Gulf War, the Balkans and Iraq has caused political and environmental effects which are complex, raising problems and questions about the effects that nuclear compounds left on human health and environment.

  16. Depleted uranium contamination by inhalation exposure and its detection after {approx} 20 years: Implications for human health assessment

    Energy Technology Data Exchange (ETDEWEB)

    Parrish, Randall R. [Department of Geology, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); NERC Isotope Geosciences Laboratory, British Geological Survey, Keyworth, Notts, NG12 5GG (United Kingdom)], E-mail: rrp@nigl.nerc.ac.uk; Horstwood, Matthew [NERC Isotope Geosciences Laboratory, British Geological Survey, Keyworth, Notts, NG12 5GG (United Kingdom); Arnason, John G. [Department of Earth and Atmospheric Sciences, University at Albany, 1400 Washington Avenue, Albany NY 12222 (United States); Chenery, Simon [British Geological Survey, Keyworth, Notts, NG12 5GG (United Kingdom); Brewer, Tim [Department of Geology, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Lloyd, Nicholas S. [Department of Geology, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); British Geological Survey, Keyworth, Notts, NG12 5GG (United Kingdom); Carpenter, David O. [Institute for Health and the Environment, University at Albany, Five University Place, Room A217, Rensselaer, NY 12144-3456 (United States)

    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 {approx} 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.

  17. Assessment of uranium exposure from total activity and 234U:238U activity ratios in urine.

    Science.gov (United States)

    Nicholas, T; Bingham, D

    2011-03-01

    Radiation workers at Atomic Weapons Establishment (AWE) are monitored for uranium exposure by routine bioassay sampling (primarily urine sampling). However, the interpretation of uranium in urine and faecal results in terms of occupational intakes is difficult because of the presence of uranium due to intakes from environmental (dietary) sources. For uranium in urine data obtained using current analytical techniques at AWE, the mean, median and standard deviation of excreted uranium concentrations were 0.006, 0.002 and 0.012 μg per g creatinine, respectively. These values are consistent with what might be expected from local dietary intakes and the knowledge that occupational exposures at AWE are likely to be very low. However, some samples do exceed derived investigation levels (DILs), which have been set up taking account of the likely contribution from environmental sources. We investigate how the activity and isotopic composition of uranium in the diet affects the sensitivity of uranium in urine monitoring for occupational exposures. We conclude that DILs based on both total uranium in urine activity and also (234)U:(238)U ratios are useful given the likely variation in dietary contribution for AWE workers. Assuming a background excretion rate and that the enrichment of the likely exposure is known, it is possible to assess exposures using (234)U:(238)U ratios and/or total uranium activity. The health implications of internalised uranium, enriched to <5-8 % by mass (235)U, centre on its nephrotoxicity; the DILs for bioassay samples at AWE are an order of magnitude below the conservative recommendations made by the literature. PMID:21036806

  18. [The assessment of no adverse effect doses for plant populations chronically exposed to radionuclides of uranium and thorium decay series].

    Science.gov (United States)

    Evseeva, T I; Maĭstrenko, T A; Belykh, E S; Geras'kin, S A

    2010-01-01

    Dose rates cause no adverse effects on natural populations of Pinus sylvestris L. and Vicia cracca L. inhabiting territories contaminated by uranium mill tailings and radium production wastes (Vodny settlement, Komi Republic) were determined. A significant increase in embryonic lethal mutation frequency in V. cracca legumes and decrease in seedlings survival rate as compared with control values were registered at dose rate equal to 1.67 mGy/day, that is 280 times higher than the one calculated for the reference site. The adverse effects in P. sylvestris expressed in increased frequency of chromosome aberrations in meristematic root tips and decreased reproductive capacity of seeds were determined at absorbed dose rate equal to 0.083 mGy/day. Data obtained show that the decrease in plant reproductive capacity in case of chronic exposure of radionuclides of uranium and thorium decay series can observe at lower weighted absorbed dose rates than in case of environmental contamination by artificial radionuclides.

  19. Hair analysis as an indicator of exposure to uranium

    International Nuclear Information System (INIS)

    Medical examinations performed on four monks of a monastery in the northern Greece revealed heavy metal contamination. Hair analysis, performed by a toxicological laboratory abroad, indicated, among other, the presence of uranium. The uranium concentrations determined in a laboratory of 'Elemental Hair Analysis' indicated a uranium level that was about five times the maximum value of the reference range, which has been adopted by the measuring laboratory. After these diagnostic findings, on request of 10 monks, uranium determination in hair and urine samples was performed by means of alpha spectrometry in GAEC's laboratory. The measured uranium concentrations in hair varied from 0.15 to 2.10 mBq g-1, which correspond to 12.1 and 170 ng g-1, respectively. The uranium concentrations in urine were between 41 and 174 ng d-1. For comparison purposes, urine and non-dyed hair samples from the staff of the laboratory were analysed. Because one of the major sources of uranium intake is through drinking water, water samples were also analysed. The mean value of the uranium concentration in the two drinking water samples collected from the residence area was found to be 2.35 μg l-1. (authors)

  20. Long-term ecological effects of exposure to uranium

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.C.; Miera, F.R. Jr.

    1976-03-01

    The consequences of releasing natural and depleted uranium to terrestrial ecosystems during development and testing of depleted uranium munitions were investigated. At Eglin Air Force Base, Florida, soil at various distances from armor plate target butts struck by depleted uranium penetrators was sampled. The upper 5 cm of soil at the target bases contained an average of 800 ppM of depleted uranium, about 30 times as much as soil at 5- to 10-cm depth, indicating some vertical movement of depleted uranium. Samples collected beyond about 20 m from the targets showed near-background natural uranium levels, about 1.3 +- 0.3 ..mu..g/g or ppM. Two explosives-testing areas at the Los Alamos Scientific Laboratory (LASL) were selected because of their use history. E-F Site soil averaged 2400 ppM of uranium in the upper 5 cm and 1600 ppM at 5-10 cm. Lower Slobovia Site soil from two subplots averaged about 2.5 and 0.6 percent of the E-F Site concentrations. Important uranium concentration differences with depth and distance from detonation points were ascribed to the different explosive tests conducted in each area. E-F Site vegetation samples contained about 320 ppM of uranium in November 1974 and about 125 ppM in June 1975. Small mammals trapped in the study areas in November contained a maximum of 210 ppM of uranium in the gastrointestinal tract contents, 24 ppM in the pelt, and 4 ppM in the remaining carcass. In June, maximum concentrations were 110, 50, and 2 ppM in similar samples and 6 ppM in lungs. These data emphasized the importance of resuspension of respirable particles in the upper few millimeters of soil as a contamination mechanism for several components of the LASL ecosystem.

  1. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure

  2. Analytical developments for the speciation of uranium in zebra fish (Danio rerio) gills after exposure

    International Nuclear Information System (INIS)

    The objective of this thesis is to study the cellular compartmentalization and the chelation of uranium (U) by cytosolic proteins of gill cells of the zebra fish (Danio rerio, model specie in aquatic toxicology) under different direct exposure conditions (chronic vs. acute, 20 and 250 μg.L-1). This study required the development of hyphenated techniques (SEC, IEF off-gel, RP-UHPLC for the separation, ICP-SFMS, ESI-FTMS/MS for the detection) with the main challenges of maintaining the non-covalent U-biomolecule interactions and enhancing sensitivity for the analysis of environmentally relevant samples. After extraction, 24% to 32% of the total U detected in the gills were present in the cytosolic fraction, in which the U distribution on the biomolecules (as a function of their MW and pI) varied depending on the exposure level. Finally, U target biomolecules mapping allowed us (i) to highlight a particular affinity of U for acidic and/or P-containing proteins and (ii) to identify 24 protein candidates for U binding. (author)

  3. Effect of acetaminophen administration to rats chronically exposed to depleted uranium

    International Nuclear Information System (INIS)

    The extensive use of depleted uranium (DU) in both civilian and military applications results in the increase of the number of human beings exposed to this compound. We previously found that DU chronic exposure induces the expression of CYP enzymes involved in the metabolism of xenobiotics (drugs). In order to evaluate the consequences of these changes on the metabolism of a drug, rats chronically exposed to DU (40 mg/l) were treated by acetaminophen (APAP, 400 mg/kg) at the end of the 9-month contamination. Acetaminophen is considered as a safe drug within the therapeutic range but in the case of overdose or in sensitive animals, hepatotoxicity and nephrotoxicity could occur. In the present work, plasma concentration of APAP was higher in the DU group compared to the non-contaminated group. In addition, administration of APAP to the DU-exposed rats increased plasma ALT (p < 0.01) and AST (p < 0.05) more rapidly than in the control group. Nevertheless, no histological alteration of the liver was observed but renal injury characterized by incomplete proximal tubular cell necrosis was higher for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an important CYP responsible for APAP bioactivation and toxicity, is increased (p < 0.01) in the DU-exposed group compared to the control group. In the liver, CYP's activities were decreased between control and DU-exposed rats. These results could explain the worse elimination of APAP in the plasma and confirm our hypothesis of a modification of the drug metabolism following a DU chronic contamination

  4. US Transuranium and Uranium Registries case study on accidental exposure to uranium hexafluoride.

    Science.gov (United States)

    Avtandilashvili, Maia; Puncher, Matthew; McComish, Stacey L; Tolmachev, Sergei Y

    2015-03-01

    The United States Transuranium and Uranium Registries' (USTUR) whole-body donor (Case 1031) was exposed to an acute inhalation of uranium hexafluoride (UF6) produced from an explosion at a uranium processing plant 65 years prior to his death. The USTUR measurements of tissue samples collected at the autopsy indicated long-term retention of inhaled slightly enriched uranium material (0.85% (235)U) in the deep lungs and thoracic lymph nodes. In the present study, the authors combined the tissue measurement results with historical bioassay data, and analysed them with International Commission on Radiological Protection (ICRP) respiratory tract models and the ICRP Publication 69 systemic model for uranium using maximum likelihood and Bayesian statistical methods. The purpose of the analysis was to estimate intakes and model parameter values that best describe the data, and evaluate their effect on dose assessment. The maximum likelihood analysis, which used the ICRP Publication 66 human respiratory tract model, resulted in a point estimate of 79 mg of uranium for the occupational intake composed of 86% soluble, type F material and 14% insoluble, type S material. For the Bayesian approach, the authors applied the Markov Chain Monte Carlo method, but this time used the revised human respiratory tract model, which is currently being used by ICRP to calculate new dose coefficients for workers. The Bayesian analysis estimated that the mean uranium intake was 160 mg, and calculated the case-specific lung dissolution parameters with their associated uncertainties. The parameters were consistent with the inhaled uranium material being predominantly soluble with a small but significant insoluble component. The 95% posterior range of the rapid dissolution fraction (the fraction of deposited material that is absorbed to blood rapidly) was 0.12 to 0.91 with a median of 0.37. The remaining fraction was absorbed slowly, with a 95% range of 0.000 22 d(-1) to 0.000 36

  5. Does uranium exposure induce genotoxicity in the teleostean Danio rerio? First experimental results

    OpenAIRE

    Barillet, S.; Buet, A.; Adam, C.; Devaux, Alain

    2005-01-01

    Zebrafish were exposed to different concentrations of waterborne uranium (0, 20, 100 and 500 $\\mu$g U.L-1) and were sacrificed for blood sampling after different exposure periods (12h, 36h, 72h, 5, 10 and 20 days) in order to assess DNA integrity in erythrocytes, using the comet assay and flow cytometry. Concurrently, uranium bioaccumulation was studied in the remaining tissues to understand the potential genotoxic biomarker responses. Both genotoxic assays revealed significant effect of wate...

  6. Uranium exposure to the tropical duckweed Lemna aequinoctialis and pulmonate snail Amerianna cumingi: fate and toxicity.

    Science.gov (United States)

    Hogan, Alicia C; van Dam, Rick A; Houston, Melanie A; Harford, Andrew J; Nou, Suthidha

    2010-08-01

    The discharge of catchment-management water from the Ranger uranium (U) mine into Magela Creek upstream of the Ramsar-listed Magela Floodplain in Kakadu National Park is an important part of the mine's water-management system. Because U is one of the primary toxicants associated with this water, a receiving-water trigger value (TV), based on chronic toxicity data from five local native species, was derived for U. To strengthen the data set underpinning the derivation of the TV, the chronic toxicity of U to two additional tropical freshwater species, duckweed Lemna aequinoctialis (96-hour growth rate), and pulmonate gastropod, Amerianna cumingi (96-hour reproduction), was determined. The fate of U within the test systems was an important component of the study because analysis of U concentrations during the snail tests indicated that a substantial proportion of U (approximately 25%) was being lost from the test solutions when integrated during the entire test duration. Analysis of the snails and their food for U indicated that only a small proportion that was lost from solution was being taken up by the snails. Therefore, the majority of U that was lost was considered unavailable to the snails, and thus the exposure concentrations used to calculate the toxicity estimates were adjusted downward. Integrating the loss of U from the L. aequinoctialis test solutions over time showed that only a small proportion (6% to 13%) was lost during the test: Of that, almost half (2-5%) was taken up by the plants (constituting exposure). Uranium was only moderately toxic to L. aequinoctialis, with no observed-effect concentrations, lowest observed-effect concentrations, and inhibition concentrations causing 10% and 50% effects (IC10 and IC50) values of 226, 404, 207, and 1435 microg/l, respectively. A. cumingi was found to be more sensitive to U than L. aequinoctialis, with NOEC, LOEC, IC10, and IC50 values of 60, 61, 15, and 278 microg/l, respectively. The data for these two

  7. Evaluation of health effects in Sequoyah Fuels Corporation workers from accidental exposure to uranium hexafluoride

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R. (Pacific Northwest Lab., Richland, WA (USA)); Swint, M.J.; Kathren, R.L. (Hanford Environmental Health Foundation, Richland, WA (USA))

    1990-05-01

    Urine bioassay measurements for uranium and medical laboratory results were studied to determine whether there were any health effects from uranium intake among a group of 31 workers exposed to uranium hexafluoride (UF{sub 6}) and hydrolysis products following the accidental rupture of a 14-ton shipping cylinder in early 1986 at the Sequoyah Fuels Corporation uranium conversion facility in Gore, Oklahoma. Physiological indicators studied to detect kidney tissue damage included tests for urinary protein, casts and cells, blood, specific gravity, and urine pH, blood urea nitrogen, and blood creatinine. We concluded after reviewing two years of follow-up medical data that none of the 31 workers sustained any observable health effects from exposure to uranium. The early excretion of uranium in urine showed more rapid systemic uptake of uranium from the lung than is assumed using the International Commission on Radiological Protection (ICRP) Publication 30 and Publication 54 models. The urinary excretion data from these workers were used to develop an improved systemic recycling model for inhaled soluble uranium. We estimated initial intakes, clearance rates, kidney burdens, and resulting radiation doses to lungs, kidneys, and bone surfaces. 38 refs., 10 figs., 7 tabs.

  8. Evaluation of health effects in Sequoyah Fuels Corporation workers from accidental exposure to uranium hexafluoride

    International Nuclear Information System (INIS)

    Urine bioassay measurements for uranium and medical laboratory results were studied to determine whether there were any health effects from uranium intake among a group of 31 workers exposed to uranium hexafluoride (UF6) and hydrolysis products following the accidental rupture of a 14-ton shipping cylinder in early 1986 at the Sequoyah Fuels Corporation uranium conversion facility in Gore, Oklahoma. Physiological indicators studied to detect kidney tissue damage included tests for urinary protein, casts and cells, blood, specific gravity, and urine pH, blood urea nitrogen, and blood creatinine. We concluded after reviewing two years of follow-up medical data that none of the 31 workers sustained any observable health effects from exposure to uranium. The early excretion of uranium in urine showed more rapid systemic uptake of uranium from the lung than is assumed using the International Commission on Radiological Protection (ICRP) Publication 30 and Publication 54 models. The urinary excretion data from these workers were used to develop an improved systemic recycling model for inhaled soluble uranium. We estimated initial intakes, clearance rates, kidney burdens, and resulting radiation doses to lungs, kidneys, and bone surfaces. 38 refs., 10 figs., 7 tabs

  9. Uranium

    International Nuclear Information System (INIS)

    The author discusses the contribution made by various energy sources in the production of electricity. Estimates are made of the future nuclear contribution, the future demand for uranium and future sales of Australian uranium. Nuclear power growth in the United States, Japan and Western Europe is discussed. The present status of the six major Australian uranium deposits (Ranger, Jabiluka, Nabarlek, Koongarra, Yeelerrie and Beverley) is given. Australian legislation relevant to the uranium mining industry is also outlined

  10. Uranium

    International Nuclear Information System (INIS)

    The development, prospecting, research, processing and marketing of South Africa's uranium industry and the national policies surrounding this industry form the headlines of this work. The geology of South Africa's uranium occurences and their positions, the processes used in the extraction of South Africa's uranium and the utilisation of uranium for power production as represented by the Koeberg nuclear power station near Cape Town are included in this publication

  11. Uranium

    International Nuclear Information System (INIS)

    The geological setting of uranium resources in the world can be divided in two basic categories of resources and are defined as reasonably assured resources, estimated additional resources and speculative resources. Tables are given to illustrate these definitions. The increasing world production of uranium despite the cutback in the nuclear industry and the uranium requirements of the future concluded these lecture notes

  12. Population Exposure to Depleted Uranium in the Han Pijesak Region

    OpenAIRE

    Zora S. Žunić; Rodoljub Simović; Zoran Ćurguz; Olivera Čuknić; Jerzy Mietelski; Predrag Ujić; Igor Čeliković; Predrag Kolarž; Branko Predojević

    2011-01-01

    In September 1995 the Han Pijesak area of Republic of Srpska was heavily attacked by Depleted Uranium (DU) ammunition. In this area, from 2003 to 2004, during one year, the components of natural ionizing radiation sources like radon, thoron, and gamma radiation were measured. In addition, during the same period, the samples of soil, moss, and lichen were collected in order to identify the content of technologically enhanced natural radionuclides in them and particularly their isotopic ratios,...

  13. Uranium hexafluoride public risk

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.; Hui, T.E.; Yurconic, M.; Johnson, J.R.

    1994-08-01

    The limiting value for uranium toxicity in a human being should be based on the concentration of uranium (U) in the kidneys. The threshold for nephrotoxicity appears to lie very near 3 {mu}g U per gram kidney tissue. There does not appear to be strong scientific support for any other improved estimate, either higher or lower than this, of the threshold for uranium nephrotoxicity in a human being. The value 3 {mu}g U per gram kidney is the concentration that results from a single intake of about 30 mg soluble uranium by inhalation (assuming the metabolism of a standard person). The concentration of uranium continues to increase in the kidneys after long-term, continuous (or chronic) exposure. After chronic intakes of soluble uranium by workers at the rate of 10 mg U per week, the concentration of uranium in the kidneys approaches and may even exceed the nephrotoxic limit of 3 {mu}g U per gram kidney tissue. Precise values of the kidney concentration depend on the biokinetic model and model parameters assumed for such a calculation. Since it is possible for the concentration of uranium in the kidneys to exceed 3 {mu}g per gram tissue at an intake rate of 10 mg U per week over long periods of time, we believe that the kidneys are protected from injury when intakes of soluble uranium at the rate of 10 mg U per week do not continue for more than two consecutive weeks. For long-term, continuous occupational exposure to low-level, soluble uranium, we recommend a reduced weekly intake limit of 5 mg uranium to prevent nephrotoxicity in workers. Our analysis shows that the nephrotoxic limit of 3 {mu}g U per gram kidney tissues is not exceeded after long-term, continuous uranium intake at the intake rate of 5 mg soluble uranium per week.

  14. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

    Science.gov (United States)

    Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

  15. Mycosis fungoides progression and chronic solvent exposure

    OpenAIRE

    Nikkels, Arjen; Quatresooz, Pascale; Delvenne, Philippe; Balsat, A.; Pierard, Gérald

    2004-01-01

    The effect of repeated exposure to specific chemicals on the initiation or progression of mycosis fungoides (MF) remains unsettled. A patient with low-grade patch stage MF progressively developed MF plaques restricted to his arms, and a tumour on his right thigh. These areas were subject to repeated exposure to solvents. His thigh was indeed in close contact with his trousers pocket where he used to store a wiping rag drenched into white spirit and cellulosic thinner. Immunophenotyping these ...

  16. The utility of in vitro solubility testing in assessment of uranium exposure

    International Nuclear Information System (INIS)

    Assessment of accidental exposures in the uranium industry requires estimation of retention and excretion rates using bioassay measurements. This task is difficult if the solubility of the inhaled uranium compound is unknown. In our research, Beagle dogs were exposed to aerosols of commercial uranium milling products containing either pure ammonium diuranate (ADU) or U308. Dogs were exposed to ADU aerosols to achieve a median retained body burden of 0.058 mg U per kg body weight, or to U308 aerosols to achieve a median retained body burden of 0.28 mg U per kg. A biokinetic model was applied to simulate retention and excretion of the two forms of uranium in vivo. Comparison of published in vitro dissolution data and modelling results with information from accidental human exposures showed that in vitro dissolution studies are necessary to characterise the differential solubilities of uranium compounds, and indicate the potential for kidney toxicity. Because variability in pulmonary clearance and urinary excretion rates is high among individual people, in vitro dissolution results are only marginally useful for estimating urinary excretion rates. (author)

  17. Psychologic sequelae of chronic toxic waste exposure

    Energy Technology Data Exchange (ETDEWEB)

    Foulks, E.; McLellen, T. (Department of Psychiatry and Neurology, Tulane University School of Medicine, New Orleans, LA (United States))

    1992-02-01

    Exposure to toxic industrial substances has been a topic of increasing concern to environmentalists, government agencies, industrial engineers, and medical specialists. Our study focuses on the psychologic symptom responses of a community to perceived long-term exposure to toxic waste products. We compared their symptom clusters, as shown by their responses to questions on the Hopkins Symptom Checklist-90 Item (SCL-90) and the Social Adjustment Scale (SAS), with symptom levels of normal and depressed subjects. Issues of media coverage, litigation, and potential for compensation complicate the psychiatric epidemiology of the subject.

  18. Assessment of uranium exposure in a community near former uranium mining and milling

    International Nuclear Information System (INIS)

    The northern region of Karnes County, Texas has been the site of extensive mining and milling of uranium-238 (238U) for over 30 years. Measurements of 238U were conducted to test the hypothesis that past mining/milling efforts have increased the environmental burden of 238U in local residential areas. 238U concentrations and lead isotope ratios were measured by ICP-MS in soil, plant tissues, household furnace filters, carpet dusts and drinking water. Soil samples (n=75) were collected from the yards of previously studied homes at the surface and 30 cm subsurface. From each home carpet vacuums, filter entrapments and dust swabs were collected (total n=15) as were water wells samples when available (n=7). A site located over 8 miles south of the study area and with no history of mining or milling facilities was found to be consistently and statistically (p238U contamination in the study area from high grade imported ore. The water sample near the largest mining/milling operation compared to the control site, indicating leaching into the groundwater. Analysis of dust samples indicates indoor contamination as 238U was as much as 10X higher in homes from the mining/milling areas compared to the control region. Data thus far indicates that uranium contamination from mining/milling activities is likely to be the cause of the previously documented biological effects and suggests increased health risks for these residents

  19. In vivo effects of a chronic contamination by uranium or cesium 137 on the pharmaceutical metabolism, of the vitamin D and cholesterol

    International Nuclear Information System (INIS)

    In conclusion, an animal model, miming the chronic contamination of the populations exposed to the uranium, was used for the first time to show that the chronic ingestion of a weak dose of depleted uranium can affect the level of active vitamin D without modifying the mineral homeostasis. This study shows that this radionuclide can lead molecular modifications of the CYPs and the nuclear receivers involved in the metabolism of the vitamin D not only at the level of the liver and kidney but also at the level of the independent metabolism in the brain. The deficiency in vitamin D can provoke osseous diseases such as the rickets at the child and the osteomalacia at the adult. The three categories of population the most exposed to this deficiency are the infants, the pregnant women and the old persons. Strong prevalence of the vitamin D deficiency associated with a chronic exposure to uranium could lead to osseous disorders. To verify this hypothesis, it will be necessary secondly to realize this study on individuals animal models predisposed to the rickets or to the osteomalacia. (N.C.)

  20. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Nielsen, M. Gissel

    1978-01-01

    Trout were exposed to selenite (Na2SeO3) solutions of varying concentrations (0.1-100 ppm Se) for periods of up to 4 wk. A chronic exposure to 0.1 ppm Se or less is non-lethal to trout. Lethality at higher concentrations depends on the length of exposure. Trout that survive for 10 days in tap-water...

  1. Polyneuropathy caused by chronic exposure to trichloroethylene

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Y.; Iwata, M.; Hisanaga, M.; Ono, Y.; Shibata, E.; Huang, J.; Takegami, T.; Okamoto, S.; Koike, Y.

    1986-01-01

    A 51-year-old woman had been exposed to a high concentration of trichloroethylene for about 12 years. She had been employed in a factory where metal screws and washers for automobiles were manufactured. She had been engaged in dipping baskets of the screws and washers into an open bath of trichloroethylene. She first experienced symptoms of dizziness and headaches after degreasing the screws and washers. She also experienced sleepiness and fatigability, as well as paresthesia in the feet, hands and around the mouth. The muscle strength and tendon reflexes of the extremities were weakened: coordination was slightly clumsy and slow; and her gait was lightly paretic. Air samples were analyzed by gas chromatography and concentrations in the breathing zone of the worker were very high (579 and 792 ppm). It can be concluded from this investigation that peripheral nerve impairment is one of the important signs in chronic trichloroethylene poisoning. 15 references, 2 figures, 1 table.

  2. Health risks following exposure to aerosols produced by the use of depleted uranium weapons

    International Nuclear Information System (INIS)

    It is shown that recent incontrovertible evidence defines the existence of a very large error in the presently accepted model for the health consequences of exposure to low-level man-made radioactivity, and that therefore this same model which underpins the presently accepted assessment of harm from Depleted Uranium, is likely to be similarly flawed. In addressing this issue, the question is asked if Scientific Method has been properly used in the historical assessment of risk from exposure to low-level radiation, and it is suggested that it has not. In order to explain how DU may be having a serious impact on health at what is conventionally seen as low dose, the cellular and molecular basis of radiation action must be examined. Two possible mechanisms which address the particular type of radiation exposure involved with Depleted Uranium are outlined, and it is argued that these types of exposure cannot be modelled by the system of assessment of risk used by ICRP and based on the external irradiation which occurred at Hiroshima. Some evidence which supports this new model is briefly reviewed and it is shown how it applies to the Depleted Uranium controversy. Recent evidence on the dispersion of battlefield DU and its consequences is also reviewed. The structure of the lecture is as follows: 1. Background; 2. Depleted uranium: properties; 3. Errors in the ICRP low level radiation risk model (The Chernobyl Infants, Minisatellite DNA in Chernobyl children); 4. Radiation risk and Scientific Method; 5. Mechanistic considerations (Averaging dose, Cellular responses to radiation: the Burlakova dose response, The Second Event Theory, Second Events from DU particles, Energy density and risk, Beta emissions from DU, Environmental mobility of the DU particles, Conclusions on mechanism); 6. Sea coast cancer risks and resuspended hot particles; and 7. Recent evidence on DU exposure risks and response by UK government (DU, leukemia, cancer and birth defects in Iraq, DU in

  3. The Toxicity of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Wayne Briner

    2010-01-01

    Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

  4. The effect of chronic exposure to fatty acids

    DEFF Research Database (Denmark)

    Xiao, J.; Gregersen, S.; Kruhøffer, Mogens;

    2001-01-01

    . In conclusion, chronic exposure to low palmitate alters insulin secretion as well as gene expression. The number of genes that changed expression was palmitate dose and exposure time dependent. Randle's fatty acid-glucose cycle seems to be operative on the gene transcription level. A modification of expression...... found that basal insulin secretion increased in cells exposed to palmitate. The response to glucose stimulation declined on d 44 in cells cultured at 200 microM palmitate. In response to 50 and 200 microM palmitate exposure, expression was changed in 11 and 99 genes on d 2 and 134 and in 159 genes on d...

  5. MEASUREMENTS OF RADON, THORON, ISOTOPIC URANIUM AND THORIUM TO DETERMINE OCCUPATIONAL & ENVIRONMENTAL EXPOSURE & RISK AT FERNALD FEED MATERIALS PRODUCTION CENTER.

    Science.gov (United States)

    The research at the Fernald Environmental Restoration Management Corporation (FERMCO) site will provide radionuclide data, and realistic risk evaluation for isotopic radon, thorium, uranium and lead exposure.We have developed and tested a passive radon monitor with proven accur...

  6. Canine neoplasia and exposure to uranium mill tailings in Mesa County, Colorado

    International Nuclear Information System (INIS)

    A canine cancer registry was established for Mesa County, Colorado in order to collect material for a case control analysis of exposure to uranium tailings. Between 1979 and 1981, 212 cases of canine cancer were confirmed histologically. Based on the address provided at the time of diagnosis, 33 dogs (15.6%) lived in a house with some exposure to uranium tailings. A control group, comprised of dogs with a histologic diagnosis other than cancer, was stratified according to hospital and matched with cases on a 1:1 basis. No significant differences were noted with respect to exposure to uranium tailings for total cancers or cancers of specific sites including lymph node, breast, liver, testicle and bone. The overall estimated relative risk was 0.70 (95% CI 0.04 to 1.16). Canine population estimates were derived for Mesa County in order to develop crude incidence rates for the major types and sites of cancer. Crude rates were compared with those published previously for Alameda County, California and Tulsa County, Oklahoma. Mesa County rates for total cancer incidence, connective tissue tumors and non melanoma skin cancer were higher than those reported for Alameda County. When compared with Tulsa County, Mesa County rates for total cancer, breast cancer, melanoma and mastocytoma were lower than expected while rates for osteosarcoma, hemangiosarcoma and fibrosarcoma significantly exceeded expected values

  7. In vivo measurements of lead-210 for assessing cumulative radon exposure in uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, R.A.; Laurer, G.R. [New York Univ. Inst. of Environmental Medicine, Tuxedo, NY (United States); Lambert, W.E.; Gilliland, F.D. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

    1995-12-01

    It has long been recognized that a major contributor to the uncertainty in risk analysis of lung cancer in uranium and other hard rock miners is the estimation of total radon progeny exposure of individual miners under study. These uncertainties arise from the fact that only a limited number of measurements of airborne {sup 222}Rn progeny concentrations were made in the mines during the times that the miners were being exposed, and that dosimeters capable of integrating the Rn progeny exposures of the miners did not exist. Historically, the cumulative exposures for individual uranium and other hard rock miners have been calculated by combining the employee`s work history, which may or may not have included time spent at different jobs within the mines and at different locations within the mines, with whatever periodic measurements of Rn and Rn progeny were available. The amount and quality of the measurement data varied enormously from mine to mine and from population to population. Because the quality of the exposure data collected during the period of active mining in the United STates cannot now be altered substantially, significant improvement in individual miner exposure estimates is only likely to be achieved if a new cumulative exposure metric is developed and implemented. The decay chain of Rn includes the production of {sup 210}Pb, which can accumulate in the skeleton in amounts proportional to the intake of Rn progeny. We hypothesize that the in vivo measurement of {sup 210}Pb in the skulls of miners will provide such a metric. In summary, the primary purpose of this pilot study to demonstrate the feasibility of measuring {sup 210}Pb in the heads of former uranium miners has been accomplished.

  8. Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

    Science.gov (United States)

    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. PMID:25643654

  9. Impact of a chronic ingestion of radionuclides on cholesterol metabolism in the rat: example of depleted uranium and cesium 137

    International Nuclear Information System (INIS)

    Depleted uranium (DU) and cesium-137 (137Cs) are radionuclides spread in the environment due to industrial activities, incidents or accidents. This pollution sets a risk of human exposure to low levels of radiations through contaminated foodstuff. The impact of a chronic ingestion of DU or 137Cs on cholesterol metabolism in the liver and the brain has been studied. Indeed, cholesterol is crucial in physiology, being a component of cell membranes and a precursor to numerous molecules (bile acids...). Disruption of its metabolism is associated to many pathologies such as atherosclerosis or Alzheimer disease. Rats daily ingested a low level of DU or 137Cs over 9 months. For each radionuclide, a reference model (rats contaminated since adulthood) and a more sensitive model (hypercholesterolemic or contaminated since fetal life) were studied. The effects mainly consist of changes in gene expression or enzymatic activity of various actors of cholesterol metabolism. DU mainly affects one catabolism enzyme in both models, as well as membrane transporters and regulation factors. 137Cs mainly affects the storage enzyme in both models as well as catabolism enzymes, apolipoproteins, and regulation factors. No change in the plasma profile or in the tissue concentration of cholesterol (hepatic/cerebral) is recorded, whatever the model and the radionuclide. Thus, a chronic internal contamination with DU or 137Cs induces molecular modifications in cholesterol metabolism in the rat, without affecting its homeostasis or the general health status in all of our experimental models. (author)

  10. Unexpected Lack of Deleterious Effects of Uranium on Physiological Systems following a Chronic Oral Intake in Adult Rat

    OpenAIRE

    2014-01-01

    Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L). B...

  11. Exposure pathways and biological receptors: baseline data for the canyon uranium mine, Coconino County, Arizona

    Science.gov (United States)

    Hinck, Jo E.; Linder, Greg L.; Darrah, Abigail J.; Drost, Charles A.; Duniway, Michael C.; Johnson, Matthew J.; Méndez-Harclerode, Francisca M.; Nowak, Erika M.; Valdez, Ernest W.; Van Riper, Charles; Wolff, S.W.

    2014-01-01

    Recent restrictions on uranium mining within the Grand Canyon watershed have drawn attention to scientific data gaps in evaluating the possible effects of ore extraction to human populations as well as wildlife communities in the area. Tissue contaminant concentrations, one of the most basic data requirements to determine exposure, are not available for biota from any historical or active uranium mines in the region. The Canyon Uranium Mine is under development, providing a unique opportunity to characterize concentrations of uranium and other trace elements, as well as radiation levels in biota, found in the vicinity of the mine before ore extraction begins. Our study objectives were to identify contaminants of potential concern and critical contaminant exposure pathways for ecological receptors; conduct biological surveys to understand the local food web and refine the list of target species (ecological receptors) for contaminant analysis; and collect target species for contaminant analysis prior to the initiation of active mining. Contaminants of potential concern were identified as arsenic, cadmium, chromium, copper, lead, mercury, nickel, selenium, thallium, uranium, and zinc for chemical toxicity and uranium and associated radionuclides for radiation. The conceptual exposure model identified ingestion, inhalation, absorption, and dietary transfer (bioaccumulation or bioconcentration) as critical contaminant exposure pathways. The biological survey of plants, invertebrates, amphibians, reptiles, birds, and small mammals is the first to document and provide ecological information on .200 species in and around the mine site; this study also provides critical baseline information about the local food web. Most of the species documented at the mine are common to ponderosa pine Pinus ponderosa and pinyon–juniper Pinus–Juniperus spp. forests in northern Arizona and are not considered to have special conservation status by state or federal agencies; exceptions

  12. Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Barillet, Sabrina, E-mail: sabrina.barillet@free.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Larno, Valerie, E-mail: valerie.larno@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Floriani, Magali, E-mail: magali.floriani@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Devaux, Alain, E-mail: alain.devaux@entpe.fr [INRA, EFPA Department, 54280, Champenoux and Environmental Science Laboratory, ENTPE, 69518 Vaulx en Velin cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France)

    2010-11-01

    Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

  13. Hepatotoxic potential of combined toluene-chronic ethanol exposure

    Energy Technology Data Exchange (ETDEWEB)

    Howell, S.R.; Christian, J.E.; Isom, G.E.

    1986-05-01

    The hepatoxic properties of concurrent chronic oral ethanol ingestion and acute toluene inhalation were evaluated. Male rats were maintained on ethanol-containing or control liquid diets for 29 days. Animals of each group were subjected to five 20-min exposures to 10 000 ppm toluene with 30 min of room air inhalation between exposures on days 22, 24, 26, and 28 of liquid diet feeding. Some of the ethanol-fed animals were withdrawn from ethanol 14 h before exposure. Ethanol-withdrawn animals displayed an increased sensitivity to the narcotic action of toluene. Animals were sacrificed and assays performed on day 29. Stress markers (plasma corticosterone, free fatty acid, and glucose) were not affected by treatments. A modest elevation in plasma aspartate amino-transferase occurred in non-withdrawn animals receiving both ethanol and toluene. Ethanol-toluene exposure increased both relative liver weight and liver triglycerides. Toluene antagonized the hypertriglyceridemia associated with chronic ethanol ingestion. This study indicates that combined ethanol and toluene exposure has minor potential to induce acute liver injury, but results in altered deposition of hepatic triglycerides.

  14. Assessment of gamma radiation exposure to drivers (contractual) engaged with transporting of uranium ore in uranium mines at Narwapahar Mines, India

    International Nuclear Information System (INIS)

    Due to radioactive nature of uranium ore and tailings sand, it is essential to assess the exposure of drivers and helpers, those are continuously engaged with transporting of it. The external exposure is due to gamma radiation, emitted by uranium progeny and its magnitude is therefore directly related to the ore grade. The major gamma emitters in the series are 214Pb and 214Bi. After uranium recovery in ore processing areas the waste generated in mill contains same magnitude of gamma emitters. Tailings sand is the waste generated from mill area, which is used for back filling in underground mine. This paper presents the results of estimation of external gamma radiation levels during transport and assesses the radiation dose to drivers and helpers

  15. Radiation exposure and attributable cancer risk in former miners of the WISMUT uranium mining company

    Energy Technology Data Exchange (ETDEWEB)

    Jacobi, W.

    1999-02-01

    Since 1990 about 5000 cases of lung cancer and nearly 1000 cases of extrapulmonary cancers among earlier workers in the WISMUT uranium facilities in East Germany have been submitted to the responsible German associations for the acknowledgement of occupational diseases and the compensation of workers. In the paper the general methods and models for the retrospective estimation of the radiation exposure of these workers and for the evaluation of the attributable cancer risk are shortly outlined. With respect to lung cancer among underground uranium miners the inhalation of the short-lived radon progenies is by far the most important exposure component. For the attributable risk of extrapulmonary cancers, however, in addition the inhalation of natural uranium included in ore dust particles has to be taken into account. The analysis indicates that under certain exposure conditions also leukemia, bone and liver cancer, as well as cancers in the oral cavity and larynx may be of some importance. (orig.) [Deutsch] Seit 1990 sind etwa 5000 Faelle von Lungenkrebs und nahezu 1000 Faelle von extrapulmonalen Krebserkrankungen bei frueheren WISMUT-Beschaeftigten bei den zustaendigen Berufsgenossenschaften zur Anerkennung als Berufskrankheit durch ionisierende Strahlen eingereicht worden. Im folgenden werden die in den vergangenen Jahren entwickelten Methoden und Modelle zur retrospektiven Einschaetzung der Strahlenexposition und zur Evaluierung des moeglichen Strahlenkrebsrisikos bei diesen Arbeitern kurz beschrieben. In Bezug auf Lungenkrebs bei Untertage-Bergarbeitern liefert die Inhalation der kurzlebigen Radon-Folgeprodukte den weitaus dominierenden Beitrag zur Dosis im Bronchialepithel. Bei extrapulmonalen Krebserkrankungen muss jedoch auch die Inhalation von natuerlichem Uran mit dem Erzstaub beruecksichtigt werden. Die Risikoanalyse zeigt, dass abgesehen von Lungenkrebs unter bestimmten Bedingungen auch Leukaemie, Knochen- und Leberkrebs, sowie Krebs im Bereich des Mund

  16. Increased oxidative stress following acute and chronic high altitude exposure.

    Science.gov (United States)

    Jefferson, J Ashley; Simoni, Jan; Escudero, Elizabeth; Hurtado, Maria-Elena; Swenson, Erik R; Wesson, Donald E; Schreiner, George F; Schoene, Robert B; Johnson, Richard J; Hurtado, Abdias

    2004-01-01

    The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.

  17. Unexpected Lack of Deleterious Effects of Uranium on Physiological Systems following a Chronic Oral Intake in Adult Rat

    Directory of Open Access Journals (Sweden)

    Isabelle Dublineau

    2014-01-01

    Full Text Available Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L. Blood biochemical and hematological indicators were measured and several different types of investigations (molecular, functional, and structural were conducted in organs (intestine, liver, kidneys, hematopoietic cells, and brain. The specific sensitivity of the organs to uranium was deduced from nondeleterious biological effects, with the following thresholds (in mg/L: 0.2 for brain, >2 for liver, >10 for kidneys, and >20 for intestine, indicating a NOAEL (No-Observed-Adverse-Effect Level threshold for uranium superior to 120 m g/L. Based on the chemical uranium toxicity, the tolerable daily intake calculation yields a guideline value for humans of 1350 μg/L. This value was higher than the WHO value of 30 μg/L, indicating that this WHO guideline for uranium content in drinking water is very protective and might be reconsidered.

  18. Laser Ablation-ICP MS of Hair Strands as a Means for Assessment of Internal Exposure to Uranium

    International Nuclear Information System (INIS)

    Assessment of internal exposure to uranium is generally carried out by analysis of urine samples, and correlating the result according to the ICRP bio-kinetic mode. Hair samples can also be used for a sensitive bio monitoring of environmental or occupational exposure. There are several advantages to analyze hair samples rather than urine. First, hair is an effective bio-concentrator for uranium and is a major excretion pathway. Second, hair samples are stable and the uranium content does not change over time. Third, hair does not require special storage and handling. And finally, hair has the unique ability to reflect the total body intake during an extended period and it is possible to trace changes over time. These features were recently demonstrated in a comprehensive joint study by groups from Finland and Israel, where hair samples were rinsed, digested and the uranium level determined by inductively coupled plasma - mass spectrometry (ICP MS). If an occupational exposure incident occurs, urine samples must be collected shortly after the incident and then several more samples need to be acquired until the uranium in urine concentration returns to its normal level. Hair samples can be collected several days, or even weeks, after the incident and the uranium content can be measured along a single strand to reflect the level before, during and after the incident in a single series of measurements with a laser-ablation ICP MS instrument

  19. Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

    Science.gov (United States)

    Bakhmutsky, Marina V; Squibb, Katherine; McDiarmid, Melissa; Oliver, Marc; Tucker, James D

    2013-10-01

    Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans. PMID:23933231

  20. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice

    OpenAIRE

    Yong ZHANG; Schlussman, Stefan D; Rabkin, Jacqui; Butelman, Eduardo R.; Ho, Ann; Kreek, Mary Jeanne

    2012-01-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-d...

  1. Biological characterization of radiation exposure and dose estimates for inhaled uranium milling effluents. Annual progress report, April 1981-March 1982

    International Nuclear Information System (INIS)

    The problems addressed are the protection of uranium will workers from occupational exposure to uranium through routine bioassay programs and the assessment of accidental worker exposures. Comparisons of chemical properties and the biological behavior of refined uranium ore (yellowcake) are made to identify important properties that influence uranium distribution patterns among organs. These studies will facilitate calculations of organ doses for specific exposures and associated health risk estimates and will identify important bioassay procedures to improve evaluations of human exposures. Sampling of airborne yellowcake at four uranium mills showed that aerosols were heterogeneous, changed with time and contained approx. 50% of the airborne uranium in particles greater than 12 μm aerodynamic diameter. Results are related to specific packaging steps and to predictions of appreciable upper respiratory tract deposition rates for the aerosols, if inhaled by a worker without respiratory protection. Previously used in vitro dissolution techniques were evaluated and the uses of the results for interpreting urinary bioassay data are described. Preliminary results from an inhalation experiment using rats indicate that the clearance patterns of inhaled uranium from lung agreed quantitatively with results from in vitro dissolution and infrared analyses of the yellowcake used. Preliminary results from an experiment to simulate contamination of a wound by yellowcake showed that more of the implanted dose of a less soluble form of yellowcake was retained at the wound site than of a more soluble form at 32 days after implantation. The results did not quantitatively agree with in vitro dissolution results. A two-year study of yellowcake from two mills was initiated. Twenty Beagle dogs were exposed by nose-only inhalation to a more soluble form of yellowcake and 20 to a less soluble form

  2. Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure.

    Science.gov (United States)

    Legrand, M; Elie, C; Stefani, J; N Florès; Culeux, C; Delissen, O; Ibanez, C; Lestaevel, P; Eriksson, P; Dinocourt, C

    2016-01-01

    The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40mg/L and 120mg/L and of GD18 fetuses exposed at 120mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network. PMID:26506049

  3. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: effects on striatal dopamine and opioid systems in C57BL/6J mice.

    Science.gov (United States)

    Zhang, Yong; Schlussman, Stefan D; Rabkin, Jacqui; Butelman, Eduardo R; Ho, Ann; Kreek, Mary Jeanne

    2013-04-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an "addiction-like cycle" in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal/13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal/14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection × 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In "re-exposure" groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states. PMID:23164614

  4. Ailing uranium millworkers seek recognition, aid

    International Nuclear Information System (INIS)

    Uranium millworkers who helped produce uranium for the U.S. nuclear defense program in the 1950's and 1960's are suing the federal government and uranium companies for compensation for illnesses that they believe are job-related. Symptoms of these illnesses include frequent blackouts, chronic bronchitis, asthma, constant fatigue, and susceptibility to colds. Research is being conducted to determine whether the millworkers' symptoms are due to excessive radiation exposure. Studies to date indicated that during the 1950's and early 1960's, radiation protection procedures at uranium milling facilities were extremely deficient

  5. Study of the biological effects of uranium exposure on zebra fish (D. rerio). Impact on life stages; Etude des effets biologiques de l'exposition a l'uranium chez le poisson zebre (D. rerio). Impact sur les stades de vie

    Energy Technology Data Exchange (ETDEWEB)

    Bourrachot, St.

    2009-05-15

    This work is part of an ongoing project (ENVIRHOM) started at IRSN in 2000, which consists in studying the environmental effects of radioactive substances at chronic low level of exposure. In this general frame, our aim was two fold: (i) to identify sensitivity of different critical life stages of zebra fish (fish of fresh water frequently used for tests standards in ecotoxicology) to uranium exposure and (ii) to evaluate underlying mechanisms. Experiments were conducted with eggs, larvae and genitors exposed to uranium at environmentally relevant concentrations (from 20 to 500 {mu}g/L) in order to study survival, hatching of eggs, growth of larvae and reproduction of genitors. Bio-markers of exposure (i.e. U bioaccumulation) and bio-markers of effects at molecular level (i.e. genotoxic effects, reproductive-toxicity) were also measured. Sensitivity of fish to uranium was dependent of the life stage of development with the early life stage being the most sensitive to U either directly or maternally exposed. It underlines the relevance of including pro-larval stages for toxicity assessments in fish. Moreover drastic effects of uranium on reproductive success and DNA damages in the germ cells foretell a strong impact on the population for low concentration of exposure (20 {mu}g/L). As it is increasingly recognized that population-level effects of toxic substances are more relevant in terms of ecological risk assessment, this study points out the need to include different life stages of organisms in eco-toxicological studies, especially the sensitive early stages. Moreover, it appears, through the comparative study of the radiological effects or by another isotope of the uranium of stronger radioactivity ({sup 233}U or by an irradiation with {sup 137}Cs), that the effects of the uranium are due to its chemo-toxicity. (author)

  6. Assessing potential risks from exposure to natural uranium in well water

    International Nuclear Information System (INIS)

    Over 50% of the wells in the Nambe region of northern New Mexico exceed the US Environmental Protection Agency's recommended drinking water standard of 20 μg l-1 for 238U; the highest in the area was measured at 1200 μg U l-1. Uranium uptake was estimated in tomato (Lycopersicon esculentum), squash (Cucurbita pepo), lettuce (Lactuca scarriola), and radish (Raphanus sativus) irrigated with Nambe well water containing -1. Plant uptake and human dose and toxicity associated with ingestion of water and produce and inhalation of irrigated soil related to gardening activities were evaluated. Uranium concentration in plants increased linearly with increasing U concentration in irrigation water, particularly in lettuce and radish. The estimated total committed effective dose for 70 years of maximum continuous exposure, via the three pathways to well water containing 1200 μg U l-1, was 0.17 mSv with a corresponding kidney concentration of 0.8 μg U g-1 kidney

  7. Assessing potential risks from exposure to natural uranium in well water

    Energy Technology Data Exchange (ETDEWEB)

    Hakonson-Hayes, A.C.; Fresquez, P.R. E-mail: fresquezp@lanl.gov; Whicker, F.W

    2002-07-01

    Over 50% of the wells in the Nambe region of northern New Mexico exceed the US Environmental Protection Agency's recommended drinking water standard of 20 {mu}g l{sup -1} for {sup 238}U; the highest in the area was measured at 1200 {mu}g U l{sup -1}. Uranium uptake was estimated in tomato (Lycopersicon esculentum), squash (Cucurbita pepo), lettuce (Lactuca scarriola), and radish (Raphanus sativus) irrigated with Nambe well water containing <1, 150, 500, and 1200 {mu}g U l{sup -1}. Plant uptake and human dose and toxicity associated with ingestion of water and produce and inhalation of irrigated soil related to gardening activities were evaluated. Uranium concentration in plants increased linearly with increasing U concentration in irrigation water, particularly in lettuce and radish. The estimated total committed effective dose for 70 years of maximum continuous exposure, via the three pathways to well water containing 1200 {mu}g U l{sup -1}, was 0.17 mSv with a corresponding kidney concentration of 0.8 {mu}g U g{sup -1} kidney.

  8. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Oluwabusayo Folarin

    2016-01-01

    Full Text Available 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.

  9. Uranium mining sites - Thematic sheets

    International Nuclear Information System (INIS)

    A first sheet proposes comments, data and key numbers about uranium extraction in France: general overview of uranium mining sites, status of waste rock and tailings after exploitation, site rehabilitation. The second sheet addresses the sources of exposure to ionizing radiations due to ancient uranium mining sites: discussion on the identification of these sources associated with these sites, properly due to mining activities or to tailings, or due to the transfer of radioactive substances towards water and to the contamination of sediments, description of the practice and assessment of radiological control of mining sites. A third sheet addresses the radiological exposure of public to waste rocks, and the dose assessment according to exposure scenarios: main exposure ways to be considered, studied exposure scenarios (passage on backfilled path and grounds, stay in buildings built on waste rocks, keeping mineralogical samples at home). The fourth sheet addresses research programmes of the IRSN on uranium and radon: epidemiological studies (performed on mine workers; on French and on European cohorts, French and European studies on the risk of lung cancer associated with radon in housing), study of the biological effects of chronic exposures. The last sheet addresses studies and expertises performed by the IRSN on ancient uranium mining sites in France: studies commissioned by public authorities, radioactivity control studies performed by the IRSN about mining sites, participation of the IRSN to actions to promote openness to civil society

  10. Miners' exposure to radon and its decay products in some Iranian non-uranium underground mines

    International Nuclear Information System (INIS)

    Measurements of radon, radon decay products and gamma exposure rate in 12 non-uranium underground mines have been carried out in order to estimate the occupational radiation exposure of miners. Continuous measurements of radon using pulse ionisation chambers and scintillation cell techniques were employed for these studies. Progenies of radon were collected on filter paper, and then a three-count procedure was used for the measurement. The equilibrium state between radon and its decay products has been determined. Concentrations of natural radionuclides (226Ra, 232Th and 40K) in ore and soil samples taken from various locations in each mine have been measured using a Canberra High Purity Germanium detector. Based on these measurements two ranges of dose were evident. Doses ranged from 0.1 to 1.52 mSv y-1 for nine mines and from 10 to 31 mSv y-1 for the other three mines. A separate grouping of the mines was recognised from radon concentrations, which varied from 2 Bq m-3 to 10 kBq m-3. In three of these mines, working level (WL) concentrations of the order of 36-1771 mWL were determined in different working areas. In all other mines, the concentrations were observed to be <45 mWL. (authors)

  11. Renal effects of uranium in drinking water.

    OpenAIRE

    Kurttio, Päivi; Auvinen, Anssi; Salonen, Laina; Saha, Heikki; Pekkanen, Juha; Mäkeläinen, Ilona; Väisänen, Sari B; Penttilä, Ilkka M; Komulainen, Hannu

    2002-01-01

    Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The media...

  12. In vivo effects of a chronic contamination by uranium or cesium 137 on the pharmaceutical metabolism, of the vitamin D and cholesterol; Effets in vivo d'une contamination chronique par l'uranium ou le cesium 137 sur le metabolisme du medicament, de la vitamine D et du cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Souidi, M

    2006-11-15

    In conclusion, an animal model, miming the chronic contamination of the populations exposed to the uranium, was used for the first time to show that the chronic ingestion of a weak dose of depleted uranium can affect the level of active vitamin D without modifying the mineral homeostasis. This study shows that this radionuclide can lead molecular modifications of the CYPs and the nuclear receivers involved in the metabolism of the vitamin D not only at the level of the liver and kidney but also at the level of the independent metabolism in the brain. The deficiency in vitamin D can provoke osseous diseases such as the rickets at the child and the osteomalacia at the adult. The three categories of population the most exposed to this deficiency are the infants, the pregnant women and the old persons. Strong prevalence of the vitamin D deficiency associated with a chronic exposure to uranium could lead to osseous disorders. To verify this hypothesis, it will be necessary secondly to realize this study on individuals animal models predisposed to the rickets or to the osteomalacia. (N.C.)

  13. Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure.

    Science.gov (United States)

    Buczynski, Matthew W; Herman, Melissa A; Hsu, Ku-Lung; Natividad, Luis A; Irimia, Cristina; Polis, Ilham Y; Pugh, Holly; Chang, Jae Won; Niphakis, Micah J; Cravatt, Benjamin F; Roberto, Marisa; Parsons, Loren H

    2016-01-26

    Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE.

  14. Chronic obstructive pulmonary disease (COPD and occupational exposures

    Directory of Open Access Journals (Sweden)

    Zeni Elena

    2006-06-01

    Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is one of the leading causes of morbidity and mortality in both industrialized and developing countries. Cigarette smoking is the major risk factor for COPD. However, relevant information from the literature published within the last years, either on general population samples or on workplaces, indicate that about 15% of all cases of COPD is work-related. Specific settings and agents are quoted which have been indicated or confirmed as linked to COPD. Coal miners, hard-rock miners, tunnel workers, concrete-manufacturing workers, nonmining industrial workers have been shown to be at highest risk for developing COPD. Further evidence that occupational agents are capable of inducing COPD comes from experimental studies, particularly in animal models. In conclusion, occupational exposure to dusts, chemicals, gases should be considered an established, or supported by good evidence, risk factor for developing COPD. The implications of this substantial occupational contribution to COPD must be considered in research planning, in public policy decision-making, and in clinical practice.

  15. Assessment of the solubility of thorium and uranium from black sand of Camargue in both simulated lung and gut fluids for dose calculation after internal exposure

    Energy Technology Data Exchange (ETDEWEB)

    Frelon, S.; Chazel, V.; Tourlonias, E.; Paquet, F. [IRSN/ DRPH/ SRBE, LRTOX, BP 166, 26702 Pierrelatte Cedex (France); Blanchardon, E. [IRSN/ DRPH/ SDI, LEDI, BP 17, 92262 Fontenay Aux Roses Cedex (France); Bouisset, P. [IRSN/ DEI/ STEME, LMRE, Bois des rames, 91400 Orsay (France); Pourcelot, L. [IRSN/ DEI/ SESURE, LERCM, BP3, 13 115 St Paul lez Durance Cedex (France)

    2006-07-01

    In the south of France, some beaches of Camargue present a high rate of natural radioactivity due to thorium and uranium from zircon and apatite heavy minerals present in the so-called black sand. These radionuclides may lead to internal exposure consecutive to inhalation or ingestion of this sand. The accurate assessment of radiological risk after internal exposure of public frequenting these beaches requires some information on the human bioavailability of U and Th from the sand. Both routes of intake were studied in this work and the consecutive dose delivered was calculated under two different scenarios for each type of exposure. As far as inhalation is concerned, the first important conclusion is that the inhalable fraction, i.e. particles with aerodynamic diameters below 50 {mu}m, was tiny (0.002%) in this sample of sand. Moreover in vitro assays of solubility were performed for this fraction and showed that U and Th as well as their progeny presented moderate solubility. Then effective doses under several scenarios were calculated and seem to demonstrate a very poor risk of exposure after inhalation. Indeed, a dose of 1 mSv would be received by a babies after inhalation of about 40 Kg of sand, that is impossible, whereas a more realistic scenario of chronic exposure only reached 31 {mu} Sv. In case of ingestion, the solubility of Th and U in the gastrointestinal fluids was found to be very low with a maximum solubility of 0.5% of the initial mass of radioelement in the sample of sand. Then the worst hypothesis studied yields an effective dose of 0.018 mSv./(g-swallowed sand) that is roughly 50 times less than the legal annual dose limit for members of the public. as a conclusion, the possible internal dose after exposure by inhalation or ingestion of black sand of Camargue seems to be very low under the conditions of this study. (N.C.)

  16. Late health effects of chronic radiation exposure of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

    2014-07-01

    infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  17. Assessment of exposure of uranium miners to radon progeny using in vivo measurement of {sup 210}Pb in bone

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, R.A.; Snipes, M.B.; Hoover, M.D. [Lovelace Respiratory Research Institute, Albuquerque (United States); Leggett, R.W. [Oak Ridge National Laboratory, Oak Ridge (United States); Laurer, G.R. [New York University Institute of Environmental Medicine, Tuxedo (United States); Lambert, W.E.; Coons, T.A. [University of New Mexico School of Medicine, Epidemiology and Cancer Control, Albuquerque (United States); Gilliland, F.D. [University of Southern California, Occupational and Environmental Health, Los Angeles (United States)

    2000-05-01

    Epidemiological studies of lung cancer incidence among uranium miners from various populations around the world have shown a significant variability in the relative risk per unit exposure - a range of a factor of 30. A significant fraction of the uncertainty associated with these risk coefficients may be due to differences in the methods and quality of data used in calculating cumulative exposures, in Working Level Months (WLM), for the various miner populations. We hypothesize that in vivo measurement of {sup 210}Pb, a long-lived radon decay product, retained in bone will provide a better measure of the exposure of individual miners to radon and progeny during their mining careers. To accomplish these in vivo measurements, the Lovelace Respiratory Research Institute (LRRI) In Vivo Bioassay Facility (IVBF) was modified to optimize a counting geometry for measuring {sup 210}Pb in the skull. Six phoswich detectors (12.7 cm diameter) were positioned about the head of a reclining subject (one posterior, one anterior, and four on the sides of the head), and photon emission from the skull was measured using anticoincidence multichannel analysis electronics. To date, we have analyzed the in vivo measurement data from about 90 former uranium miners from the Grants, New Mexico (NM), mining district. The recorded WLM exposures for each uranium miner (data from the UNM epidemiological data base) were compared with a WLM exposure calculated using a Pb biokinetic model coupled to the ICRP Publication 66 respiratory tract dosimetry model. The analyses show that the independent measures of exposure are statistically correlated but vary greatly among individual values. (author)

  18. Assessment of exposure of uranium miners to radon progeny using in vivo measurement of 210Pb in bone

    International Nuclear Information System (INIS)

    Epidemiological studies of lung cancer incidence among uranium miners from various populations around the world have shown a significant variability in the relative risk per unit exposure - a range of a factor of 30. A significant fraction of the uncertainty associated with these risk coefficients may be due to differences in the methods and quality of data used in calculating cumulative exposures, in Working Level Months (WLM), for the various miner populations. We hypothesize that in vivo measurement of 210Pb, a long-lived radon decay product, retained in bone will provide a better measure of the exposure of individual miners to radon and progeny during their mining careers. To accomplish these in vivo measurements, the Lovelace Respiratory Research Institute (LRRI) In Vivo Bioassay Facility (IVBF) was modified to optimize a counting geometry for measuring 210Pb in the skull. Six phoswich detectors (12.7 cm diameter) were positioned about the head of a reclining subject (one posterior, one anterior, and four on the sides of the head), and photon emission from the skull was measured using anticoincidence multichannel analysis electronics. To date, we have analyzed the in vivo measurement data from about 90 former uranium miners from the Grants, New Mexico (NM), mining district. The recorded WLM exposures for each uranium miner (data from the UNM epidemiological data base) were compared with a WLM exposure calculated using a Pb biokinetic model coupled to the ICRP Publication 66 respiratory tract dosimetry model. The analyses show that the independent measures of exposure are statistically correlated but vary greatly among individual values. (author)

  19. Temperature modulates phototrophic periphyton response to chronic copper exposure.

    Science.gov (United States)

    Lambert, Anne Sophie; Dabrin, Aymeric; Morin, Soizic; Gahou, Josiane; Foulquier, Arnaud; Coquery, Marina; Pesce, Stéphane

    2016-01-01

    Streams located in vineyard areas are highly prone to metal pollution. In a context of global change, aquatic systems are generally subjected to multi-stress conditions due to multiple chemical and/or physical pressures. Among various environmental factors that modulate the ecological effects of toxicants, special attention should be paid to climate change, which is driving an increase in extreme climate events such as sharp temperature rises. In lotic ecosystems, periphyton ensures key ecological functions such as primary production and nutrient cycling. However, although the effects of metals on microbial communities are relatively well known, there is scant data on possible interactions between temperature increase and metal pollution. Here we led a study to evaluate the influence of temperature on the response of phototrophic periphyton to copper (Cu) exposure. Winter communities, collected in a 8 °C river water, were subjected for six weeks to four thermal conditions in microcosms in presence or not of Cu (nominal concentration of 15 μg L(-1)). At the initial river temperature (8 °C), our results confirmed the chronic impact of Cu on periphyton, both in terms of structure (biomass, distribution of algal groups, diatomic composition) and function (photosynthetic efficiency). At higher temperatures (13, 18 and 23 °C), Cu effects were modulated. Indeed, temperature increase reduced Cu effects on algal biomass, algal class proportions, diatom assemblage composition and photosynthetic efficiency. This reduction of Cu effects on periphyton may be related to lower bioaccumulation of Cu and/or to selection of more Cu-tolerant species at higher temperatures. PMID:26608872

  20. Temperature modulates phototrophic periphyton response to chronic copper exposure.

    Science.gov (United States)

    Lambert, Anne Sophie; Dabrin, Aymeric; Morin, Soizic; Gahou, Josiane; Foulquier, Arnaud; Coquery, Marina; Pesce, Stéphane

    2016-01-01

    Streams located in vineyard areas are highly prone to metal pollution. In a context of global change, aquatic systems are generally subjected to multi-stress conditions due to multiple chemical and/or physical pressures. Among various environmental factors that modulate the ecological effects of toxicants, special attention should be paid to climate change, which is driving an increase in extreme climate events such as sharp temperature rises. In lotic ecosystems, periphyton ensures key ecological functions such as primary production and nutrient cycling. However, although the effects of metals on microbial communities are relatively well known, there is scant data on possible interactions between temperature increase and metal pollution. Here we led a study to evaluate the influence of temperature on the response of phototrophic periphyton to copper (Cu) exposure. Winter communities, collected in a 8 °C river water, were subjected for six weeks to four thermal conditions in microcosms in presence or not of Cu (nominal concentration of 15 μg L(-1)). At the initial river temperature (8 °C), our results confirmed the chronic impact of Cu on periphyton, both in terms of structure (biomass, distribution of algal groups, diatomic composition) and function (photosynthetic efficiency). At higher temperatures (13, 18 and 23 °C), Cu effects were modulated. Indeed, temperature increase reduced Cu effects on algal biomass, algal class proportions, diatom assemblage composition and photosynthetic efficiency. This reduction of Cu effects on periphyton may be related to lower bioaccumulation of Cu and/or to selection of more Cu-tolerant species at higher temperatures.

  1. Depleted uranium: Metabolic disruptor?

    International Nuclear Information System (INIS)

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  2. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreased lung elastance

    OpenAIRE

    Hartney, John M.; Chu, HongWei; Pelanda, Roberta; Torres, Raul M.

    2012-01-01

    Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks) exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmo...

  3. Chronic cadmium exposure stimulates SDF-1 expression in an ERα dependent manner.

    Directory of Open Access Journals (Sweden)

    Esmeralda Ponce

    Full Text Available Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line chronically exposed to 10(-7 M CdCl2 serves as our model system. Data suggest that prolonged cadmium exposures result in the development of more aggressive cancer phenotypes - increased cell growth, migration and invasion. The results from this study show for the first time that chronic cadmium exposure stimulates the expression of SDF-1 by altering the molecular interactions between ERα, c-jun and c-fos. This study provides a mechanistic link between chronic cadmium exposure and ERα and demonstrates that prolonged, low-level cadmium exposure contributes to breast cancer progression.

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

    Science.gov (United States)

    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 ...

  5. The Impact of Chronic Pesticide Exposure on Neuropsychological Functioning

    Science.gov (United States)

    Schultz, Caitlin G.; Ferraro, F. Richard

    2013-01-01

    This study compared neuropsychological test performance of individuals (n = 18) with an occupational history of pesticide exposure to individuals (n = 35) with no such exposure history. Results showed that a history of pesticide-related occupation exposure led to deficits in only Digit Symbol performance. Additionally, the correlation between…

  6. Consideration of measurement errors in the analysis of the risk related to the exposure to ionising radiation in an occupational cohort: application to the French cohort of uranium miners

    International Nuclear Information System (INIS)

    In epidemiological studies, measurement errors in exposure can substantially bias the estimation of the risk associated to exposure. A broad variety of methods for measurement error correction has been developed, but they have been rarely applied in practice, probably because their ability to correct measurement error effects and their implementation are poorly understood. Another important reason is that many of the proposed correction methods require to know measurement errors characteristics (size, nature, structure and distribution). The aim of this thesis is to take into account measurement error in the analysis of risk of lung cancer death associated to radon exposure based on the French cohort of uranium miners. The mains stages were (1) to assess the characteristics (size, nature, structure and distribution) of measurement error in the French uranium miners cohort, (2) to investigate the impact of measurement error in radon exposure on the estimated excess relative risk (ERR) of lung cancer death associated to radon exposure, and (3) to compare the performance of methods for correction of these measurement error effects. The French cohort of uranium miners includes more than 5000 miners chronically exposed to radon with a follow-up duration of 30 years. Measurement errors have been characterized taking into account the evolution of uranium extraction methods and of radiation protection measures over time. A simulation study based on the French cohort of uranium miners has been carried out to investigate the effects of these measurement errors on the estimated ERR and to assess the performance of different methods for correcting these effects. Measurement error associated to radon exposure decreased over time, from more than 45% in the early 70's to about 10% in the late 80's. Its nature also changed over time from mostly Berkson to classical type from 1983. Simulation results showed that measurement error leads to an attenuation of the ERR towards the null

  7. Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

    OpenAIRE

    Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A.; Kash, Thomas L.

    2014-01-01

    Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased a...

  8. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro

    OpenAIRE

    Scherzad, Agmal; HACKENBERG, STEPHAN; FROELICH, KATRIN; RAK, KRISTEN; HAGEN, RUDOLF; TAEGER, JOHANNES; BREGENZER, MAXIMILLIAN; KLEINSASSER, NORBERT

    2016-01-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induc...

  9. Further studies of long-term ecological effects of exposure to uranium

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.C.; Miera, F.R. Jr.

    1978-07-01

    Spatial variability in sampling for soil uranium distribution by a polar coordinate system was evaluated in randomly selected soil cores at the Los Alamos Scientific Laboratory. Variations for surface (0- to 2.5-cm-deep) soils were 0.18 at 10 m from the nuclear weapons test detonation point and 0.96 at 50 m. Results were strongly influenced by past uranium dispersal patterns, variable leaching of uranium debris, and surface water runoff. A total surface (0- to 5-cm) soil uranium inventory within a 12.6-ha circle centered on the E-F detonation point was estimated to be 3000 kg when calculated by soil uranium concentration isopleths and 4500 kg when using annuli of a polar coordinate sampling system. Uranium concentrations in tissues of deer mice (Peromyscus maniculatus) and pocket gophers (Thomomys bottae) were sufficiently different to conclude that the greater bioavailability of uranium in the top few millimeters of soil at E-F Site, combined with the difference in grooming and food habits of the animals, resulted in greater contamination of deer mice than of pocket gophers.

  10. Continued studies of long-term ecological effects of exposure to uranium

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.C.; Miera, F.R. Jr.

    1977-06-01

    Studies of the long-term consequences of exposing terrestrial ecosystems to natural and depleted uranium dispersed during explosives tests at Los Alamos Scientific Laboratory (LASL) and test firing at Eglin Air Force Base (EAFB), Florida, were continued. Soils from EAFB, sampled before and after firing of depleted uranium penetrators against armor plate targets, indicated that the upper (0- to 5-cm-deep) soil usually contained more uranium than lower (5- to 10-cm-deep) soil. However, no significant changes were apparent in samples taken before and after the test firing. E-F explosive testing site at LASL was selected for intensive study of uranium redistribution during its 33-yr use. Highest surface soil (0- to 2.5-cm-deep) uranium concentrations occurred 0 and 10 m from the detonation point and averaged 4500 ppM. Concentrations in surface soil 50 and 200 m from the firing point were usually < 15% of that value. The uranium distribution to 30-cm depths showed significant penetration into the soil. Alluvium collected 250 m from the E-F detonation area in Potrillo Canyon indicated that surface (0- to 2.5-cm-deep) uranium concentrations were about 10% of those at the detonation point, and at 2.8 km they were twice background levels.

  11. Occupational diseases in uranium and ore miners related to radiation exposure in the Czech Republic in 2002 - 2007

    International Nuclear Information System (INIS)

    Dozens cases of disease of former or present uranium and ore miners are submitted to judgment as occupational diseases every year in the Czech Republic. Patients or attending physicians suggest that these cases are caused by occupational ionizing radiation. Only a part of these cases is qualified as occupational disease, nevertheless they can cause many juridical problems. The term 'occupational disease' is rather juridical term which underlies the right to financial compensation. The causal association with exposure to ionizing radiation cannot be indisputably verified by expert medical opinion. Most diseases in uranium and ore miners, which are proposed as occupational disease, are malignant tumors. The majority of judged cases are lung cancers from radioactive agents. The poster gives general information about all judged cases of occupational diseases in former uranium and ore miners in the Czech Republic in the years 2002-2007. It also provides short information about standards of professional radiation exposure assessment valid in the other countries. Most frequent diseases were lung cancers. Nevertheless the rate of lung cancers acknowledged as occupational disease decreases during the last two decades. Non-melanoma skin cancers are on the second place. The rate of skin cancers increases. We can explain this fact by better diagnostics and by new method which allows more precious assessment of the skin dose. The method is used since 2005. Leukemias are on the third place (1-2 cases in the year). (authors)

  12. Occupational diseases in uranium and ore miners related to radiation exposure in the Czech Republic in 2002 - 2007

    International Nuclear Information System (INIS)

    Dozens cases of disease of former or present uranium and ore miners are submitted to judgment as occupational diseases every year in the Czech Republic. Patients or attending physicians suggest that these cases are caused by occupational ionizing radiation. Only a part of these cases is qualified as occupational disease, nevertheless they can cause many juridical problems. The term 'occupational disease' is rather juridical term which underlies the right to financial compensation. The causal association with exposure to ionizing radiation cannot be indisputably verified by expert medical opinion. Most diseases in uranium and ore miners, which are proposed as occupational disease, are malignant tumors. The majority of judged cases are lung cancers from radioactive agents. The poster gives general information about all judged cases of occupational diseases in former uranium and ore miners in the Czech Republic in the years 2002 -2007. It also provides short information about standards of professional radiation exposure assessment valid in the other countries. Most frequent diseases were lung cancers. Nevertheless the rate of lung cancers acknowledged as occupational disease decreases during the last two decades. Non-melanoma skin cancers are on the second place. The rate of skin cancers increases. We can explain this fact by better diagnostics and by new method which allows more precious assessment of the skin dose. The method is used since 2005. Leukemias are on the third place (1-2 cases in the year). (authors)

  13. Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

    OpenAIRE

    Ahn, Joong Hyun; Kim, Chi Hong; Kim, Yong Hyun; Kim, Seung Joon; Lee, Sook-Young; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak; Kwon, Soon Seog

    2007-01-01

    Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twen...

  14. Effect of Chronic Exposure to Acidic Environment on Radiosensitivity of Gliosarcoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sora; Kim, Eunhee [Seoul National Univ., Seoul (Korea, Republic of)

    2014-05-15

    In this study, the chronic exposure of cells to acid culture medium, prior or posterior to irradiation, has been investigated for its effect on clonogenic cell survival. Unconventional high-dose radiation therapy, such as SRS, SBRT and MRT, may cause severe vascular damage in tumors, thereby a number of tumor cells facing chronic hypoxia and thus acidosis. According to our observation, gliosarcoma cells become more vulnerable to radiation damage by chronic exposure to acidic condition before irradiation. The longer the preirradiation exposure is, the more vulnerable to radiation damage the cells become. However, the repair of PLD by post-irradiation exposure to acid medium is efficient enough to eliminate the difference in number of the cells carrying PLDs due to different durations of preirradiation exposure to acidic condition.

  15. A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

    Science.gov (United States)

    Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

    2012-01-01

    The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

  16. A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Kathi A Lefebvre

    Full Text Available The neurotoxic amino acid, domoic acid (DA, is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

  17. Development of risk maps to minimize uranium exposures in the Navajo Churchrock mining district

    Directory of Open Access Journals (Sweden)

    Rock Tommy

    2009-07-01

    Full Text Available Abstract Background Decades of improper disposal of uranium-mining wastes on the Navajo Nation has resulted in adverse human and ecological health impacts as well as socio-cultural problems. As the Navajo people become increasingly aware of the contamination problems, there is a need to develop a risk-communication strategy to properly inform tribal members of the extent and severity of the health risks. To be most effective, this strategy needs to blend accepted risk-communication techniques with Navajo perspectives such that the strategy can be used at the community level to inform culturally- and toxicologically-relevant decisions about land and water use as well as mine-waste remediation. Objective The objective of this study was to develop GIS-based thematic maps as communication tools to clearly identify high risk exposure areas and offer alternatives to minimize public and ecological health impacts. Methods Thematic maps were produced that incorporated data derived from environmental sampling and public health surveys. The maps show the location and quality of unregulated water resources and identify regulated water sources that could be used as alternatives. In addition, the maps show the location of contaminated soil and sediment areas in which disturbance of surface deposits should be avoided. Preliminary feedback was collected from an informal Navajo working group to assess the clarity and efficacy of this proposed communication method. Results The working group found the maps to be both clear and effective, and made suggestions for improvements, such as the addition of more map features. The working group predicted that once the maps are presented to the public, water hauling and soil use behaviors will change, and dialogue with chapter officials will be initiated to accelerate further risk reduction efforts. Implications Because risk communication is complicated by language barriers, lack of infrastructure, and historical mistrust

  18. Uptake of uranium in Atlantic salmon gills following exposure experiments demonstrated by SR-XRF tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lind, O.C.; Cagno, S.; Brit Salbu, H.C.T. [Centre of Excellence in Environmental Radioactivity - CERAD, Norwegian University of Life Sciences - UMB (Norway); Vanmeert, F.; Nuyts, G.; Janssens, K. [University of Antwerp (Belgium); Alfeld, M.; Falkenberg, G. [Deutsches Elektronen-Synchrotron - DESY (Germany)

    2014-07-01

    Uranium is a naturally occurring radionuclide as well as a heavy metal that can be found in elevated concentrations (mg/L) in the aquatic environment and therefore may pose a risk to aquatic organisms including fish. The major challenges in monitoring the fate of U in complex media, such as soils, sediments and water are to identify mobile and bioavailable U species, interactions with environmental components, transfer to organisms via sorption to surfaces and across membranes, and the internal distribution of target organs. As part of a larger study, U accumulation in gills and internal organs (e.g. liver) as well as mortality of Atlantic Salmon (Salmo salar) were studied as a function of U concentration as well as pH of the exposure water. As Atlantic salmon does not ingest freshwater, the major pathway for uptake of U in the liver is hypothesized to be by transfer across the gills. However, to our best knowledge, active uptake of U within gill filaments has never been proven. In the present work, we demonstrate that following 96 hours exposure of 6 mg U/l in freshwater at pH 7 and 1 mg U/l at pH 5, U was actively taken up in the Atlantic Salmon gill filaments. The internal distribution of U within exposed organisms was visualized using μXRF/μXRD two-dimensional scanning and XRF/XRD tomography at the microprobe end-station of the PETRA III P06 beamline. The recently developed and highly efficient Maia detector array was successfully employed to record extended high-resolution element-specific maps of the tissue samples. First, conventional 2D μXRF/μXRD mapping allowed to identify the axial planes in the samples actually containing U. On the same samples, higher resolution virtual cross-sections were obtained (18 keV, 0.6 μm beam size) by means of μXRF/μXRD tomography of the planes in which U was encountered. The results proved that U not only adheres to the external boundary of the fish gills, but it is also taken up via gills. The results of this work

  19. Biological Monitoring for Depleted Uranium Exposure in U.S. Veterans

    OpenAIRE

    Dorsey, Carrie D.; Engelhardt, Susan M.; Squibb, Katherine S.; McDiarmid, Melissa A.

    2009-01-01

    Background As part of an ongoing medical surveillance program for U.S. veterans exposed to depleted uranium (DU), biological monitoring of urine uranium (U) concentrations is offered to any veteran of the Gulf War and those serving in more recent conflicts (post-Gulf War veterans). Objectives Since a previous report of surveillance findings in 2004, an improved methodology for determination of the isotopic ratio of U in urine (235U:238U) has been developed and allows for more definitive evalu...

  20. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M;

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

  1. Influence of radon-daughter exposure rate and uranium ore dust concentration on occurrence of lung tumors

    International Nuclear Information System (INIS)

    Groups of male SPF Wistar rats were exposed concurrently to several levels of radon daughters and uranium ore dust to study the effect of these variables on pulmonary disease states. Clinical pathology data at 1 yr postexposure indicate no significant differences among exposed animals when compared with controls. Preliminary histopathologic data suggest a trend toward increasing lung tumor risk as the exposure rate is decreased (constant total dose), but the differences are not statistically significant at the 0.05 level. A similar trend occurs with decrease in ore dust concentration (except for the 2560-WLM exposure group), but these differences are also not significant at the 0.05 level. The tumor risk is significantly (0.05 level) increased as the exposure level increases from approximately 320 and 640 WLM to 2560 WLM at the high ore dust concentration

  2. Oral Methylphenidate Alleviates the Fine Motor Dysfunction Caused by Chronic Postnatal Manganese Exposure in Adult Rats

    OpenAIRE

    Beaudin, Stéphane A.; Strupp, Barbara J.; Lasley, Stephen M.; Fornal, Casimir A.; Mandal, Shyamali; Smith, Donald R

    2015-01-01

    Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. R...

  3. Response to 'Comments upon human exposure to depleted uranium during and after the Gulf and Balkans conflicts'

    International Nuclear Information System (INIS)

    Dear Sir, Eric Hamilton takes the Royal Society and myself to task for investigating the health hazards of depleted uranium munitions. In his view the matter appears to be clear. Exposures to uranium have been studied extensively for decades in the nuclear industry and there is little evidence of adverse health consequences. Exposures to DU on the battlefield are therefore unlikely to have health consequences and setting up an independent working group to look at the scientific issues only suggests there are doubts about the science, and leads to mistrust and confusion in the minds of the public. This type of robust approach to addressing the risks of exposure to radioactive materials, and of attempting to assuage the concerns of veterans exposed to DU during the Gulf War, may have worked in the past but it doesn't work today. The Royal Society is accused of having failed to address the main issue, which Hamilton considers to be the failure to implement well established and validated monitoring procedures at the time DU weapons were deployed, so that intakes and risks could have been calculated. This is a curious perspective as, from the outset, the remit of the Royal Society working group was to provide an independent view of the science, rather than the deficiencies in procedures, in response to public concerns and to the very different pronouncements about the dangers to health and the environment arising from the deployment of over 300 tonnes of DU munitions in the Gulf War. Some of the comments in the Royal Society reports and the editorial are considered to be questionable or not acceptable. It is not clear which particular aspects cause offence. One aspect appears to be the claim that DU measurements are difficult, where Hamilton appears to misunderstand the nature of the problem of quantifying exposures to DU. Of course uranium concentrations and isotope ratios are routinely measured in the nuclear industry and in geochemical laboratories, but the problem

  4. Professional exposure: a cohort study among the French nuclear industry service contractors. New-Mexico: workers employed in uranium extraction

    International Nuclear Information System (INIS)

    Two short articles on workers' exposure. First, this document briefly reports and comments the results of a retrospective cohort study performed on service providers intervening in the French nuclear industry. It comments the identification of workers, and briefly comments the results of statistical analysis of mortality due to different forms of cancer. It also outlines the problem of dosimetric data acquisition. The second part presents and comments a similar study concerning workers exposed to uranium bore dust in New-Mexico between 1955 and 1990

  5. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreases lung elastance

    Directory of Open Access Journals (Sweden)

    John M. Hartney

    2012-07-01

    Full Text Available Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6 mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1–/– that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction.

  6. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia.

    Science.gov (United States)

    Radivoyevitch, Tomas; Sachs, Rainer K; Gale, Robert Peter; Smith, Mitchell R; Hill, Brian T

    2016-04-01

    Exposure to ionizing radiation is not thought to cause chronic lymphocytic leukemia (CLL). Challenging this notion are recent data suggesting CLL incidence may be increased by radiation exposure from the atomic bombs (after many decades), uranium mining and nuclear power facility accidents. To assess the effects of therapeutic ionizing radiation for the treatment of solid neoplasms we studied CLL risks in data from the Surveillance, Epidemiology, and End Results (SEER) Program. Specifically, we compared the risks of developing CLL in persons with a 1(st) non-hematologic cancer treated with or without ionizing radiation. We controlled for early detection effects on CLL risk induced by surveillance after 1(st) cancer diagnoses by forming all-time cumulative CLL relative risks (RR). We estimate such CLL RR to be 1.20 (95% confidence interval, 1.17, 1.23) for persons whose 1(st) cancer was not treated with ionizing radiation and 1.00 (0.96, 1.05) for persons whose 1(st) cancer was treated with ionizing radiations. These results imply that diagnosis of a solid neoplasm is associated with an increased risk of developing CLL only in persons whose 1(st) cancer was not treated with radiation therapy.

  7. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia.

    Science.gov (United States)

    Radivoyevitch, Tomas; Sachs, Rainer K; Gale, Robert Peter; Smith, Mitchell R; Hill, Brian T

    2016-04-01

    Exposure to ionizing radiation is not thought to cause chronic lymphocytic leukemia (CLL). Challenging this notion are recent data suggesting CLL incidence may be increased by radiation exposure from the atomic bombs (after many decades), uranium mining and nuclear power facility accidents. To assess the effects of therapeutic ionizing radiation for the treatment of solid neoplasms we studied CLL risks in data from the Surveillance, Epidemiology, and End Results (SEER) Program. Specifically, we compared the risks of developing CLL in persons with a 1(st) non-hematologic cancer treated with or without ionizing radiation. We controlled for early detection effects on CLL risk induced by surveillance after 1(st) cancer diagnoses by forming all-time cumulative CLL relative risks (RR). We estimate such CLL RR to be 1.20 (95% confidence interval, 1.17, 1.23) for persons whose 1(st) cancer was not treated with ionizing radiation and 1.00 (0.96, 1.05) for persons whose 1(st) cancer was treated with ionizing radiations. These results imply that diagnosis of a solid neoplasm is associated with an increased risk of developing CLL only in persons whose 1(st) cancer was not treated with radiation therapy. PMID:26922774

  8. 28 CFR 79.57 - Proof of chronic renal disease.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.57... EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Uranium Millers § 79.57 Proof of chronic renal disease. (a) In determining whether a claimant developed chronic renal disease following...

  9. Metabolic effects of chronic ozone exposure on rats

    Energy Technology Data Exchange (ETDEWEB)

    Hathway, J.A.; Terrill, R.E.

    1962-01-01

    Rats were exposed to 0.8 to 1.5 ppm O/sub 3/ for 6 hr/day, 4 days/wk for 19 weeks. Lower titratable acidity after 91 days exposure and higher urine pH after 98 days exposure were observed. No significant differences in urine creatine, creatinine, uric acid/creatinine, or amino acid/creatinine were observed. pH differences suggest respiratory alkalosis, possibly due to subjectively noticed hyperventilation in exposed group.

  10. Modelling the effects of ionizing radiation on survival of animal population: acute versus chronic exposure.

    Science.gov (United States)

    Kryshev, A I; Sazykina, T G

    2015-03-01

    The objective of the present paper was application of a model, which was originally developed to simulate chronic ionizing radiation effects in a generic isolated population, to the case of acute exposure, and comparison of the dynamic features of radiation effects on the population survival in cases of acute and chronic exposure. Two modes of exposure were considered: acute exposure (2-35 Gy) and chronic lifetime exposure with the same integrated dose. Calculations were made for a generic mice population; however, the model can be applied for other animals with proper selection of parameter values. In case of acute exposure, in the range 2-11 Gy, the population response was in two phases. During a first phase, there was a depletion in population survival; the second phase was a recovery period due to reparation of damage and biosynthesis of new biomass. Model predictions indicate that a generic mice population, living in ideal conditions, has the potential for recovery (within a mouse lifetime period) from acute exposure with dose up to 10-11 Gy, i.e., the population may recover from doses above an LD50 (6.2 Gy). Following acute doses above 14 Gy, however, the mice population went to extinction without recovery. In contrast, under chronic lifetime exposures (500 days), radiation had little effect on population survival up to integrated doses of 14-15 Gy, so the survival of a population subjected to chronic exposure was much better compared with that after an acute exposure with the same dose. Due to the effect of "wasted radiation", the integrated dose of chronic exposure could be about two times higher than acute dose, producing the same effect on survival. It is concluded that the developed generic population model including the repair of radiation damage can be applied both to acute and chronic modes of exposure; results of calculations for generic mice population are in qualitative agreement with published data on radiation effects in mice. PMID

  11. Reversible loss of reproductive fitness in zebrafish on chronic alcohol exposure.

    Science.gov (United States)

    Dewari, Pooran Singh; Ajani, Funmilola; Kushawah, Gopal; Kumar, Damera Santhosh; Mishra, Rakesh K

    2016-02-01

    Alcoholism is one of the most prevalent diseases in society and causes significant health and social problems. Alcohol consumption by pregnant women is reported to cause adverse effects on the physical and psychological growth of the fetus. However, the direct effect of chronic alcohol consumption on reproductive fitness has not been tested. In recent years, the zebrafish (Danio rerio) has emerged as a versatile model system to study the effects of alcohol on behavior and embryonic development. We utilized the zebrafish model system to address the effect of chronic alcohol exposure (0.5% alcohol in the holding tank for 9 weeks) on reproductive capacity. We found a dramatic decrease in fecundity, measured by counting the number of eggs laid, when at least one of the parents is subject to chronic alcohol exposure. Interestingly, a 9-week alcohol withdrawal program completely restored the reproductive capacity of the treated subjects. In agreement with observations on fecundity, the chronic alcohol exposure leads to increased anxiety, as measured by the novel-tank diving assay. Conversely, the withdrawal program diminished heightened anxiety in alcohol-exposed subjects. Our results highlight the adverse effects of chronic alcohol exposure on the reproductive capacity of both males and females, and underscore the utility of the zebrafish model system to understand the biology of chronic alcoholism. PMID:26781213

  12. Biological characterization of radiation exposure and dose estimates for inhaled uranium milling effluents. Annual progress report April 1, 1982-March 31, 1983

    International Nuclear Information System (INIS)

    The problems addressed are the protection of uranium mill workers from occupational exposure to uranium through routine bioassay programs and the assessment of accidental worker exposures. Comparisons of chemical properties and the biological behavior of refined uranium ore (yellowcake) are made to identify important properties that influence uranium distribution patterns among organs. These studies will facilitate calculations of organ doses for specific exposures and associated health risk estimates and will identify important bioassay procedures to improve evaluations of human exposures. A quantitative analytical method for yellowcake was developed based on the infrared absorption of ammonium diuranate and U3O8 mixtures in KBr. The method was applied to yellowcake samples obtained from six operating mills. The composition of yellowcake from the six mills ranged from nearly pure ammonium diuranate to nearly pure U3O8. The composition of yellowcake samples taken from lots from the same mill was only somewhat less variable. Because uranium mill workers might be exposed to yellowcake either by contamination of a wound or by inhalation, a study of retention and translocation of uranium after subcutaneous implantation in rats was done. The results showed that 49% of the implanted yellowcake cleared from the body with a half-time (T sub 1/2) in the body of 0.3 days, and the remainder was cleared with a T sub 1/2 of 11 to 30 days. Exposures of Beagle dogs by nose-only inhalation to aerosols of commercial yellowcake were completed. Biochemical indicators of kidney dysfunction that appeared in blood and urine 4 to 8 days after exposure to the more soluble yellowcake showed significant changes in dogs, but levels returned to normal by 16 days after exposure. No biochemical evidence of kidney dysfunction was observed in dogs exposed to the less soluble yellowcake form. 18 figures, 9 tables

  13. Chronic and acute effects of coal tar pitch exposure and cardiopulmonary mortality among aluminum smelter workers.

    Science.gov (United States)

    Friesen, Melissa C; Demers, Paul A; Spinelli, John J; Eisen, Ellen A; Lorenzi, Maria F; Le, Nhu D

    2010-10-01

    Air pollution causes several adverse cardiovascular and respiratory effects. In occupational studies, where levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) are higher, the evidence is inconsistent. The effects of acute and chronic PAH exposure on cardiopulmonary mortality were examined within a Kitimat, Canada, aluminum smelter cohort (n = 7,026) linked to a national mortality database (1957-1999). No standardized mortality ratio was significantly elevated compared with the province's population. Smoking-adjusted internal comparisons were conducted using Cox regression for male subjects (n = 6,423). Ischemic heart disease (IHD) mortality (n = 281) was associated with cumulative benzo[a]pyrene (B(a)P) exposure (hazard ratio = 1.62, 95% confidence interval: 1.06, 2.46) in the highest category. A monotonic but nonsignificant trend was observed with chronic B(a)P exposure and acute myocardial infarction (n = 184). When follow-up was restricted to active employment, the hazard ratio for IHD was 2.39 (95% confidence interval: 0.95, 6.05) in the highest cumulative B(a)P category. The stronger associations observed during employment suggest that risk may not persist after exposure cessation. No associations with recent or current exposure were observed. IHD was associated with chronic (but not current) PAH exposure in a high-exposure occupational setting. Given the widespread workplace exposure to PAHs and heart disease's high prevalence, even modest associations produce a high burden.

  14. Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

    Science.gov (United States)

    Albertini, Richard J; Vacek, Pamela M; Carter, Elizabeth W; Nicklas, Janice A; Squibb, Katherine S; Gucer, Patricia W; Engelhardt, Susan M; McDiarmid, Melissa A

    2015-08-01

    A total of 70 military Veterans have been monitored for HPRT T-cell mutations in five separate studies at 2-year intervals over an 8-year period. Systemic depleted uranium (DU) levels were measured at the time of each study by determining urinary uranium (uU) excretion. Each HPRT study included 30-40 Veterans, several with retained DU-containing shrapnel. Forty-nine Veterans were evaluated in multiple studies, including 14 who were in all five studies. This permitted a characterization of the HPRT mutation assay over time to assess the effects of age, smoking and non-selected cloning efficiencies, as well as the inter- and intra-individual variability across time points. Molecular analyses identified the HPRT mutation and T-cell receptor (TCR) gene rearrangement in 1,377 mutant isolates. An unexpected finding was that in vivo clones of HPRT mutant T-cells were present in some Veterans, and could persist over several years of the study. The calculated HPRT mutant frequencies (MFs) were repeatedly elevated in replicate studies in three outlier Veterans with elevated urinary uranium excretion levels. However, these three outlier Veterans also harbored large and persistent in vivo HPRT mutant T-cell clones, each of which was represented by a single founder mutation. Correction for in vivo clonality allowed calculation of HPRT T-cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in HPRT MFs in some Veterans, the results presented here demonstrate that HPRT mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with HPRT mutations and none were found. PMID:25914368

  15. Acute and chronic respiratory effects of occupational exposure to ammonia.

    Science.gov (United States)

    Holness, D L; Purdham, J T; Nethercott, J R

    1989-12-01

    In a soda ash plant, 58 workers exposed to mean airborne ammonia levels of 9.2 +/- 1.4 ppm were compared with 31 control workers with a mean exposure of 0.3 +/- 0.1 ppm. There were no differences between the groups in the reporting of respiratory or cutaneous symptoms, sense of smell, baseline lung function, or change in lung function over a work shift at the beginning and end of a workweek. No relationships between level or length of ammonia exposure and lung function results were demonstrated. PMID:2596404

  16. Study of internal exposure to uranium compounds in fuel fabrication plants in Brazil

    International Nuclear Information System (INIS)

    The International Commission on Radiological Protection (ICRP) Publication 66 and Supporting Guidance 3) strongly recommends that specific information on lung retention parameters should be used in preference to default values wherever appropriate, for the derivation of effective doses and for bioassay interpretation of monitoring data. A group of 81 workers exposed to UO2 at the fuel fabrication facility in Brazil was selected to evaluate the committed effective dose. The workers were monitored for determination of uranium content in the urinary and faecal excretion. The contribution of intakes by ingestion and inhalation were assessed on the basis of the ratios of urinary to fecal excretion. For the selected workers it was concluded that inhalation dominated intake. According to ICRP 66, uranium oxide is classified as insoluble Type S compound. The ICRP Supporting Guidance 3 and some recent studies have recommended specific lung retention parameters to UO2. The solubility parameters of the uranium oxide compound handled by the workers at the fuel fabrication facility in Brazil was evaluated on the basis of the ratios of urinary to fecal excretion. Excretion data were corrected for dietary intakes. This paper will discuss the application of lung retention parameters recommended by the ICRP models to these data and also the dependence of the effective committed dose on the lung retention parameters. It will also discuss the problems in the interpretation of monitoring results, when the worker is exposed to several uranium compounds of different solubilities. (author)

  17. Assessment of radiation exposure around abandoned uranium mining area of Stara planina Mt., Serbia

    Directory of Open Access Journals (Sweden)

    Tanić Milan N.

    2014-01-01

    Full Text Available The aim of this work was to estimate the health and radiation hazard due to external irradiation from terrestrial radionuclides in the Stara planina Mt. region, which is important because of past uranium mining activities on the mountain. Soil samples were collected inside the flotation processing facilities, their surroundings and more distant locations, i.e. from areas considered certainly affected, potentially affected, and unaffected by former mining and uranium ore processing activities. The radiological and health risk assessments were done by calculating the six main parameters, based on the activity concentration of 238U, 232Th, and 40K in soil samples as determined by gamma-ray spectrometry. Increased values of the risk parameters were observed only for sites where uranium ore was processed, while the location surrounding these compounds showed values that are usual for this mountain or slightly above them. Calculations of the risk parameters for the background area showed no radiation risk for the local and seasonal population. The presence of U and Th was detected in all water samples from creeks surrounding the facilities, but only in the water from the facility drainage pipe did their concentration exceed the limits given for the uranium content in drinking water. In conclusion, the results obtained in this study fall within the range of values in similar studies conducted worldwide and are below the values which can cause a significant radiation hazard. [Projekat Ministarstva nauke Republike Srbije, br. III43009 i br. III41005

  18. Impacts of chronic low-level nicotine exposure on Caenorhabditis elegans reproduction: Identification of novel gene targets

    OpenAIRE

    Michael A Smith; Zhang, Yanqiong; Polli, Joseph R.; Wu, Hongmei; Zhang, Baohong; Xiao, Peng; Farwell, Mary A.; Pan, Xiaoping

    2013-01-01

    Effects and mechanisms of chronic exposure to low levels of nicotine is an area fundamentally important however less investigated. We employed the model organism Caenorhabditis elegans to investigate potential impacts of chronic (24 h) and low nicotine exposure (6.17–194.5 μM) on stimulus-response, reproduction, and gene expressions. Nicotine significantly affects the organism's response to touch stimulus (p = 0.031), which follows a dose-dependent pattern. Chronic nicotine exposure promotes ...

  19. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

    Science.gov (United States)

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Ellis, Jonathan D; Walters, Elliot T; Stout, Kristen A; McIntosh, J Michael; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2015-12-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection. PMID:26391161

  20. Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Sean H Ling

    2009-06-01

    Full Text Available Sean H Ling, Stephan F van EedenJames Hogg iCAPTURE Centre for Pulmonary and Cardiovascular Research and Heart and Lung Institute, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary. Strong epidemiological evidence suggests that exposure to particulate matter (PM air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD resulting in increased morbidity and mortality. However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD. The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces. Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease. This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD.Keywords: chronic obstructive pulmonary disease, particulate matter, air pollution, alveolar macrophage

  1. Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study

    DEFF Research Database (Denmark)

    Andersen, Zorana J; Hvidberg, Martin; Jensen, Steen S;

    2011-01-01

    Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood....

  2. Impairment induced by chronic occupational cadmium exposure during brazing process

    International Nuclear Information System (INIS)

    Cadmium (CD) is considered a metal of the 20th century to which all inhabitants of develop societies are exposed. Long-term occupational and environmental exposure to CD often results in renal dysfunction as the kidney is considered the critical target organ. The aim of this work was to evalutate both resporatory and renal manifestations induced by occupational exposure to CD compounds during brazing process, and suggesting a protocol for prevention and control for CD- induced health effects. This study was conducted on 20 males occupationally exposed workers. They are divided into two groups: Group-1 included (10) exposed smokers and group-2 included (10) exposed non-smokers. Results of both groups were compared with those of 10 healthy age and sex matched non-smokers. All subjects were subjected to detailed history taking and laboratory investigations including blood and urinary CD, liver profile (SGOT, SGPT and alkline phosphates), kindey function tests (blood urea, creatinine and urinary beta2- microglobulin). The level of Cd in the atmosphere of the work plase air was also assessed to detect the degree of exposure as it was about 6 times greater than thesave level (1 mu /m3).(1) This study demonstrated elevation levels of blood CD, urea, creatinine and urinary CD and beta2 -microglobulin for both exposed worker groups than the controls. In additions no appreciable were noted for liver function tests, although the levels fell within normal range

  3. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-01-01

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother. PMID:27399225

  4. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-06-15

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

  5. Study of biological effects induced in Arabidopsis thaliana following uranium exposure, including mixed exposure to cadmium or external gamma radiation: applying a multi-biomarkers approach

    OpenAIRE

    Vanhoudt, Nathalie

    2009-01-01

    The aim of this study was first to investigate uranium toxicity effects and to unravel mechanisms by which plants respond to uranium stress. In a next phase, the influence of secondary stressors on uranium induced effects was investigated. The highest uranium concentration of 100 µM uranium is extremely toxic for Arabidopsis thaliana plants with a completely inhibited growth, a fully disturbed nutrient profile, wilting and although making an effort to increase antioxidative defense, suffering...

  6. An intake prior for the Bayesian analysis of plutonium and uranium exposures in an epidemiology study.

    Science.gov (United States)

    Puncher, M; Birchall, A; Bull, R K

    2014-12-01

    In Bayesian inference, the initial knowledge regarding the value of a parameter, before additional data are considered, is represented as a prior probability distribution. This paper describes the derivation of a prior distribution of intake that was used for the Bayesian analysis of plutonium and uranium worker doses in a recent epidemiology study. The chosen distribution is log-normal with a geometric standard deviation of 6 and a median value that is derived for each worker based on the duration of the work history and the number of reported acute intakes. The median value is a function of the work history and a constant related to activity in air concentration, M, which is derived separately for uranium and plutonium. The value of M is based primarily on measurements of plutonium and uranium in air derived from historical personal air sampler (PAS) data. However, there is significant uncertainty on the value of M that results from paucity of PAS data and from extrapolating these measurements to actual intakes. This paper compares posterior and prior distributions of intake and investigates the sensitivity of the Bayesian analyses to the assumed value of M. It is found that varying M by a factor of 10 results in a much smaller factor of 2 variation in mean intake and lung dose for both plutonium and uranium. It is concluded that if a log-normal distribution is considered to adequately represent worker intakes, then the Bayesian posterior distribution of dose is relatively insensitive to the value assumed of M. PMID:24191121

  7. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.

    Science.gov (United States)

    Pleil, Kristen E; Lowery-Gionta, Emily G; Crowley, Nicole A; Li, Chia; Marcinkiewcz, Catherine A; Rose, Jamie H; McCall, Nora M; Maldonado-Devincci, Antoniette M; Morrow, A Leslie; Jones, Sara R; Kash, Thomas L

    2015-12-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry.

  8. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.

    Science.gov (United States)

    Pleil, Kristen E; Lowery-Gionta, Emily G; Crowley, Nicole A; Li, Chia; Marcinkiewcz, Catherine A; Rose, Jamie H; McCall, Nora M; Maldonado-Devincci, Antoniette M; Morrow, A Leslie; Jones, Sara R; Kash, Thomas L

    2015-12-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry. PMID:26188147

  9. Induction of vascular remodeling in the lung by chronic house dust mite exposure.

    Science.gov (United States)

    Rydell-Törmänen, Kristina; Johnson, Jill R; Fattouh, Ramzi; Jordana, Manel; Erjefält, Jonas S

    2008-07-01

    Structural changes to the lung are associated with chronic asthma. In addition to alterations to the airway wall, asthma is associated with vascular modifications, although this aspect of remodeling is poorly understood. We sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. Because many ovalbumin-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we used a protocol of chronic respiratory exposure to house dust mite extract (HDME), which has been shown to induce persistent airway inflammation consistent with that seen in humans with asthma. Mice were exposed to HDME intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks after the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I production, endothelial and smooth muscle cell proliferation, smooth muscle area, and presence of myofibroblasts, were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content, which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased after 7 and/or 20 weeks of allergen exposure but returned to baseline after allergen withdrawal. We conclude that respiratory HDME exposure induces airway remodeling and pulmonary vascular remodeling, and, in accordance with airway remodeling, some components of these structural changes may be irreversible. PMID:18314535

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

    Directory of Open Access Journals (Sweden)

    Balmes John

    2005-05-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  11. Chronic occupational exposure to asbestos: more than medical effects

    Energy Technology Data Exchange (ETDEWEB)

    Lebovits, A.H.; Byrne, M.; Bernstein, J.; Strain, J.J.

    1988-01-01

    One hundred and twenty-nine workers chronically exposed to asbestos were interviewed regarding their perceived health status and concerns, their health behaviors, particularly their smoking behavior, and their psychologic well-being. In contrast to a non-exposed comparison group of postal workers, asbestos workers exhibited significantly elevated levels of somatic concern (P less than .03), and significantly lower levels of mental health functioning only when experiencing high levels of stress (P less than .01). Despite feeling significantly more susceptible to developing cancer (P less than .0001), 34% of asbestos workers were cigarette smokers (compared to 32% of the postal group) and long-term mask usage was minimal. Asbestos workers' increased sensitivity to stress and changes in health status along with the lack of adaptation of health-promotive behaviors indicate the need for interventions to attend to the psychologic effects of increased risk status.

  12. Lung cancer risk, exposure to radon and tobacco consumption in a nested case-control study of French uranium miners

    International Nuclear Information System (INIS)

    Introduction: A nested case-control study was conducted among the French uranium miners cohort in order to assess the effect of protract ed radon exposure on lung cancer risk taking into account tobacco consumption. Material and methods: One hundred uranium miners employed by the French company CEA-COGEMA and who died of a lung cancer between 1980 and 1994 were identified as cases among the cohort. For each case, five controls were randomly matched on birth period and attained age at the time of death of the corresponding case. Cumulated radon exposure during employment was reconstructed for each of these 100 cases and 500 controls. Smoking habits were retrospectively determined from three complementary sources: 1) medical files, 2) forms filled in by occupational physicians and 3) questionnaires applied in face-to-face interviews, phone calls or mailings. Analysis was performed by conditional logistic regression using a linear excess relative risk (ERR) model. A multiplicative model was fitted to assess the joint effect of radon exposure and smoking on lung cancer risk. Results: Smoking status was established for 62 cases and 320 controls and two categories ('ever smokers' vs. 'never smokers') were defined. Ninety percent of the cases and 73% of the controls were classified as 'ever smokers'. Mean five-year lagged cumulated radon exposures were 82.0 and 47.6 working level months (WLM) for the cases and the controls, respectively. The excess relative risk per WLM (ERR/WLM) was 1.1% with a 95%-confidence interval (CI) of 0.2-2.0%. When adjusting for smoking, radon exposure effect was little modified (ERR/WLM = 0.8%, 95% -CI = 0.1- 2.8%). The effect of smoking on lung cancer risk was comparable to results reported in previous miners cohorts (OR = 3.04, 95% -CI = 1.20-7.70). Discussion: A consequent effort was carried out to collect smoking status from three sources for the miners included in this nested case-control study. This analysis shows that, when adjusting on

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

    Science.gov (United States)

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

    2016-01-19

    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

  14. Non-neoplastic pulmonary disease from inhaled radon daughters with uranium ore dust in beagle dogs

    International Nuclear Information System (INIS)

    Daily exposures of adult beagle dogs to inhaled radon daughters plus uranium ore dust, with and without concurrent cigarette smoking, for 2 to 5-1/2 yr have produced massive pulmonary fibrosis and severe emphysema. The cumulative exposure doses are similar to those associated with a 5-fold or greater increase in death rate of uranium miners due to chronic respiratory insufficiency, including pneumoconiosis, pulmonary fibrosis, and emphysema

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

    Science.gov (United States)

    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. PMID:27600395

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

    Science.gov (United States)

    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

  17. Graded exposure for chronic low back pain in older adults : a pilot study

    NARCIS (Netherlands)

    Leonhardt, Corinna; Kuss, Katrin; Becker, Annette; Basler, Heinz-Dieter; de jong, Jeroen; Flatau, Brigitta; Laekeman, Marjan; Mattenklodt, Peter; Schuler, Matthias; Vlaeyen, Johan; Quint, Sabine

    2016-01-01

    BACKGROUND AND PURPOSE: Fear-avoidance beliefs in older adults with chronic low back pain (CLBP) can lead to disability. Graded exposure-based active physical therapy could be an option to enhance physical ability in older patients with CLBP. The purpose of this study was to develop a standardized g

  18. Lung functions at school age and chronic exposure to outdoor and indoor air pollution

    Energy Technology Data Exchange (ETDEWEB)

    Neuberger, M.; Kundi, M.; Wiesenberger, W. [Vienna Univ. (Austria). Dept. of Preventive Medicine

    1995-12-31

    Early signs of lung function impairment have been found correlated with annual concentrations of outdoor air pollutants and with passive smoking. To investigate the combined effects of both indicators of chronic exposure to air pollution pulmonary functions in all elementary and high school children of an Austrian town was examined for 5 years. (author)

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

    Science.gov (United States)

    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...

  20. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: role of the TNF signaling axis

    Science.gov (United States)

    Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-alpha signaling. The effects in mice are unreported....

  1. RESPONSES OF SUBJECTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AFTER EXPOSURES TO 0.3 PPM OZONE

    Science.gov (United States)

    The authors previously reported (1982) that the respiratory mechanics of intermittently exercising persons with chronic obstructive pulmonary disease (COPD) were unaffected by a 2-h exposure to 0.2 ppm ozone. Employing a single-blind cross-over design protocol, 13 white men with ...

  2. Depleted uranium: Metabolic disruptor?; Uranium appauvri: perturbateur metabolique?

    Energy Technology Data Exchange (ETDEWEB)

    Souidi, Maamar; Dublineau, Isabelle; Lestaevel, Philippe [Institut de Radioprotection et de Surete Nucleaire - IRSN, Direction de la radioprotection de l' homme, Laboratoire de radiotoxicologie experimentale, Service de radiobiologie et d' epidemiologie, BP 17, 92262 Fontenay-aux-Roses cedex (France)

    2011-11-15

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  3. Inequitable Chronic Lead Exposure: A Dual Legacy of Social and Environmental Injustice.

    Science.gov (United States)

    Leech, Tamara G J; Adams, Elizabeth A; Weathers, Tess D; Staten, Lisa K; Filippelli, Gabriel M

    2016-01-01

    Both historic and contemporary factors contribute to the current unequal distribution of lead in urban environments and the disproportionate impact lead exposure has on the health and well-being of low-income minority communities. We consider the enduring impact of lead through the lens of environmental justice, taking into account well-documented geographic concentrations of lead, legacy sources that produce chronic exposures, and intergenerational transfers of risk. We discuss the most promising type of public health action to address inequitable lead exposure and uptake: primordial prevention efforts that address the most fundamental causes of diseases by intervening in structural and systemic inequalities. PMID:27214670

  4. Mutagenicity monitoring following battlefield exposures: Molecular analysis of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

    Science.gov (United States)

    Nicklas, Janice A; Albertini, Richard J; Vacek, Pamela M; Ardell, Stephanie K; Carter, Elizabeth W; McDiarmid, Melissa A; Engelhardt, Susan M; Gucer, Patricia W; Squibb, Katherine S

    2015-08-01

    Molecular studies that involved cDNA and genomic DNA sequencing as well as multiplex PCR of the HPRT gene were performed to determine the molecular mutational spectrum for 1,377 HPRT mutant isolates obtained from 61 Veterans of the 1991 Gulf War, most of whom were exposed to depleted uranium (DU). Mutant colonies were isolated from one to four times from each Veteran (in 2003, 2005, 2007, and/or 2009). The relative frequencies of the various types of mutations (point mutations, deletions, insertions, etc.) were compared between high versus low DU exposed groups, (based on their urine U concentration levels), with HPRT mutant frequency (as determined in the companion paper) and with a database of historic controls. The mutational spectrum includes all classes of gene mutations with no significant differences observed in Veterans related to their DU exposures. PMID:25914382

  5. Chronic exposure to hexachlorobenzene results in down-regulation of connexin43 in the breast.

    Science.gov (United States)

    Delisle, Ariane; Ferraris, Emanuelle; Plante, Isabelle

    2015-11-01

    Decreased expression of connexins has been associated with cancer, but the underlying mechanisms are poorly understood. We have previously shown that a 5 day exposure to hexachlorobenzene (HCB) resulted in decreased connexins expression in hepatocytes 45 days later, and that this down-regulation was linked to activation of Akt through the ILK pathway. Because HCB promotes cancer in both the liver and breast, the present study aimed to determine if the mechanisms are similar in both tissues. MCF-12A breast cells were thus transfected with vectors coding for either Akt or a constitutively active form of Akt. In those cells, activation of Akt was correlated with decreased Cx43 levels. Female rats were then exposed to HCB by gavage either following the same protocol used previously for the liver or through a chronic exposure. While no changes were observed after the 5 days exposure protocol, chronic exposure to HCB resulted in increased Akt levels and decreased Cx43 levels in breast cells. In vitro, Akt was activated in MCF-12A cells exposed to HCB either for 7 days or chronically, but no changes were observed in junctional proteins. Together, these results suggested that, while activation of Akt can decrease Cx43 expression in breast cells in vitro, other mechanisms are involved during HCB exposure, leading to a decrease in Cx43 levels in a model- and duration-dependent manner. Finally, we showed that HCB effects are tissue specific, as we did not observe the same results in breast and liver tissues.

  6. No effect of low-level chronic neonicotinoid exposure on bumblebee learning and fecundity.

    Science.gov (United States)

    Piiroinen, Saija; Botías, Cristina; Nicholls, Elizabeth; Goulson, Dave

    2016-01-01

    In recent years, many pollinators have declined in abundance and diversity worldwide, presenting a potential threat to agricultural productivity, biodiversity and the functioning of natural ecosystems. One of the most debated factors proposed to be contributing to pollinator declines is exposure to pesticides, particularly neonicotinoids, a widely used class of systemic insecticide. Also, newly emerging parasites and diseases, thought to be spread via contact with managed honeybees, may pose threats to other pollinators such as bumblebees. Compared to honeybees, bumblebees could be particularly vulnerable to the effects of stressors due to their smaller and more short-lived colonies. Here, we studied the effect of field-realistic, chronic clothianidin exposure and inoculation with the parasite Nosema ceranae on survival, fecundity, sugar water collection and learning using queenless Bombus terrestris audax microcolonies in the laboratory. Chronic exposure to 1 ppb clothianidin had no significant effects on the traits studied. Interestingly, pesticide exposure in combination with additional stress caused by harnessing bees for Proboscis Extension Response (PER) learning assays, led to an increase in mortality. In contrast to previous findings, the bees did not become infected by N. ceranae after experimental inoculation with the parasite spores, suggesting variability in host resistance or parasite virulence. However, this treatment induced a slight, short-term reduction in sugar water collection, potentially through stimulation of the immune system of the bees. Our results suggest that chronic exposure to 1 ppb clothianidin does not have adverse effects on bumblebee fecundity or learning ability. PMID:27014515

  7. Injury of the blood-testies barrier after low-dose-rate chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Young Hoon; Bae Min Ji; Lee, Chang Geun; Yang, Kwang Mo; Jur, Kyu; Kim, Jong Sun [Dongnam Institute of Radiological and Medical Science, Busan (Korea, Republic of)

    2014-04-15

    The systemic effect of radiation increases in proportionally with the dose and dose rate. Little is known concerning the relationships between harmful effects and accumulated dose, which is derived from continuous low-dose rate radiation exposure. Recent our studies show that low-dose-rate chronic radiation exposure (3.49 mGy/h) causes adverse effects in the testis at a dose of 2 Gy (6 mGy/h). However, the mechanism of the low-dose-rate 2 Gy irradiation induced testicular injury remains unclear. The present results indicate that low-dose rate chronic radiation might affect the BTB permeability, possibly by decreasing levels of ZO-1, Occludin-1, and NPC-2. Furthermore, our results suggest that there is a risk of male infertility through BTB impairment even with low-dose-rate radiation if exposure is continuous.

  8. Inflammation mediators in employees in chronic exposure to neurotoxicants

    Directory of Open Access Journals (Sweden)

    Galina Bodienkova

    2014-08-01

    Full Text Available Objectives: The aim of this work is to perform comparative estimation of cytokines levels in chlorinated hydrocarbons and metallic mercury exposure in employees in the dynamics of neurologic disorders formation. Material and Methods: The contents of cytokines IL-1β, IL-2, IL-4, IL-6, TNF-α, INF-γ were determined in blood sera using the method of hardphasic immunoferment analysis. The significance of different average values was assessed using the parametric and non-parametric criteria - Student (in normal distribution and Mann-Whitney tests taking into account the Bonferonni correction (non-difference from normal distribution. Results: It was shown that, a number of inflammation mediators with the dominance, depending on the expositional toxicant and expression of neurological deficiency, take part in the neurointoxication development. Healthy employees show pro-inflammatory responses with different expression degree, which dominate in the immune regulation processes regardless of the expositional factors (metallic mercury vapors and chlorinated hydrocarbons. Conclusions: The production intensity and interconnection between the pro- and anti-inflammatory cytokines may change in the occupational injuries of the nervous system development process. The decrease in the serum concentrations of cytokines along with the increase of clinical manifestation severity may prove dysregulation of the immune system, which promotes maintaining of pathological process and progradient process of neurointoxication. The most obvious is the imbalance of cytokines in the employees exposed to metallic mercury (in all the examined groups that increases neurointoxication in the distant period.

  9. Characterisation of cochlear inflammation in mice following acute and chronic noise exposure.

    Science.gov (United States)

    Tan, Winston J T; Thorne, Peter R; Vlajkovic, Srdjan M

    2016-08-01

    Oxidative stress has been established as the key mechanism of the cochlear damage underlying noise-induced hearing loss, however, emerging evidence suggests that cochlear inflammation may also be a major contributor. This study aimed to improve our understanding of the cochlear inflammatory response associated with acute and chronic noise exposure. C57BL/6 mice were exposed to acute traumatic noise (100 dBSPL, 8-16 kHz for 24 h) and their cochleae collected at various intervals thereafter, up to 7 days. Using quantitative RT-PCR and immunohistochemistry, changes in expression levels of proinflammatory cytokines (TNF-α, IL-1β), chemokines (CCL2) and cell adhesion molecules (ICAM-1) were studied. All gene transcripts displayed similar dynamics of expression, with an early upregulation at 6 h post-exposure, followed by a second peak at 7 days. ICAM-1 immunoexpression increased significantly in the inferior region of the spiral ligament, peaking 24 h post-exposure. The early expression of proinflammatory mediators likely mediates the recruitment and extravasation of inflammatory cells into the noise-exposed cochlea. The occurrence of the latter expression peak is not clear, but it may be associated with reparative processes initiated in response to cochlear damage. Chronic exposure to moderate noise (90 dBSPL, 8-16 kHz, 2 h/day, up to 4 weeks) also elicited an inflammatory response, reaching a maximum after 2 weeks, suggesting that cochlear damage and hearing loss associated with chronic environmental noise exposure may be linked to inflammatory processes in the cochlea. This study thus provides further insight into the dynamics of the cochlear inflammatory response induced by exposure to acute and chronic noise. PMID:27109494

  10. Exposure of critical group of population to water radionuclides in area affected by uranium ore mining

    International Nuclear Information System (INIS)

    Waste waters from the uranium industry are decontaminated and then discharged into water courses. Inhabitants of the nearest village on the river form the critical group with regard to radiation burden. The critical radionuclides are Usub(nat), Ra 226, Pb 210 and Po 210 whose concentrations were determined in drinking water, in the water course and in plants watered with water from the river. From obtained data on the consumption of foods of own production and of water for drinking and cooking, a weighted sum was made of the intake of critical radionuclides per year on the conservative assumption that ingestion is the sole form of intake (permissible ingestion under Notice 59/72, Coll. of Laws). Under the said criteria the intake of radionuclides from water and foods of own production is for the critical population group 27 times less than the permissible intake for the population. Decontaminated waste waters from the operation of uranium industries contribute to the radiation burden of the population only negligibly. Radionuclides from the investigated sources represent a minute fraction of permissible intake. (author)

  11. Public radiation exposure due to radon transport from a uranium mine

    International Nuclear Information System (INIS)

    Radon and radon daughter concentrations at locations several kilometres away from a uranium mine are due both to the background sources and the mine-related sources. The contribution of these two types of sources should be distinguished because the authorised limits on public radiation dose apply only to the mine-related sources. Such a distinction can be achieved by measuring radon and radon daughter concentration in the wind sectors containing only the background sources and those in the wind sectors containing both the background and the mine-related sources. This approach has been used to make estimates of public radiation dose due to radon transport from the Ranger Uranium Mine in Australia. The residential town of Jabiru, the non-residential working town of Jabiru East, and the aboriginal camp sites in the vicinity of the mine were considered. The results indicate that, for the groups of population considered, the annual mine-related dose varies between 0.04 and 0.2 mSv. (author)

  12. Assessment of radiation exposure and evaluation of remedial measures for the uranium mining and milling area of Mailuu Suu, Kyrgyzstan

    Energy Technology Data Exchange (ETDEWEB)

    Vandenhove, Hildegarde; Sweeck, Lieve [SCK-CEN, Boeretang 200, BR1 Building, B-2400 Mol (Belgium); Clerc, Jean-Jacques [Arcadis, 10 avenue Newton, 92350 Le Plessis-Robinson (France); Aitaliev, Anarkul [Ministry of Ecology and Disaster Situations, Bishkek (Kyrgyzstan)

    2006-07-01

    The area of the town of Mailuu Suu, Kyrgyzstan, is polluted by radionuclides and heavy metals in tailing dumps and heaps resulting from the historic exploitation of uranium mines. Radioactive substances are stored in 23 tailings and 10 heaps situated along the Mailuu Suu River. The stability of many tailings is at risk. Attention is mostly directed to Tailing 3, because of its important radionuclide inventory and since threatened by the borders of a major landslide. In the frame of a European Commission-TACIS funded project, a radiological monitoring programme was set up and a radiological assessment was performed for critical group members living in the city of Mailuu Suu, located downstream the tailings, or in the village of Kara Agach, partially located on a uranium mine-waste dump. The actual radiological situation is of no immediate concern for most of the population of Mailuu Suu. The actual external exposure and exposure from radon are, respectively, around 1.2 mSv a{sup -1} and 5 mSv a{sup -1}, at both locations. Ingestion dose was negligible for a critical group member living at Mailuu Suu. At Kara Agach, however, under the hypothesis that all food and fodder is cultivated locally, exposure from ingestion is much higher ({approx}10-30 mSv a{sup -1}). Additional dose from irrigation with Mailuu Suu river water is small in actual conditions (< 0.1 mSv a{sup -1}). However, there is an important possibility that, triggered by an earthquake or a landslide, (part of the) tailing(s) content may be directed to the river Mailuu Suu. In case the content of Tailing 3 is thrust to river, calculated maximum doses are 45 and 77 mSv a{sup -1} for an adult and a child, respectively, for an assumed exposure duration of 2 years. To impede the consequences of a potential disaster, under the TACIS project different remedial options were evaluated for Tailing 3 including in situ stabilisation and tailing translocation. Also more global remedial options for the Mailuu Suu River

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-11-16

    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.

  15. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    Science.gov (United States)

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  16. The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures

    Directory of Open Access Journals (Sweden)

    Ebere Anyanwu

    2003-01-01

    Full Text Available Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40�C (104�F, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide

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

    Science.gov (United States)

    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.

  18. Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature

    Science.gov (United States)

    Razavi, Seyed Mansour; Abdollahi, Mohammad; Salamati, Payman

    2016-01-01

    Background: Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings. Methods: The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed. Results: Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma. Conclusions: SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure. PMID:27280012

  19. Reaction of fresh water zooplankton community to chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Osipov, D.; Pryakhin, E. [Urals Research Center for Radiation Medicine - URCRM (Russian Federation); Ivanov, I. [FSUE Mayak PA (Russian Federation)

    2014-07-01

    The characteristic features of ecological community as a whole and cenosis of zooplankton organisms as part of it determine the intensity of the processes of self-purification of water and the formation of a particular body of water. Identifying features of the structure and composition of the zooplankton community of aquatic ecosystems exposed to different levels of radiation exposure, it is necessary to identify patterns of changes in zooplankton and hydro-biocenosis as a whole. Industrial reservoirs, the storage of liquid low-level radioactive waste 'Mayak' for decades, have high radiation load. A large range of levels of radioactive contamination (total volume beta-activity in water varies from 2.2x10{sup 3} to 2.3x10{sup 7} Bq/l, total volume alpha-activity - from 2.6x10{sup -1} to 3.1x10{sup 3} Bq/l) provides a unique opportunity to study ecosystems in a number of reservoirs with increasing impact of radiation factor. We studied five reservoirs that were used as the storage of low-and intermediate-level liquid radioactive waste pond and one comparison water body. In parallel with zooplankton sampling water samples were collected for hydro-chemical analysis. 41 indicators were analysed in order to assess the water chemistry. To determine the content of radionuclides in the various components of the ecosystem samples were collected from water, bottom sediments and plankton. Sampling of zooplankton for the quantitative analysis was performed using the method of weighted average auto bathometer. Apshteyn's plankton net of the surface horizon was used for qualitative analysis of the species composition of zooplankton. Software package ERICA Assessment Tool 2012 was used for the calculation of the absorbed dose rate. Species diversity and biomass of zooplankton, the share of rotifers in the number of species, abundance and biomass decrease with the increase of the absorbed dose rate and salinity. The number of species in a sample decreases with the

  20. Analysis of chronic radiation exposure at small doses

    Energy Technology Data Exchange (ETDEWEB)

    Krestinina, L.Y. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2000-05-01

    The purpose of the study was to analyze the late effects of radiation exposure among residents of settlements located on the territory of the East-Urals Radiation Trace (EURT) in the Southern Urals. In 1957 an explosion occurred at the depot of radioactive waste in the Southern Urals. An area of 23000 km{sup 2} was contaminated, with contamination density of over 0.1 Ci/m{sup 2} for {sup 90}Sr. There were 217 populated ares on that territory with total population about 270000. The residents of 22 villages with contamination density of over 4 Ci/km{sup 2} for {sup 90}Sr were evacuated. The times of evacuation differed from 7 to 670 days since the accident, depending on the level of contamination. In 1988-1993 an individualized registry was created at the Urals Research Center for Radiation Medicine (URCRM) which included information on the residents of 22 evacuated villages and a proportion of unevacuated residents of the EURT area. Currently, the registry contains data on 30000 residents. Of that number 17000 persons were born before, and 12000 after the accident (including about 9000 offspring of exposed residents evacuated from the EURT, and about 3000 persons who were born after the accident and have been living permanently in the EURT area). Over the 35-year period since the accident the residents have received mean effective doses ranging from 23 to 530 mSv. The mean effective doses received by permanent residents range from 5 to 60 mSv. The cohort of people exposed on the EURT territory was identified based on the information contained in the registry. If a person happened to be in the EURT area at the time of the accident, he/she was considered to be eligible for inclusion in the cohort. Over the 35-year period (from 1957 through 1992) 29.5% of 17872 residents died, and 35% of the original cohort were lost to follow-up for different reasons. To enable an analysis a control group was established which included residents of villages located outside, but close

  1. Measurement methods and optimization of radiation protection: the case of internal exposure by inhalation to natural uranium compounds; Methodes de mesure et optimisation de la radioprotection: le cas des expositions internes par inhalation aux composes d'uranium naturel

    Energy Technology Data Exchange (ETDEWEB)

    Degrange, J.P. [Centre d' Etudes sur l' Evaluation de la Protection dans le domaine Nucleaire (CEPN), 92 - Fontenay-aux-Roses (France); Gibert, B. [Societe pour la Conversion de l' Uranium en Metal et Hexafluorure (COMURHEX), 11 - Narbonne (France)

    1998-07-01

    The aim of this presentation is to discuss the ability of different measurement methods (air sampling and biological examinations) to answer to demands in the particular case of internal exposure by inhalation to natural uranium compounds. The realism and the sensitivity of each method are studied, on the base of new dosimetric models of the ICRP. The ability of analysis of these methods in order to optimize radiation protection are then discussed. (N.C.)

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

    Science.gov (United States)

    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...

  3. Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat

    Energy Technology Data Exchange (ETDEWEB)

    Tissandie, E.; Gueguen, Y.; Paquet, F.; Aigueperse, J.; Souidi, M. [Institute for Radiological Protection and Nuclear Safety, Laboratory of Experimental Toxicology, BP n 17, Fontenay-aux-Roses Cedex (France); Lobaccaro, J.M.A. [UMR Universite Blaise Pascal-CNRS, Compared Physiology and Molecular Endocrinology, 24 avenue des Landais, 6547, Aubiere Cedex (France)

    2006-08-15

    Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D{sub 3} biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D{sub 3}-target genes (ECaC1, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels. (orig.)

  4. Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat

    International Nuclear Information System (INIS)

    Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D3 biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D3-target genes (ECaC1, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels. (orig.)

  5. Consideration of measurement errors in the analysis of the risk related to the exposure to ionising radiation in an occupational cohort: application to the French cohort of uranium miners; Prise en compte des erreurs de mesure dans l'analyse du risque associe a l'exposition aux rayonnements ionisants dans une cohorte professionnelle: application a la cohorte francaise des mineurs d'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Allodji, Rodrigue Setcheou

    2011-12-09

    In epidemiological studies, measurement errors in exposure can substantially bias the estimation of the risk associated to exposure. A broad variety of methods for measurement error correction has been developed, but they have been rarely applied in practice, probably because their ability to correct measurement error effects and their implementation are poorly understood. Another important reason is that many of the proposed correction methods require to know measurement errors characteristics (size, nature, structure and distribution). The aim of this thesis is to take into account measurement error in the analysis of risk of lung cancer death associated to radon exposure based on the French cohort of uranium miners. The mains stages were (1) to assess the characteristics (size, nature, structure and distribution) of measurement error in the French uranium miners cohort, (2) to investigate the impact of measurement error in radon exposure on the estimated excess relative risk (ERR) of lung cancer death associated to radon exposure, and (3) to compare the performance of methods for correction of these measurement error effects. The French cohort of uranium miners includes more than 5000 miners chronically exposed to radon with a follow-up duration of 30 years. Measurement errors have been characterized taking into account the evolution of uranium extraction methods and of radiation protection measures over time. A simulation study based on the French cohort of uranium miners has been carried out to investigate the effects of these measurement errors on the estimated ERR and to assess the performance of different methods for correcting these effects. Measurement error associated to radon exposure decreased over time, from more than 45% in the early 70's to about 10% in the late 80's. Its nature also changed over time from mostly Berkson to classical type from 1983. Simulation results showed that measurement error leads to an attenuation of the ERR towards

  6. Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood

    Directory of Open Access Journals (Sweden)

    Fernando Jáuregui-Huerta

    2011-01-01

    Full Text Available Increasing evidence indicates that chronic exposure to environmental noise may permanently affect the central nervous system. The aim of this study was to evaluate the long-term effects of early exposure to environmental noise on the hippocampal cell proliferation of the adult male rat. Early-weaned Wistar rats were exposed for 15 days to a rats′ audiogram-fitted adaptation to a noisy environment. Two months later, the rats were injected with the cellular proliferation marker 5΄bromodeoxiuridine (BrdU, and their brains were processed for immunohistochemical analysis. Coronal sections were immunolabeled with anti-BrdU antibodies to identify new-born cells in dentate gyrus (DG, cornu amonis areas CA1 and CA3. In addition, blood samples were obtained to evaluate corticosterone serum levels after noise exposure. All data are expressed as mean΁standard deviation. For mean comparisons between groups, we used the Student t test. We found an increase in corticosterone serum levels after environmental noise exposure. Interestingly, noise-exposed rats showed a long-term reduction of proliferating cells in the hippocampal formation, as compared to controls. These findings indicate that chronic environmental noise exposure at young ages produces persistent non-auditory impairment that modifies cell proliferation in the hippocampal formation.

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

    Science.gov (United States)

    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.

  8. Vascular Dysfunction in Patients with Chronic Arsenosis Can Be Reversed by Reduction of Arsenic Exposure

    OpenAIRE

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P.; Kumagai, Yoshito

    2004-01-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3′,5′-monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs an...

  9. Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: Mechanisms and reversal by exogenous ACTH

    OpenAIRE

    Boyd, Kevin N.; Kumar, Sandeep; O'Buckley, Todd K.; Morrow, A. Leslie

    2010-01-01

    Acute ethanol administration increases potent GABAergic neuroactive steroids, specifically (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP) and (3α,5α)-3,21-dihydroxypregnan-20-one. In addition, neuroactive steroids contribute to ethanol actions. Chronic ethanol exposure results in tolerance to many effects of ethanol, including ethanol-induced increases in neuroactive steroid levels. To determine the mechanisms of tolerance to ethanol-induced increases in neuroactive steroids, we investigated cri...

  10. Pulmonary function and exercise-associated changes with chronic low-level paraquat exposure

    OpenAIRE

    Schenker, M B; Stoecklin, Maria T; Lee, Kiyoung; Lupercio, Rafael; Zeballos, R. Jorge; Enright, Paul; Hennessy, Tamara E.; Laurel A. Beckett

    2004-01-01

    The present study was undertaken to test the hypothesis that chronic, low-level paraquat exposure causes restrictive lung function with gas transfer impairment. Three hundred thirty-eight Costa Rican farm workers from banana, coffee and palm oil farms completed a questionnaire, spirometry and single-breath carbon monoxide diffusing capacity. Subjects 40 years of age or older, without other medical risk factors, completed maximal cardiopulmonary exercise tests. Most (66.6%) were paraquat hand...

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

    Science.gov (United States)

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

    2015-01-01

    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.

  12. Chronic estradiol exposure induces oxidative stress in the hypothalamus to decrease hypothalamic dopamine and cause hyperprolactinemia

    OpenAIRE

    MohanKumar, Sheba M.J.; Kasturi, Badrinarayanan S.; Shin, Andrew C.; Balasubramanian, Priya; Gilbreath, Ebony T.; Subramanian, Madhan; MohanKumar, Puliyur S

    2010-01-01

    Estrogens are known to cause hyperprolactinemia, most probably by acting on the tuberoinfundibular dopaminergic (TIDA) system of the hypothalamus. Dopamine (DA) produced by TIDA neurons directly inhibits prolactin secretion and, therefore, to stimulate prolactin secretion, estrogens inhibit TIDA neurons to decrease DA production. However, the mechanism by which estrogen produces this effect is not clear. In the present study, we used a paradigm involving chronic exposure to low levels of estr...

  13. The Consequences of adolescent chronic unpredictable stress exposure on brain and behavior

    OpenAIRE

    Hollis, Fiona; Isgor, Ceylan; Kabbaj, Mohamed

    2013-01-01

    There is increasing evidence for adolescence as a time period vulnerable to environmental perturbations such as stress. What is unclear is the persistent nature of the effects of stress and how specific these effects are to the type of stressor. In this review, we describe the effects of chronic, unpredictable stress (CUS) exposure during adolescence on adult behavior and brain morphology and function in animal models. We provide evidence for adolescence as a critical window for the effects o...

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

    Science.gov (United States)

    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. PMID:25795925

  15. Comparative transcriptomic responses to chronic cadmium, fluoranthene, and atrazine exposure in Lumbricus rubellus.

    Science.gov (United States)

    Svendsen, C; Owen, J; Kille, P; Wren, J; Jonker, M J; Headley, B A; Morgan, A J; Blaxter, M; Stürzenbaum, S R; Hankard, P K; Lister, L J; Spurgeon, D J

    2008-06-01

    Transcriptional responses of a soil-dwelling organism (the earthworm Lumbricus rubellus) to three chemicals, cadmium (Cd), fluoranthene (FA), and atrazine (AZ), were measured following chronic exposure, with the aim of identifying the nature of any shared transcriptional response. Principal component analysis indicated full or partial separation of control and exposed samples for each compound but not for the composite set of all control and exposed samples. Partial least-squares discriminant analysis allowed separation of the control and exposed samples for each chemical and also for the composite data set, suggesting a common transcriptional response to exposure. Genes identified as changing in expression level (by the least stringent test for significance) following exposure to two chemicals indicated a substantial number of common genes (> 127). The three compound overlapping gene set, however, comprised only 25 genes. We suggest that the low commonality in transcriptional response may be linked to the chronic concentrations (approximately 10% EC50) and chronic duration (28 days) used. Annotations of the three compound overlapping gene set indicated that genes from pathways most often associated with responses to environmental stress, such as heat shock, phase I and II metabolism, antioxidant defense, and cation balance, were not represented. The strongest annotation signature was for genes important in mitochondrial function and energy metabolism. PMID:18589989

  16. Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism.

    Science.gov (United States)

    Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2011-12-01

    The biometals iron (Fe), manganese (Mn) and copper (Cu) have been associated to Parkinson's disease (PD) and Parkinsonism. In this work, we report for the first time that acute (15 mM for up to 5 days) or chronic (0.5 mM for up to 15 days) Fe, Mn and Cu exposure significantly reduced life span and locomotor activity (i.e. climbing capabilities) in Drosophila melanogaster. It is shown that the concentration of those biometals dramatically increase in Drosophila's brain acutely or chronically fed with metal. We demonstrate that the metal accumulation in the fly's head is associated with the neurodegeneration of several dopaminergic neuronal clusters. Interestingly, it is found that the PPL2ab DAergic neuronal cluster was erode by the three metals in acute and chronic metal exposure and the PPL3 DAergic cluster was also erode by the three metals but in acute metal exposure only. Furthermore, we found that the chelator desferoxamine, ethylenediaminetetraacetic acid, and D: -penicillamine were able to protect but not rescue D. melanogaster against metal intoxication. Taken together these data suggest that iron, manganese and copper are capable to destroy DAergic neurons in the fly's brain, thereby impairing their movement capabilities. This work provides for the first time metal-induced Parkinson-like symptoms in D. melanogaster. Understanding therefore the effects of biometals in the Drosophila model may provide insights into the toxic effect of metal ions and more effective therapeutic approaches to Parkinsonism. PMID:21594680

  17. Age influence on mice lung tissue response to [i]Aspergillus fumigatus[/i] chronic exposure

    Directory of Open Access Journals (Sweden)

    Marta Kinga Lemieszek

    2015-02-01

    Full Text Available [b]Introduction and objective[/b]. Exposure to conidia of [i]Aspergillus fumigatus[/i] was described as a causative factor of a number of the respiratory system diseases, including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis and bronchopulmonary aspergillosis. The study investigates the effects of the repeated exposure to [i]A. fumigatus[/i] in mice pulmonary compartment. Our work tackles two, so far insufficiently addressed, important aspects of interaction between affected organism and[i] A. fumigatus[/i]: 1 recurrent character of exposure (characteristic for pathomechanism of the abovementioned disease states and 2 impact of aging, potentially important for the differentiation response to an antigen. [b]Materials and methods[/b]. In order to dissect alterations of the immune system involved with both aging and chronic exposure to [i]A. fumigatus[/i], we used 3- and 18-month-old C57BL/6J mice exposed to repeated[i] A. fumigatus[/i] inhalations for 7 and 28 days. Changes in lung tissue were monitored by histological and biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in lung homogenates was assessed by ELISA tests. [b]Results and conclusions. [/b]Our study demonstrated that chronic inflammation in pulmonary compartment, characterized by the significant increase of proinflammatory cytokines (IL1, IL6, IL10 levels, was the dominant feature of mice response to repeated [i]A. fumigatus[/i] inhalations. The pattern of cytokines’ profile in the course of exposure was similar in both age groups, however in old mice the growth of the cytokines’ levels was more pronounced (especially in case of IL1.

  18. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Osterndorff-Kahanek

    Full Text Available 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.

  19. Chronic Exposure to Cadmium Disrupts the Adrenal Gland Activity of the Newt Triturus carnifex (Amphibia, Urodela

    Directory of Open Access Journals (Sweden)

    Flaminia Gay

    2013-01-01

    Full Text Available We intended to verify the safety of the freshwater values established for cadmium by the European Community and the Italian Ministry of Health in drinking water (5 μg/L and sewage waters (20 μg/L. Therefore, we chronically exposed the newt Triturus carnifex to 5 μg/L and 20 μg/L doses of cadmium, respectively, during 3 and 9 months and verified the effects on the adrenal gland. We evaluated the serum concentrations of adrenocorticotropic hormone (ACTH, corticosterone, aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both doses of cadmium decreased ACTH and corticosterone serum levels and increased aldosterone and epinephrine serum levels. During the 9-month exposure, the 5 μg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels; the 20 μg/L dose decreased norepinephrine and epinephrine serum levels, without affecting the other hormones. It was concluded that (1 chronic exposure to the safety values established for cadmium disrupted the adrenal gland activity and (2 the effects of cadmium were related both to the length of exposure and the dose administered. Moreover, our results suggest probable risks to human health, due to the use of water contaminated by cadmium.

  20. Chronic Exposure to Cadmium Disrupts the Adrenal Gland Activity of the Newt Triturus carnifex (Amphibia, Urodela)

    Science.gov (United States)

    Gay, Flaminia; Laforgia, Vincenza; Caputo, Ivana; Esposito, Carla; Lepretti, Marilena

    2013-01-01

    We intended to verify the safety of the freshwater values established for cadmium by the European Community and the Italian Ministry of Health in drinking water (5 μg/L) and sewage waters (20 μg/L). Therefore, we chronically exposed the newt Triturus carnifex to 5 μg/L and 20 μg/L doses of cadmium, respectively, during 3 and 9 months and verified the effects on the adrenal gland. We evaluated the serum concentrations of adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both doses of cadmium decreased ACTH and corticosterone serum levels and increased aldosterone and epinephrine serum levels. During the 9-month exposure, the 5 μg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels; the 20 μg/L dose decreased norepinephrine and epinephrine serum levels, without affecting the other hormones. It was concluded that (1) chronic exposure to the safety values established for cadmium disrupted the adrenal gland activity and (2) the effects of cadmium were related both to the length of exposure and the dose administered. Moreover, our results suggest probable risks to human health, due to the use of water contaminated by cadmium. PMID:23971036

  1. Does chronic occupational exposure to volatile anesthetic agents influence the rate of neutrophil apoptosis?

    LENUS (Irish Health Repository)

    Goto, Y

    2012-02-03

    PURPOSE: The purpose of this preliminary investigation was to determine whether the rate of neutrophil apoptosis in health care workers is influenced by exposure to volatile anesthetic agents. METHODS: Percentage neutrophil apoptosis (Annexin-V FITC assay) was measured in health care workers (n = 20) and unexposed volunteers (n = 10). For the health care workers, time weighted personal exposure monitoring to N2O, sevoflurane and isoflurane was carried out. RESULTS: The sevoflurane and isoflurane concentrations to which health care workers were exposed were less than recommended levels in all 20 cases. Percent apoptosis was less at 24 (but not at one and 12) hr culture in health care workers [50.5 (9.7)%; P = 0.008] than in unexposed volunteers [57.3 (5.1)%]. CONCLUSION: Inhibition of neutrophil apoptosis at 24 hr culture was demonstrated in health care workers chronically exposed to volatile anesthetic agents. Exposure was well below recommended levels in the both scavenged and unscavenged work areas in which the study was carried out. Further study is required to assess the effect of greater degrees of chronic exposure to volatile anesthetic agents on neutrophil apoptosis.

  2. Chronic fluoride exposure-induced testicular toxicity is associated with inflammatory response in mice.

    Science.gov (United States)

    Wei, Ruifen; Luo, Guangying; Sun, Zilong; Wang, Shaolin; Wang, Jundong

    2016-06-01

    Previous studies have indicated that fluoride (F) can affect testicular toxicity in humans and rodents. However, the mechanism underlying F-induced testicular toxicity is not well understood. This study was conducted to evaluate the sperm quality, testicular histomorphology and inflammatory response in mice followed F exposure. Healthy male mice were randomly divided into four groups with sodium fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the end of the exposure, significantly increased percentage of spermatozoa abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of sperm cells were also observed in the NaF treated group. In addition, chronic F exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C (IL-17RC), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in transcriptional levels, as well as IL-17 and TNF-α levels in translational levels. Interestingly, we observed that F treated group elevated testicular inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO) concentration. Taken together, these results indicated that testicular inflammatory response could contribute to chronic F exposure induced testicular toxicity in mice.

  3. Influence of UF4 physico-chemical properties on the assessment of the chronic exposure to this compound

    International Nuclear Information System (INIS)

    A method was developed in order to assess uranium exposure hazards at work stations based on the industrial experience acquired by Comurhex Malvesi at Narbonne. Applied to uranium tetrafluoride (UF4) the method involves 4 steps: 1. characterization of the industrial compound, including its physico-chemical properties (density, surface area, X-ray spectrum and uranium enrichment); 2. assessment of work station concentrations and particle size distribution (AMAD); 3. In vitro biological solubility with different synthetic fluids such as Gamble solutions with different gases or compounds added (oxygen or superoxide ions O2-) in order to determine the solubility class D, W or Y; 4. workers' monitoring by routine measurements of urinary excretion completed, if necessary, by fecal excretion and γ-spectrometry. Results and present data on UF4 are presented. 3 tabs., 4 figs

  4. TBBPA chronic exposure produces sex-specific neurobehavioral and social interaction changes in adult zebrafish.

    Science.gov (United States)

    Chen, Jiangfei; Tanguay, Robert L; Simonich, Michael; Nie, Shangfei; Zhao, Yuxin; Li, Lelin; Bai, Chenglian; Dong, Qiaoxiang; Huang, Changjiang; Lin, Kuangfei

    2016-01-01

    The toxicity of tetrabromobisphenol A (TBBPA) has been extensively studied because of its high production volume. TBBPA is toxic to aquatic fish based on acute high concentration exposure tests, and few studies have assessed the behavioral effects of low concentration chronic TBBPA exposures in aquatic organisms. The present study defined the developmental and neurobehavioral effects associated with exposure of zebrafish to 0, 5 and 50nM TBBPA during 1-120days post-fertilization (dpf) following by detoxification for four months before the behaviors assessment. These low concentration TBBPA exposures were not associated with malformations and did not alter sex ratio, but resulted in reduced zebrafish body weight and length. Adult behavioral assays indicated that TBBPA exposed males had significantly higher average swim speeds and spent significantly more time in high speed darting mode and less time in medium cruising mode compared to control males. In an adult photomotor response assay, TBBPA exposure was associated with hyperactivity in male fish. Female zebrafish responses in these assays followed a similar trend, but the magnitude of TBBPA effects was generally smaller than in males. Social interaction evaluated using a mirror attack test showed that 50nM TBBPA exposed males had heightened aggression. Females exposed to 50nM TBBPA spent more time in the vicinity of the mirror, but did not show increased aggression toward the mirror compared to unexposed control fish. Overall, the hyperactivity and social behavior deficits ascribed here to chronic TBBPA exposure was most profound in males. Our findings indicate that TBBPA can cause developmental and neurobehavioral deficits, and may pose significant health risk to humans. PMID:27221227

  5. Chronic caffeine exposure attenuates blast-induced memory deficit in mice

    Institute of Scientific and Technical Information of China (English)

    Ya-Lei Ning; Nan Yang; Xing Chen; Zi-Ai Zhao; Xiu-Zhu Zhang; Xing-Yun Chen; Ping Li

    2015-01-01

    Objective:To investigate the effects of three different ways of chronic caffeine administration on blastinduced memory dysfunction and to explore the underlying mechanisms.Methods:Adult male C57BL/6 mice were used and randomly divided into five groups:control:without blast exposure,con-water:administrated with water continuously before and after blast-induced traumatic brain injury (bTBI),con-caffeine:administrated with caffeine continuously for 1 month before and after bTBI,pre-caffeine:chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI,post-caffeine:chronically administrated with caffeine after bTBI.After being subjected to moderate intensity of blast injury,mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1,4,and 8 weeks post-blast injury.Neurological deficit scoring,glutamate concentration,proinflammatory cytokines production,and neuropathological changes at 24 h,1,4,and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages.Adenosine A1 receptor expression was detected using qPCR.Results:All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit,which is correlated with the neuroprotective effects against excitotoxicity,inflammation,astrogliosis and neuronal loss at different stages of injury.Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI;pre-bTBl and post-bTBl treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively.Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.Conclusion:Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get,the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  6. NOTCH1, HIF1A and other cancer-related proteins in lung tissue from uranium miners : variation by occupational exposure and subtype of lung cancer

    OpenAIRE

    Pesch, Beate; Casjens, Swaantje; Stricker, Ingo; Westerwick, Daniela; Taeger, Dirk; Rabstein, Sylvia; Wiethege, Thorsten; Tannapfel, Andrea; Brüning, Thomas; Johnen, Georg

    2012-01-01

    Background Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative exposure to these carcinogens with NOTCH1, HIF1A and other cancer-specific proteins in lung tissue from uranium miners. Methodology/Principal Findings Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy repository by type of lung tissue, comprising adenocarcinoma (AdCa), squamous cell carcinoma (SqCC), small cell lung cancer (SCLC), and cancer-free tissue....

  7. Induction of Oxidative Stress and Antioxidative Mechanisms in Arabidopsis thaliana after Uranium Exposure at pH 7.5

    Directory of Open Access Journals (Sweden)

    Eline Saenen

    2015-06-01

    Full Text Available To evaluate the environmental impact of uranium (U contamination, it is important to investigate the effects of U at ecologically relevant conditions. Since U speciation, and hence its toxicity, strongly depends on environmental pH, the present study aimed to investigate dose-dependent effects of U at pH 7.5. Arabidopsis thaliana plants (Mouse-ear Cress were exposed for three days to different U concentrations at pH 7.5. In the roots, the increased capacities of ascorbate peroxidase and glutathione reductase indicate an important role for the ascorbate-glutathione cycle during U-induced stress. However, a significant decrease in the ascorbate redox state was observed after exposure to 75 and 100 µM U, indicating that those roots are severely stressed. In accordance with the roots, the ascorbate-glutathione cycle plays an important role in the antioxidative defence systems in A. thaliana leaves exposed to U at pH 7.5 as the ascorbate and glutathione biosynthesis were upregulated. In addition, small inductions of enzymes of the antioxidative defence system were observed at lower U concentrations to counteract the U-induced stress. However, at higher U concentrations it seems that the antioxidative defence system of the leaves collapses as reductions in enzyme activities and gene expression levels were observed.

  8. Induction of Oxidative Stress and Antioxidative Mechanisms in Arabidopsis thaliana after Uranium Exposure at pH 7.5.

    Science.gov (United States)

    Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; Van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

    2015-01-01

    To evaluate the environmental impact of uranium (U) contamination, it is important to investigate the effects of U at ecologically relevant conditions. Since U speciation, and hence its toxicity, strongly depends on environmental pH, the present study aimed to investigate dose-dependent effects of U at pH 7.5. Arabidopsis thaliana plants (Mouse-ear Cress) were exposed for three days to different U concentrations at pH 7.5. In the roots, the increased capacities of ascorbate peroxidase and glutathione reductase indicate an important role for the ascorbate-glutathione cycle during U-induced stress. However, a significant decrease in the ascorbate redox state was observed after exposure to 75 and 100 µM U, indicating that those roots are severely stressed. In accordance with the roots, the ascorbate-glutathione cycle plays an important role in the antioxidative defence systems in A. thaliana leaves exposed to U at pH 7.5 as the ascorbate and glutathione biosynthesis were upregulated. In addition, small inductions of enzymes of the antioxidative defence system were observed at lower U concentrations to counteract the U-induced stress. However, at higher U concentrations it seems that the antioxidative defence system of the leaves collapses as reductions in enzyme activities and gene expression levels were observed. PMID:26042463

  9. Oxidative stress responses induced by uranium exposure at low pH in leaves of Arabidopsis thaliana plants.

    Science.gov (United States)

    Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

    2015-12-01

    Anthropogenic activities have led to a widespread uranium (U) contamination in many countries. The toxic effects of U at the cellular level have mainly been investigated at a pH around 5.5, the optimal pH for hydroponically grown plants. However, since the speciation of U, and hence its toxicity, is strongly dependent on environmental factors such as the pH, it is important to investigate the effects of U at different environmentally relevant pH levels. Although U is poorly translocated from the roots to the shoots, resulting in a low U concentration in the leaves, it has been demonstrated that toxic effects in the leaves were already visible after 1 day exposure at pH 5.5, although only when exposed to relatively high U concentrations (100 μM). Therefore, the present study aimed to analyse the effects of different U concentrations (ranging from 0 to 100 μM) at pH 4.5 in leaves of Arabidopsis thaliana plants. Results indicate that U induces early senescence in A. thaliana leaves as was suggested by a decreased expression of CAT2 accompanied by an induction of CAT3 expression, a decreased CAT capacity and an increased lipid peroxidation. In addition, miRNA398b/c is involved in the regulation of the SOD response in the leaves. As such, an increased MIR398b/c expression was observed leading to a decreased transcript level of CSD1/2. Finally, the biosynthesis of ascorbate was induced after U exposure. This can point towards an important role for this metabolite in the scavenging of reactive oxygen species under U stress.

  10. Oxidative stress responses induced by uranium exposure at low pH in leaves of Arabidopsis thaliana plants.

    Science.gov (United States)

    Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

    2015-12-01

    Anthropogenic activities have led to a widespread uranium (U) contamination in many countries. The toxic effects of U at the cellular level have mainly been investigated at a pH around 5.5, the optimal pH for hydroponically grown plants. However, since the speciation of U, and hence its toxicity, is strongly dependent on environmental factors such as the pH, it is important to investigate the effects of U at different environmentally relevant pH levels. Although U is poorly translocated from the roots to the shoots, resulting in a low U concentration in the leaves, it has been demonstrated that toxic effects in the leaves were already visible after 1 day exposure at pH 5.5, although only when exposed to relatively high U concentrations (100 μM). Therefore, the present study aimed to analyse the effects of different U concentrations (ranging from 0 to 100 μM) at pH 4.5 in leaves of Arabidopsis thaliana plants. Results indicate that U induces early senescence in A. thaliana leaves as was suggested by a decreased expression of CAT2 accompanied by an induction of CAT3 expression, a decreased CAT capacity and an increased lipid peroxidation. In addition, miRNA398b/c is involved in the regulation of the SOD response in the leaves. As such, an increased MIR398b/c expression was observed leading to a decreased transcript level of CSD1/2. Finally, the biosynthesis of ascorbate was induced after U exposure. This can point towards an important role for this metabolite in the scavenging of reactive oxygen species under U stress. PMID:26263174

  11. The effect of chronic exposure to highly aggressive mice on hippocampal gene expression of non-aggressive subordinates

    NARCIS (Netherlands)

    Feldker, DEM; Morsink, MC; Veenema, AH; Datson, NA; Proutski, [No Value; Lathouwers, D; de Kloet, ER; Vreugdenhil, E

    2006-01-01

    Exposure to a chronic psychosocial stressor changes the behavioral and neuroendocrine response pattern and causes structural changes in the rodent hippocampus. However, the underlying molecular mechanism of these changes induced by chronic stress is largely unknown. Recently, it was shown that expos

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

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov

    2013-12-01

    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. - 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

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

    International Nuclear Information System (INIS)

    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. - 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 relationship

  14. Diffuse parenchymal lung disease in a case of chronic arsenic exposure

    Directory of Open Access Journals (Sweden)

    Somnath Bhattacharya

    2016-01-01

    Full Text Available A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD. Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date.

  15. Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.

    Directory of Open Access Journals (Sweden)

    Birger Scholz

    Full Text Available L-3,4-dihydroxypheylalanine (L-dopa-induced dyskinesia represent a debilitating complication of therapy for Parkinson's disease (PD that result from a progressive sensitization through repeated L-dopa exposures. The MPTP macaque model was used to study the proteome in dopamine-depleted striatum with and without subsequent acute and chronic L-dopa treatment using two-dimensional difference in-gel electrophoresis (2D-DIGE and mass spectrometry. The present data suggest that the dopamine-depleted striatum is so sensitive to de novo L-dopa treatment that the first ever administration alone would be able (i to induce rapid post-translational modification-based proteomic changes that are specific to this first exposure and (ii, possibly, lead to irreversible protein level changes that would be not further modified by chronic L-dopa treatment. The apparent equivalence between first and chronic L-dopa administration suggests that priming would be the direct consequence of dopamine loss, the first L-dopa administrations only exacerbating the sensitization process but not inducing it.

  16. Effects of chronic occupational exposure to anaesthetic gases on the rate of neutrophil apoptosis among anaesthetists.

    LENUS (Irish Health Repository)

    Tyther, R

    2012-02-03

    BACKGROUND AND OBJECTIVE: Volatile anaesthetic agents are known to influence neutrophil function. The aim was to determine the effect of chronic occupational exposure to volatile anaesthetic agents on the rate of neutrophil apoptosis among anaesthetists. To test this hypothesis, we compared the rate of neutrophil apoptosis in anaesthetists who had been chronically exposed to volatile anaesthetic agents with that in unexposed volunteers. METHODS: Venous blood (20 mL) was withdrawn from 24 ASA I-II volunteers, from which neutrophils were isolated, and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. RESULTS: At 1 h (but not at 12 and 24 h) in culture, the rate of neutrophil apoptosis was significantly less in the anaesthetists--13.8 (12.9%) versus 34.4 (12.1%) (P = 0.001). CONCLUSIONS: Chronic occupational exposure to volatile anaesthetic agents may inhibit neutrophil apoptosis. This may have implications for anaesthetists and similarly exposed healthcare workers in terms of the adequacy of their inflammatory response.

  17. Diffuse parenchymal lung disease in a case of chronic arsenic exposure.

    Science.gov (United States)

    Bhattacharya, Somnath; Dey, Atin; Saha, Sayantan; Kar, Saurav

    2016-01-01

    A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD). Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date. PMID:27625453

  18. The effect of chronic exposure to tobacco smoke on the antibacterial defenses of the lung.

    Science.gov (United States)

    Huber, G L; Pochay, V E; Mahajan, V K; McCarthy, C R; Hinds, W C; Davies, P; Drath, D B; Sornberger, G C

    1977-01-01

    To evaluate the effects of cigarette smoking on the host defenses of the lung, male CD rats were exposed to fresh whole smoke for up to 60 consecutive days. Intrapulmonary deposition of smoke and animal exposure levels, quantified with decachlorobiphenyl and other smoke tracers, indicated a daily cigarette exposure equivalent to approximately a pack and a half per day in man. Pulmonary alveolar macrophage function in situ was quantified by the inactivation of an aerosolized challenge of Staphylococcus aureus six hours after inoculation. Controls (n=120) inactivated 88.8+/-0.64% of the staphylococci. Exposure to whole smoke did not impair intrapulmonary antistaphylococcal defenses, with inactivation rates of 89.8+/-0.97% (n=49) and 89.1+/-0.46% (n=74) at 30 and 60 days, respectively. Inactivation distribution frequency analysis in controls revealed that 7% of animals had inactivation values greater than two standard deviations from the mean. With prolonged exposure mean with less skewing towards the abnormal. Alveolar macrophages harvested from smoked animals were comparable in viability and in vitro antistaphylococcal activity to controls, appeared to be metabolically activated and had specific stereologic ultrastructural alterations. These studies indicate that chronic exposure to tobacco smoke does not impair, and in fact may stimulate, the host defenses of the lung, as evaluated by in vivo and in vitro pulmonary alveolar macrophage function. PMID:843645

  19. Effects of chronic carbon monoxide exposure on fetal growth and development in mice

    Directory of Open Access Journals (Sweden)

    Venditti Carolina C

    2011-12-01

    Full Text Available Abstract 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 Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

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

    International Nuclear Information System (INIS)

    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 infiltration 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

  1. Reproduction recovery of the crustacean Daphnia magna after chronic exposure to ibuprofen.

    Science.gov (United States)

    Hayashi, Yuya; Heckmann, Lars-Henrik; Callaghan, Amanda; Sibly, Richard M

    2008-05-01

    In mammals, the pharmaceutical ibuprofen (IB), a non-steroidal anti-inflammatory drug, primarily functions by reversibly inhibiting the cyclooxygenase (COX) pathway in the synthesis of eicosanoids (e.g. prostaglandins). Previous studies suggest that IB may act in a similar manner to interrupt production of eicosanoids reducing reproduction in the model crustacean Daphnia magna. On this basis withdrawal of IB should lead to the recovery of D. magna reproduction. Here we test whether the effect of IB is reversible in D. magna, as it is in mammals, by observing reproduction recovery following chronic exposure. D. magna (5-days old) were exposed to a range of IB concentrations (0, 20, 40 and 80 mg l(-1)) for 10 days followed by a 10 day recovery period in uncontaminated water. During the exposure period, individuals exposed to higher concentrations produced significantly fewer offspring. Thereafter, IB-stressed individuals produced offspring faster during recovery, having similar average population growth rates (PGR) (1.15-1.28) to controls by the end of the test. It appears that maternal daphnids are susceptible to IB during egg maturation. This is the first recorded recovery of reproduction in aquatic invertebrates that suffered reproductive inhibition during chronic exposure to a chemical stressor. Our results suggest a possible theory behind the compensatory fecundity that we referred to as 'catch-up reproduction'. PMID:18214676

  2. Transient and persistent metabolomic changes in plasma following chronic cigarette smoke exposure in a mouse model.

    Directory of Open Access Journals (Sweden)

    Charmion I Cruickshank-Quinn

    Full Text Available Cigarette smoke exposure is linked to the development of a variety of chronic lung and systemic diseases in susceptible individuals. Metabolomics approaches may aid in defining disease phenotypes, may help predict responses to treatment, and could identify biomarkers of risk for developing disease. Using a mouse model of chronic cigarette smoke exposure sufficient to cause mild emphysema, we investigated whether cigarette smoke induces distinct metabolic profiles and determined their persistence following smoking cessation. Metabolites were extracted from plasma and fractionated based on chemical class using liquid-liquid and solid-phase extraction prior to performing liquid chromatography mass spectrometry-based metabolomics. Metabolites were evaluated for statistically significant differences among group means (p-value≤0.05 and fold change ≥1.5. Cigarette smoke exposure was associated with significant differences in amino acid, purine, lipid, fatty acid, and steroid metabolite levels compared to air exposed animals. Whereas 60% of the metabolite changes were reversible, 40% of metabolites remained persistently altered even following 2 months of smoking cessation, including nicotine metabolites. Validation of metabolite species and translation of these findings to human plasma metabolite signatures induced by cigarette smoking may lead to the discovery of biomarkers or pathogenic pathways of smoking-induced disease.

  3. Vascular dysfunction in patients with chronic arsenosis can be reversed by reduction of arsenic exposure.

    Science.gov (United States)

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P; Kumagai, Yoshito

    2005-03-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3 ,5 -monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean +/- SEM: male, 37.0 +/- 6.1; female, 37.2 +/- 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 +/- 5.6; female, 70.6 +/- 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure.

  4. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Sven Kroener

    Full Text Available In the present study, we used a mouse model of chronic intermittent ethanol (CIE exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC. In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP showed that CIE exposure was associated with altered expression of long-term potentiation (LTP. Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC.

  5. Quantifying Chronic Stress Exposure for Cumulative Risk Assessment: Lessons Learned from a Case Study of Allostatic Load

    Science.gov (United States)

    Although multiple methods of quantifying environmental chemical exposures have been validated for use in human health risk assessment, quantifying chronic stress exposure is more challenging. Stress is a consequence of perceiving an “exposure” (e.g., violence, poverty) as more th...

  6. Biological effects and oxidative stress responses in Arabidopsis thaliana following exposure to uranium and copper

    Energy Technology Data Exchange (ETDEWEB)

    Horemans, N.; Saenen, E.; Vandenhove, H.; Vanhoudt, N.; Wannijn, J.; Nauts, R. [Belgian Nuclear Research Centre SCK-CEN (Belgium); Vangronsveld, J.; Cuypers, A. [Hasselt University (Belgium)

    2014-07-01

    Since organisms are almost always exposed to multiple stressors, it is important to investigate the toxicity effects in plants in a multiple stressor context to provide a more realistic estimate of environmental risks. Therefore, we evaluated the toxicity of U and Cu individually and in combination. Arabidopsis thaliana plants were exposed during 3 days to 25 μM U, 2.5 μM Cu or 12.5 μM U + 1.25 μM Cu at pH 7.5. The concentrations of U and Cu administered to the plants were the derived EC30 values for plant growth reduction based on the single-dose response curves. When plants were exposed to U or Cu, this resulted in an increased metal concentration in both roots and shoots as compared to the control plants. The increased Cu content of the plant, led to a significant decrease in leaf and root growth, while U exposure did not affect plant growth. By exposing plants to both metals, it seems that Cu interferes with the translocation of U from the roots to the leaves. In addition, U interferes with the Cu uptake, since less Cu was found in the roots than expected. This can probably be explained by the fact that U causes a shift in the Cu speciation in our medium. As such, the percentage of the bioavailable fractions of Cu decreased, while the percentage Cu-EDTA (i.e. non-available fraction) increased. No effects on plant growth were observed by exposing plants to U+Cu. Exposing plants to heavy metals can lead to an increased production of reactive oxygen species (ROS). After U or Cu exposure, the transcript levels of different ROS-producing enzymes (NADPH oxidases and lipoxygenases (LOX)) were up-regulated in the roots. Furthermore, exposing plants to U+Cu resulted in a 20-fold increase in the expression of LOX1 as compared to the single stressor conditions. This possibly indicates an enhanced ROS production. In addition, the increased expression of LOX1 can also indicate an increased production of oxylipins, important molecules in inter-organ signalling. In the

  7. Chronic exposure to a beta 2-adrenoceptor agonist increases the airway response to methacholine.

    Science.gov (United States)

    Witt-Enderby, P A; Yamamura, H I; Halonen, M; Palmer, J D; Bloom, J W

    1993-09-01

    Scheduled chronic administration of beta 2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta 2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 +/- 0.11 g vs. treated group = 1.50 +/- 0.13 g, P airway smooth muscle to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901034

  8. Occupational dust exposure and chronic obstructive pulmonary disease. A systematic overview of the evidence.

    Science.gov (United States)

    Oxman, A D; Muir, D C; Shannon, H S; Stock, S R; Hnizdo, E; Lange, H J

    1993-07-01

    The object of this study was to assess the relationship between occupational dust exposure and chronic obstructive pulmonary disease (COPD). Studies were identified using MEDLINE (January 1966 to July 1991), SCISEARCH, manual review of reference lists, and personal contact with more than 30 international experts. Studies of COPD, lung function, emphysema, chronic bronchitis, or mortality in workers exposed to nonorganic dust were retrieved. Studies were included if dust exposure was measured quantitatively, and a quantitative relationship between dust exposure and one of the outcomes of interest was calculated while controlling at least for smoking and age. Methodological rigor was assessed, and data regarding the study populations, prognostic factors, and outcomes were extracted independently by two reviewers. Thirteen reports derived from four cohorts of workers met our inclusion criteria. Three of the cohorts were of coal miners and one was of gold miners. All of the studies found a statistically significant association between loss of lung function and cumulative respirable dust exposure. It was estimated that 80 (95% CI, 34 to 137) of 1,000 nonsmoking coal miners with a cumulative respirable dust exposure of 122.5 gh/m3 (considered equivalent to 35 years of work with a mean respirable dust level of 2 mg/m3) could be expected to develop a clinically important (> 20%) loss of FEV1 attributable to dust. Among 1,000 smoking miners the comparable estimate was 66 (95% CI, 49 to 84). The risk of a clinically important loss of lung function attributable to dust among nonsmoking gold miners was estimated to be three times as large as for coal miners at less than one fifth of the cumulative respirable dust exposure (21.3 gh/m3), the maximal exposure observed among the cohort of gold miners. We conclude that occupational dust is an important cause of COPD, and the risk appears to be greater for gold miners than for coal miners. One possible explanation of the greater

  9. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Parsons, Loren H; Roberto, Marisa

    2016-07-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor (CB1 ) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not Type 2 cannabinoid receptor (CB2 ) antagonism. After 2-3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naive CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naive and ethanol-exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling.

  10. Exposure to Outdoor Air Pollution and Chronic Bronchitis in Adults: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    M Waked

    2012-09-01

    Full Text Available Background: Although Lebanon is a highly polluted country, so far no study has specifically been designed to assess the association between outdoor air pollution and chronic bronchitis in this country.Objective: To assess the association between exposure to outdoor air pollution and chronic bronchitis in Lebanon. Methods: A pilot case-control study was conducted in two tertiary care hospitals. Cases consisted of patients diagnosed with chronic bronchitis by a pulmonologist and those epidemiologically confirmed. Controls included individuals free of any respiratory signs or symptoms. After obtaining informed consent, a standardized questionnaire was administered.Results: Bivariate, stratified (over smoking status and gender and multivariate analyses revealed that passive smoking at home (ORa: 2.56, 95% CI: 1.73–3.80 and at work (ORa: 1.89, 95% CI: 1.13–3.17; older age (ORa: 1.75, 95% CI: 1.55–2.39; lower education (ORa: 1.44, 95% CI: 1.21–1.72; living close to a busy road (ORa: 1.95, 95% CI: 1.31– 2.89 and to a local power plant (ORa: 1.62, 95% CI: 1.07–2.45; and heating home by hot air conditioning (ORa: 1.85, 95% CI: 1.00–3.43 were moderately associated with chronic bronchitis; an inverse association was found with heating home electrically (ORa: 0.58, 95% CI: 0.39–0.85. A positive dose-effect relationship was observed in those living close to a busy road and to a local diesel exhaust source.Conclusion: Chronic bronchitis is associated with outdoor air pollution.

  11. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus).

    Science.gov (United States)

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L(-1) for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The OCRs in all groups were significantly different than control (P muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained. PMID:27382568

  12. Uranium-induced sensory alterations in the zebrafish Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Faucher, K., E-mail: kfaucher@hotmail.fr [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France); Floriani, M.; Gilbin, R.; Adam-Guillermin, C. [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France)

    2012-11-15

    The effect of chronic exposure to uranium ions (UO{sub 2}{sup 2+}) on sensory tissues including the olfactory and lateral line systems was investigated in zebrafish (Danio rerio) using scanning electron microscopy. The aim of this study was to determine whether exposure to uranium damaged sensory tissues in fish. The fish were exposed to uranium at the concentration of 250 {mu}g l{sup -1} for 10 days followed by a depuration period of 23 days. Measurements of uranium uptake in different fish organs: olfactory rosettes and bulbs, brain, skin, and muscles, were also determined by ICP-AES and ICP-MS during the entire experimental period. The results showed that uranium displayed a strong affinity for sensory structures in direct contact with the surrounding medium, such as the olfactory and lateral line systems distributed on the skin. A decreasing gradient of uranium concentration was found: olfactory rosettes > olfactory bulbs > skin > muscles > brain. At the end of the experiment, uranium was present in non-negligible quantities in sensory tissues. In parallel, fish exposed to uranium showed severe sensory tissue alterations at the level of the olfactory and lateral line systems. In both sensory systems, the gross morphology was altered and the sensory hair cells were significantly damaged very early after the initiation of exposure (from the 3rd day). At the end of the experiment, after 23 days of depuration, the lateral line system still displayed slight tissue alterations, but approximately 80% of the neuromasts in this system had regenerated. In contrast, the olfactory system took more time to recover, as more than half of the olfactory rosettes observed remained destroyed at the end of the experiment. This study showed, for the first time, that uranium is able to damage fish sensory tissues to such an extent that tissue regeneration is delayed.

  13. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

    Science.gov (United States)

    Johnson, Jill R; Wiley, Ryan E; Fattouh, Ramzi; Swirski, Filip K; Gajewska, Beata U; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Ellis, Russ; Inman, Mark D; Jordana, Manel

    2004-02-01

    It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly. PMID:14597485

  14. Sub-chronic exposure to methylmercury at low levels decreases butyrylcholinesterase activity in rats.

    Science.gov (United States)

    Valentini, Juliana; Vicentini, Juliana; Grotto, Denise; Tonello, Raquel; Garcia, Solange C; Barbosa, Fernando

    2010-02-01

    In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 microg/kg/day) by gavage; (Group III) received MeHg (100 microg/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

  15. Chelation therapy for treatment of systemic intoxication with uranium: A review.

    Science.gov (United States)

    Šömen Joksić, Agnes; Katz, Sidney A

    2015-01-01

    Elevated levels of naturally occurring uranium have been found in small geographic areas throughout the world. Exposure of the general public to uranium is most often by the ingestion of food and water containing natural uranium from the hydrogeological environment, but this likelihood is remote. However, the risk is increased in regions where uranium is mined, milled, processed and/or fabricated as well as in the vicinity of former battlefields where depleted uranium munitions were deployed. Exposure in such cases is by the inhalation route. Internalized uranium is a long-term hazard the toxicity of which depends upon the dose and the dose rate as well as other parameters such as the chemical form and site of deposition of the uranium and the physiology of the host. The radiological toxicity and the chemical toxicity of uranium and its compounds are responsible for kidney damage and lung cancer. The vulnerable groups are the very young and the very old, individuals predisposed to hypertension or osteoporosis and individuals with chronic kidney disease. Those subject to long-term exposure from internalized uranium are a greater risk for the long-term implications. The accumulation of uranium may be mitigated by decreasing its absorption, distribution and deposition and increasing its elimination with chelating agents. The formation of soluble chelates may enhance the mobilization of uranium deposited in tissue and expedite its transport to and elimination from the renal system. The focus of this review is on the use of chelating agents to enhance decorporation of uranium thereby reducing the risk of intoxication.

  16. Chemical and biological risk assessment of chronic exposure to PAH contaminated sediments

    Energy Technology Data Exchange (ETDEWEB)

    Means, J.; McMillin, D.; Kondapi, N. [Louisiana State Univ., Baton Rouge, LA (United States)

    1995-12-31

    Chronically contaminated sediments represent a long-term source of mixtures of contaminants, exposing aquatic ecosystems to PAH through desorption and bioaccumulation. Chronic toxicity assessments must address potential of these bond contaminants. Environmental impacts and ecological health hazards of sediment-bound normal, alkylated and heterocyclic aromatic hydrocarbons are functions of their entry into aquatic food webs and are controlled by both abiotic and biotic factors. Laboratory and field microcosm exposures of fish and invertebrates were conducted followed by assessments of effects using chemical analysis and biomarkers of potential genotoxic effects. Chemical analysis of accumulated residues of 62 individual PAH were conducted in oysters, Crassostrea virginica exposed to PAH contaminated sediments in the field. The rates and equilibrium bioaccumulation constants for each were determined. Fish were exposed to the same contaminated sediments in laboratory and field exposures. Measurements of ethoxy-resorufin-o-deethylase activity induction as well as alterations in the expression of the p53 tumor suppressor gene were performed on exposed fish liver samples. EROD activities were increased significantly relative to unexposed and laboratory/field control sediment-exposed fish, however, the responses of individuals were highly variable. Fundulus grandis or Gambusia affinis, exposed to contaminated sediments in the laboratory, revealed changes in the expression of the p53 tumor suppressor gene. The degree to which mutations within the gene occurred was assessed using PCR followed by measurement of single stranded DNA polymorphisms using gel electrophoresis chromatography.

  17. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants

    Science.gov (United States)

    Reichwaldt, Elke S.; Stone, Daniel; Barrington, Dani J.; Sinang, Som C.; Ghadouani, Anas

    2016-01-01

    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a ‘high’ risk to develop Day Away From Work illness, and lakes that present a ‘low’ or ‘medium’ risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants. PMID:27589798

  18. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    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.

  19. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants.

    Science.gov (United States)

    Reichwaldt, Elke S; Stone, Daniel; Barrington, Dani J; Sinang, Som C; Ghadouani, Anas

    2016-01-01

    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a 'high' risk to develop Day Away From Work illness, and lakes that present a 'low' or 'medium' risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants. PMID:27589798

  20. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    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. PMID:26965573

  1. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants

    Directory of Open Access Journals (Sweden)

    Elke S. Reichwaldt

    2016-08-01

    Full Text Available Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a ‘high’ risk to develop Day Away From Work illness, and lakes that present a ‘low’ or ‘medium’ risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants.

  2. Chronic Ethanol Exposure Effects on Vitamin D Levels Among Subjects with Alcohol Use Disorder

    Science.gov (United States)

    Ogunsakin, Olalekan; Hottor, Tete; Mehta, Ashish; Lichtveld, Maureen; McCaskill, Michael

    2016-01-01

    Vitamin D has been previously recognized to play important roles in human immune system and function. In the pulmonary system, vitamin D regulates the function of antimicrobial peptides, especially cathelicidin/LL-37. Human cathelicidin/LL-37 is a bactericidal, bacteriostatic, and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce levels of vitamin D (inactive vitamin D [25(OH)D3] and active vitamin D [1, 25(OH)2D3]) and leads to downregulation of cathelicidin/LL-37. Alcohol-mediated reduction of LL-37 may be partly responsible for increased incidence of more frequent and severe respiratory infections among subjects with alcohol use disorder (AUD). The objective of this study was to investigate the mechanisms by which alcohol exerts its influence on vitamin D metabolism. In addition, the aim was to establish associations between chronic alcohol exposures, levels of pulmonary vitamin D, and cathelicidin/LL-37 using broncho-alveolar lavage fluid samples of subjects with AUD and healthy controls. Findings from the experiment showed that levels of inactive vitamin D (25(OH)D3), active vitamin D (1, 25(OH)2D3), cathelicidin/LL-37, and CYP27B1 proteins were significantly reduced (P vitamin D and results in subsequent downregulation of the antimicrobial peptide, LL-37, in the human pulmonary system.

  3. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  4. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    Science.gov (United States)

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  5. Effects of Chronic Exposure to Sodium Arsenate on Kidney of Rats

    Directory of Open Access Journals (Sweden)

    Namdar Yousofvand

    2015-09-01

    Full Text Available Background: In the present study, histopathological effects of chronic exposure to sodium arsenate in drinkable water were studied on a quantity of organs of rat. Methods: Rats were divided into two groups, group I; served as control group, were main-tained on deionized drinkable water for 2 months, and group II; the study group were given 60 g/ml of sodium arsenate in deionized drinkable water for 2 months. Blood and urine samples from two groups of animals were collected under anesthesia and the animals were sacrificed under deep anesthesia (a-chloralose, 100 mg/kg, I.P. Their kidney, liver, aorta, and heart were dissected out and cleaned of surrounding connective tissue. The organs were kept in formaldehyde (10% for histopathologic examination. Serum and urine samples from two groups were collected and analyzed for arsenic level. Total quantity of arsenic in serum and urine of animal was measured through graphic furnace atomic absorption spectrometry (GF-AAS. Results:Examination with light microscopy did not show any visible structural changes in the aorta, myocardium, and liver of chronic arsenic treated animals.However, a significant effect was observed in the kidneys of chronic arsenic treated rats showing distinct changes in proxi-mal tubular cells. There was high concentration of arsenic in serum and urine of arsenic ex-posed animals (group II significantly (P<0.001. Conclusion:Swollen tubular cells in histopathologic study of kidney may suggest toxic effects of arsenic in the body.

  6. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    Science.gov (United States)

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  7. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    International Nuclear Information System (INIS)

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

  8. Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice.

    Science.gov (United States)

    Li, Quanxi; Davila, Juanmahel; Kannan, Athilakshmi; Flaws, Jodi A; Bagchi, Milan K; Bagchi, Indrani C

    2016-05-01

    Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although 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 this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:27022677

  9. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    International Nuclear Information System (INIS)

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 µg cm−2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the

  10. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    Science.gov (United States)

    Zhang, Hanyuan; Lohcharoenkal, Warangkana; Sun, Jianbo; Li, Xiang; Wang, Liying; Wu, Nianqiang; Rojanasakul, Yon; Liu, Yuxin

    2016-01-01

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 μg cm−2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the

  11. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    Science.gov (United States)

    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.

  12. Chronic toxicity of heavy fuel oils to fish embryos using multiple exposure scenarios.

    Science.gov (United States)

    Martin, Jonathan D; Adams, Julie; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V

    2014-03-01

    The chronic toxicity to rainbow trout (Oncorhynchus mykiss) embryos of heavy fuel oil (HFO) 6303, weathered HFO 6303, HFO 7102, and medium South American (MESA) crude oil was assessed by different exposure regimes. These included water accommodated fractions (WAF; water in contact with floating oil), chemically enhanced WAF (CEWAF; oil dispersed with Corexit 9500), and effluent from columns of gravel coated with stranded oil. Heavy fuel oil WAF was nontoxic and did not contain detectable concentrations of hydrocarbons, likely because the high density and viscosity of HFO prevented droplet formation. In contrast, chemically dispersed HFO and effluent from columns of stranded HFO contained measurable concentrations of alkyl polycyclic aromatic hydrocarbons (PAH), coincident with embryo toxicity. These exposure regimes enhanced the surface area of oil in contact with water, facilitating oil-water partitioning of hydrocarbons. Heavy fuel oil was consistently more toxic to fish than crude oil and the rank order of alkyl PAH concentrations in whole oil were sufficient to explain the rank order of toxicity, regardless of exposure method. Thus, the propensity of HFO to sink and strand in spawning shoals creates a long-term risk to developing fish because of the sustained release of PAHs from HFO to interstitial waters. Further, PAH monitoring is key to accurate risk assessment.

  13. Chronic neonicotinoid pesticide exposure and parasite stress differentially affects learning in honeybees and bumblebees.

    Science.gov (United States)

    Piiroinen, Saija; Goulson, Dave

    2016-04-13

    Learning and memory are crucial functions which enable insect pollinators to efficiently locate and extract floral rewards. Exposure to pesticides or infection by parasites may cause subtle but ecologically important changes in cognitive functions of pollinators. The potential interactive effects of these stressors on learning and memory have not yet been explored. Furthermore, sensitivity to stressors may differ between species, but few studies have compared responses in different species. Here, we show that chronic exposure to field-realistic levels of the neonicotinoid clothianidin impaired olfactory learning acquisition in honeybees, leading to potential impacts on colony fitness, but not in bumblebees. Infection by the microsporidian parasiteNosema ceranaeslightly impaired learning in honeybees, but no interactive effects were observed.Nosemadid not infect bumblebees (3% infection success). Nevertheless,Nosema-treated bumblebees had a slightly lower rate of learning than controls, but faster learning in combination with neonicotinoid exposure. This highlights the potential for complex interactive effects of stressors on learning. Our results underline that one cannot readily extrapolate findings from one bee species to others. This has important implications for regulatory risk assessments which generally use honeybees as a model for all bees. PMID:27053744

  14. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure.

    Science.gov (United States)

    Jessop, Forrest; Hamilton, Raymond F; Rhoderick, Joseph F; Shaw, Pamela K; Holian, Andrij

    2016-10-15

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5(fl/fl)LysM-Cre(+) mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5(fl/fl)LysM-Cre(+) mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis.

  15. Effects of Chronic Ochratoxin A Exposure on p53 Heterozygous and p53 Homozygous Mice.

    Science.gov (United States)

    Bondy, Genevieve S; Caldwell, Donald S; Aziz, Syed A; Coady, Laurie C; Armstrong, Cheryl L; Curran, Ivan H A; Koffman, Robyn L; Kapal, Kamla; Lefebvre, David E; Mehta, Rekha

    2015-07-01

    Exposure to the mycotoxin ochratoxin A (OTA) causes nephropathy in domestic animals and rodents and renal tumors in rodents and poultry. Humans are exposed to OTA by consuming foods made with contaminated cereal grains and other commodities. Management of human health risks due to OTA exposure depends, in part, on establishing a mode of action (MOA) for OTA carcinogenesis. To further investigate OTA's MOA, p53 heterozygous (p53+/-) and p53 homozygous (p53+/+) mice were exposed to OTA in diet for 26 weeks. The former are susceptible to tumorigenesis upon chronic exposure to genotoxic carcinogens. OTA-induced renal damage but no tumors were observed in either strain, indicating that p53 heterozygosity conferred little additional sensitivity to OTA. Renal changes included dose-dependent increases in cellular proliferation, apoptosis, karyomegaly, and tubular degeneration in proximal tubules, which were consistent with ochratoxicosis. The lowest observed effect level for renal changes in p53+/- and p53+/+ mice was 200 μg OTA/kg bw/day. Based on the lack of tumors and the severity of renal and body weight changes at a maximum tolerated dose, the results were interpreted as suggestive of a primarily nongenotoxic (epigenetic) MOA for OTA carcinogenesis in this mouse model.

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

    Science.gov (United States)

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

    2015-05-01

    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. PMID:25634958

  17. Histopathologic alterations associated with global gene expression due to chronic dietary TCDD exposure in juvenile zebrafish.

    Directory of Open Access Journals (Sweden)

    Qing Liu

    Full Text Available The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb and male (18.04 ppb fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption.

  18. NOTCH1, HIF1A and other cancer-related proteins in lung tissue from uranium miners--variation by occupational exposure and subtype of lung cancer.

    Directory of Open Access Journals (Sweden)

    Beate Pesch

    Full Text Available BACKGROUND: Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative exposure to these carcinogens with NOTCH1, HIF1A and other cancer-specific proteins in lung tissue from uranium miners. METHODOLOGY/PRINCIPAL FINDINGS: Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy repository by type of lung tissue, comprising adenocarcinoma (AdCa, squamous cell carcinoma (SqCC, small cell lung cancer (SCLC, and cancer-free tissue. Within each stratum, we additionally stratified by low or high level of exposure to radon or arsenic. Lifetime exposure to radon and arsenic was estimated using a quantitative job-exposure matrix developed for uranium mining. For 22 cancer-related proteins, immunohistochemical scores were calculated from the intensity and percentage of stained cells. We explored the associations of these scores with cumulative exposure to radon and arsenic with Spearman rank correlation coefficients (r(s. Occupational exposure was associated with an up-regulation of NOTCH1 (radon r(s = 0.18, 95% CI 0.02-0.33; arsenic: r(s = 0.23, 95% CI 0.07-0.38. Moreover, we investigated whether these cancer-related proteins can classify lung cancer using supervised and unsupervised classification. MUC1 classified lung cancer from cancer-free tissue with a failure rate of 2.1%. A two-protein signature discriminated SCLC (HIF1A low, AdCa (NKX2-1 high, and SqCC (NKX2-1 low with a failure rate of 8.4%. CONCLUSIONS/SIGNIFICANCE: These results suggest that the radiation-sensitive protein NOTCH1 can be up-regulated in lung tissue from uranium miners by level of exposure to pulmonary carcinogens. We evaluated a three-protein signature consisting of a physiological protein (MUC1, a cancer-specific protein (HIF1A, and a lineage-specific protein (NKX2-1 that could discriminate lung cancer and its major subtypes with a low failure rate.

  19. Kalrn promoter usage and isoform expression respond to chronic cocaine exposure

    Directory of Open Access Journals (Sweden)

    Ma Xin-Ming

    2011-02-01

    Full Text Available Abstract Background The long-term effects of cocaine on behavior are accompanied by structural changes in excitatory glutamatergic synapses onto the medium spiny neurons of the striatum. The Kalrn gene encodes several functionally distinct isoforms; these multidomain guanine nucleotide exchange factors (GEFs contain additional domains known to interact with phosphatidylinositides as well as with a number of different proteins. Through their activation of Rho proteins and their interactions with other proteins, the different Kalirin isoforms affect cytoskeletal organization. Chronic exposure of adult male rodents to cocaine increases levels of Kalirin 7 in the striatum. When exposed chronically to cocaine, mice lacking Kalirin 7, the major adult isoform, fail to show an increase in dendritic spine density in the nucleus accumbens, show diminished place preference for cocaine, and exhibit increased locomotor activity in response to cocaine. Results The use of alternate promoters and 3'-terminal exons of the mouse Kalrn gene were investigated using real-time quantitative polymerase chain reaction. While the two most distal full-length Kalrn promoters are used equally in the prefrontal cortex, the more proximal of these promoters accounts for most of the transcripts expressed in the nucleus accumbens. The 3'-terminal exon unique to the Kalirin 7 isoform accounts for a greater percentage of the Kalrn transcripts in prefrontal cortex than in nucleus accumbens. Western blot analyses confirmed these differences. Chronic cocaine treatment increases usage of the promoter encoding the Δ-Kalirin isoforms but does not alter full-length Kalirin promoter usage. Usage of the 3'-terminal exon unique to Kalirin 7 increases following chronic cocaine exposure. Conclusions Kalrn promoter and 3'-terminal exon utilization are region-specific. In the nucleus accumbens, cocaine-mediated alterations in promoter usage and 3'-terminal exon usage favor expression of

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

    Science.gov (United States)

    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

  1. Impact of chronic neonicotinoid exposure on honeybee colony performance and queen supersedure.

    Directory of Open Access Journals (Sweden)

    Christoph Sandrock

    Full Text Available 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

  2. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus)

    OpenAIRE

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The...

  3. Chronic uranium contamination alters spinal motor neuron integrity via modulation of SMN1 expression and microglia recruitment.

    Science.gov (United States)

    Saint-Marc, Brice; Elie, Christelle; Manens, Line; Tack, Karine; Benderitter, Marc; Gueguen, Yann; Ibanez, Chrystelle

    2016-07-01

    Consequences of uranium contamination have been extensively studied in brain as cognitive function impairments were observed in rodents. Locomotor disturbances have also been described in contaminated animals. Epidemiological studies have revealed increased risk of motor neuron diseases in veterans potentially exposed to uranium during their military duties. To our knowledge, biological response of spinal cord to uranium contamination has not been studied even though it has a crucial role in locomotion. Four groups of rats were contaminated with increasing concentrations of uranium in their drinking water compared to a control group to study cellular mechanisms involved in locomotor disorders. Nissl staining of spinal cord sections revealed the presence of chromatolytic neurons in the ventral horn. This observation was correlated with a decreased number of motor neurons in the highly contaminated group and a decrease of SMN1 protein expression (Survival of Motor Neuron 1). While contamination impairs motor neuron integrity, an increasing number of microglial cells indicates the trigger of a neuroinflammation process. Potential overexpression of a microglial recruitment chemokine, MCP-1 (Monocyte Chimioattractant Protein 1), by motor neurons themselves could mediate this process. Studies on spinal cord appear to be relevant for risk assessment of population exposed via contaminated food and water. PMID:27153795

  4. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

    Science.gov (United States)

    Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

    2007-01-01

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. PMID:16762466

  5. Regional alterations of brain biogenic amines in young rats following chronic lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dubas, T.C.; Stevenson, A.; Singhal, R.L.; Hrdina, P.D.

    1978-02-01

    An examination was made of neurochemical changes that occur in discrete brain regions of rats that have been chronically exposed to low levels of lead from birth, in order to provide further information on the involvement of brain biogenic amines in lead-induced neurotoxicity. Results indicate a relationship between exposure to lead and alterations in the brain levels of various putative neurotransmitters. However, changes in the functional activity of the neurotransmitter may not be adequately reflected in the change of its steady-state levels or may occur even in the absence of any changes in the actual concentrations. Lead may influence central neurotransmitter function by affecting one or several of the processes involved in the synthesis, release and/or disposition of biogenic amines.

  6. Chronic estrogen exposure maintains elevated levels of progesterone receptor mRNA in guinea pig hypothalamus.

    Science.gov (United States)

    Bayliss, D A; Millhorn, D E

    1991-05-01

    We performed in situ hybridization on hypothalamic sections from ovariectomized guinea pig using a cocktail of three 35S-labeled oligonucleotides complementary to mammalian progesterone receptor (PR) cDNA. PR mRNA was readily detected in hypothalamic neurons from guinea pigs pretreated with 17 beta-estradiol benzoate (E2B), but not from animals which did not receive supplemental E2B. The distribution of PR mRNA-containing cells corresponded well with previous localizations of PR in guinea pig. In contrast to earlier reports of E2B regulation of PR mRNA in rat hypothalamus, however, we found that PR mRNA remained elevated during chronic exposure to E2B (up to 10 days) in guinea pig. PMID:2072827

  7. Assessing Cumulative Thermal Stress in Fish During Chronic Exposure to High Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Bevelhimer, M.S.; Bennett, W.R.

    1999-11-14

    As environmental laws become increasingly protective, and with possible future changes in global climate, thermal effects on aquatic resources are likely to receive increasing attention. Lethal temperatures for a variety of species have been determined for situations where temperatures rise rapidly resulting in lethal effects. However, less is known about the effects of chronic exposure to high (but not immediately lethal) temperatures and even less about stress accumulation during periods of fluctuating temperatures. In this paper we present a modeling framework for assessing cumulative thermal stress in fish. The model assumes that stress accumulation occurs above a threshold temperature at a rate depending on the degree to which the threshold is exceeded. The model also includes stress recovery (or alleviation) when temperatures drop below the threshold temperature as in systems with large daily variation. In addition to non-specific physiological stress, the model also simulates thermal effects on growth.

  8. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

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    Adamcakova-Dodd Andrea

    2012-06-01

    Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

  9. Effect of head-only sub-chronic GSM exposure on spatial memory of rats

    International Nuclear Information System (INIS)

    Full text: Introduction: Low power electromagnetic fields (EMF) are suspected to produce deficit memory in rats. The study of Dubreuil et al (2003) showed that a short-term (10-15 days) exposure 'head-only' to GSM 900 MHz radio frequencies does not produce a deficit memory in adult rats. The aim of our experiment was to determine if head-only sub-chronic exposure (2 months) of rats to GSM signal for 45 min at a SAR = 1.5 W/Kg and for 15 min at 6 W/Kg induce deficit in spatial memory of rats in radial maze test. Materials and methods: Exposure system: Animals were placed in Plexiglas rockets with an individual loop antenna placed above the rat's head. Four animals were exposed at the time. Loop antennas were connected to a generator and emitted a GSM signal (900 MHz, pulsed at 217 Hz, 1/8 duty factor) 5 days / week for 8 weeks. Experimental group: 30 Sprague-Dawley male rats were randomly assigned to 5 different groups: a) 6 rats exposed 15 min at SAR = 6 W/Kg; b) 6 rats exposed 45 min at SAR = 1.5 W/g; c) 6 rats sham controls (3 for 5 min and 3 for 45 min, SAR = 0 W/Kg); d) 6 rats without any treatment and manipulation (cage control); e) 6 rats were injected (i.p) S.B.H 0.1 mg/Kg (Sigma Aldrich) as positive control group. Behavioural procedure: The radial maze protocol consists of two consecutive phases: the training task (10 days) and the test task (8 days). In the first phase, rats were trained to visit the 8 arms of the maze without returning to an arm already visited. In the second phase (8 days), a 45-min intra-trial delay was introduced after four visited arms. After the intra-delay, the rat was placed in the maze to finish the test task, which is visiting four other arms he had not visited. During the training task, exposure took place before the behavioural task. During the test task, exposure or sham-exposure took place during the intra-delay. Results and discussion: In all experiments, performance of exposed rats (1.5 and 6 W/Kg) was compared with that of

  10. Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

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    Jill R Johnson

    Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.

  11. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  12. Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

    Directory of Open Access Journals (Sweden)

    B Balali-Mood

    2008-01-01

    Full Text Available The widespread use of sulphur mustard (SM as an incapacitating chemical warfare agent in the past century has proved its long-lasting toxic effects. It may also be used as a chemical terrorist agent. Therefore, all health professionals should have sufficient knowledge and be prepared for any such chemical attack. SM exerts direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, immunological, haematological, digestive, and reproductive systems. SM is an alkylating agent that affects DNA synthesis, and, thus, delayed complications have been seen since the First World War. Cases of malignancies in the target organs, particularly in haematopoietic, respiratory, and digestive systems, have been reported. Important delayed respiratory complications include chronic bronchitis, bronchiectasis, frequent bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with time. Severe dry skin, delayed keratitis, and reduction of natural killer cells with subsequent increased risk of infections and malignancies are also among the most distressing long-term consequences of SM intoxication. However, despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Immunological and neurological dysfunction, as well as the relationship between SM exposure and mutagenicity, carcinogenicity, and teratogenicity are important fields that require further studies, particularly on Iranian veterans with chronic health effects of SM poisoning. There is also a paucity of information on the medical management of acute and delayed toxic effects of SM poisoning—a subject that greatly challenges health care specialists.

  13. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

    Institute of Scientific and Technical Information of China (English)

    潘宝龙

    2013-01-01

    Objective To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in SpragueDawley (SD) rats.Methods Thirty-two male SD rats were randomly and equally divided into 4 groups:control group and high-,middle-,and low-dose exposure groups.The rats in high-,middle-,and low-dose expo-

  14. Creatine kinase isoenzyme patterns upon chronic exposure to cigarette smoke: protective effect of Bacoside A.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2005-01-01

    Cigarette smoking is implicated as a major risk factor in the development of cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the assessment of cardiac and cerebral damage. Therefore, in the present study, we report the isoenzyme patterns of CK in rats upon exposure to cigarette smoke and the protective effect of Bacoside A against chronic smoking induced toxicity. Adult male albino rats were exposed to cigarette smoke and simultaneously administered with Bacoside A, the active constituent from the plant Bacopa monniera, for a period of 12 weeks. The activity of CK was assayed in serum, heart and brain, and its isoenzymes in serum were separated electrophoretically. Rats exposed to cigarette smoke showed significant increase in serum CK activity with concomitant decrease in heart and brain. Also cigarette smoke exposure resulted in a marked increase in all the three isoforms in serum. Administration of Bacoside A prevented these alterations induced by cigarette smoking. Cigarette smoking is known to cause free radical mediated lipid peroxidation leading to increased membrane permeability and cellular damage in the heart and brain resulting in the release of CK into the circulation. The protective effect of Bacoside A on the structural and functional integrity of the membrane prevented the leakage of CK from the respective tissues, which could be attributed to its free radical scavenging and anti-lipid peroxidative effect.

  15. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    Science.gov (United States)

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  16. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

    Energy Technology Data Exchange (ETDEWEB)

    Jager, Tjalling [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)]. E-mail: tjalling@bio.vu.nl; Crommentuijn, Trudie [Ministry of Spatial Planning, Housing and the Environment (VROM), Rijnstraat 8, P.O. Box 30945, 2500 GX, The Hague (Netherlands); Gestel, Cornelis A.M. van [Department of Animal Ecology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands); Kooijman, Sebastiaan A.L.M. [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)

    2007-01-15

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms.

  17. [MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].

    Science.gov (United States)

    Byelinska, I V; Lynchak, O V; Tsyvinska, S M; Rybalchenko, V K

    2015-01-01

    The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug PMID:26552308

  18. Effects of Sub-chronic Aluminum Exposure on Renal Structure in Rats

    Institute of Scientific and Technical Information of China (English)

    Li Yan-fei; Liu Jian-yu; Cao Zheng

    2015-01-01

    To investigate the effects of aluminum (Al) exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 (control group, GC), 64.18 (low-dose group, GL), 128.36 (middle-dose group, GM), and 256.72 (high-dose group, GH) mg• kg-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC (P<0.05;P<0.01). After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic Al exposure slowed the weight of rats and caused the kidney pathologic damage in rats.

  19. Response of tibialis anterior tendon to a chronic exposure of stretch-shortening cycles: age effects

    Directory of Open Access Journals (Sweden)

    Baker Brent B

    2009-06-01

    Full Text Available Abstract Background The purpose of the current study was to investigate the effects of aging on tendon response to repetitive exposures of stretch-shortening cycles (SSC's. Methods The left hind limb from young (3 mo, N = 4 and old (30 mo, N = 9 male Fisher 344 × Brown Norway rats were exposed to 80 maximal SSCs (60 deg/s, 50 deg range of motion 3x/week for 4.5 weeks in vivo. After the last exposure, tendons from the tibialis anterior muscle were isolated, stored at -80°C, and then tested using a micro-mechanical testing machine. Deformation of each tendon was evaluated using both relative grip-to-grip displacements and reference marks via a video system. Results At failure, the young control tendons had higher strain magnitude than the young exposed (p Conclusion The chronic protocol enhanced the elastic stiffness of young tendon and the loads in both the young and old tendons. The old exposed tendons were found to exhibit higher load capacity than their younger counterparts, which differed from our initial hypothesis.

  20. Pulmonary and hepatic injury after sub-chronic exposure to sublethal doses of microcystin-LR.

    Science.gov (United States)

    Carvalho, Giovanna Marcella Cavalcante; Oliveira, Vinícius Rosa; Casquilho, Natália Vasconcelos; Araujo, Andressa Cristine Pereira; Soares, Raquel Moraes; Azevedo, Sandra Maria F O; Pires, Karla Maria Pereira; Valença, Samuel Santos; Zin, Walter Araujo

    2016-03-15

    We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 μL, CTRL) or different doses of MCLR (5 μg/kg, TOX5), 10 μg/kg (TOX10), 15 μg/kg (TOX15) and 20 μg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group. PMID:26844922

  1. Deer carcass decomposition and potential scavenger exposure to chronic wasting disease

    Science.gov (United States)

    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.

  2. Alteration of Pentylenetetrazol-induced kindling parameters by prenatal chronic Lead exposure in rats

    Directory of Open Access Journals (Sweden)

    Kebriyaei Zadeh A

    2001-08-01

    Full Text Available The effect of prenatal chronic lead exposure on pentylenetetrazol (PTZ-induced kindling parameters (seizure index, seizure latency and seizure stage in rats was studied. Adult female rats with a weight range of 140-180 g were selected and pretreated with lead acetate (0.05% w/v orally, 25 days prior to mating. The control group was given distilled water containing sodium acetate solution (0.05% w/v. After delivery, treatment was ceased, and after lactation, male neonates were separated from the females in both groups. After maturation of male rats, the PTZ-kindling was induced by daily interapritoneally injection of PTZ (30 mg/kg. Kindling parameters in the control and treated groups were determined. The results indicated that animals with prenatal lead exposure have full kindling state with 9-19 (16.87±1.54 injections, whereas this value for control group was 12-23 (18.62±1.48 injections. The seizure latency for the treated group was lower (P<0.05 than the control (2.29±0.44 min versus 3.65±0.45 min. The seizure severity (regarding to seizure index was statistically higher in the treated group (P<0.05. The seizure stages were also different in the treated and control groups (P<0.05. The seizure frequency of first and second stages of kindling in the control group was higher than that of treated one (P<0.05. Also the seizure frequency in the third and fourth kindling stages of case group was higher than controls (P<0.05. It is concluded that prenatal lead exposure alters seizure susceptibility in rat PTZ-Kindling model.

  3. Agricultural adjuvants: acute mortality and effects on population growth rate of Daphnia pulex after chronic exposure.

    Science.gov (United States)

    Stark, John D; Walthall, William K

    2003-12-01

    Acute and chronic toxicity of eight agricultural adjuvants (Bond, Kinetic, Plyac, R-11, Silwet L-77, Sylgard 309, X-77, and WaterMaxx) to Daphnia pulex were evaluated with 48-h acute lethal concentration estimates (LC50) and a 10-d population growth-rate measurement, the instantaneous rate of increase (r1). Based on LC50, the order of toxicity was R-11 > X-77 = Sylgard 309 = Silwet L-77 > Kinetic > Bond > Plyac > WaterMaxx; all LC50 estimates were higher than the expected environmental concentration (EEC) of 0.79 mg/L, indicating that none of these adjuvants should cause high levels of mortality in wild D. pulex populations. Extinction, defined as negative population growth rate, occurred after exposure to 0.9 mg/L R-11, 13 mg/L X-77, 25 mg/L Kinetic, 28 mg/L Silwet, 18 mg/L Sylgard, 450 mg/L Bond, 610 mg/L Plyac, and 1,600 mg/L WaterMaxx. Concentrations that caused extinction were substantially below the acute LC50 for R-11, Kinetic, Plyac, X-77, and Bond. The no-observable-effects concentration (NOEC) and lowest-observable-effects concentration (LOEC) for the number of offspring per surviving female after exposure to R-11 were 0.5 and 0.75 mg/L, respectively. The NOEC and LOEC for population size after exposure to R-11 were (1.25 and 0.5 mg/L, respectively. Both of these values were lower than the EEC, indicating that R-11 does have the potential to cause damage to D. pulex populations after application at recommended field rates. The wide range of concentrations causing extinction makes it difficult to generalize about the potential impacts that agricultural adjuvants might have on aquatic ecosystems. Therefore, additional studies that examine effects on other nontarget organisms and determine residues in aquatic ecosystems may be warranted.

  4. Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival.

    Directory of Open Access Journals (Sweden)

    Giuseppe Pani

    Full Text Available During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays or during chronic (Californium-252 exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight.

  5. Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival.

    Science.gov (United States)

    Pani, Giuseppe; Verslegers, Mieke; Quintens, Roel; Samari, Nada; de Saint-Georges, Louis; van Oostveldt, Patrick; Baatout, Sarah; Benotmane, Mohammed Abderrafi

    2016-01-01

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight. PMID:27203085

  6. Effects of chronic exposure to ionising radiation in the Pacific oyster Crassostrea gigas

    Energy Technology Data Exchange (ETDEWEB)

    Fievet, B.; Devos, A.; Voiseux, C.; Leconte-Pradines, C. [Institut de Radioprotection et de Surete' Nucleaire (France); Dallas, L.; Jha, A. [University of Plymouth (United Kingdom)

    2014-07-01

    The Cotentin peninsula (Normandy, France) hosts nuclear industry facilities which operate with controlled discharges of radionuclides in the marine environment. Compared to natural radioactivity, the increase by artificial radionuclides is small but constant. As a consequence, marine species are chronically exposed to low additional doses of ionizing radiation (IR). The effects of chronic exposure to radionuclides were investigated in early stages of development of the Japanese oyster Crassostrea gigas. On the basis of literature, mollusks are expected to be particularly resistant to acute IR (UNSCEAR, 1996. Sources and effects of ionizing radiation. Report to the General Assembly, with Scientific Annex. 86 p). Two different chronic exposure conditions consisted in external ({sup 137}Cs) and internal ({sup 241}Am) irradiation for two weeks. Biological endpoints were analyzed in parallel at both the integrated (growth) and molecular (target stress gene expression) levels. To identify potential biological targets of IR, oysters were first exposed to very high dose rates and radionuclide activities with the perspective to reduce the levels and to derive dose-response curves. Although the initial exposure levels ({sup 137}Cs 30 000 μGy.h{sup -1}; {sup 241}Am 57 000 Bq.L{sup -1}) were many orders of magnitude higher than those encountered in the natural environment, no significant change in the measured parameters was observed. This result was surprising because data from the literature showed that exposure of mussel Mytilus edulis to {sup 3}H at lower doses rates (10-100 μGy.h{sup -1}) induced DNA damage in hemocytes (Jha et al., 2005. Impact of low doses of tritium on the marine mussel, Mytilus edulis: Genotoxic effects and tissue-specific bioconcentration. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 586, 47-57). To understand this apparent discrepancy between those two filtering bivalves, a new experiment was performed to compare the response

  7. HEALTH RISKS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER: FINDINGS FROM THE CLINICAL INVESTIGATIONS DATA IN INNER MONGOLIA, CHINA

    Science.gov (United States)

    Prior studies have reported a large number of arsenicism cases in the Mongolia Autonomous Region of China due to drinking arsenic-contaminated water with concentrations up to 1.8 mg/L. However, the endemic health risks from chronic exposure to arsenic in this population have not...

  8. A novel mouse model for the study of the inhibitory effects of chronic ethanol exposure on direct bone formation

    Science.gov (United States)

    Excessive alcohol consumption has been reported to interfere with human bone homeostasis and repair in multiple ways. Previous studies have demonstrated that chronic ethanol exposure in the rat via an intragastric dietary delivery system inhibits direct bone formation during distraction osteogenesis...

  9. Evaluation of the developmental and reproductive toxicity of methoxychlor using an anuran (Xenopus tropicalis) chronic exposure model.

    Science.gov (United States)

    Fort, Douglas J; Thomas, John H; Rogers, Robert L; Noll, Andra; Spaulding, Clinton D; Guiney, Patrick D; Weeks, John A

    2004-10-01

    The chronic toxicity of methoxychlor to the South African clawed frog, Xenopus (Silurana) tropicalis, was evaluated using a life cycle approach. The chronic exposure period ranged from mid-cell blastula stage [NF (Nieuwkoop and Faber, 1994) stage 8] to 90 days of exposure, during which time the organisms generally completed metamorphosis and emerged as juvenile frogs. Methoxychlor concentrations ranged from 1 to 100 micrograms/l. Methoxychlor concentrations >10 micrograms/l caused delayed development. Organisms exposed to 10 micrograms/l methoxychlor for 30 days showed enlarged thyroid glands with follicular hyperplasia. No increase in mortality or external malformation was observed at any of the test concentrations during early embryo-larval development (NF stage 8 to NF stage 46; ca. 2 days exposure). A concentration-dependent increase in external malformations and internal abnormalities of the liver and gonads were noted after 90 days of exposure, however. Skewing of the sex ratio toward the female gender decreased ovary weight and number of oocytes, and increased oocyte immaturity and necrosis were noted at methoxychlor concentrations of 100 micrograms/l. Reductions in testis weight and sperm cell count were also detected at 100 micrograms/l methoxychlor. Results from these studies suggested that methoxychlor was capable of altering the rate of larval development, but did not adversely affect early embryo-larval development (2 days of exposure) as manifested in external malformations. Internal malformations, increases in the ratio of phenotypic females, were induced by chronic methoxychlor exposure. In addition, reproductive endpoints, most notably in the female specimens, were adversely affected by methoxychlor exposure. These studies add to the standardization and validation of a useful amphibian test methods capable of evaluating both reproductive and developmental effects of potential endocrine disrupting chemicals over a life cycle exposure.

  10. Review of the chronic exposure pathways models in MACCS [MELCOR Accident Consequence Code System] and several other well-known probabilistic risk assessment models

    International Nuclear Information System (INIS)

    The purpose of this report is to document the results of the work performed by the author in connection with the following task, performed for US Nuclear Regulatory Commission, (USNRC) Office of Nuclear Regulatory Research, Division of Systems Research: MACCS Chronic Exposure Pathway Models: Review the chronic exposure pathway models implemented in the MELCOR Accident Consequence Code System (MACCS) and compare those models to the chronic exposure pathway models implemented in similar codes developed in countries that are members of the OECD. The chronic exposures concerned are via: the terrestrial food pathways, the water pathways, the long-term groundshine pathway, and the inhalation of resuspended radionuclides pathway. The USNRC has indicated during discussions of the task that the major effort should be spent on the terrestrial food pathways. There is one chapter for each of the categories of chronic exposure pathways listed above

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

    Directory of Open Access Journals (Sweden)

    Sakwari Gloria

    2011-11-01

    Full Text Available Abstract 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

  12. Influence of bicarbonate and humic acid on effects of chronic waterborne lead exposure to the fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Mager, Edward M; Brix, Kevin V; Grosell, Martin

    2010-01-31

    Historically, the USEPA has only considered water hardness when establishing acute and chronic water quality criteria (WQC) for lead (Pb) in freshwater. Yet, recent evidence suggests that hardness may not be protective during chronic Pb exposure and that other factors (e.g., dissolved organic carbon (DOC) and alkalinity) influence toxicity. In fact, we have recently shown that Ca(2+) (as CaSO(4)) does not protect against Pb accumulation in fathead minnows (Pimephales promelas) during chronic exposures whereas DOC as humic acid (HA) clearly does. To more clearly define the water chemistry parameters mediating chronic Pb toxicity we carried out 300 d exposures to study the influence of DOC and alkalinity on Pb accumulation and toxicity to fathead minnows at 2 different Pb concentrations (170 and 580 nM (35 and 120 microg/L)). Alkalinity was adjusted by addition of 500 microM NaHCO(3) and DOC by addition of 4 mg/L HA. Fish were collected at 4, 30, 150 and 300 d of exposure to measure growth and Pb accumulation. Breeding assays (21 d) were performed at the end of these exposures to assess reproductive and larval behavioral endpoints. To determine whether effects were acute or chronic, switched breeding exposures were performed in which control breeders were transferred to either high or low Pb conditions and Pb-exposed breeders transferred to tap water without Pb. Mortality and growth effects were observed primarily in the high Pb treatments and within the first 10 d of exposure. Strong protection against Pb accumulation was afforded by increased DOC at both Pb concentrations. Increased alkalinity also appeared to moderately reduce Pb accumulation although not to the level of statistical significance. Tissue distribution of Pb was analyzed at 300 d and was found to accumulate mostly in bone, gill, intestine and kidney. Unexpectedly, high Pb reduced total reproductive output and increased average egg mass in the HCO(3)(-) and DOC treatments but not in the control water

  13. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    Science.gov (United States)

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  14. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood.

    Science.gov (United States)

    Stansfield, Kirstie H; Kirstein, Cheryl L

    2007-04-01

    Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency and drug use at this time is associated with an increased risk. Human adolescents are predisposed toward an increased likelihood of risk-taking behaviors [Zuckerman M. Sensation seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr 1986;74:59-70.], including drug use or initiation. In the present study, adolescent animals were exposed to twenty days of either saline (0.9% sodium chloride), cocaine (20 mg/kg) or ethanol (1 g/kg) i.p. followed by a fifteen-day washout period. All animals were tested as adults on several behavioral measures including locomotor activity induced by a novel environment, time spent in the center of an open field, novelty preference and novel object exploration. Animals exposed to cocaine during adolescence and tested as adults exhibited a greater locomotor response in a novel environment, spent less time in the center of the novel open field and spent less time with a novel object, results that are indicative of a stress or anxiogenic response to novelty or a novel situation. Adolescent animals chronically administered ethanol and tested as adults, unlike cocaine-exposed were not different from controls in a novel environment, indicated by locomotor activity or time spent with a novel object. However, ethanol-exposed animals approached the novel object more, suggesting that exposure to ethanol during development may result in less-inhibited behaviors during adulthood. The differences in adult behavioral responses after drug exposure during adolescence are likely due to differences in the mechanisms of action of the drugs and subsequent reward and/or stress responsivity. Future studies are needed to determine the neural substrates of these long lasting drug-induced changes. PMID

  15. Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task.

    Directory of Open Access Journals (Sweden)

    Shawn K Acheson

    Full Text Available Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0 g/kg 30 min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0 g/kg for 16 days (PND30 To PND46 prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.

  16. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn Exposure on Sea Cucumbers (Apostichopus japonicus

    Directory of Open Access Journals (Sweden)

    Li Li

    2016-01-01

    Full Text Available Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus exposed to heavy metals. Acute toxicity values (96 h LC50 were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR decreased. The OCRs in all groups were significantly different than control (P muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained.

  17. Ways of pharmacological prophylaxis of stochastic and deterministic effects of chronical radiation exposure

    International Nuclear Information System (INIS)

    The prophylactics of late effects of exposure is the actual medico-social problem, because now there are large groups of persons who were exposed during occupational contact and living on territories contaminated by radionuclides. Most probable consequences of external and internal chronic influence of radiation may be the increase of malignant tumour frequency, the development of secondary myelo- and immuno-depressions, the earlier forming of sclerous and destructive processes, and the acceleration of senescence. The role of damages in immune system was not yet understood in pathogenesis of the late effects of radiation, but there are evidences that the decreasing of the immunologic supervision in period of forming the consequences of radiation influence enables to realize the cancerogenic effect of radiation. The purposes of this investigation are to decrease the frequency or to prevent the development of radiation consequences dangerous for health and life by using the method of modification of radiogenic damages in hemopoietic and immune systems by applying the pharmacological preparations with immunomodulating effects. The investigation tasks include: the study of modifying influence of pharmacological substances with different mechanisms of effect: myelopid (immunomodulating, and regulatory), β-carotin, Calendula officinalis (immunomodulating, and antioxidant), lipamid (detoxicating); the separate or complex applications of these substances; and the development of the optimum medico-prophylactic schemes. The advantages of these indicated preparations in comparison with the known (T-activin, thymogen, cytokines, etc.) are the absence of contraindications and the possibility to use per os. (author)

  18. HIGH-Resolution CT in Chronic Pulmonary Changes after Mustard Gas Exposure

    International Nuclear Information System (INIS)

    Purpose: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. Material and Methods: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. Results: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. Conclusion: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury

  19. Modelling the propagation of effects of chronic exposure to ionising radiation from individuals to populations

    Energy Technology Data Exchange (ETDEWEB)

    Alonzo, F. [Laboratory of Environmental Modelling, DEI/SECRE/LME, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache, Building 159, BP3, 13115 St-Paul-lez-Durance Cedex (France); Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France)], E-mail: frederic.alonzo@irsn.fr; Hertel-Aas, T. [Department of Plant and Environmental Sciences, P.O. Box 5003, Norwegian University of Life Sciences, 1432 Aas (Norway); Gilek, M. [School of Life Sciences, Soedertoern University College, 14189 Huddinge (Sweden); Gilbin, R. [Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France); Oughton, D.H. [Department of Plant and Environmental Sciences, P.O. Box 5003, Norwegian University of Life Sciences, 1432 Aas (Norway); Garnier-Laplace, J. [Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France)

    2008-09-15

    This study evaluated the potential effect of ionising radiation on population growth using simple population models and parameter values derived from chronic exposure experiments in two invertebrate species with contrasting life-history strategies. In the earthworm Eisenia fetida, models predicted increasing delay in population growth with increasing gamma dose rate (up to 0.6 generation times at 11 mGy h{sup -1}). Population extinction was predicted at 43 mGy h{sup -1}. In the microcrustacean Daphnia magna, models predicted increasing delay in population growth with increasing alpha dose rate (up to 0.8 generation times at 15.0 mGy h{sup -1}), only after two successive generations were exposed. The study examined population effects of changes in different individual endpoints (including survival, number of offspring produced and time to first reproduction). Models showed that the two species did not respond equally to equivalent levels of change, the fast growing daphnids being more susceptible to reduction in fecundity or delay in reproduction than the slow growing earthworms. This suggested that susceptibility of a population to ionising radiation cannot be considered independent of the species' life history.

  20. Hypertension during chronic exposure to cold: Comparison between Sprague Dawley (SD) and Long Evans (LE) strains

    Energy Technology Data Exchange (ETDEWEB)

    Riesselmann, A.; Baron, A.; Fregly, M.J. (Univ. of Florida, Gainesville (United States))

    1991-03-11

    Hypertension accompanies chronic exposure of SD rats to cold (5-6C), including elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy. The renin-angiotensin system may play an important role. Earlier studies suggested that the LE strain may have a decrease in angiotensin I converting enzyme (ACE) activity. Measurement of ACE activity in plasmas of SE and LE strains revealed that basal activity of ACE in the plasma of the LE strain was significantly less than that of the SD strain. A second study was carried out in which both strains were exposed to cold for 7 weeks. There were clear differences between strains. Rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine (NE) and epinephrine (E); and significant increases in weights of heart, kidneys, adrenals, and brown adipose tissue (IBAT) compared to their controls maintained at 26C. In contrast, rats of the LE strain were less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level; NE and E outputs, as well as weights of heart and IBAT were significantly less than those of rats of the cold-treated SD strain. Thus, the lower ACE activity in plasma of LE strain, as well as a reduced secretion of catecholamines, may protect these rats against the rise of blood pressure characteristically observed when rats of the SD strain are exposed to cold.

  1. HIGH-Resolution CT in Chronic Pulmonary Changes after Mustard Gas Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bagheri, M.H.; Mostafavi, S.H. [Shiraz Univ. of Medical Siences (Iran, Islamic Republic of). Dept. of Radiology; Hosseini, S.K. [Shiraz Univ. of Medical Siences (Iran, Islamic Republic of). Dept. of Internal Medicine; Alavi, S.A. [Medical Center for Chemical Warfare Victims Foundation, Shiraz (Iran, Islamic Republic of)

    2003-05-01

    Purpose: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. Material and Methods: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. Results: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. Conclusion: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury.

  2. Biochemical and histological alterations in liver following sub chronic exposure of arsenic

    Directory of Open Access Journals (Sweden)

    Madhuri Mehta

    2015-07-01

    Full Text Available Objective: Contamination of groundwater with arsenic is of global concern. The present work was aimed to evaluate the biochemical and histological changes in liver of female rats induced by sodium arsenite at doses naturally found in groundwater of Punjab. Method: Twenty four female rats were divided into four groups of 6 animals each. Group I animals received distilled water and served as control; Group II-IV received arsenic at the dose of 10, 30 and 50 ppb (μg/L dissolved in distilled water ad libitum for 30 days. At the end of experiment, animals were sacrificed and liver was collected for biochemical and histological evaluation. Results: Biochemical analysis showed an increase in the activity of hepatic marker enzymes including transferases, phosphatases and lactate dehydrogenase (LDH. Also, the levels of antioxidant enzymes (catalase, reduced glutathione and glutathione-S-transferase decreased significantly (P<0.05 in treated animals when compared to control. A significant (P<0.05 dose dependent increase in the levels of lipid peroxidation and arsenic concentration in liver tissue was observed. Histological examination showed the presence of pyknotic bodies (necrosis and sinusoidal dilation in hepatocytes of treated groups. Conclusion: Sub chronic exposure of arsenic at these doses induces hepatotoxicity leading to oxidative stress.

  3. New data on uranium nephro-toxicity

    International Nuclear Information System (INIS)

    Uranium is an element and also a heavy metal to which humans can be exposed due to its natural presence or human activities. It has mainly a chemical toxicity on the proximal convoluted tubules of the kidney after acute or chronic exposure. At high dose exposure, acute tubular nephritis is observed, as indicated by proteinuria and a decreased glomerular filtration rate. More recently, the use of structural bio-markers such as beta 2-microglobulin or tubular enzymes has been correlated with histo-pathological injury of the proximal convoluted tubules. During chronic exposure at a low level, the use of some of these sensitive and specific bio-markers would be necessary, particularly when the injury is slight. Recent experimental studies in the laboratory have shown the relevance of such new bio-markers as Kim-1 to detect slight renal injury. Uranium exerts its toxicity on epithelial tubular cells in which it accumulates mainly in the nucleus when it is not precipitated. The mechanisms leading to cell death are not totally elucidated but oxidative stress seems to play an important role. (authors)

  4. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    Science.gov (United States)

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

    2016-09-01

    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

  5. Mortality patterns among a retrospective cohort of uranium mill workers

    International Nuclear Information System (INIS)

    The long-term health effects associated with the milling of uranium ore are of interest particularly because of exposures to uranium and thorium-230. Excess risks of pulmonary and lymphatic malignancies have been suggested by previous epdiemiologic studies of persons milling or smelting uranium ores, and nephrotoxic effects of uranium have been reported in both man and animals. To test these three previously reported associations and to assess all cause-specific mortality patterns among uranium mill workers, we carried out a retrospective cohort study of 2002 uranium millers employed in any of seven mills at least one year before 1972. Ninety-eight percent (98%) followup of the cohort through 1977 resulted in 533 deaths observed versus 605 expected from US White male mortality rates. Mortality from most causes was lower than expected. Significant excess risks were found only for nonmalignant respiratory disease and miscellaneous accidents but not for any of the three diseases of a priori interest. However, nonsignificant excesses were found for lymphatic malignancies after 20 years latency and for death due to chronic nephritis among short-term workers

  6. Chronic exposures to low and high concentrations of ibuprofen elicit different gene response patterns in a euryhaline fish.

    Science.gov (United States)

    Jeffries, Ken M; Brander, Susanne M; Britton, Monica T; Fangue, Nann A; Connon, Richard E

    2015-11-01

    Ibuprofen is one of the most commonly detected pharmaceuticals in wastewater effluent; however, the effects of ibuprofen on aquatic organisms are poorly understood. This study presents the transcriptome-wide response of the inland silverside, Menidia beryllina, to chronic exposure to ibuprofen. At the lowest exposure concentration (0.0115 mg/L), we detected a downregulation of many genes involved in skeletal development, aerobic respiration, and immune function. At the highest exposure concentration (1.15 mg/L), we detected increased expression of regulatory genes in the arachidonic acid metabolism pathway and several immune genes involved in an inflammatory response. Additionally, there was differential expression of genes involved in oxidative stress responses and a downregulation of genes involved in osmoregulation. This study provides useful information for monitoring the effects of this common wastewater effluent contaminant in the environment and for the generation of biomarkers of exposure to ibuprofen that may be transferable to other fish species.

  7. Field measurements of mixed exposure of operators to radioactive aerosol, gas and quartz in confinement of mining equipment cabs during open-pit mining of high-grade uranium ores

    International Nuclear Information System (INIS)

    A series of field measurements of miners mixed exposure to radon and daughters, uranium ore dust and respirable quartz, was conducted in an open-pit mine in Northern Saskatchewan during 1980-81. Control of radon gas levels in the mining equipment cabs is required. Dust may be reduced by minimizing the resuspension of dust from contaminated surfaces within the cabs

  8. Uranium tailings bibliography

    International Nuclear Information System (INIS)

    A bibliography containing 1,212 references is presented with its focus on the general problem of reducing human exposure to the radionuclides contained in the tailings from the milling of uranium ore. The references are divided into seven broad categories: uranium tailings pile (problems and perspectives), standards and philosophy, etiology of radiation effects, internal dosimetry and metabolism, environmental transport, background sources of tailings radionuclides, and large-area decontamination

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

    Science.gov (United States)

    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

  10. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Islam Md

    2012-06-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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.

  14. Acute but not chronic ethanol exposure impairs retinol oxidation in the small and large intestine of the rat

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Ellendt, K.; Lindros, K.;

    2005-01-01

    BACKGROUND AND AIM: Ethanol has been shown to inhibit retinol oxidation at the level of alcohol dehydrogenase in liver and colon but not previously in the small intestine. In the present study we investigated how chronic alcohol feeding and acute ethanol exposure affects retinol dehydrogenase...... activity in the colon and small intestine of the rat. METHODS: Rats were fed ethanol in a liquid diet for six weeks. Control rats received a similar diet but with ethanol isocalorically replaced by carbohydrates. Retinol dehydrogenase was analyzed from cell cytosol samples from the small and the large...... higher, respectively). While chronic alcohol feeding did not affect these parameters, acute ethanol exposure reduced V(max) and V(max)/K(m) dose-dependently (p retinol...

  15. PROVANN: Model System for Chronic Exposure of Larval and Adult Fish to Releases from Offshore Petroleum Platforms

    Energy Technology Data Exchange (ETDEWEB)

    Reed, M.; Rye, H. [IKU Petroleumsforskning A/S, Trondheim (Norway); Melbye, A.; Johnsen, S.

    1996-12-31

    Produced water from offshore oil and gas production platforms contains a variety of hydrocarbons, heavy metals, and production chemicals. Vertical and horizontal mixing generally brings concentrations in discharge plumes below level associated with acute effects within 500 or 1000 m of the source. Chronic effects outside this region remain a potential problem. The purpose of PROVANN, the system of models described in this paper, is to assess the potential for chronic effects from produced water. The preliminary focus is on potential bioaccumulation and boimagnification of produced water constituents in the marine food web. Other possible types of chronic effects, such as reduced fecundity, or pheromone response interference, can also be assessed to the extent that such effects may be correlated with exposure. PROVANN simulates 3-dimensional transport, dilution, and degradation of chemicals released into the water, from one or more simultaneous sources. 8 refs., 10 figs., 3 tabs.

  16. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice.

    OpenAIRE

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima; Trak-Smayra, Viviane; Martinais, Sophie; Porceddu, Mathieu; Robin, Marie-Anne; Fromenty, Bernard

    2014-01-01

    International audience Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations r...

  17. Chronic CO2 exposure markedly increases the incidence of cataracts in juvenile Atlantic cod Gadus morhua L

    DEFF Research Database (Denmark)

    Moran, Damian; Tubbs, Lincoln; Støttrup, Josianne G.

    2012-01-01

    A study was undertaken to test the affect of chronic exposure to elevated dissolved carbon dioxide on juvenile Atlantic cod. The CO2 treatment concentrations were designated as low (1–2mgL−1, 1000μatm), medium (8mgL−1, 3500μatm) and high (18mgL−1, 8500μatm), and the fish were reared at 10°C and 2...

  18. CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure

    OpenAIRE

    Huang, S.; Guo, S.; Guo, F; Yang, Q.; XIAO, X.; Murata, M.; Ohnishi, S.; Kawanishi, S; Ma, N

    2013-01-01

    Inorganic arsenic is a well-known human skin carcinogen. Chronic arsenic exposure results in various types of human skin lesions, including squamous cell carcinoma (SCC). To investigate whether mutant stem cells participate in arsenic-associated carcinogenesis, we repeatedly exposed the human spontaneously immortalized skin keratinocytes (HaCaT) cell line to an environmentally relevant level of arsenic (0.05 ppm) in vitrofor 18 weeks. Following sodium arsenite administration, cell cycle, colo...

  19. Effects of acute and chronic waterborne lead exposure on the swimming performance and aerobic scope of fathead minnows (Pimephales promelas).

    Science.gov (United States)

    Mager, Edward M; Grosell, Martin

    2011-06-01

    Fathead minnows were subjected to an incremental velocity test using swim tunnel respirometry for the analysis of aerobic scope and swimming performance, as critical aerobic swim speed (U(crit)), following chronic exposures (33-57 ) to 0.9±0.4, 157±18 or 689±66 nmol L⁻¹ Pb and an acute exposure (24 h) to 672±35 nmol L⁻¹ Pb (mean±SEM). Assessment of Pb-induced anemia and neurological impairment were evaluated by blood hemoglobin (Hb) concentrations and a cost of transport (COT) analysis, respectively. Fish from the acute 672±35 nmol L⁻¹ Pb (24.4±1.2 BL s⁻¹) and chronic 689±66 nmol L⁻¹ Pb (24.6±0.9 BL s⁻¹) treatments exhibited reduced U(crits) compared to control fish (27.6±0.8 BL s⁻¹). Aerobic scope was reduced by acute Pb exposure (8.6±2.6 μmol O₂ g⁻¹ h⁻¹ vs. 22.6±3.8 μmol O₂ g⁻¹ h⁻¹ from controls) owing to a decrease in maximum oxygen consumption rate (38.8±0.8 μmol O₂ g⁻¹ h⁻¹ vs. 54.0±4.2 μmol O₂ g⁻¹ h⁻¹ from controls). However, no effect on aerobic scope was observed with fish chronically exposed to Pb. Significant differences were not observed for Hb concentrations or COT. These findings suggest that the impaired swimming performances arising from acute and chronic Pb exposures reflect different mechanisms of toxicity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    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 autonomous 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 provide a

  1. Prenatal exposure to tobacco and alcohol are associated with chronic daily headaches at childhood: A population-based study

    OpenAIRE

    Marco Antônio Arruda; Vincenzo Guidetti; Federica Galli; Regina Célia Ajeje Pires de Albuquerque; Marcelo Eduardo Bigal

    2011-01-01

    The influence of prenatal events on the development of headaches at childhood has not been investigated and is the scope of our study. Of 2,173 children identified as the target sample, consents and analyzable data were provided by 1,440 (77%). Parents responded to a standardized questionnaire with a validated headache module and specific questions about prenatal exposures. Odds of chronic daily headache (CDH) were significantly higher when maternal tabagism was reported. When active and pass...

  2. Effects of Chronic and Acute Ozone Exposure on Lipid Peroxidation and Antioxidant Capacity in Healthy Young Adults

    OpenAIRE

    Chen, Connie; Arjomandi, Mehrdad; Balmes, John; Tager, Ira; Holland, Nina

    2007-01-01

    Background There is growing evidence for the role of oxidative damage in chronic diseases. Although ozone (O3) is an oxidant pollutant to which many people are exposed, few studies have examined whether O3 induces oxidative stress in humans. Objectives This study was designed to assess the effect of short-and long-term O3 exposures on biomarkers of oxidative stress in healthy individuals. Methods Biomarkers of lipid peroxidation, 8-isoprostane (8-iso-PGF), and antioxidant capacity ferric redu...

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

    International Nuclear Information System (INIS)

    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 autonomous 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 provide a

  4. Neutralisation of interleukin-13 in mice prevents airway pathology caused by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Kate L Tomlinson

    Full Text Available BACKGROUND: Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13 in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM. METHODOLOGY/PRINCIPAL FINDINGS: Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb administered subcutaneously (s.c.. Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR by invasive measurement of lung resistance (R(L and dynamic compliance (C(dyn. Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05 the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05 the increase in baseline R(L and the decrease in baseline C(dyn caused by chronic exposure to inhaled HDM. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.

  5. Considerations when using longitudinal cohort studies to assess dietary exposure to inorganic arsenic and chronic health outcomes.

    Science.gov (United States)

    Scrafford, Carolyn G; Barraj, Leila M; Tsuji, Joyce S

    2016-07-01

    Dietary arsenic exposure and chronic health outcomes are of interest, due in part to increased awareness and data available on inorganic arsenic levels in some foods. Recent concerns regarding levels of inorganic arsenic, the primary form of arsenic of human health concern, in foods are based on extrapolation from adverse health effects observed at high levels of inorganic arsenic exposure; the potential for the occurrence of these health effects from lower levels of dietary inorganic arsenic exposure has not been established. In this review, longitudinal cohort studies are evaluated for their utility in estimating dietary inorganic arsenic exposure and quantifying statistically reliable associations with health outcomes. The primary limiting factor in longitudinal studies is incomplete data on inorganic arsenic levels in foods combined with the aggregation of consumption of foods with varying arsenic levels into a single category, resulting in exposure misclassification. Longitudinal cohort studies could provide some evidence to evaluate associations of dietary patterns related to inorganic arsenic exposure with risk of arsenic-related diseases. However, currently available data from longitudinal cohort studies limit causal analyses regarding the association between inorganic arsenic exposure and health outcomes. Any conclusions should therefore be viewed with knowledge of the analytical and methodological limitations.

  6. Association between Blood Dioxin Level and Chronic Kidney Disease in an Endemic Area of Exposure.

    Directory of Open Access Journals (Sweden)

    Chien-Yuan Huang

    Full Text Available Dioxin is an industrial pollutant related to various diseases, but epidemiological data on its effects on the kidney are limited. Therefore, we conducted a study to evaluate the association between dioxin exposure and chronic kidney disease (CKD and identify the related factors.We conducted a community-based cross-sectional study and recruited participants from an area where the residents were exposed to dioxin released from a factory. We defined a "high dioxin level" as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs ≥ 20 pg WHO98-TEQDF/g lipid in the serum and defined CKD as having an estimated glomerular filtration rate (e-GFR ≤ 60 mL/min/1.73m2 or a diagnosis of CKD by a physician. The renal function was assessed between 2005 and 2010, and we excluded those who had had kidney diseases before the study started. Comparisons between patients of CKD and those who did not have CKD were made to identify the risk factors for CKD.Of the 2898 participants, 1427 had high dioxin levels, and 156 had CKD. In the univariate analyses, CKD was associated with high dioxin levels, age, gender, metabolic syndrome, diabetes mellitus, hypertension, and high insulin and uric acid levels. After adjusting for other factors, we found high dioxin levels (adjusted odds ratio [AOR] = 1.76, 95% confidence interval [CI]: 1.04-2.99, female gender (AOR = 1.74, 95%CI: 1.20-2.53, hypertension (AOR = 1.68, 95%CI: 1.17-2.42, high insulin levels (AOR = 2.14, 95% CI: 1.26-3.61, high uric acid levels (AOR = 4.25, 95% CI: 2.92-6.20, and older age (AOR = 4.66, 95% CI: 1.87-11.62 for 40-64 year and AOR = 26.66, 95% CI: 10.51-67.62 for age ≥ 65 year were independent predictors of CKD.A high dioxin level was associated with an increased prevalence of CKD. Therefore, the kidney function of populations with exposure to dioxin should be monitored.

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

    Science.gov (United States)

    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.

  8. The potential immune modulatory effect of chronic bisphenol A exposure on gene regulation in male medaka (Oryzias latipes) liver.

    Science.gov (United States)

    Qiu, Wenhui; Shen, Yang; Pan, Chenyuan; Liu, Shuai; Wu, Minghong; Yang, Ming; Wang, Ke-Jian

    2016-08-01

    Bisphenol A (BPA) is a well-known estrogenic endocrine disrupting chemical (EDC) ubiquitously present in various environmental media. The present study aims to identify the responsive genes in male fish chronically exposed to low concentrations of BPA at the transcription level. We screened genes from a suppression subtractive hybridization library constructed from male medaka (Oryzias latipes) livers after 60-d exposure to 10μg/L BPA under the condition at which changes of hepatic antioxidant parameters have been previously reported. The identified genes were predicted to be involved in multiple biological processes including antioxidant physiology, endocrine system, detoxification, notably associated with the immune response processes. With real time PCR analysis, the immune-associated genes including hepcidin-like precursor, complement component and factors, MHC class I, alpha-2-macroglobulin and novel immune-type receptor 6 isoform were significantly up-regulated in a nonmonotonic dose response pattern in livers upon exposure to different concentrations of BPA (0.1, 1, 10, 100, 1000μg/L). Our results demonstrated a negative impact on gene regulation in fish chronically exposed to relatively low and environmentally relevant concentrations of BPA, and suggested the potential immune modulatory effect of chronic EDC exposure on fish. The immunotoxicity of BPA and other EDCs should be much concerned for the health of human beings and other vertebrates exposed to it. PMID:27104808

  9. Uncertainty and sensitivity analysis of chronic exposure results with the MACCS reactor accident consequence model

    International Nuclear Information System (INIS)

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the chronic exposure pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 75 imprecisely known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, water ingestion dose, milk growing season dose, long-term groundshine dose, long-term inhalation dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, total latent cancer fatalities, area-dependent cost, crop disposal cost, milk disposal cost, population-dependent cost, total economic cost, condemnation area, condemnation population, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: dry deposition velocity, transfer of cesium from animal feed to milk, transfer of cesium from animal feed to meat, ground concentration of Cs-134 at which the disposal of milk products will be initiated, transfer of Sr-90 from soil to legumes, maximum allowable ground concentration of Sr-90 for production of crops, fraction of cesium entering surface water that is consumed in drinking water, groundshine shielding factor, scale factor defining resuspension, dose reduction associated with decontamination, and ground concentration of 1-131 at which disposal of crops will be initiated due to accidents that occur during the growing season

  10. Effect of chronic pesticide exposure in farm workers of a Mexico community.

    Science.gov (United States)

    Payán-Rentería, Rolando; Garibay-Chávez, Guadalupe; Rangel-Ascencio, Raul; Preciado-Martínez, Veronica; Muñoz-Islas, Laura; Beltrán-Miranda, Claudia; Mena-Munguía, Salvador; Jave-Suárez, Luis; Feria-Velasco, Alfredo; De Celis, Ruth

    2012-01-01

    Pesticides are frequently used substances worldwide, even when the use of some of them is forbidden due to the recognized adverse effect they have on the health of not only the people who apply the pesticides, but also of those that consume the contaminated products. The objectives of this study were to know the health issues of farm workers chronically exposed to pesticides, to evaluate possible damage at genetic level, as well as to explore some hepatic, renal, and hematological alterations. A transversal comparative study was performed between 2 groups, one composed of 25 farm workers engaged in pesticide spraying, and a control group of 21 workers not exposed to pesticides; both groups belonged to the Nextipac community in Jalisco, Mexico. Each member of both groups underwent a full medical history. Blood samples were taken from all farm workers in order to obtain a complete blood count and chemistry, clinical chemistry, lipid profile, liver and kidney function tests, erythrocyte cholinesterase quantification, lipid peroxidation profile, and free DNA fragment quantification. For the information analysis, central tendency and dispersion measurements were registered. In order to know the differences between groups, a cluster multivariate method was used, as well as prevalence reasons. The most used pesticides were mainly organophosphates, triazines and organochlorine compounds. The exposed group showed acute poisoning (20% of the cases) and diverse alterations of the digestive, neurological, respiratory, circulatory, dermatological, renal, and reproductive system probably associated to pesticide exposure. More importantly, they presented free DNA fragments in plasma (90.8 vs 49.05 ng/mL) as well as a higher level of lipid peroxidation (41.85 vs. 31.91 nmol/mL) in comparison with those data from unexposed farm workers. These results suggest that there exist health hazards for those farm workers exposed to pesticides, at organic and cellular levels. PMID:22315932

  11. Uncertainty and sensitivity analysis of chronic exposure results with the MACCS reactor accident consequence model

    Energy Technology Data Exchange (ETDEWEB)

    Helton, J.C. [Arizona State Univ., Tempe, AZ (United States); Johnson, J.D.; Rollstin, J.A. [Gram, Inc., Albuquerque, NM (United States); Shiver, A.W.; Sprung, J.L. [Sandia National Labs., Albuquerque, NM (United States)

    1995-01-01

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the chronic exposure pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 75 imprecisely known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, water ingestion dose, milk growing season dose, long-term groundshine dose, long-term inhalation dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, total latent cancer fatalities, area-dependent cost, crop disposal cost, milk disposal cost, population-dependent cost, total economic cost, condemnation area, condemnation population, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: dry deposition velocity, transfer of cesium from animal feed to milk, transfer of cesium from animal feed to meat, ground concentration of Cs-134 at which the disposal of milk products will be initiated, transfer of Sr-90 from soil to legumes, maximum allowable ground concentration of Sr-90 for production of crops, fraction of cesium entering surface water that is consumed in drinking water, groundshine shielding factor, scale factor defining resuspension, dose reduction associated with decontamination, and ground concentration of 1-131 at which disposal of crops will be initiated due to accidents that occur during the growing season.

  12. Micronucleus assay in human lymphocytes as a bio dosimeter of in vivo acute and chronic exposures

    International Nuclear Information System (INIS)

    To assess the persistence over time of micronuclei (MN) in lymphocytes of cancer patients after radiotherapy and, consequently, to verify the suitability of MN test as a dosimeter for monitoring in vivo ionizing radiation damage, the cytokinesis-blocked MN assay was applied in peripheral blood lymphocytes of cervix and head and neck cancer patients (n = 34). The evaluation of data suggests that: 1) MN frequency increases linearly with the equivalent total-body absorbed dose (R2 = 0,9; P=0,015); 2) The distribution of the MN yields deviates significantly from Poisson with the increase of equivalent total-body dose (σ2/y = 1,14 mean value); 3) The comparison of spontaneous MN frequencies in healthy subjects with those in cancer patients, prior to radiotherapy, shows significant differences (p<0,01); and 4) It is observed a general decline in MN frequencies with time after radiotherapy, with considerable variations between patients. The kinetics of elimination of MN seems to follow a two-term exponential function, with a short and a long term. Patients with the highest equivalent total-body dose (total tumoral dose: 60-80 Gy) initially tend to have the fastest decline. At 6-18 months of follow-up time 11 of the 17 patients, evaluated 2-480 months post-treatment, showed higher frequencies of MN than their respective levels before radiation therapy, indicating persistence of radiation induced cytogenetic damage. Further studies modeling changes in chromosome aberrations with acute and chronic exposures should provide perspectives on biological dosimetry in accident situations in which there is a blood sampling delay and on biological monitoring of human populations exposed to ionizing radiation. (author)

  13. Effects of Gestational and Postnatal Exposure to Chronic Intermittent Hypoxia on Diaphragm Muscle Contractile Function in the Rat

    Science.gov (United States)

    McDonald, Fiona B.; Dempsey, Eugene M.; O'Halloran, Ken D.

    2016-01-01

    Alterations to the supply of oxygen during early life presents a profound stressor to physiological systems with aberrant remodeling that is often long-lasting. Chronic intermittent hypoxia (CIH) is a feature of apnea of prematurity, chronic lung disease, and sleep apnea. CIH affects respiratory control but there is a dearth of information concerning the effects of CIH on respiratory muscles, including the diaphragm—the major pump muscle of breathing. We investigated the effects of exposure to gestational CIH (gCIH) and postnatal CIH (pCIH) on diaphragm muscle function in male and female rats. CIH consisted of exposure in environmental chambers to 90 s of hypoxia reaching 5% O2 at nadir, once every 5 min, 8 h a day. Exposure to gCIH started within 24 h of identification of a copulation plug and continued until day 20 of gestation; animals were studied on postnatal day 22 or 42. For pCIH, pups were born in normoxia and within 24 h of delivery were exposed with dams to CIH for 3 weeks; animals were studied on postnatal day 22 or 42. Sham groups were exposed to normoxia in parallel. Following gas exposures, diaphragm muscle contractile, and endurance properties were examined ex vivo. Neither gCIH nor pCIH exposure had effects on diaphragm muscle force-generating capacity or endurance in either sex. Similarly, early life exposure to CIH did not affect muscle tolerance of severe hypoxic stress determined ex vivo. The findings contrast with our recent observation of upper airway dilator muscle weakness following exposure to pCIH. Thus, the present study suggests a relative resilience to hypoxic stress in diaphragm muscle. Co-ordinated activity of thoracic pump and upper airway dilator muscles is required for optimal control of upper airway caliber. A mismatch in the force-generating capacity of the complementary muscle groups could have adverse consequences for the control of airway patency and respiratory homeostasis. PMID:27462274

  14. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

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

  15. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  16. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    International Nuclear Information System (INIS)

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  17. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qing [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States); Rise, Matthew L. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Spitsbergen, Jan M. [Department of Microbiology, Oregon State University, 220 Nash Hall, Corvallis, OR 97331 (United States); Hori, Tiago S. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Mieritz, Mark; Geis, Steven [Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706 (United States); McGraw, Joseph E. [School of Pharmacy, Concordia University Wisconsin, 12800 North Lake Shore Drive, Mequon, WI 53097 (United States); Goetz, Giles [School of Aquatic and Fishery Sciences, University of Washington, 1122 Northeast Boat Street, Seattle, WA 98195 (United States); Larson, Jeremy; Hutz, Reinhold J. [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); Carvan, Michael J., E-mail: carvanmj@uwm.edu [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States)

    2013-09-15

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  18. Perseveration in the presence of punishment: the effects of chronic cocaine exposure and lesions to the prefrontal cortex.

    Science.gov (United States)

    Allen, Craig P; Leri, Francesco

    2014-03-15

    Perseveration is the repetition of a previously appropriate response in a manner, or context, which is detrimental to the individual. Although both cocaine exposure and prefrontal cortex (PFC) dysfunctions have been implicated in perseverative-like behaviours, the underlying nature of the impairments has been debated. The current study tested whether chronic cocaine exposure and PFC lesions induce perseverative-like behaviours by causing insensitivity to punishment. Food-restricted male Sprague-Dawley rats were trained to respond for sucrose on concurrent schedules of reinforcement. After initial training, rats received either a sensitizing regimen of cocaine exposure, or excitotoxic lesions to subregions of the PFC. The test of perseveration involved a choice of responding between two levers associated with fixed ratio and progressive ratio (PR) schedules. Responding on the PR lever was punished by a 1 min timeout period. It was found that, unlike control subjects, those exposed to chronic cocaine, or with lesions to the medial prefrontal cortex, were significantly slower in adapting their responding to avoid punishment. The current study provides evidence that both cocaine exposure and lesions to the prefrontal cortex can increase perseverative-like responding, although the magnitude and permanence of these effects are contingent on the nature of the task.

  19. Changes in carotid body and nTS neuronal excitability following neonatal sustained and chronic intermittent hypoxia exposure.

    Science.gov (United States)

    Mayer, C A; Wilson, C G; MacFarlane, P M

    2015-01-01

    We investigated whether pre-treatment with neonatal sustained hypoxia (SH) prior to chronic intermittent hypoxia (SH+CIH) would modify in vitro carotid body (CB) chemoreceptor activity and the excitability of neurons in the caudal nucleus of the solitary tract (nTS). Sustained hypoxia followed by CIH exposure simulates an oxygen paradigm experienced by extremely premature infants who developed persistent apnea. Rat pups were treated with 5 days of SH (11% O2) from postnatal age 1 (P1) followed by 10 days of subsequent chronic intermittent hypoxia (CIH, 5% O2/5 min, 8 h/day, between P6 and P15) as described previously (Mayer et al., Respir. Physiol. Neurobiol. 187(2): 167-75, 2013). At the end of SH+CIH exposure (P16), basal firing frequency was enhanced, and the hypoxic sensory response of single unit CB chemoafferents was attenuated. Further, basal firing frequency and the amplitude of evoked excitatory post-synaptic currents (ESPC's) of nTS neurons was augmented compared to age-matched rats raised in normoxia. These effects were unique to SH+CIH exposure as neither SH or CIH alone elicited any comparable effect on chemoafferent activity or nTS function. These data indicated that pre-treatment with neonatal SH prior to CIH exposure uniquely modified mechanisms of peripheral (CB) and central (nTS) neural function in a way that would be expected to disturb the ventilatory response to acute hypoxia.

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

    Directory of Open Access Journals (Sweden)

    Gunther Antonissen

    2015-02-01

    Full Text Available 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%.

  1. PARAMETER EVALUATION AND MODEL VALIDATION OF OZONE EXPOSURE ASSESSMENT USING HARVARD SOUTHERN CALIFORNIA CHRONIC OZONE EXPOSURE STUDY DATA

    Science.gov (United States)

    To examine factors influencing long-term ozone exposures by children living in urban communities, we analyzed longitudinal data on personal, indoor, and outdoor ozone concentrations as well as related housing and other questionnaire information collected in the one-year-long Harv...

  2. Prevalence of chronic obstructive pulmonary disease and its association with tobacco smoking and environmental tobacco smoke exposure among rural population

    Directory of Open Access Journals (Sweden)

    B G Parasuramalu

    2014-01-01

    Full Text Available A field survey was conducted for chronic obstructive pulmonary disease (COPD epidemiology in the rural field practice area of Kempegowda Institute of Medical Sciences, Bangalore, India, which covers a population of 44,387 to find out the prevalence of COPD in adult subjects of 35 years and above using cluster sampling technique and to determine the association of tobacco smoking, environmental tobacco smoking (ETS exposure and type of cooking fuel used with COPD. The overall prevalence of COPD was 4.36%. The prevalence among males and females were 5.32% and 3.41% respectively. The prevalence was found to be increasing with an increase in age. The tobacco smoke and exposure to ETS was significantly associated with higher odds of COPD with adjusted odds ratio 2.97 and 2.67 respectively. Thus, there was a significant association between tobacco smoking and ETS exposure with COPD.

  3. Uranium induces oxidative stress in lung epithelial cells

    OpenAIRE

    Periyakaruppan, Adaikkappan; Kumar, Felix; Sarkar, Shubhashish; Sharma, Chidananda S.; Ramesh, Govindarajan T.

    2006-01-01

    Uranium compounds are widely used in the nuclear fuel cycle, antitank weapons, tank armor, and also as a pigment to color ceramics and glass. Effective management of waste uranium compounds is necessary to prevent exposure to avoid adverse health effects on the population. Health risks associated with uranium exposure includes kidney disease and respiratory disorders. In addition, several published results have shown uranium or depleted uranium causes DNA damage, mutagenicity, cancer and neur...

  4. Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine in rats

    Directory of Open Access Journals (Sweden)

    Martin eZack

    2014-02-01

    Full Text Available Addiction is considered to be a brain disease caused by chronic exposure to drugs. Sensitization of brain dopamine (DA systems partly mediates this effect. Pathological gambling (PG is considered to be a behavioral addiction. Therefore, PG may be caused by chronic exposure to gambling. Identifying a gambling-induced sensitization of DA systems would support this possibility. Gambling rewards evoke DA release. One episode of slot machine play shifts the DA response from reward delivery to onset of cues (spinning reels for reward, in line with temporal difference learning principles. Thus, conditioned stimuli (CS play a key role in DA responses to gambling. In primates, DA response to a CS is strongest when reward probability is 50%. Under this schedule the CS elicits an expectancy of reward but provides no information about whether it will occur on a given trial. During gambling, a 50% schedule should elicit maximal DA release. This closely matches reward frequency (46% on a commercial slot machine. DA release can contribute to sensitization, especially for amphetamine. Chronic exposure to a CS that predicts reward 50% of the time could mimic this effect. We tested this hypothesis in 3 studies with rats. Animals received 15 x 45-min exposures to a CS that predicted reward with a probability of 0, 25, 50, 75 or 100%. The CS was a light; the reward was a 10% sucrose solution. After training, rats received a sensitizing regimen of 5 separate doses (1 mg/kg of d-amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to a 90-min locomotor activity test. In all 3 studies the 50% group displayed greater activity than the other groups in response to both challenge doses. Effect sizes were modest but consistent, as reflected by a significant group x rank association ( = .986, p = .025. Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine much like exposure to

  5. Effects of sub-chronic exposure to SO{sub 2} on lipid and carbohydrate metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lovati, M.R. [Institute of Pharmacological Sciences, Milan (Italy); Manzoni, C. [Institute of Pharmacological Sciences, Milan (Italy); Daldossi, M. [Institute of Pharmacological Sciences, Milan (Italy); Spolti, S. [Institute of Pharmacological Sciences, Milan (Italy); Sirtori, C.R. [Institute of Pharmacological Sciences, Milan (Italy)

    1996-01-01

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO{sub 2} have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO{sub 2} on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed controlinert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO{sub 2} at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO{sub 2} exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO{sub 2} resulted in a fall (-41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO{sub 2} exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO{sub 2} exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals. (orig.)

  6. Chronic ethanol exposure increases the non-dominant glucocorticoid, corticosterone, in the near-term pregnant guinea pig.

    Science.gov (United States)

    Hewitt, Amy J; Dobson, Christine C; Brien, James F; Wynne-Edwards, Katherine E; Reynolds, James N

    2014-08-01

    Maternal-fetal signaling is critical for optimal fetal development and postnatal outcomes. Chronic ethanol exposure alters programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in a myriad of neurochemical and behavioral alterations in postnatal life. Based on a recent study which showed that human intra-partum fetal stress increased fetal secretion of corticosterone, the non-dominant glucocorticoid, this investigation tested the hypothesis that an established model of HPA axis programming, chronic maternal ethanol administration to the pregnant guinea pig, would result in preferential elevation of corticosterone, which is also the non-dominant glucocorticoid. Starting on gestational day (GD) 2, guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding. Each treatment was administered daily and continued until GD 45, 55, or 65 (approximately 3 days pre-term), when pregnant animals were euthanized and fetuses delivered by Caesarean section. Maternal and fetal plasma samples were collected. After sample preparation (protein precipitation and C-18 solid phase extraction), plasma cortisol and corticosterone concentrations were determined simultaneously by liquid chromatography coupled to tandem mass spectrometry. As predicted, chronic ethanol exposure increased both fetal and maternal plasma corticosterone concentration in late gestation. In contrast, plasma cortisol did not differ across maternal treatments in maternal or fetal samples. The plasma concentration of both maternal glucocorticoids increased with gestational age. Thus, corticosterone, the non-dominant glucocorticoid, but not cortisol, was elevated by chronic ethanol exposure, which may have effects on HPA function in later life.

  7. Chronic glucocorticoids exposure enhances neurodegeneration in the frontal cortex and hippocampus via NLRP-1 inflammasome activation in male mice.

    Science.gov (United States)

    Hu, Wen; Zhang, Yaodong; Wu, Wenning; Yin, Yanyan; Huang, Dake; Wang, Yuchan; Li, Weiping; Li, Weizu

    2016-02-01

    Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD) and depression. Chronic glucocorticoids (GCs) exposure has deleterious effects on the structure and function of neurons and is associated with development and progression of AD. However, little is known about the proinflammatory effects of chronic GCs exposure on neurodegeneration in brain. Therefore, the aim of this study was to evaluate the effects of chronic dexamethasone (DEX) treatment (5mg/kg, s.c. for 7, 14, 21 and 28 days) on behavior, neurodegeneration and neuroinflammatory parameters of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 1 (NLRP-1) inflammasome in male mice. The results showed that DEX treatment for 21 and 28 days significantly reduced the spontaneous motor activity and exploratory behavior of the mice. In addition, these mice showed significant neurodegeneration and a decrease of microtubule-associated protein 2 (MAP2) in the frontal cortex and hippocampus CA3. DEX treatment for 7, 14, 21 and 28 days significantly decreased the mRNA and protein expression of glucocorticoid receptor (GR). Moreover, DEX treatment for 21 and 28 days significantly increased the proteins expression of NLRP-1, Caspase-1, Caspase-5, apoptosis associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p-NF-κB, interleukin-1β (IL-1β), IL-18 and IL-6 in the frontal cortex and hippocampus brain tissue. DEX treatment for 28 days also significantly increased the mRNA expression levels of NLRP-1, Caspase-1, ASC and IL-1β. These results suggest that chronic GCs exposure may increase brain inflammation via NLRP-1 inflammasome activation and induce neurodegeneration.

  8. Accumulation and effects of Cr(VI) in Japanese medaka (Oryzias latipes) during chronic dissolved and dietary exposures.

    Science.gov (United States)

    Chen, Hongxing; Mu, Lei; Cao, Jinling; Mu, Jingli; Klerks, Paul L; Luo, Yongju; Guo, Zhongbao; Xie, Lingtian

    2016-07-01

    Chromium (Cr) is an essential metal and a nutritional supplement for both human and agricultural uses. It is also a pollutant from a variety of industrial uses. These uses can lead to elevated Cr levels in aquatic environments, where it can enter and affect aquatic organisms. Its accumulation and subsequent effects in fish have received relatively little attention, especially for chronic exposure. In the present study, Japanese medaka were chronically exposed to dissolved or dietary Cr(VI) for 3 months. Cr accumulation in liver, gills, intestine, and brain was evaluated. Effects on the antioxidant system, nervous system (acetylcholinesterase, AChE), digestive system (α-glucosidase, α-Glu), and tissue histology (liver and gills) were also assessed. Cr accumulation was observed in the intestine and liver of fish exposed to Cr-contaminated brine shrimp. However, chronic dissolved Cr exposure led to significant Cr accumulation in all organs tested. Analysis of the subcellular distribution of Cr in medaka livers revealed that 37% of the Cr was present in the heat stable protein fraction. The dissolved Cr exposure had pronounced effects on the antioxidant system in the liver, with an elevated ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) and decreases in GSH and glutathione S-transferase (GST). The α-Glu activity in the intestine was significantly inhibited. In addition, Cr exposure caused histopathological alterations in the gills and liver. In general, the effects of dietary Cr were relatively minor, possible due to the much lower accumulation in the fish. Our results imply that Japanese medaka accumulate Cr mainly via uptake of dissolved Cr(VI).

  9. Accumulation and effects of Cr(VI) in Japanese medaka (Oryzias latipes) during chronic dissolved and dietary exposures.

    Science.gov (United States)

    Chen, Hongxing; Mu, Lei; Cao, Jinling; Mu, Jingli; Klerks, Paul L; Luo, Yongju; Guo, Zhongbao; Xie, Lingtian

    2016-07-01

    Chromium (Cr) is an essential metal and a nutritional supplement for both human and agricultural uses. It is also a pollutant from a variety of industrial uses. These uses can lead to elevated Cr levels in aquatic environments, where it can enter and affect aquatic organisms. Its accumulation and subsequent effects in fish have received relatively little attention, especially for chronic exposure. In the present study, Japanese medaka were chronically exposed to dissolved or dietary Cr(VI) for 3 months. Cr accumulation in liver, gills, intestine, and brain was evaluated. Effects on the antioxidant system, nervous system (acetylcholinesterase, AChE), digestive system (α-glucosidase, α-Glu), and tissue histology (liver and gills) were also assessed. Cr accumulation was observed in the intestine and liver of fish exposed to Cr-contaminated brine shrimp. However, chronic dissolved Cr exposure led to significant Cr accumulation in all organs tested. Analysis of the subcellular distribution of Cr in medaka livers revealed that 37% of the Cr was present in the heat stable protein fraction. The dissolved Cr exposure had pronounced effects on the antioxidant system in the liver, with an elevated ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) and decreases in GSH and glutathione S-transferase (GST). The α-Glu activity in the intestine was significantly inhibited. In addition, Cr exposure caused histopathological alterations in the gills and liver. In general, the effects of dietary Cr were relatively minor, possible due to the much lower accumulation in the fish. Our results imply that Japanese medaka accumulate Cr mainly via uptake of dissolved Cr(VI). PMID:27162070

  10. Hair analysis following chronic smoked-drugs-of-abuse exposure in adults and their toddler: a case report

    Directory of Open Access Journals (Sweden)

    Papaseit Esther

    2011-12-01

    Full Text Available Abstract Introduction Over the past two decades, the study of chronic cocaine and crack cocaine exposure in the pediatric population has been focused on the potential adverse effects, especially in the prenatal period and early childhood. Non-invasive biological matrices have become an essential tool for the assessment of a long-term history of drug of abuse exposure. Case report We analyze the significance of different biomarker values in hair after chronic crack exposure in a two-year-old Caucasian girl and her parents, who are self-reported crack smokers. The level of benzoylecgonine, the principal metabolite of cocaine, was determined in segmented hair samples (0 cm to 3 cm from the scalp, and > 3 cm from the scalp following washing to exclude external contamination. Benzoylecgonine was detectable in high concentrations in the child's hair, at 1.9 ng/mg and 7.04 ng/mg, respectively. Benzoylecgonine was also present in the maternal and paternal hair samples at 7.88 ng/mg and 6.39 ng/mg, and 13.06 ng/mg and 12.97 ng/mg, respectively. Conclusion Based on the data from this case and from previously published poisoning cases, as well as on the experience of our research group, we conclude that, using similar matrices for the study of chronic drug exposure, children present with a higher cocaine concentration in hair and they experience more serious deleterious acute effects, probably due to a different and slower cocaine metabolism. Consequently, children must be not exposed to secondhand crack smoke under any circumstance.

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

    Directory of Open Access Journals (Sweden)

    Klett Martin

    2005-10-01

    Full Text Available Abstract 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

  12. Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

    Directory of Open Access Journals (Sweden)

    Yen Chia-Hung

    2012-07-01

    Full Text Available Abstract Background Nonylphenol (NP, an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS synthesis. Chronic exposure to low-dose adenine (AD has been reported to induce chronic kidney disease (CKD. Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control, group 2 (AD in fodder at a concentration of 0.25%, group 3 (NP: 2 mg/kg/day, group 4 (combined AD & NP, and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day. Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p  Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

  13. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice

    International Nuclear Information System (INIS)

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and anti-sperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h-1) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation. (authors)

  14. Growth, oxidative stress responses, and gene transcription of juvenile bighead carp (Hypophthalmichthys nobilis) under chronic-term exposure of ammonia.

    Science.gov (United States)

    Sun, Hongjie; Wang, Wenqian; Li, Jiajia; Yang, Zhou

    2014-08-01

    Ammonia toxicity has become a universal problem for aquatic animals, especially fish. The purpose of the present study was to assess the chronic toxicity of ammonia to the juvenile bighead carp (Hypophthalmichthys nobilis). The authors measured the responses of growth performance (specific growth rate, condition factor, body weight, and body length), oxidative stress, and related gene transcription of juvenile bighead carp exposed to solutions with different concentrations of un-ionized ammonia (UIA; 0 mg L(-1) , 0.053 mg L(-1) , 0.106 mg L(-1) , 0.159 mg L(-1) , and 0.212 mg L(-1) ). The results showed that UIA had no effect on growth performance, glutathione content, or glutathione S-transferase gene transcription, but superoxide dismutase (SOD) activity was significantly elevated. In addition, different concentrations of UIA produced different degrees of damage to juvenile bighead carp: compared with control, lower UIA levels significantly decreased gene transcription of catalase (CAT) and increased malondialdehyde (MDA) levels; higher UIA concentration (0.212 mg L(-1) ) significantly increased gene transcription of the antioxidant enzymes CAT and SOD and reduced MDA levels. The data clearly demonstrate that chronic exposure of UIA at lower concentrations can result in some degree of impairment of antioxidative function, and chronic exposure at higher concentrations can enhance damage to juvenile bighead carp by modulating antioxidant enzyme activities and gene transcription. PMID:24839064

  15. Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-03-01

    Full Text Available Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the

  16. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    Science.gov (United States)

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. PMID:26349946

  17. Exposure to daily ambient particulate polycyclic aromatic hydrocarbons and cough occurrence in adult chronic cough patients: A longitudinal study

    Science.gov (United States)

    Anyenda, Enoch Olando; Higashi, Tomomi; Kambayashi, Yasuhiro; Thao, Nguyen Thi Thu; Michigami, Yoshimasa; Fujimura, Masaki; Hara, Johsuke; Tsujiguchi, Hiromasa; Kitaoka, Masami; Asakura, Hiroki; Hori, Daisuke; Yamada, Yohei; Hayashi, Koichiro; Hayakawa, Kazuichi; Nakamura, Hiroyuki

    2016-09-01

    The specific components of airborne particulates responsible for adverse health effects have not been conclusively identified. We conducted a longitudinal study on 88 adult patients with chronic cough to evaluate whether exposure to daily ambient levels of particulate polycyclic aromatic hydrocarbons (PAH) has relationship with cough occurrence. Study participants were recruited at Kanazawa University Hospital, Japan and were physician-diagnosed to at least have asthma, cough variant asthma and/or atopic cough during 4th January to 30th June 2011. Daily cough symptoms were collected by use of cough diaries and simultaneously, particulate PAH content in daily total suspended particles collected on glass fiber filters were determined by high performance liquid chromatography coupled with fluorescence detector. Population averaged estimates of association between PAH exposure and cough occurrence for entire patients and subgroups according to doctor's diagnosis were performed using generalized estimating equations. Selected adjusted odds ratios for cough occurrence were 1.088 (95% confidence interval (CI): 1.031, 1.147); 1.209 (95% CI: 1.060, 1.379) per 1 ng/m3 increase for 2-day lag and 6-day moving average PAH exposure respectively. Likewise, 5 ring PAH had higher odds in comparison to 4 ring PAH. On the basis of doctor's diagnosis, non-asthma group had slightly higher odds ratio 1.127 (95% CI: 1.033, 1.228) per 1 ng/m3 increase in 2-day lag PAH exposure. Our findings suggest that ambient PAH exposure is associated with cough occurrence in adult chronic cough patients. The association may be stronger in non-asthma patients and even at low levels although there is need for further study with a larger sample size of respective diagnosis and inclusion of co-pollutants.

  18. Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Zelmina Lubovac-Pilav

    Full Text Available Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12, this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc. and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.. Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.

  19. Chronic copper exposure and fatty acid composition of the amphipod Dikerogammarus villosus: Results from a field study

    International Nuclear Information System (INIS)

    Field study allows assessment of long-term effects on fatty acid (FA) composition of organisms under chronic exposure to metals. One expected effect of copper is peroxidation of lipids and essentially polyunsaturated fatty acids (PUFA). FA analysis was established for the amphipod Dikerogammarus villosus subjected to different degrees of copper exposure (4-40 μg Cu L-1). A previous study in our team showed that this species regulates its body Cu concentration (106-135 mg Cu kg-1 dry weight). Despite the high capacity of bioaccumulation, the absence of a correlation between copper concentration in D. villosus and water prevents its use as bioindicator of copper pollution. Both sexes from the most polluted site showed the lowest total FA content, but the highest PUFA percent, mainly of the long-chained variety (C20-C22). Mechanisms leading to the prevention of lipid peroxidation in this species were discussed (metallothioneins and intracellular granules) and proposed with support from literature data. - Under chronic copper exposure, Dikerogammarus villosus loses in total fatty acids content but increases its essential ω3 and ω6 PUFA percent

  20. Chronic copper exposure and fatty acid composition of the amphipod Dikerogammarus villosus: Results from a field study

    Energy Technology Data Exchange (ETDEWEB)

    Maazouzi, Chafik [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: maazouzi@univ-metz.fr; Masson, Gerard [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: masson1@univ-metz.fr; Izquierdo, Maria Soledad [Grupo de Investigacion en Acuicultura, ULPGC and ICCM, P.O. Box 56, 35200 Telde, Las Palmas de Gran Canaria (Spain)], E-mail: mizquierdo@dbio.ulpgc.es; Pihan, Jean-Claude [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: pihan@univ-metz.fr

    2008-11-15

    Field study allows assessment of long-term effects on fatty acid (FA) composition of organisms under chronic exposure to metals. One expected effect of copper is peroxidation of lipids and essentially polyunsaturated fatty acids (PUFA). FA analysis was established for the amphipod Dikerogammarus villosus subjected to different degrees of copper exposure (4-40 {mu}g Cu L{sup -1}). A previous study in our team showed that this species regulates its body Cu concentration (106-135 mg Cu kg{sup -1} dry weight). Despite the high capacity of bioaccumulation, the absence of a correlation between copper concentration in D. villosus and water prevents its use as bioindicator of copper pollution. Both sexes from the most polluted site showed the lowest total FA content, but the highest PUFA percent, mainly of the long-chained variety (C20-C22). Mechanisms leading to the prevention of lipid peroxidation in this species were discussed (metallothioneins and intracellular granules) and proposed with support from literature data. - Under chronic copper exposure, Dikerogammarus villosus loses in total fatty acids content but increases its essential {omega}3 and {omega}6 PUFA percent.

  1. Risk Analysis of Acute Or Chronic Exposure to Arsenic of the Inhabitants in a District of Buenos Aires, Argentina

    Directory of Open Access Journals (Sweden)

    Cristina Vázquez

    2016-09-01

    Full Text Available The arsenic occurrence in the water constitutes a serious world health concern due to its toxicity. Depending on the intensity and duration of exposure, this element can be acutely lethal or may have a wide range of health effects in humans and animals. In Argentina, the origin of arsenic is mainly natural, and related to different geological processes. The Argentinean concern about arsenic and its influence on human health dates back to the previous century. The disease ascribed to arsenic contamination was called ‘chronic regional endemic hydroarsenism’. It is produced by the consumption of water with high levels of this element. In our study, we focused in La Matanza district, a very populated site in the Buenos Aires Province. An increasing concern of the inhabitants of the area regarding health problems was detected. In order to establish a full view of arsenic exposure in the area, several matrices and targets were analyzed. As matrices, water and soil samples were analyzed. As targets, canine and human hair was studied. The aim of this study was to investigate acute and chronically exposure to arsenic of La Matanza inhabitants.

  2. Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

    Science.gov (United States)

    Monsey, Melissa S; Boyle, Lara M; Zhang, Melinda L; Nguyen, Caroline P; Kronman, Hope G; Ota, Kristie T; Duman, Ronald S; Taylor, Jane R; Schafe, Glenn E

    2014-01-01

    Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT) on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs) in the lateral nucleus of the amygdala (LA). Rats received chronic exposure to CORT (50 μg/ml) in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM) is not affected, while long-term memory (LTM) is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

  3. Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

    Directory of Open Access Journals (Sweden)

    Melissa S Monsey

    Full Text Available Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs in the lateral nucleus of the amygdala (LA. Rats received chronic exposure to CORT (50 μg/ml in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM is not affected, while long-term memory (LTM is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    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 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 muscle 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 deactivation were

  5. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  6. Pulmonary sensitivity to ozone exposure in sedentary versus chronically trained, female rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Pulmonary effects to ozone with rats that have chronically exercised or have been continuously sedentary. Also includes body composition of both groups throughout...

  7. Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study

    Directory of Open Access Journals (Sweden)

    Francisco Moreira Mattos Júnior

    2015-07-01

    Full Text Available The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001 and in its intensity (p < 0.001. Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics.

  8. Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

    OpenAIRE

    Nguyen, Long P.; Omoluabi, Ozozoma; Parra, Sergio; Frieske, Joanna M.; Clement, Cecilia; Ammar-Aouchiche, Zoulikha; Ho, Samuel B.; Ehre, Camille; Kesimer, Mehmet; Knoll, Brian J.; Tuvim, Michael J; Dickey, Burton F.; Bond, Richard A.

    2007-01-01

    Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers de...

  9. Chronic exposure of ecosystems and public to elements in trace contributions

    International Nuclear Information System (INIS)

    The needs in radiation protection come towards the question of chronic contaminations by trace elements or radioactive compounds. The chronicity induces to take into account a whole of redistribution mechanisms more important than the only ways of the most direct transfer. In the case of environment, that is going to become one of the way of public contamination is a target to protect, the important work is to link the contamination situation to eventual consequences on the ecosystems situation. (N.C.)

  10. INDUCTION OF CHRONIC KIDNEY FAILURE IN A LONG-TERM PERITONEAL EXPOSURE MODEL IN THE RAT: EFFECTS ON FUNCTIONAL AND STRUCTURAL PERITONEAL ALTERATIONS

    NARCIS (Netherlands)

    F. Vrtovsnik; A. Coester; D. Lopes-Barreto; D.R. de Waart; A. van der Wal; D.G. Struijk; R. Krediet; M. Zweers

    2010-01-01

    Background: A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialys

  11. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

    Science.gov (United States)

    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.

  12. Chronic Exposure to Arsenic in the Drinking Water Alters the Expression of Immune Response Genes in Mouse Lung

    Science.gov (United States)

    Kozul, Courtney D.; Hampton, Thomas H.; Davey, Jennifer C.; Gosse, Julie A.; Nomikos, Athena P.; Eisenhauer, Phillip L.; Weiss, Daniel J.; Thorpe, Jessica E.; Ihnat, Michael A.; Hamilton, Joshua W.

    2009-01-01

    Background Chronic exposure to drinking water arsenic is a significant worldwide environmental health concern. Exposure to As is associated with an increased risk of lung disease, which may make it a unique toxicant, because lung toxicity is usually associated with inhalation rather than ingestion. Objectives The goal of this study was to examine mRNA and protein expression changes in the lungs of mice exposed chronically to environmentally relevant concentrations of As in the food or drinking water, specifically examining the hypothesis that As may preferentially affect gene and protein expression related to immune function as part of its mechanism of toxicant action. Methods C57BL/6J mice fed a casein-based AIN-76A defined diet were exposed to 10 or 100 ppb As in drinking water or food for 5–6 weeks. Results Whole genome transcriptome profiling of animal lungs revealed significant alterations in the expression of many genes with functions in cell adhesion and migration, channels, receptors, differentiation and proliferation, and, most strikingly, aspects of the innate immune response. Confirmation of mRNA and protein expression changes in key genes of this response revealed that genes for interleukin 1β, interleukin 1 receptor, a number of toll-like receptors, and several cytokines and cytokine receptors were significantly altered in the lungs of As-exposed mice. Conclusions These findings indicate that chronic low-dose As exposure at the current U.S. drinking-water standard can elicit effects on the regulation of innate immunity, which may contribute to altered disease risk, particularly in lung. PMID:19654921

  13. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

    Directory of Open Access Journals (Sweden)

    G. Morais-Silva

    2016-01-01

    Full Text Available 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.

  14. [Effect of chronic exposure to low doses of ionized radiation on embryonal development of the Japanese quail].

    Science.gov (United States)

    Gur'eva, T S; Dadasheva, O A; Tsetlin, V V; Mednikova, E I; Lebedeva, Z N

    2007-01-01

    Experiments on Japanese quail embryogenesis on a background of chronic exposure to gamma- and neutron doses comparable with the doses of ionized radiation inside the orbital space stations Mir and ISS, and exploration vehicles gave evidence that permanent absorption of low gamma-doses (0,15 cgy/d) did not impact development of the Japanese quail embryos. On the contrary, the neutron dose of 200 microgy/d imparted by the neutron flux of 30 particles/cm2s was hazardous to embryos as it caused morphological disorders in 12% of embryos. PMID:18672515

  15. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.;

    2005-01-01

    . The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

  16. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats.

    Science.gov (United States)

    Walters, Jennifer L; Lansdell, Theresa A; Lookingland, Keith J; Baker, Lisa E

    2015-12-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 μg/kg atrazine, 10mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning.

  17. Impact of water-accommodated fractions of crude oil on Atlantic cod, Gadus morhua following chronic exposure

    International Nuclear Information System (INIS)

    This study examined the long-term effects of hydrocarbon exposure on the gonadal development of fish. Mature Atlantic cod (Gadus morhua) were exposed to low concentrations of water accommodated fractions (WAFs) of polycyclic aromatic hydrocarbons (PAHs) in an ambient flowthrough seawater system. Some PAH-exposed cod groups were depurated afterwards for 38 to 287 days. Mortality was rare, and external lesions occurred only in the PAH-exposed groups. The gonado-somatic index revealed that gonadal development was disrupted in both sexes and spawning and spermiation was delayed in the 33 depurated PAH-groups. The findings indicate that chronic exposure to WAFs in the water column may have an adverse effect on reproduction in Atlantic cod.

  18. Effects of chronic produced water exposure on the expression of some immune-related genes of juvenile Atlantic cod

    International Nuclear Information System (INIS)

    This study assessed the impacts of exposure to processed water produced by offshore oil operators on immune-related genes of juvenile Atlantic cod exposed to processed water for a period of 22 weeks. The study investigated the influence of processed water concentrations on growth parameters; food consumption; plasma cortisol; respiratory burst activity (RB); and mRNA expression. The study showed that the RB of circulating leukocytes was significantly elevated. Significant up-regulation of the mRNA expression of microglobulin, immunoglobulin light chain, and interleukins was observed in some fish. The down-regulation of the interferon stimulated gene was also observed. The study indicated that chronic exposure to significant amounts of processed water causes modulations of the immune system of juvenile Atlantic cod.

  19. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Science.gov (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2016-01-01

    Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI. PMID:26784694

  20. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Directory of Open Access Journals (Sweden)

    Dhananjay R Namjoshi

    Full Text Available Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE, a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS. How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  1. Treatment of the X and γ rays lung monitoring spectra obtained by using HP-Ge detectors in case of exposures to uranium

    International Nuclear Information System (INIS)

    A lung monitoring counting spectrum can be described as a random phenomenon. Channel-by-channel Poisson-type modelling was verified for cases of pure background. When carrying out spectral analysis for qualitative research, one must work with the sum of the detectors. The quantification must be calculated detector by detector. Statistical tests make it possible to certify that one or several peaks are really present in the organism. The calculations are currently made with automatic spectral analysis, peak search, specific area, statistics and probability of the real presence of analytic photo peak taking into account the morphological parameters of the worker. The results are analysed detector by detector, with and without the background of the room. Detection limits obtained in Pierrelatte in monitoring measurement conditions were assessed for variable tissues covering the range of subjects to be examined. For each subject, the calculations are made taking into account the equivalent tissue thicknesses derived from individual morphological parameters. This method makes it possible to quantify lung activities with a detection limit of 3.9 Bq (235U; thirty minutes counting time; reference man parameters) and to monitor exposure to the different compounds of uranium. (author)

  2. Short-term respiratory effects of 0. 12 ppm ozone exposure in volunteers with chronic obstructive pulmonary disease

    Energy Technology Data Exchange (ETDEWEB)

    Linn, W.S.; Fischer, D.A.; Medway, D.A.; Anzar, U.T.; Spier, C.E.; Valencia, L.M.; Venet, T.G.; Hackney, J.D.

    1982-06-01

    Twenty-five volunteers with chronic obstructive pulmonary disease of mild to moderately severe degree underwent 1-h exposures to 0.12 ppm ozone (O/sub 2/) in purified air with intermittent mild exercise. Their responses were assessed in terms of forced expiratory performance, ear oximetry, and reported symptoms. Control studied consisted of similar exposures to purified air alone. Control studies were separated from O/sub 2/ exposures by 1 month, and the order was randomized. All studies took place in a controlled-environment chamber, and were preceded by approximately 1 h of rest in a purified-air environment. No significant disturbances in forced expiratory performance or symptoms attributable to O/sub 2/ exposure were found. A slight but significant tendency to decreased arterial hemoglobin oxygen saturation (SaO/sub 2/) during exercise in O/sub 2/ was observed. The decrement in SaO/sub 2/ with O/sub 2/ relative to clean air (mean 1.3%) was near the limit of resolution of the ear oximeter test and was detected by signal averaging, thus its physiologic or clinical significance is uncertain.

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

    Directory of Open Access Journals (Sweden)

    Abul Hasnat Milton

    2012-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  5. Chronic exposure to perfluorooctane sulfonate induces behavior defects and neurotoxicity through oxidative damages, in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Na Chen

    Full Text Available Perfluorooctane sulfonate (PFOS is an emerging persistent pollutant which shows multiple adverse health effects. However, the neurotoxicity of PFOS and its mechanisms have not been fully elucidated. Using a combination of in vivo and in vitro methods, the present study provides a detailed description of PFOS-induced neurotoxicity. Results showed that the median lethal concentration of PFOS was 2.03 mM in Caenorhabditis elegans for 48 h exposure. 20 µM PFOS caused decrease of locomotor behaviors including forward movement, body bend and head thrash. Additionally, PFOS exposure reduced chemotaxis index of C. elegans, which indicates the decline of chemotaxis learning ability. Using green fluorescent protein (GFP labelled transgenic strains, we found that PFOS caused down-regulated expression of a chemoreceptor gene, gcy-5, in ASE chemosensory neurons, but did not affect cholinergic neurons and dopaminergic neurons. In SH-SY5Y cells, 48 h exposure to 25 µM and 50 µM PFOS induced cell damage, apoptosis and the reactive oxygen species (ROS generation. PFOS caused significant increases of lipid peroxidation and superoxide dismutase activity, but an actual decrease of glutathione peroxidase activity. Furthermore, antioxidant N-acetylcysteine rescued cells from PFOS-induced apoptosis via blocking ROS. Our results demonstrate that chronic exposure to PFOS can cause obvious neurotoxicity and behavior defects. Oxidative damage and anti-oxidative deficit are crucial mechanisms in neurotoxicity of PFOS.

  6. Cytogenotoxicity assessment of monocrotophos and butachlor at single and combined chronic exposures in the fish Catla catla (Hamilton).

    Science.gov (United States)

    Anbumani, S; Mohankumar, Mary N

    2015-04-01

    Cytogenotoxic effects in the form of micronuclei and deformed nucleus, nuclear buds, binucleated cells, vacuolated nucleus, vacuolated cytoplasm, echinocytes, and enucleus induced by two compounds belonging to two different chemical classes of agrochemicals (monocrotophos and butachlor) at sublethal concentrations (0.625, 1.3, and 2.3 ppm and 0.016, 0.032, and 0.064 ppm) in single and combined chronic exposures were studied under laboratory conditions for a period of 35 days in the economically important Indian fish Catla catla. Statistically significant duration-dependent increases in the frequencies of micronucleus (MN) and other cytological anomalies were observed. Compared to single exposures, a twofold increase in micronuclei frequency was noted at combined exposures indicating the synergistic phenomenon. Binucleated and enucleated cells appeared only in fishes exposed to sublethal concentrations of butachlor. The present study is the first of its kind in exploring a significant positive correlation between micronuclei and other nuclear anomalies suggesting them as new possible biomarkers of genotoxicity after agrochemical exposures. The study highlights the sensitivity of the assay in exploring various predictive biomarkers of genotoxic and cytotoxic events and also elicits the synergistic effects of agrochemicals in apparently healthy fishes. C. catla can be considered as a suitable aquatic biomonitoring sentinel species of contaminated water bodies.

  7. Acute and chronic effects of pulse exposure of Daphnia magna to dimethoate and pirimicarb.

    Science.gov (United States)

    Andersen, Tobias Henrik; Tjørnhøj, Rikke; Wollenberger, Leah; Slothuus, Tina; Baun, Anders

    2006-05-01

    Short-term (Daphnia magna exposed to pulses of 0.5 to 8 h in duration. During a 21-d postexposure observation period, the following parameters were monitored: Mortality, mobility, day for first offspring, animal size, weight of offspring and adults, and number of offspring produced. In general, animals exposed to a single pulse of dimethoate or pirimicarb regained mobility after 24 to 48 h in clean media. Animals exposed to repeated pulses of dimethoate did not recover mobility during a 48-h postexposure observation period, and mortality was significantly increased. Animals exposed to two pulses of pirimicarb showed less recovery of mobility compared with those exposed to one pulse. Exposure of D. magna to 30 mg/L of dimethoate or 100 microg/L of pirimicarb for 2 to 6 h resulted in a significant reduction in the number of offspring and in the average weight of offspring. The average body length was reduced after pulse exposure to 30 mg/L of dimethoate for 3 h or 70 microg/L of pirimicarb for 4 h, and these exposure concentrations caused a delay in the day for first offspring at exposure durations of 2 to 6 h. The most important new findings in the present study are that short-term (<4 h) pulse exposure of neonates to acetylcholinesterase-inhibiting pesticides caused reproductive damage in D. magna and that repeated-pulse exposure significantly increased mortality in animals that apparently had recovered after a single-pulse exposure. PMID:16704047

  8. Chronic ethanol exposure increases voluntary home cage intake in adult male, but not female, Long-Evans rats.

    Science.gov (United States)

    Morales, Melissa; McGinnis, Molly M; McCool, Brian A

    2015-12-01

    The current experiment examined the effects of 10 days of chronic intermittent ethanol (CIE) exposure on anxiety-like behavior and home cage ethanol intake using a 20% intermittent access (M, W, F) paradigm in male and female Long-Evans rats. Withdrawal from alcohol dependence contributes to relapse in humans and increases in anxiety-like behavior and voluntary ethanol consumption in preclinical models. Our laboratory has shown that 10 days of CIE exposure produces both behavioral and neurophysiological alterations associated with withdrawal in male rats; however, we have yet to examine the effects of this exposure regime on ethanol intake in females. During baseline, females consumed more ethanol than males but, unlike males, did not show escalations in intake. Rats were then exposed to CIE and were again given intermittent access to 20% ethanol. CIE males increased their intake compared to baseline, whereas air-exposed males did not. Ethanol intake in females was unaffected by CIE exposure. Notably, both sexes expressed significantly elevated withdrawal-associated anxiety-like behavior in the plus maze. Finally, rats were injected with the cannabinoid CB1 receptor antagonist, SR141716A (0, 1, 3, 10mg/kg, i.p.) which reduced ethanol intake in both sexes. However, females appear to be more sensitive to lower doses of this CB1 receptor antagonist. Our results show that females consume more ethanol than males; however, they did not escalate their intake using the intermittent access paradigm. Unlike males, CIE exposure had no effect on drinking in females. It is possible that females may be less sensitive than males to ethanol-induced increases in drinking after a short CIE exposure. Lastly, our results demonstrate that males and females may have different pharmacological sensitivities to CB1 receptor blockade on ethanol intake, at least under the current conditions.

  9. Chronic exposure to combined carcinogens enhances breast cell carcinogenesis with mesenchymal and stem-like cell properties.

    Directory of Open Access Journals (Sweden)

    Lenora Ann Pluchino

    Full Text Available Breast cancer is the most common type of cancer affecting women in North America and Europe. More than 85% of breast cancers are sporadic and attributable to long-term exposure to small quantities of multiple carcinogens. To understand how multiple carcinogens act together to induce cellular carcinogenesis, we studied the activity of environmental carcinogens 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK and benzo[a]pyrene (B[a]P, and dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP using our breast cell carcinogenesis model. Our study revealed, for the first time, that combined NNK and B[a]P enhanced breast cell carcinogenesis chronically induced by PhIP in both non-cancerous and cancerous breast cells. Co-exposure was more potent than sequential exposure to combined NNK and B[a]P followed by PhIP in inducing carcinogenesis. Initiation of carcinogenesis was measured by transient endpoints induced in a single exposure, while progression of carcinogenesis was measured by acquisition of constitutive endpoints in cumulative exposures. Transient endpoints included DNA damage, Ras-Erk-Nox pathway activation, reactive oxygen species elevation, and increased cellular proliferation. Constitutive endpoints included various cancer-associated properties and signaling modulators, as well as enrichment of cancer stem-like cell population and activation of the epithelial-to-mesenchymal transition program. Using transient and constitutive endpoints as targets, we detected that a combination of the green tea catechins ECG and EGCG, at non-cytotoxic levels, was more effective than individual agents in intervention of cellular carcinogenesis induced by combined NNK, B[a]P, and PhIP. Thus, use of combined ECG and EGCG should be seriously considered for early intervention of breast cell carcinogenesis associated with long-term exposure to environmental and dietary carcinogens.

  10. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

    International Nuclear Information System (INIS)

    OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency

  11. The Association between Chronic Arsenic Exposure and Hypertension: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Tanvir Abir

    2012-01-01

    Full Text Available Background. There is inconclusive evidence from cross-sectional and cohort studies that arsenic exposure is a risk factor involved in the development of hypertension. Methods. A database search, using several keywords, was conducted to identify relevant studies. Separate odds ratio estimates for arsenic exposure with concentration only and arsenic exposure with duration, including biomarker, were extracted from studies that met all inclusion criteria. The extracted odds ratios (OR comparing the highest exposure categories with the lowest in each study were pooled using the random effects methods of meta-analysis. Heterogeneity of odds ratios in the included studies were analyzed using I2 statistics. Results. Eight studies were analyzed. Using the exposure as arsenic concentration in the drinking water, the OR estimate was 1.9 (95% CI: 1.2–3.0, with the I2 = 92%, while using the exposure as concentration and duration, the OR estimate was 1.4 (95% CI: 0.95–2.0 with the I2 = 80%. Meta-regression was done and the quality of exposure measurement was found to be significantly associated with the effect measure. For a one unit increase in the score from exposure assessment, the odds ratio decreased by 6%. No publication bias was evident. The only major weaknesses of this study were heterogeneity across studies and small sample size. Conclusions. The study findings provide limited evidence for a relationship between arsenic and hypertension. In summary, the relationship between arsenic exposure and hypertension is still inconclusive and needs further validation through prospective cohort studies.

  12. Spatial variations in estimated chronic exposure to traffic-related air pollution in working populations: A simulation

    Directory of Open Access Journals (Sweden)

    Cloutier-Fisher Denise

    2008-07-01

    Full Text Available Abstract Background Chronic exposure to traffic-related air pollution is associated with a variety of health impacts in adults and recent studies show that exposure varies spatially, with some residents in a community more exposed than others. A spatial exposure simulation model (SESM which incorporates six microenvironments (home indoor, work indoor, other indoor, outdoor, in-vehicle to work and in-vehicle other is described and used to explore spatial variability in estimates of exposure to traffic-related nitrogen dioxide (not including indoor sources for working people. The study models spatial variability in estimated exposure aggregated at the census tracts level for 382 census tracts in the Greater Vancouver Regional District of British Columbia, Canada. Summary statistics relating to the distributions of the estimated exposures are compared visually through mapping. Observed variations are explored through analyses of model inputs. Results Two sources of spatial variability in exposure to traffic-related nitrogen dioxide were identified. Median estimates of total exposure ranged from 8 μg/m3 to 35 μg/m3 of annual average hourly NO2 for workers in different census tracts in the study area. Exposure estimates are highest where ambient pollution levels are highest. This reflects the regional gradient of pollution in the study area and the relatively high percentage of time spent at home locations. However, for workers within the same census tract, variations were observed in the partial exposure estimates associated with time spent outside the residential census tract. Simulation modeling shows that some workers may have exposures 1.3 times higher than other workers residing in the same census tract because of time spent away from the residential census tract, and that time spent in work census tracts contributes most to the differences in exposure. Exposure estimates associated with the activity of commuting by vehicle to work were

  13. Shotgun proteomic analysis unveils survival and detoxification strategies by Caulobacter crescentus during exposure to uranium, chromium, and cadmium.

    Science.gov (United States)

    Yung, Mimi C; Ma, Jincai; Salemi, Michelle R; Phinney, Brett S; Bowman, Grant R; Jiao, Yongqin

    2014-04-01

    The ubiquitous bacterium Caulobacter crescentus holds promise to be used in bioremediation applications due to its ability to mineralize U(VI) under aerobic conditions. Here, cell free extracts of C. crescentus grown in the presence of uranyl nitrate [U(VI)], potassium chromate [Cr(VI)], or cadmium sulfate [Cd(II)] were used for label-free proteomic analysis. Proteins involved in two-component signaling and amino acid metabolism were up-regulated in response to all three metals, and proteins involved in aerobic oxidative phosphorylation and chemotaxis were down-regulated under these conditions. Clustering analysis of proteomic enrichment revealed that the three metals also induce distinct patterns of up- or down-regulated expression among different functional classes of proteins. Under U(VI) exposure, a phytase enzyme and an ABC transporter were up-regulated. Heat shock and outer membrane responses were found associated with Cr(VI), while efflux pumps and oxidative stress proteins were up-regulated with Cd(II). Experimental validations were performed on select proteins. We found that a phytase plays a role in U(VI) and Cr(VI) resistance and detoxification and that a Cd(II)-specific transporter confers Cd(II) resistance. Interestingly, analysis of promoter regions in genes associated with differentially expressed proteins suggests that U(VI) exposure affects cell cycle progression.

  14. The impact of repetitive and chronic exposure to terror attacks on Israeli mothers' and children's functioning.

    Science.gov (United States)

    Shechory-Bitton, Mally

    2013-01-01

    Studies point to the pathogenic impact of exposure to terror. however, most focus on specific traumatic events. the current study focused on the impact of continuous ongoing exposure to terror attacks. it examined the extent to which children's PtSD and behavior problems are a function of mothers' PtSD, child and mother exposure to terror events, and child and mother fear. a sample of 152 mother and children dyads, all living in communities on israel's southern border, were surveyed. results indicate that children's posttraumatic symptoms are significantly and positively predicted by their exposure to terror events, their fear, and their mothers' posttraumatic symptoms. in addition, children's current behavioral and social problems are positively predicted by mothers' posttraumatic symptoms. results are discussed in light of the importance of subjective interpretation. the findings suggest that further research should examine additional cognitive and social contextual factors.

  15. NEUROSENSORY EFFECTS OF CHRONIC HUMAN EXPOSURE TO ARSENIC ASSOCIATED WITH BODY BURDEN AND ENVIRONMENTAL MEASURES

    Science.gov (United States)

    Exposure to arsenic in drinking water is known to produce a variety of health problems including peripheral neuropathy. Auditory, visual and somatosensory impairments have been reported in Mongolian farmers living in the Yellow River Valley where drinking water is contami...

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

    Directory of Open Access Journals (Sweden)

    Weeks Jennifer

    2008-06-01

    Full Text Available Abstract 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.

  17. Chronic exposure to sublethal hexavalent chromium affects organ histopathology and serum cortisol profile of a teleost, Channa punctatus (Bloch).

    Science.gov (United States)

    Mishra, Ashish K; Mohanty, Banalata

    2009-09-01

    Effects of chronic exposures (one and two months) to sublethal doses of hexavalent chromium (2 and 4 mg/L potassium dichromate) on organ histopathology and serum cortisol profile were investigated and their overall impact on growth and behavior of a teleost fish, Channa punctatus was elucidated. Histopathological lesions were distinct in the vital organs gill, kidney and liver. The gill lamellae became lifted, fused, and showed oedema. Hyperplasia and hypertrophy of lamellar epithelial cells were distinct with desquamation. Hypertrophy of epithelial cells of renal tubules and reduction in tubular lumens were observed in the trunk kidney. The atrophy of the head kidney interrenal cells and decreased serum cortisol level indicated exhaustion of interrenal activity. Hepatocyte vacuolization and shrinkage, nuclear pyknosis and increase of sinusoidal spaces were observed in the liver. Abnormal behavioral patterns and reduced growth rate were also noticed in the exposed fish. The chronic hexavalent chromium exposure thus by affecting histopathology of gill, kidney (including interrenal tissue) and liver could impair the vital functions of respiration, excretion, metabolic regulation and maintenance of stress homeostasis which in the long-run may pose serious threat to fish health and affect their population.

  18. Chronic exposure to sublethal hexavalent chromium affects organ histopathology and serum cortisol profile of a teleost, Channa punctatus (Bloch)

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Ashish K. [Department of Zoology, University of Allahabad, Allahabad-211002 (India); Mohanty, Banalata, E-mail: drbana_mohanty@rediffmail.com [Department of Zoology, University of Allahabad, Allahabad-211002 (India)

    2009-09-01

    Effects of chronic exposures (one and two months) to sublethal doses of hexavalent chromium (2 and 4 mg/L potassium dichromate) on organ histopathology and serum cortisol profile were investigated and their overall impact on growth and behavior of a teleost fish, Channa punctatus was elucidated. Histopathological lesions were distinct in the vital organs gill, kidney and liver. The gill lamellae became lifted, fused, and showed oedema. Hyperplasia and hypertrophy of lamellar epithelial cells were distinct with desquamation. Hypertrophy of epithelial cells of renal tubules and reduction in tubular lumens were observed in the trunk kidney. The atrophy of the head kidney interrenal cells and decreased serum cortisol level indicated exhaustion of interrenal activity. Hepatocyte vacuolization and shrinkage, nuclear pyknosis and increase of sinusoidal spaces were observed in the liver. Abnormal behavioral patterns and reduced growth rate were also noticed in the exposed fish. The chronic hexavalent chromium exposure thus by affecting histopathology of gill, kidney (including interrenal tissue) and liver could impair the vital functions of respiration, excretion, metabolic regulation and maintenance of stress homeostasis which in the long-run may pose serious threat to fish health and affect their population.

  19. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats

    Directory of Open Access Journals (Sweden)

    Samarghandian Saeed

    2015-09-01

    Full Text Available Cadmium (Cd is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control. The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2 in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, reduced glutathione (GSH, malondialdehyde (MDA and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation.

  20. Chronic methamphetamine exposure prior to middle cerebral artery occlusion increases infarct volume and worsens cognitive injury in Male mice.

    Science.gov (United States)

    Zuloaga, Damian G; Wang, Jianming; Weber, Sydney; Mark, Gregory P; Murphy, Stephanie J; Raber, Jacob

    2016-08-01

    Emerging evidence indicates that methamphetamine (MA) abuse can impact cardiovascular disease. In humans, MA abuse is associated with an increased risk of stroke as well as an earlier age at which the stroke occurs. However, little is known about how chronic daily MA exposure can impact ischemic outcome in either humans or animal models. In the present study, mice were injected with MA (10 mg/kg, i.p.) or saline once daily for 10 consecutive days. Twenty-four hours after the final injection, mice were subjected to transient middle cerebral artery occlusion (tMCAO) for one hour followed by reperfusion. Mice were tested for novel object memory at 96 h post-reperfusion, just prior to removal of brains for quantification of infarct volume using 2,3,5-Triphenyltetrazolium Chloride (TTC) staining. Mice treated with MA prior to tMCAO showed decreased object memory recognition and increased infarct volume compared to saline-treated mice. These findings indicate that chronic MA exposure can worsen both cognitive and morphological outcomes following cerebral ischemia. PMID:27021292

  1. The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures

    OpenAIRE

    Ebere Anyanwu; Campbell, Andrew W.; Joseph Jones; Ehiri, John E; Akpan I. Akpan

    2003-01-01

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological signif...

  2. Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure

    OpenAIRE

    Lu, Cai-Ling; Tang, Shen; Meng, Zhi-Juan; He, Yi-Yuan; Song, Ling-Yong; Liu, Yin-Pin; Ma, Ning; Li, Xi-Yi; Guo, Song-Chao

    2014-01-01

    Background Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. Results The escape latency in the Morris Water Maz...

  3. Evidence for effects of chronic lead exposure on blood pressure in experimental animals: an overview.

    OpenAIRE

    Victery, W

    1988-01-01

    Information obtained in a number of experimental studies conducted over the last 40 years on the effects of lead on blood pressure is reviewed. Differences in animal species, age at beginning of exposure, level of lead exposure, indices of lead burden, and blood pressure effects of each study are reported. In several of the high-dose experiments, hypertension was observed, but nephrotoxicity of lead may have contributed to its development. Moreover, in other high-dose experiments, no hyperten...

  4. Evaluation of growth, biochemical and bioaccumulation parameters in Pelophylax perezi tadpoles, following an in-situ acute exposure to three different effluent ponds from a uranium mine

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Sérgio M., E-mail: s.reis.marques@gmail.com [Departamento de Biologia da Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Chaves, Sandra [Universidade de Lisboa, Faculdade de Ciências, Centro de Biodiversidade, Genómica Integrativa e Funcional (BioFIG), Edifício ICAT, Campus da FCUL Campo Grande, Lisboa (Portugal); Gonçalves, Fernando [Departamento de Biologia da Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Pereira, Ruth [CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Departamento de Biologia da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto (Portugal)

    2013-02-15

    Mining activities invariably produce metal contaminated effluents. Depending on factors such as pH and metal concentration the toxicity of the effluent may vary. To assess the effects of three characteristically different effluent ponds from a deactivated uranium mine, with toxicologically relevant data, an in situ exposure with Pelophylax perezi tadpoles, was conducted. Tadpoles were exposed to the three effluent ponds, ranked by increasing order of metals concentrations (REF, M1, M2). Survival, growth, metal accumulation, antioxidant enzymes (catalase, glutathione peroxidase and glutathione reductase) and lipid peroxidation (LPO) were determined in tadpoles. As well, physical and chemical variables of the effluents were measured. Death percentage in the effluents was 3.17 (REF), 9.84 (M1) and 42.86% (M2) and was not coincident with metal accumulation which was highest in tadpoles exposed to M1, while metal contents in M2 tadpoles were quite similar to those recorded in REF tadpoles. However, high mortality in M2 was attributed to the extremely low pH (≈ 3.77). From the three effluents M2 tadpoles had the lowest growth and the antioxidant enzymatic activity was only affected in the case glutathione peroxidase (GPx) with significantly higher activity in M1, being in accordance with the highest accumulation of metals. LPO, usually associated with metal accumulation, had the following pattern M1 > REF > M2. Overall, effluent toxicity in tadpoles exposed to M2 effluent seems to be primarily an effect of pH while in M1 toxicity is mainly owed to high metal concentrations. The effluent acidity seems to reduce metal accumulation probably due to damage in the integument, affecting ion uptake. The results obtained bring a better understanding of the toxicological processes that local P. perezi population is subjected to, mainly in the early life stages. Furthermore this study highlights the influence of pH in the toxicity of metal rich effluents. - Highlights:

  5. Evaluation of growth, biochemical and bioaccumulation parameters in Pelophylax perezi tadpoles, following an in-situ acute exposure to three different effluent ponds from a uranium mine

    International Nuclear Information System (INIS)

    Mining activities invariably produce metal contaminated effluents. Depending on factors such as pH and metal concentration the toxicity of the effluent may vary. To assess the effects of three characteristically different effluent ponds from a deactivated uranium mine, with toxicologically relevant data, an in situ exposure with Pelophylax perezi tadpoles, was conducted. Tadpoles were exposed to the three effluent ponds, ranked by increasing order of metals concentrations (REF, M1, M2). Survival, growth, metal accumulation, antioxidant enzymes (catalase, glutathione peroxidase and glutathione reductase) and lipid peroxidation (LPO) were determined in tadpoles. As well, physical and chemical variables of the effluents were measured. Death percentage in the effluents was 3.17 (REF), 9.84 (M1) and 42.86% (M2) and was not coincident with metal accumulation which was highest in tadpoles exposed to M1, while metal contents in M2 tadpoles were quite similar to those recorded in REF tadpoles. However, high mortality in M2 was attributed to the extremely low pH (≈ 3.77). From the three effluents M2 tadpoles had the lowest growth and the antioxidant enzymatic activity was only affected in the case glutathione peroxidase (GPx) with significantly higher activity in M1, being in accordance with the highest accumulation of metals. LPO, usually associated with metal accumulation, had the following pattern M1 > REF > M2. Overall, effluent toxicity in tadpoles exposed to M2 effluent seems to be primarily an effect of pH while in M1 toxicity is mainly owed to high metal concentrations. The effluent acidity seems to reduce metal accumulation probably due to damage in the integument, affecting ion uptake. The results obtained bring a better understanding of the toxicological processes that local P. perezi population is subjected to, mainly in the early life stages. Furthermore this study highlights the influence of pH in the toxicity of metal rich effluents. - Highlights:

  6. Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus.

    Science.gov (United States)

    Frank, Matthew G; Hershman, Sarah A; Weber, Michael D; Watkins, Linda R; Maier, Steven F

    2014-02-01

    Chronic stress as well as chronic treatment with glucocorticoids (GCs) primes the neuroinflammatory response to a subsequent pro-inflammatory challenge. However, it remains unclear whether chronic GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. In the present set of studies, male Sprague-Dawley rats underwent sham surgery or were adrenalectomized and then treated with varying concentrations of corticosterone (CORT; 0, 25, 50, and 75 μg/ml) administered in their drinking water. After 10 days of CORT exposure, whole hippocampus was collected and expression of glial activation markers measured or hippocampal microglia were isolated and challenged with LPS to probe for CORT-induced sensitization of pro-inflammatory responses. Chronic CORT exposure increased the gene expression of NLRP3, Iba-1, MHCII, and NF-κBIα in a concentration dependent manner. Chronic CORT (75 μg/ml) exposure potentiated the microglial proinflammatory response (TNFα, IL-1β, IL-6 and NLRP3) to LPS compared to the microglial response of sham surgery animals treated with vehicle. The present set of results demonstrate that chronic exposure to GCs primes microglia to pro-inflammatory stimuli and add to a growing body of evidence suggesting that a permissive function of GCs is that of an endogenous danger signal or alarmin.

  7. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

    Directory of Open Access Journals (Sweden)

    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  8. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  9. Pyranocoumarin Tissue Distribution, Plasma Metabolome and Prostate Transcriptome Impacts of Sub-Chronic Exposure to Korean Angelica Supplement in Mice.

    Science.gov (United States)

    Zhang, Jinhui; Li, Li; Tang, Suni; Zhang, Yong; Markiewski, Maciej; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

    2016-04-01

    Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown the anticancer activities of AGN supplements in mouse models. To facilitate human anticancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) ([Formula: see text]% in AGN) and their metabolite decursinol (DOH), assessed the safety of sub-chronic AGN dietary exposure in mice, and explored its impact on plasma aqueous metabolites and the prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater levels of DA and D than the liver did. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diets with 0.5 and 1% AGN for six weeks. No adverse effects were observed on the plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examinations of the liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from mice fed the 1%-AGN diet suggested metabolic shifts of key amino acids especially in the methionine-cysteine cycle, purine cycle, and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes in the metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with a daily [Formula: see text] injection of AGN extract (100-300[Formula: see text]mg/kg) for four weeks, which resulted in much greater systemic pyranocoumarin exposure than the dietary route did. PMID:27080944

  10. Projection neurons in the cortex and hippocampus: differential effects of chronic khat and ethanol exposure in adult male rats

    Science.gov (United States)

    Alele, Paul E; Matovu, Daniel; Imanirampa, Lawrence; Ajayi, Abayomi M; Kasule, Gyaviira T

    2016-01-01

    Background Recent evidence suggests that many individuals who chew khat recreationally also drink ethanol to offset the stimulating effect of khat. The objective of this study was to describe the separate and interactive effects of chronic ethanol and khat exposure on key projection neurons in the cortex and hippocampus of young adult male rats. Methods Young adult male Sprague Dawley rats were divided into six treatment groups: 2 g/kg khat, 4 g/kg khat, 4 g/kg ethanol, combined khat and ethanol (4 g/kg each), a normal saline control, and an untreated group. Treatments were administered orally for 28 continuous days; brains were then harvested, sectioned, and routine hematoxylin–eosin staining was done. Following photomicrography, ImageJ® software captured data regarding neuron number and size. Results No differences occurred in counts of both granular and pyramidal projection neurons in the motor cortex and all four subfields of the hippocampal formation. Khat dose-dependently increased pyramidal neuron size in the motor cortex and the CA3 region, but had different effects on granular neuron size in the dentate gyrus and the motor cortex. Mean pyramidal neuron size for the ethanol-only treatment was larger than that for the 2 g/kg khat group, and the saline control group, in CA3 and in the motor cortex. Concomitant khat and ethanol increased granular neuron size in the motor cortex, compared to the 2 g/kg khat group, the 4 g/kg khat group, and the 4 g/kg ethanol group. In the CA3 region, the 4 g/kg ethanol group showed a larger mean pyramidal neuron size than the combined khat and ethanol group. Conclusion These results suggest that concomitant khat and ethanol exposure changes granular and pyramidal projection neuron sizes differentially in the motor cortex and hippocampus, compared to the effects of chronic exposure to these two drugs separately.

  11. Pyranocoumarin Tissue Distribution, Plasma Metabolome and Prostate Transcriptome Impacts of Sub-Chronic Exposure to Korean Angelica Supplement in Mice.

    Science.gov (United States)

    Zhang, Jinhui; Li, Li; Tang, Suni; Zhang, Yong; Markiewski, Maciej; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

    2016-01-01

    Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown the anticancer activities of AGN supplements in mouse models. To facilitate human anticancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) ([Formula: see text]% in AGN) and their metabolite decursinol (DOH), assessed the safety of sub-chronic AGN dietary exposure in mice, and explored its impact on plasma aqueous metabolites and the prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater levels of DA and D than the liver did. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diets with 0.5 and 1% AGN for six weeks. No adverse effects were observed on the plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examinations of the liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from mice fed the 1%-AGN diet suggested metabolic shifts of key amino acids especially in the methionine-cysteine cycle, purine cycle, and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes in the metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with a daily [Formula: see text] injection of AGN extract (100-300[Formula: see text]mg/kg) for four weeks, which resulted in much greater systemic pyranocoumarin exposure than the dietary route did.

  12. Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers

    Directory of Open Access Journals (Sweden)

    Ren Xiao-Bin

    2011-04-01

    Full Text Available Abstract Background Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI exposure can cause DNA damage in electroplating workers. Methods 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%. Urinary 8-OHdG levels were measured by ELISA. Results Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L than that in control subjects (1.54 μg/L, P P P P Conclusion The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage.

  13. High levels of uranium in groundwater of Ulaanbaatar, Mongolia

    Energy Technology Data Exchange (ETDEWEB)

    Nriagu, Jerome, E-mail: stoten@umich.edu [Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109 (United States); Nam, Dong-Ha; Ayanwola, Titilayo A. [Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109 (United States); Dinh, Hau [College of Literature, Science and Arts, University of Michigan (United States); Erdenechimeg, Erdenebayar; Ochir, Chimedsuren [Department Of Preventive Medicine, School Of Public Health, Health Science University, Mongolia, Ulaanbaatar (Mongolia); Bolormaa, Tsend-Ayush [Central Water Laboratory of Water Supply and Sewerage Authority (USUG), Ulaanbaatar (Mongolia)

    2012-01-01

    Water samples collected from 129 wells in seven of the nine sub-divisions of Ulaanbaatar were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) using Clean Lab methods. The levels of many trace elements were found to be low with the average concentrations (ranges in brackets) being 0.9 (< 0.1-7.9) {mu}g/L for As; 7.7 (0.12-177) {mu}g/L for Mn; 0.2 (< 0.05-1.9) {mu}g/L for Co; 16 (< 0.1-686) {mu}g/L for Zn; 0.7 (< 0.1-1.8) {mu}g/L for Se; < 0.1 (< 0.02-0.69) {mu}g/L for Cd; and 1.3 (< 0.02-32) {mu}g/L for Pb. The levels of uranium were surprisingly elevated (mean, 4.6 {mu}g/L; range < 0.01-57 {mu}g/L), with the values for many samples exceeding the World Health Organization's guideline of 15 {mu}g/L for uranium in drinking water. Local rocks and soils appear to be the natural source of the uranium. The levels of uranium in Ulaanbaatar's groundwater are in the range that has been associated with nephrotoxicity, high blood pressure, bone dysfunction and likely reproductive impairment in human populations. We consider the risk associated with drinking the groundwater with elevated levels of uranium in Ulaanbaatar to be a matter for some public health concern and conclude that the paucity of data on chronic effects of low level exposure is a risk factor for continuing the injury to many people in this city. - Highlights: Black-Right-Pointing-Pointer We analyzed water samples from wells across the city of Ulaanbaatar, Mongolia for total uranium along with arsenic, manganese, cobalt, zinc, selenium, cadmium and lead. Black-Right-Pointing-Pointer We found that compared to other trace metals and metalloids, the levels of uranium were surprisingly elevated with the values for many samples exceeding the World Health Organization's guideline for drinking water. Black-Right-Pointing-Pointer Local rocks and soils appear to be the natural source of the uranium. Black-Right-Pointing-Pointer The health risk associated with drinking the groundwater

  14. E.N.V.I.R.H.O.M.. Bioaccumulation of radionuclides in situations of chronic exposure of ecosystems and members of the public; Progress Report 2 covering the period June 2003 - September 2005

    International Nuclear Information System (INIS)

    The main objective of E.N.V.I.R.H.O.M. is to better assess real effects caused by chronic exposure to low levels of radioactive contaminants. This includes for example consequences on nervous system, immunity or metabolisms, consequences on reproduction, consequences on feeding processes and consequences on ecosystem productivity. E.N.V.I.R.O.M. has set a priority on radionuclides that are suspected of accumulation in organisms., it has also a priority on radionuclides that act not only with gamma rays. The program was started in 2001 and uranium was chosen to test the methodology. The two first years of E.N.V.I.R.H.O.M. demonstrated clearly that a signal can be seen even as a consequence of moderate exposure. It was also found that some simplifying hypothesis may be false. For example the simple biokinetic model assuming that the result of a continuous feeding is equivalent to the convolution of successive punctual inputs is not always true. When the input is constant, it should involve a steady state following an increase. Instead of that, a decrease has been observed in some cases (rats, crayfish). The second two years period ( 2004-2005) used the same strategy in a larger scale. As regard biota, the list of test organisms was extended (daphnia, insects)and also the tested radionuclides (Se, Tc, Am). The list of studied functions was extended (behavior and sleep, neurotransmission, genomic effects, intestinal immune capacity, drug metabolism, vitamin D metabolism). The E.N.V.I.R.H.O.M. program is the main experimental part of a container program devoted to chronic risks. (N.C.)

  15. Honey Bees' Behavior Is Impaired by Chronic Exposure to the Neonicotinoid Thiacloprid in the Field.

    Science.gov (United States)

    Tison, Léa; Hahn, Marie-Luise; Holtz, Sophie; Rößner, Alexander; Greggers, Uwe; Bischoff, Gabriela; Menzel, Randolf

    2016-07-01

    The decline of pollinators worldwide is of growing concern and has been related to the use of plant-protecting chemicals. Most studies have focused on three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) currently subject to a moratorium in the EU. Here, we focus on thiacloprid, a widely used cyano-substituted neonicotinoid thought to be less toxic to honey bees and of which use has increased in the last years. Honey bees (Apis mellifera carnica) were exposed chronically to thiacloprid in the field for several weeks at a sublethal concentration. Foraging behavior, homing success, navigation performance, and social communication were impaired, and thiacloprid residue levels increased both in the foragers and the nest mates over time. The effects observed in the field were not due to a repellent taste of the substance. For the first time, we present the necessary data for the risk evaluation of thiacloprid taken up chronically by honey bees in field conditions. PMID:27268938

  16. Estimation of doses to patients with chronic radiation sickness from external occupational exposure

    International Nuclear Information System (INIS)

    The doses to patients with chronic radiation sickness who had engaged in diagnostic radiology have been estimated according to the radiation work load, type and capacity of X-ray equipment, protection conditions, data of nationwide survey on doses to X-ray workers in China, or the data of dose monitoring in working places. Based on the activities of radium sources, time taken up in performing radium therapy, distance to radium sources and radiation work load, the doses to patients who had engaged in radium therapy have been estimated. The results of estimated average doses for 29 cases of chronic radiation sickness are given. Their average red marrow dose, trunk dose and effective dose equivalent are 1.3 Gy, 1.2 Gy and 1.6 Sv, respectively

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

    OpenAIRE

    Cai, Ping; König, Rolf; Boor, Paul J; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    2007-01-01

    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 an...

  18. Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production.

    Science.gov (United States)

    Suman, Shubhankar; Rodriguez, Olga C; Winters, Thomas A; Fornace, Albert J; Albanese, Chris; Datta, Kamal

    2013-08-01

    Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion 56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation. PMID:23928451

  19. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    Directory of Open Access Journals (Sweden)

    Picano Eugenio

    2012-04-01

    Full Text Available Abstract Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906, the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of Conclusions At this point, a systematic assessment of brain (cancer and non-cancer effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.

  20. Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

    International Nuclear Information System (INIS)

    Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

  1. Chronic aflatoxin exposure in children living in Bhaktapur, Nepal: Extension of the MAL-ED study

    Science.gov (United States)

    Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are toxic chemicals produced by molds. The molds that produce these two toxic chemicals are commonly found in corn and their co-occurence in corn has been demonstrated in many surveys. This study was conducted because it is suspected that exposure to eith...

  2. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    DEFF Research Database (Denmark)

    Barfod, Kenneth K; Poulsen, Steen Seier; Hammer, Maria;

    2010-01-01

    The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt) based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF), clearance of bacteria from the lung...

  3. Using Spot Biomarker Data to Inform Chronic Exposure and Health Risk

    Science.gov (United States)

    The U.S. NHANES and other health surveys frequently collect and analyze spot biological specimens to inform chemical exposures. These spot measurements can be compared to biomarker-based reference levels, such as “Biomonitoring Equivalents” (BEs), to evaluate health r...

  4. Antioxidative responses and bioaccumulation in Japanese flounder larvae and juveniles under chronic mercury exposure.

    Science.gov (United States)

    Huang, Wei; Cao, Liang; Ye, Zhenjiang; Yin, Xuebo; Dou, Shuozeng

    2010-06-01

    This study investigated the sub-lethal effects of waterborne mercury on growth, bioaccumulation and antioxidative responses of larvae and juveniles of Japanese flounder (Paralichthys olivaceus). Fish were exposed to 0-10 microg Hg(2)(+)L(-1) solutions from embryonic to the juvenile stages for 80 days. Antioxidative responses to mercury exposure were studied in metamorphosing larvae (18 days post hatching, dph), settling larvae (33 dph) and juveniles (78 dph). Results showed that increasing mercury concentration led to increased mercury bioaccumulation and reduced flounder growth. Of the antioxidants investigated, superoxide dismutase (SOD) and catalase (CAT) activities at the three developmental stages were sensitive to mercury exposure and increased with increasing mercury concentration. Glutathione (GSH) content was elevated in metamorphosing larvae, but decreased in juveniles as mercury concentration increased. Glutathione-S-transferase (GST) activity did not significantly vary with mercury concentration in either larvae or juveniles. Mercury exposure did not affect malondialdehyde (MDA) content of larvae, but significantly increased MDA content of juveniles. Results suggest that flounder larvae and juveniles have the potential to manipulate the levels of antioxidants such as SOD, CAT and GSH, which protect flounder from oxidative stress induced by mercury exposure. These antioxidants could serve as biomarkers of mercury contamination in the aquatic environment.

  5. Molecular, cellular, and tissue impact of depleted uranium on xenobiotic-metabolizing enzymes.

    Science.gov (United States)

    Gueguen, Yann; Rouas, Caroline; Monin, Audrey; Manens, Line; Stefani, Johanna; Delissen, Olivia; Grison, Stéphane; Dublineau, Isabelle

    2014-02-01

    Enzymes that metabolize xenobiotics (XME) are well recognized in experimental models as representative indicators of organ detoxification functions and of exposure to toxicants. As several in vivo studies have shown, uranium can alter XME in the rat liver or kidneys after either acute or chronic exposure. To determine how length or level of exposure affects these changes in XME, we continued our investigation of chronic rat exposure to depleted uranium (DU, uranyl nitrate). The first study examined the effect of duration (1-18 months) of chronic exposure to DU, the second evaluated dose dependence, from a level close to that found in the environment near mining sites (0.2 mg/L) to a supra-environmental dose (120 mg/L, 10 times the highest level naturally found in the environment), and the third was an in vitro assessment of whether DU exposure directly affects XME and, in particular, CYP3A. The experimental in vivo models used here demonstrated that CYP3A is the enzyme modified to the greatest extent: high gene expression changed after 6 and 9 months. The most substantial effects were observed in the liver of rats after 9 months of exposure to 120 mg/L of DU: CYP3A gene and protein expression and enzyme activity all decreased by more than 40 %. Nonetheless, no direct effect of DU by itself was observed after in vitro exposure of rat microsomal preparations, HepG2 cells, or human primary hepatocytes. Overall, these results probably indicate the occurrence of regulatory or adaptive mechanisms that could explain the indirect effect observed in vivo after chronic exposure. PMID:24146111

  6. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Trak-Smayra, Viviane [Pathology Department, Saint-Joseph University, Beirut (Lebanon); Martinais, Sophie [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Porceddu, Mathieu [Mitologics SAS, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris (France); Robin, Marie-Anne [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Fromenty, Bernard, E-mail: bernard.fromenty@inserm.fr [INSERM, U991, Université de Rennes 1, 35000 Rennes (France)

    2014-04-01

    Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10{sup 6} ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10{sup 6} ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10{sup 2}–10{sup 3} ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace

  7. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

    International Nuclear Information System (INIS)

    Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 106 ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 106 ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 102–103 ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace pharmaceuticals could

  8. A Case of Bowen’s Disease and Small-Cell Lung Carcinoma: Long-Term Consequences of Chronic Arsenic Exposure in Chinese Traditional Medicine

    OpenAIRE

    Lee, Linda; Bebb, Gwyn

    2004-01-01

    Chronic arsenic toxicity occurs primarily through inadvertent ingestion of contaminated water and food or occupational exposure, but it can also occur through medicinal ingestion. This case features a 53-year-old lifetime nonsmoker with chronic asthma treated for 10 years in childhood with Chinese traditional medicine containing arsenic. The patient was diagnosed with Bowen’s disease and developed extensive-stage small-cell carcinoma of the lung 10 years and 47 years, respectively, after the ...

  9. Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats

    OpenAIRE

    Torregrossa, Mary M.; Xie, Maylene; Taylor, Jane R.

    2012-01-01

    Chronic stress during adolescence is associated with an increased risk for alcoholism and addictive disorders. Addiction is also associated with increased impulsivity, and stress during adolescence could alter cortical circuits responsible for response inhibition. Therefore, the present study determined the effect of chronic exposure to the stress hormone corticosterone (CORT) during adolescence on tests of impulsivity in adulthood and examined possible biochemical mechanisms. Male Sprague-Da...

  10. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    Shaonan Li; Yajun Tan

    2011-01-01

    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 μg/L and 0.01 to 2.00 μg/L, respectively.For exposure to triazophos, ChE was induced up to 176.5% at 1.5 μg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 μg/L and day 10 when measured by butyrylthiocholine (BTCh).For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectivly, with both maximal inductions detected at 0.l μg/L and day 8.Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days.Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition.In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture.This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population.

  11. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos.

    Science.gov (United States)

    Li, Shaonan; Tan, Yajun

    2011-01-01

    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 microg/L and 0.01 to 2.00 microg/L, respectively. For exposure to triazophos, ChE was induced up to 176.5% at 1.5 microg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 microg/L and day 10 when measured by butyrylthiocholine (BTCh). For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectively, with both maximal inductions detected at 0.1 microg/L and day 8. Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days. Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition. In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture. This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population. PMID:21790060

  12. Association between Chronic Arsenic Exposure and Nutritional Status among the Women of Child Bearing Age: A Case-Control Study in Bangladesh

    Directory of Open Access Journals (Sweden)

    Abul H. Milton

    2010-07-01

    Full Text Available 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 µg/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 µg/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.

  13. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish.

    Science.gov (United States)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Li, Wei-Ye

    2016-08-01

    Based on the same toxic level of 0.6% LC50 for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180μgL(-1)) and Cd exposures (30μgL(-1)) on growth, survival, histology, ultrastructure, and oxidative stress in the liver of zebrafish for 5 weeks. Growth performance and survival rate remained relatively constant under Zn stress, but was reduced under Cd exposure. Cd exposure also induced severe pyknotic nuclei, evident ultrastructure damage, and considerable lipid inclusions in the hepatocytes. However, these phenomena were not pronounced under Zn exposure. The negative effects caused by Cd may be explained by an increase in hepatic oxidative damage, as reflected by the enhanced levels of lipid peroxidation (LPO) and protein carbonylation (PC). The reduced activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) may result in the enhanced hepatic oxidative damage, though the mRNA and protein levels of both genes increased and remained unchanged respectively. On the contrary, Zn up-regulated the levels of mRNA, protein and activity of Cu/Zn-SOD, which may contribute to the decreased LPO levels. Nonetheless, the sharply up-regulated mRNA levels of CAT did not induce an increase in the protein and activity levels of CAT under Zn stress. Furthermore, transcription factor NF-E2-related factor 2 (Nrf2) expression parelleled with its target genes, suggesting that Nrf2 is required for the protracted induction of antioxidant genes. In conclusion, our data demonstrated that essential and non-essential metals induced some differences in oxidative damage in fish. The differences were not caused by the transcriptional level of related genes but depended on post-transcriptional modifications. PMID:27323295

  14. Radiation exposure in the former uranium mining sites in Saxony and Thuringia. What was accomplished in 20 years of decontamination?; Strahlenexposition an ehemaligen Uranbergbau-Standorten in Sachsen und Thueringen. Was wurde in 20 Jahren Sanierung erreicht?

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Peter [Wismuth GmbH, Chemnitz (Germany); Sperrhacke, Andrea [Saechsisches Landesamt fuer Umwelt, Landwirtschaft und Geologie, Dresden (Germany). Referat 54 - Natuerliche Radioaktivitaet

    2012-07-01

    The residuals of uranium mining and uranium ore processing ca results in considerable radiation exposures of the general public. Effective doses up to 20 mS/a are possible, especially if mine dumps, mines and industrial facilities were operated close to housing settlements, as has been the case for SDAG Wismut in Saxony and Thuringia. The activities of the radiation protection authorities have accomplished that the effective doses for the public of 1 mSv/a exceeded only very locally. The radiation protection goals will only be reached when the stability of spreading barriers in case of stored radioactive materials will be proven and the resulting radioactive concentration in aquifers and air will be faded out. The still existing radiation protection problems are summarized.

  15. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

    International Nuclear Information System (INIS)

    Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/− 7 mg/m3) and 24 administrative workers (reference group, mean levels 0.21 +/− 0.02 mg/m3) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r = − .36, p < 0.05), as well as for IL6 promoter methylation levels (r = .44, p < 0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p = 0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r = − .37, p < 0.05 and r = − .34, p < 0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. - Highlights: • We investigated gene-specific methylation in persons chronically exposed to toluene. • In a previous study, a reduced CYP2E1 activity was observed in these participants. • CYP2E1 promoter

  16. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez-Garza, Octavio, E-mail: ojimenezgarza@ugto.mx [Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato (Mexico); Baccarelli, Andrea A.; Byun, Hyang-Min [Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115 (United States); Márquez-Gamiño, Sergio [Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato (Mexico); Barrón-Vivanco, Briscia Socorro [Environmental Toxicology and Pollution Laboratory, Nayarit Autonomous University, Av. Ciudad de la Cultura s/n, “Amado Nervo”, Tepic, Nayarit C.P. 63155 (Mexico); Albores, Arnulfo [Department of Toxicology, CINVESTAV, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, 07360 Mexico DF (Mexico)

    2015-08-01

    Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/− 7 mg/m{sup 3}) and 24 administrative workers (reference group, mean levels 0.21 +/− 0.02 mg/m{sup 3}) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r = − .36, p < 0.05), as well as for IL6 promoter methylation levels (r = .44, p < 0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p = 0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r = − .37, p < 0.05 and r = − .34, p < 0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. - Highlights: • We investigated gene-specific methylation in persons chronically exposed to toluene. • In a previous study, a reduced CYP2E1 activity was observed in these participants. • CYP2E1

  17. The association between chronic exposure to video game violence and affective picture processing: an ERP study.

    Science.gov (United States)

    Bailey, Kira; West, Robert; Anderson, Craig A

    2011-06-01

    Exposure to video game violence (VGV) is known to result in desensitization to violent material and may alter the processing of positive emotion related to facial expressions. The present study was designed to address three questions: (1) Does the association between VGV and positive emotion extend to stimuli other than faces, (2) is the association between VGV and affective picture processing observed with a single presentation of the stimuli, and (3) is the association between VGV and the response to violent stimuli sensitive to the relevance of emotion for task performance? The data revealed that transient modulations of the event-related potentials (ERPs) related to attentional orienting and sustained modulations of the ERPs related to evaluative processing were sensitive to VGV exposure. PMID:21461985

  18. Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system

    Science.gov (United States)

    Meinertz, J.R.; Schreier, T.M.; Bernardy, J.A.; Franz, J.L.

    2010-01-01

    Diphenhydramine hydrochloride (DH; Benadryl TM, an over-the-counter antihistamine) and erythromycin thiocyanate (ET; a commonly used macrolide antibiotic) are pharmaceutical compounds whose chronic toxicity to Daphnia magna had not been characterized. Continuous exposure to DH concentrations about 5 times greater than the maximum reported environmental concentration of 0.023 lg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 (mu or u)g/L for 21 days did not significantly impact D. magna survival and production. In this study the no observable effect concentration for DH was 0.12 (mu or u)g/L and for ET was 248 (mu or u)g/L.

  19. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    Science.gov (United States)

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus. PMID:21315145

  20. Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability

    OpenAIRE

    Lowen, Steven B.; Rohan, Michael L.; Timothy E Gillis; Thompson, Britta S.; Clara B.W. Wellons; Andersen, Susan L.

    2015-01-01

    Adolescents are highly vulnerable to addiction and are four times more likely to become addicted at first exposure than at any other age. The dopamine D1 receptor, which is typically overexpressed in the normal adolescent prefrontal cortex, is involved in drug cue responses and is associated with relapse in animal models. In human drug addicts, imaging methods have detected increased activation in response to drug cues in reward- and habit-associated brain regions. These same methods can be a...

  1. Chronic exposure to dietary selenomethionine increases gonadal steroidogenesis in female rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Wiseman, Steve, E-mail: steve.wiseman@usask.ca [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Thomas, Jith K.; Higley, Eric; Hursky, Olesya [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Pietrock, Michael [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B4 (Canada); Raine, Jason C. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Giesy, John P. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B4 (Canada); Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong (Hong Kong); School of Biological Sciences, University of Hong Kong, Hong Kong (Hong Kong); Department of Zoology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing (China); Janz, David M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B4 (Canada); Hecker, Markus [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, S7N 5C8 (Canada)

    2011-10-15

    Selenomethionine (Se-Met) is the major dietary form of selenium (Se). Detrimental effects have been associated with exposure to elevated dietary selenium. Previous studies have demonstrated effects of Se on the endocrine system, in particular effects on cortisol and thyroid hormones. However, no information is available regarding effects of Se on sex steroid hormones. In the present study, effects of dietary exposure to an environmentally relevant concentration (4.54 mg/kg wet weight (ww)) of Se-Met for 126 days on concentrations of sex steroid hormones in blood plasma of female rainbow trout were determined. Furthermore, the molecular basis for effects of Se-Met on plasma sex steroid hormone concentrations was investigated. Concentrations of androstenedione (A), estrone (E1), and estradiol (E2) were 39.5-, 3.8-, and 12.7-fold greater in plasma of treated females than the untreated controls, respectively. Testosterone (T) was detected only in plasma of treated females. The greater E2 concentration stimulated greater transcript abundance of vitellogenin (vtg) and zona-radiata protein (zrp). Female rainbow trout exposed to Se-Met had greater transcript abundance of key steroidogenic proteins and enzymes, including peripheral benzodiazepine receptor (pbr), cytochrome P450 side-chain cleavage (P450scc), and 3{beta}-hydroxysteroid dehydrogenase (3{beta}-hsd). Exposure to Se-Met did not affect transcript abundance of luteinizing hormone (lh) or follicle stimulating hormone (fsh). Similarly, there was no change in transcript abundance of luteinizing hormone receptor (lhr) or follicle stimulating hormone receptor (fshr). Long-term exposure to dietary Se-Met has the potential to stimulate vitellogenesis in female rainbow trout by directly stimulating ovarian tissue steroidogenesis. This is the first study to report effects of Se on sex steroid hormone production in fish.

  2. Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival

    OpenAIRE

    Giuseppe Pani; Mieke Verslegers; Roel Quintens; Nada Samari; Louis de Saint-Georges; Patrick Van Oostveldt; Sarah Baatout; Mohammed Abderrafi Benotmane

    2016-01-01

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during ch...

  3. Chronic exposure to diclofenac on two freshwater cladocerans and Japanese medaka.

    Science.gov (United States)

    Lee, Jinyoung; Ji, Kyunghee; Lim Kho, Young; Kim, Pilje; Choi, Kyungho

    2011-07-01

    Consequences of long-term exposure to diclofenac up to 3 months were evaluated using freshwater crustaceans (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). Marked decrease of reproduction was observed at 25 mg/L for D. magna, and at 50 mg/L for M. macrocopa. Three-month exposure of fish to 0.001-10 mg/L of diclofenac resulted in significant decreasing trend in hatching success and delay in hatch. The hatching of the eggs produced from the fish exposed to 10 mg/L was completely interfered, while fertility of the parent generation was not affected. Gonadosomatic index (GSI) of female fish was also affected at 10 mg/L. Predicted no effect concentration of diclofenac was estimated at 0.1 mg/L, which is a few orders of magnitude greater than those observed in ambient water. Therefore direct impact of diclofenac exposure is not expected. However its bioaccumulati