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Sample records for chronic palmitate exposure

  1. Stevioside counteracts the alpha-cell hypersecretion caused by long-term palmitate exposure

    DEFF Research Database (Denmark)

    Hong, J; Chen, L; Jeppesen, P B;

    2006-01-01

    Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We......-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (Pacids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha......-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes....

  2. The effect of chronic exposure to fatty acids

    DEFF Research Database (Denmark)

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

    2001-01-01

    Fatty acids affect insulin secretion of pancreatic beta-cells. Investigating gene expression profiles may help to characterize the underlying mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 microM) for up to 44 d. Insulin secretion and expressions of 8740 genes were studied. We...... 44, respectively. Genes involved in fatty acid oxidation were up-regulated, whereas those involved in glycolysis were down-regulated with 200 microM palmitate. A suppression of insulin receptor and insulin receptor substate-2 gene expression was found on d 44 in cells cultured at 200 microM palmitate....... 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...

  3. Fasting increases palmitic acid incorporation into rat hind-limb intramuscular acylglycerols while short-term cold exposure has no effect.

    Science.gov (United States)

    Synak, M; Zarzeczny, R; Górecka, M; Langfort, J; Kaciuba-Uściłko, H; Zernicka, Ewa

    2011-09-01

    The aim of the study was to investigate the palmitic acid incorporation into intramuscular acylglycerols in perfused hind-limb skeletal muscles of different fibre types in rats either fasted for 48 h or exposed to cold (6 °C) for 12 h. Hind-limb preparations of fasted and cold exposed rats were perfused with buffers containing tritium labelled and cold palmitic acid. Palmitic acid incorporation into intracellular lipid pools in the soleus, plantaris, red and white gastrocnemius and red and white quadriceps was measured. It was found that fasting increased approximately 2-fold palmitic acid incorporation in all muscles examined regardless of the fibre type composition of the muscle. On the other hand, exposure to cold had no effect on the palmitic acid incorporation into intramuscular acylglycerols regardless the muscle fibre type. The increased incorporation of palmitic acid into acylglycerols in fasted animals is in line with data showing that 48 h fasting stimulates the expression of plasma membrane proteins putatively facilitating fatty acid uptake. It appears that although 12 h cold exposure increases the use of fatty acids as energy substrates it does not alter the incorporation of palmitic acid into intramuscular acylglycerols in the perfused rat hind-limb.

  4. Enteric neuropathy can be induced by high fat diet in vivo and palmitic acid exposure in vitro.

    Directory of Open Access Journals (Sweden)

    Ulrikke Voss

    Full Text Available OBJECTIVE: Obese and/or diabetic patients have elevated levels of free fatty acids and increased susceptibility to gastrointestinal symptoms. Since the enteric nervous system is pivotal in regulating gastrointestinal functions alterations or neuropathy in the enteric neurons are suspected to occur in these conditions. Lipid induced intestinal changes, in particular on enteric neurons, were investigated in vitro and in vivo using primary cell culture and a high fat diet (HFD mouse model. DESIGN: Mice were fed normal or HFD for 6 months. Intestines were analyzed for neuronal numbers, remodeling and lipid accumulation. Co-cultures of myenteric neurons, glia and muscle cells from rat small intestine, were treated with palmitic acid (PA (0 - 10(-3 M and / or oleic acid (OA (0 - 10(-3 M, with or without modulators of intracellular lipid metabolism. Analyses were by immunocyto- and histochemistry. RESULTS: HFD caused substantial loss of myenteric neurons, leaving submucous neurons unaffected, and intramuscular lipid accumulation in ileum and colon. PA exposure in vitro resulted in neuronal shrinkage, chromatin condensation and a significant and concentration-dependent decrease in neuronal survival; OA exposure was neuroprotective. Carnitine palmitoyltransferase 1 inhibition, L-carnitine- or alpha lipoic acid supplementation all counteracted PA-induced neuronal loss. PA or OA alone both caused a significant and concentration-dependent loss of muscle cells in vitro. Simultaneous exposure of PA and OA promoted survival of muscle cells and increased intramuscular lipid droplet accumulation. PA exposure transformed glia from a stellate to a rounded phenotype but had no effect on their survival. CONCLUSIONS: HFD and PA exposure are detrimental to myenteric neurons. Present results indicate excessive palmitoylcarnitine formation and exhausted L-carnitine stores leading to energy depletion, attenuated acetylcholine synthesis and oxidative stress to be main

  5. Occupational Exposures and Chronic Airflow Limitation

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    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.

  6. Do chronic workplace irritant exposures cause asthma?

    OpenAIRE

    Dumas, Orianne; Le Moual, Nicole

    2016-01-01

    International audience; The present review summarizes the recent literature on the relation between chronic workplace irritant exposures and asthma, focusing on exposures of low to moderate levels. We discuss results from epidemiological surveys, potential biological mechanisms, and needs for further research. These aspects are largely illustrated by studies on exposure to cleaning products. Recent results from nine population-based and workplace-based epidemiological studies, mostly cross-se...

  7. Defining the role of DAG, mitochondrial function, and lipid deposition in palmitate-induced proinflammatory signaling and its counter-modulation by palmitoleate.

    Science.gov (United States)

    Macrae, Katherine; Stretton, Clare; Lipina, Christopher; Blachnio-Zabielska, Agnieszka; Baranowski, Marcin; Gorski, Jan; Marley, Anna; Hundal, Harinder S

    2013-09-01

    Chronic exposure of skeletal muscle to saturated fatty acids, such as palmitate (C16:0), enhances proinflammatory IKK-NFκB signaling by a mechanism involving the MAP kinase (Raf-MEK-ERK) pathway. Raf activation can be induced by its dissociation from the Raf-kinase inhibitor protein (RKIP) by diacylglycerol (DAG)-sensitive protein kinase C (PKC). However, whether these molecules mediate the proinflammatory action of palmitate, an important precursor for DAG synthesis, is currently unknown. Here, involvement of DAG-sensitive PKCs, RKIP, and the structurally related monounsaturated fatty acid palmitoleate (C16:1) on proinflammatory signaling are investigated. Palmitate, but not palmitoleate, induced phosphorylation/activation of the MEK-ERK-IKK axis and proinflammatory cytokine (IL-6, CINC-1) expression. Palmitate increased intramyocellular DAG and invoked PKC-dependent RKIP(Ser153) phosphorylation, resulting in RKIP-Raf1 dissociation and MEK-ERK signaling. These responses were mimicked by PMA, a DAG mimetic and PKC activator. However, while pharmacological inhibition of PKC suppressed PMA-induced activation of MEK-ERK-IKK signaling, activation by palmitate was upheld, suggesting that DAG-sensitive PKC and RKIP were dispensable for palmitate's proinflammatory action. Strikingly, the proinflammatory effect of palmitate was potently repressed by palmitoleate. This repression was not due to reduced palmitate uptake but linked to increased neutral lipid storage and enhanced cellular oxidative capacity brought about by palmitoleate's ability to restrain palmitate-induced mitochondrial dysfunction.

  8. In Vitro Palmitate Treatment of Myotubes from Postmenopausal Women Leads to Ceramide Accumulation, Inflammation and Affected Insulin Signaling

    DEFF Research Database (Denmark)

    Abildgaard, Julie; Henstridge, Darren C; Pedersen, Anette Tønnes;

    2014-01-01

    Palmitoyltransferase1 (SPT1) after one day of palmitate treatment (p = 0.03) in post-myotubes compared with pre-myotubes. Our findings indicate that post-myotubes are more prone to develop lipid accumulation and defective insulin signaling following chronic saturated fatty acid exposure as compared to pre-myotubes....

  9. Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

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    Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: yangdongren@yahoo.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)

    2016-07-15

    Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

  10. 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...

  11. Chronic lead exposure reduces junctional resistance at an electrical synapse.

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    Audesirk, G; Audesirk, T

    1984-01-01

    Both acute and chronic lead exposure have been found to inhibit transmission at chemical synapses, possibly by interfering with inward calcium current. We have found that chronic lead exposure slightly reduces input resistance and greatly reduces the junctional resistance between two strongly electrically coupled neurons in the pond snail Lymnaea stagnalis. The net effect is to increase the strength of electrical coupling. A reduction in gap junctional resistance would also be expected to increase the flow of small molecules between cells. However, Lucifer Yellow injections did not reveal dye-coupling between the cells. Lead exposure also increases the capacitance of the neurons.

  12. 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 ...

  13. Chronic boron exposure and human semen parameters.

    Science.gov (United States)

    Robbins, Wendie A; Xun, Lin; Jia, Juan; Kennedy, Nola; Elashoff, David A; Ping, Liu

    2010-04-01

    Boron found as borates in soil, food, and water has important industrial and medical applications. A panel reviewing NTP reproductive toxicants identified boric acid as high priority for occupational studies to determine safe versus adverse reproductive effects. To address this, we collected boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood, semen, and urine from boron workers and two comparison worker groups (n=192) over three months and determined correlations between boron and semen parameters (total sperm count, sperm concentration, motility, morphology, DNA breakage, apoptosis and aneuploidy). Blood boron averaged 499.2 ppb for boron workers, 96.1 and 47.9 ppb for workers from high and low environmental boron areas (pBoron concentrated in seminal fluid. No significant correlations were found between blood or urine boron and adverse semen parameters. Exposures did not reach those causing adverse effects published in animal toxicology work but exceeded those previously published for boron occupational groups.

  14. Regulation of Insulin Secretion and Expression of SUR1 Gene by Chronic Exposure to Free Fatty Acids in Rat Pancreatic β Cells

    Institute of Scientific and Technical Information of China (English)

    袁莉; 邓秀玲; 陈璐璐; 周愍

    2004-01-01

    To study the effects of free fatty acids on insulin secretion and expression of SUR1 gene in rat pancreatic B cells in vitro, and to explore the molecular mechanisms in lipotoxicity inducing insulin secretion dysfunction, pancreatic islet cells were isolated and digested from male SD rats.Purified islets were incubated with either 0.25 mmol/L palmitate or 0. 125 mmol/L oleate for 48 h in vitro. Then islets were stimulated with either 5.6 mmol/L or 16.7 mmol/L glucose for 1 h. Insulin release was measured by using radioimmunoassay, and the expression of SUR1 gene mRNA was quantified by reserve transcription-polymerase chain reaction (RT-PCR). The islets exposed to both palmitate and oleate for 48 h showed an increased basal and a decreased glucose-indused insulin release as compared with control islets. Palmitate increased basal insulin secretion by 110 % (P<0.01), decreased glucose stimulated insulin secretion by 43 % (P<0.01) ; while oleate increased basal insulin secretion by 80 % (P<0.01) and decreased glucose stimulated insulin secretion by 32 % (P<0.05). RT-PCR showed that oleate significantly suppressed SUR1 gene expression by 64 % (P<0.01)as compared with the control group, while palmitate group manifested a light decrease of 15 % (P >0.05) of SUR1 gene expression. Our results suggested that chronic exposure to free fatty acids of pancreatic β cells inhibited glucose stimulated insulin secretion. Regulation of SUR1 gene expression may be involved in such effects, which may also be one of the molecular mechanisms in lipotoxocity inducing β cells secretion dysfunction.

  15. Polyneuropathy caused by chronic exposure to trichloroethylene

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    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.

  16. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

    Science.gov (United States)

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

  17. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice

    OpenAIRE

    Jia-Qing Zhang; Bin-Wen Gao; Jing Wang; Xian-Wei Wang; Qiao-Ling Ren; Jun-Feng Chen; Qiang Ma; Bao-Song Xing

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granu...

  18. Paliperidone palmitate-induced sialorrhoea

    Directory of Open Access Journals (Sweden)

    Cengiz Cengisiz

    2016-03-01

    Full Text Available Extrapyramidal, metabolic, and cardiac side effects were reported for atypical antipsychotics; although a few resources show paliperidone-induced sialorrhea, there are no resources that show paliperidone palmitate-induced sialorrhea. In this paper, we present the paliperidone palmitate-induced sialorrhea side effects of a patient who applied on our clinic [Cukurova Med J 2016; 41(0.100: 8-13

  19. Chronic exposure to ELF fields may induce depression

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    Wilson, B.W.

    1988-01-01

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

  20. 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.

  1. Estimation of Chronic Personal Exposure to Airborne Polycyclic Aromatic Hydrocarbons

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    Choi, Hyunok; Zdeb, Michael; Perera, Frederica; Spengler, John

    2015-01-01

    Background Polycyclic aromatic hydrocarbons (PAH) exposure from solid fuel burning represents an important public health issue for the majority of the global population. Yet, understanding of individual-level exposures remains limited. Objectives To develop regionally adaptable chronic personal exposure model to pro-carcinogenic PAH (c-PAH) for the population in Kraków, Poland. Methods We checked the assumption of spatial uniformity in eight c-PAH using the coefficients of divergence (COD), a marker of absolute concentration differences. Upon successful validation, we developed personal exposure models for eight pro-carcinogenic PAH by integrating individual-level data with area-level meteorological or pollutant data. We checked the resulting model for accuracy and precision against home outdoor monitoring data. Results During winter, COD of 0.1 for Kraków suggest overall spatial uniformity in the ambient concentration of the eight c-PAH. The three models that we developed were associated with index of agreement approximately equal to 0.9, root mean square error < 2.6 ng/m3, and 90th percentile of absolute difference ≤ 4 ng/m3 for the predicted and the observed concentrations for eight pro-carcinogenic PAH. Conclusions Inexpensive and logistically feasible information could be used to estimate chronic personal exposure to PAH profiles, in lieu of costly and labor-intensive personal air monitoring at wide scale. At the same time, thorough validation through direct personal monitoring and assumption checking are critical for successful model development. PMID:25965038

  2. 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

  3. Responses of Hyalella azteca to acute and chronic microplastic exposures.

    Science.gov (United States)

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

    2015-11-01

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

  4. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

    Science.gov (United States)

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas.

  5. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice.

    Directory of Open Access Journals (Sweden)

    Jia-Qing Zhang

    Full Text Available Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals.

  6. High-density lipoprotein and apolipoprotein A-I inhibit palmitate-induced translocation of toll-like receptor 4 into lipid rafts and inflammatory cytokines in 3T3-L1 adipocytes.

    Science.gov (United States)

    Yamada, Hodaka; Umemoto, Tomio; Kawano, Mikihiko; Kawakami, Masanobu; Kakei, Masafumi; Momomura, Shin-Ichi; Ishikawa, San-E; Hara, Kazuo

    2017-03-04

    Saturated fatty acids (SFAs) activate toll-like receptor 4 (TLR4) signal transduction in macrophages and are involved in the chronic inflammation accompanying obesity. High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) produce anti-inflammatory effects via reverse cholesterol transport. However, the underlying mechanisms by which HDL and apoA-I inhibit inflammatory responses in adipocytes remain to be determined. Here we examined whether palmitate increases the translocation of TLR4 into lipid rafts and whether HDL and apoA-I inhibit inflammation in adipocytes. Palmitate exposure (250 μM, 24 h) increased interleukin-6 and tumor necrosis factor-α gene expressions and translocation of TLR4 into lipid rafts in 3T3-L1 adipocytes. Pretreatment with HDL and apoA-I (50 μg/mL, 6 h) suppressed palmitate-induced inflammatory cytokine expression and TLR4 translocation into lipid rafts. Moreover, HDL and apoA-I inhibited palmitate-induced phosphorylation of nuclear factor-kappa B. HDL showed an anti-inflammatory effect via ATP-binding cassette transporter G1 and scavenger receptor class B, member 1, whereas apoA-I showed an effect via ATP-binding cassette transporter A1. These results demonstrated that HDL and apoA-I reduced palmitate-potentiated TLR4 trafficking into lipid rafts and its related inflammation in adipocytes via these specific transporters.

  7. [Effects of palmitic acid on activity of uncoupling proteins and proton leak in in vitro cerebral mitochondria from the rats exposed to simulated high altitude hypoxia].

    Science.gov (United States)

    Xu, Yu; Liu, Jun-Ze; Xia, Chen

    2008-02-25

    To reveal the roles of uncoupling proteins (UCPs) in disorder of mitochondrial oxidative phosphorylation induced by free fatty acid during hypoxic exposure, the effects of palmitic acid on activity of UCPs, proton leak and mitochondrial membrane potential in hypoxia-exposed rat brain mitochondria were observed in vitro. Adult Sprague-Dawley (SD) rats were set randomly into control, acute hypoxia and chronic hypoxia groups (n=8 in each group). The acute and chronic hypoxic rats were exposed to simulated 5000 m high altitude in a hypobaric chamber 23 h/d for 3 d and 30 d, respectively. The brain mitochondria were isolated by centrifugation. UCP content and activity were detected by [(3)H]-GTP binding method. The proton leak was measured by TPMP(+) electrode and oxygen electrode. The membrane potential of mitochondria was calculated by detecting the fluorescence from Rodamine 123. Hypoxic exposure resulted in an increase in UCP activity and content as well as proton leak, but a decrease in the membrane potential of rat brain mitochondria. Palmitic acid resulted in further increases in UCP activity and content as well as proton leak, and further decrease in membrane potential of brain mitochondria in vitro from hypoxia-exposed rats, but hypoxic exposure decreased the reactivity of cerebral mitochondria to palmitic acid, especially in the acute hypoxia group. There was a negative correlation between mitochondrial proton leak and K(d) value (representing derivative of UCP activity, PB(max) (representing the maximal content of UCPs in mitochondrial inner membrane, P<0.01, r = 0.856). Cerebral mitochondrial membrane potential was negatively correlated with proton leak (P<0.01, r = -0.880). It is suggested that hypoxia-induced proton leak enhancement and membrane potential decrease are correlated with the increased activity of UCPs. Hypoxia can also decrease the sensitivity of cerebral mitochondria to palmitic acid, which may be a self-protective mechanism in high altitude

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

    Science.gov (United States)

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

  10. 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.

  11. 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)

  12. 21 CFR 186.1771 - Sodium palmitate.

    Science.gov (United States)

    2010-04-01

    ..., CAS Reg. No. 408-35-5) is the sodium salt of palmitic acid (hexadecanoic acid). It exists as a white... hydroxide and palmitic acid. (b) In accordance with § 186.1(b)(1), the ingredient is used as a...

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

    Science.gov (United States)

    Ponce, Esmeralda; Aquino, Natalie B; Louie, Maggie C

    2013-01-01

    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.

  14. 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.

  15. Transversal Descriptive Study of Xenobiotic Exposures in Patients with Chronic Pancreatitis and Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Cara Yvonne Jeppe

    2008-03-01

    Full Text Available There have been a substantial number of reports in the literature linking pancreatitis and pancreatic cancer to certain xenobiotics and occupations. It has been hypothesized that exposure to volatile hydrocarbons and particularly petrochemicals increases susceptibility to pancreatitis. We performed a study aimed to enumerate occupational and environmental xenobiotics described in the literature as potential risk factors for pancreatitis and to document exposures to these in chronic pancreatitis patients presenting with chronic pain for surgery.

  16. 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...

  17. Palmitic Acid and Health: Introduction.

    Science.gov (United States)

    Agostoni, Carlo; Moreno, Luis; Shamir, Raanan

    2016-09-09

    Interest in the dietary role and metabolic effect of saturated fatty acids has been recently renewed on the basis of epidemiologic observations and economical approach to health and well-being. Saturated fats may favorably increase blood HDL-Cholesterol levels without significant changes of the total cholesterol/HDL-Cholesterol ratio. Also, the negative effect of saturated fat on cardiovascular diseases risk has recently been challenged. Palmitic acid, among all, may have special structural and functional roles in utero and in infancy, and indeed is it is being delivered in a unique form in human milk. Future research should include objective cost-benefit analyses when disentangling the role of saturated fats in dietary recommendations.

  18. 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.

  19. 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.

  20. Health effects of chronic noise exposure in pregnancy and childhood: A systematic review initiated by ENRIECO

    NARCIS (Netherlands)

    Hohmann, C.; Grabenhenrich, L.; Kluizenaar, Y. de; Tischer, C.; Heinrich, J.; Chen, C.-M.; Thijs, C.; Nieuwenhuijsen, M.; Keil, T.

    2013-01-01

    Background: Chronic noise is an environmental pollutant and well-known to cause annoyance and sleep disturbance. Its association with clinical and subclinical adverse health effects has been discussed. Objectives: This systematic review aimed to examine associations between chronic noise exposure du

  1. The Prevalence of Chronic Diseases by Exposure to Nitrates from Environmental Factors

    OpenAIRE

    Beatrice Severin; Floarea Damaschin; Ileana Ion; Cecilia Adumitresi; Victoria Oancea; Broasca V.; Mocanu Elena; Chirila S.

    2014-01-01

    The study aims to analyze the health effects caused by chronic exposure to elevated levels of nitrates in the water in order to improve prevention of some diseases. We analyze water quality from two villages of Constanta County in the period 2006-2012 and we take data about chronic diseases from family doctors of these localities. Analyzes on water samples were made in the laboratory of the Public Health Department. We found a significant increase of prevalence for chronic diseases in localit...

  2. Palmitic Acid in Early Human Development.

    Science.gov (United States)

    Innis, Sheila M

    2016-09-09

    Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental.

  3. 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...

  4. Palmitic acid but not palmitoleic acid induces insulin resistance in a human endothelial cell line by decreasing SERCA pump expression.

    Science.gov (United States)

    Gustavo Vazquez-Jimenez, J; Chavez-Reyes, Jesus; Romero-Garcia, Tatiana; Zarain-Herzberg, Angel; Valdes-Flores, Jesus; Manuel Galindo-Rosales, J; Rueda, Angelica; Guerrero-Hernandez, Agustin; Olivares-Reyes, J Alberto

    2016-01-01

    Palmitic acid is a negative regulator of insulin activity. At the molecular level, palmitic acid reduces insulin stimulated Akt Ser473 phosphorylation. Interestingly, we have found that incubation with palmitic acid of human umbilical vein endothelial cells induced a biphasic effect, an initial transient elevation followed by a sustained reduction of SERCA pump protein levels. However, palmitic acid produced a sustained inhibition of SERCA pump ATPase activity. Insulin resistance state appeared before there was a significant reduction of SERCA2 expression. The mechanism by which palmitic acid impairs insulin signaling may involve endoplasmic reticulum stress, because this fatty acid induced activation of both PERK, an ER stress marker, and JNK, a kinase associated with insulin resistance. None of these effects were observed by incubating HUVEC-CS cells with palmitoleic acid. Importantly, SERCA2 overexpression decreased the palmitic acid-induced insulin resistance state. All these results suggest that SERCA pump might be the target of palmitic acid to induce the insulin resistance state in a human vascular endothelial cell line. Importantly, these data suggest that HUVEC-CS cells respond to palmitic acid-exposure with a compensatory overexpression of SERCA pump within the first hour, which eventually fades out and insulin resistance prevails.

  5. 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.

  6. Stability of ascorbyl palmitate in topical microemulsions.

    Science.gov (United States)

    Spiclin, P; Gasperlin, M; Kmetec, V

    2001-07-17

    Ascorbyl palmitate and sodium ascorbyl phosphate are derivatives of ascorbic acid, which differ in stability and hydro-lipophilic properties. They are widely used in cosmetic and pharmaceutical preparations. In the present work the stability of both derivatives was studied in microemulsions for topical use as carrier systems. The microemulsions were of both o/w and w/o types and composed of the same ingredients. The stability of the less stable derivative ascorbyl palmitate was tested under different conditions to evaluate the influence of initial concentration, location in microemulsion, dissolved oxygen and storage conditions. High concentrations of ascorbyl palmitate reduced the extent of its degradation. The location of ascorbyl palmitate in the microemulsion and oxygen dissolved in the system together significantly influence the stability of the compound. Light accelerated the degradation of ascorbyl palmitate. In contrast, sodium ascorbyl phosphate was stable in both types of microemulsions. Sodium ascorbyl phosphate is shown to be convenient as an active ingredient in topical preparations. In the case of ascorbyl palmitate, long-term stability in selected microemulsions was not adequate. To formulate an optimal carrier system for this ingredient other factors influencing the stability have to be considered.

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

    Science.gov (United States)

    Scherzad, Agmal; Hackenberg, Stephan; Froelich, Katrin; Rak, Kristen; Hagen, Rudolf; Taeger, Johannes; Bregenzer, Maximillian; Kleinsasser, Norbert

    2016-03-01

    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 induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems.

  8. Acute and chronic effects from pulse exposure of D. magna to silver and copper oxide nanoparticles

    DEFF Research Database (Denmark)

    Sørensen, Sara Nørgaard; Lützhøft, Hans-Christian Holten; Rasmussen, Rose

    2016-01-01

    , and afterwards transferred to clean medium and observed for 48 h (post-exposure period) for acute effects and for 21 d for chronic effects. AgNO3 and CuCl2 were used as reference materials for dissolved silver and copper, respectively. For all test materials, a 3 h pulse caused comparable immobility in D. magna...... decreased more with increasing concentrations than for CuCl2 exposures when taking the measured dissolved copper into account. This indicates a nanoparticle-specific effect for CuONPs, possibly related to the CuONPs accumulated in the gut of D. magna during the pulse exposure. Pulse exposure...

  9. Isosteviol has beneficial effects on palmitate-induced α-cell dysfunction and gene expression.

    Directory of Open Access Journals (Sweden)

    Xiaoping Chen

    Full Text Available BACKGROUND: Long-term exposure to high levels of fatty acids impairs insulin secretion and exaggerates glucagon secretion. The aim of this study was to explore if the antihyperglycemic agent, Isosteviol (ISV, is able to counteract palmitate-induced α-cell dysfunction and to influence α-cell gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Long-term incubation studies with clonal α-TC1-6 cells were performed in the presence of 0.5 mM palmitate with or without ISV. We investigated effects on glucagon secretion, glucagon content, cellular triglyceride (TG content, cell proliferation, and expression of genes involved in controlling glucagon synthesis, fatty acid metabolism, and insulin signal transduction. Furthermore, we studied effects of ISV on palmitate-induced glucagon secretion from isolated mouse islets. Culturing α-cells for 72-h with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01 increase in glucagon secretion. Concomitantly, the TG content of α-cells increased by 78% (p<0.01 and cell proliferation decreased by 19% (p<0.05. At 18 mM glucose, ISV (10(-8 and 10(-6 M reduced palmitate-stimulated glucagon release by 27% (p<0.05 and 27% (p<0.05, respectively. ISV (10(-6 M also counteracted the palmitate-induced hypersecretion of glucagon in mouse islets. ISV (10(-6 M reduced α-TC1-6 cell proliferation rate by 25% (p<0.05, but ISV (10(-8 and 10(-6 M had no effect on TG content in the presence of palmitate. Palmitate (0.5 mM increased Pcsk2 (p<0.001, Irs2 (p<0.001, Fasn (p<0.001, Srebf2 (p<0.001, Acaca (p<0.01, Pax6 (p<0.05 and Gcg mRNA expression (p<0.05. ISV significantly (p<0.05 up-regulated Insr, Irs1, Irs2, Pik3r1 and Akt1 gene expression in the presence of palmitate. CONCLUSIONS/SIGNIFICANCE: ISV counteracts α-cell hypersecretion and apparently contributes to changes in expression of key genes resulting from long-term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with potential as a

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

    Science.gov (United States)

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

    2017-02-01

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

  11. 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

  12. Neurotoxicity of chronic low-dose exposure to organic solvents: a skeptical review.

    Science.gov (United States)

    Lees-Haley, P R; Williams, C W

    1997-11-01

    The health effects of long-term, low-level exposure to organic solvents have been studied for many years. While the volume of literature is great, definitive conclusions regarding chronic neurobehavioral effects of environmental exposure are premature. Methodological shortcomings in research preclude confidence in studies allegedly supporting a causal link between chronic low-dose solvent exposure and lasting neurobehavioral deficits. In this article, the shortcomings reviewed include selection bias in recruitment of research subjects, overreliance on subjective recall in determining levels and duration of exposure, between-study variability in kinds of solvents examined, variability in tests selected to assess neurobehavioral functioning, and diversity in reported findings. The implications of these for characterizing the state of organic solvent research are discussed.

  13. 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.......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....

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

    Energy Technology Data Exchange (ETDEWEB)

    Linn, W.S.; Fischer, D.A.; Shamoo, D.A.; Spier, C.E.; Valencia, L.M.; Anzar, U.T.; Hackney, J.D.

    1985-08-01

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

  15. Chronic Cadmium Exposure Stimulates SDF-1 Expression in an ERα Dependent Manner

    OpenAIRE

    2013-01-01

    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,...

  16. 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.

  17. 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.

  18. 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.

  19. Specific IgG(4) responses during chronic and transient antigen exposure in aspergillosis

    NARCIS (Netherlands)

    Tomee, JFC; Dubois, AEJ; Koeter, GH; Beaumont, F; vanderWerf, TS; Kauffman, HF

    1996-01-01

    The factors that lead to increased production of specific IgG subclasses are still largely unknown. Recent studies suggest that increased IgG(4) responses may be related to prolonged antigen exposure. We present data showing that increased IgG(4) responses are found under conditions of chronic expos

  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. Epidemiological studies of the relationship between occupational exposures and chronic non-specific lung disease.

    NARCIS (Netherlands)

    Heederik, D.

    1990-01-01

    In this thesis the relationship between occupational exposures, lung function and Chronic Non-Specific Lung Disease is studied. The study comprises an epidemiological analysis of data from the British Pneumoconiosis Field Research among coal miners and an analysis of data gathered in the Zutphen

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

    Science.gov (United States)

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

  3. 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)

  4. Chronic Exposure to Particulate Chromate Induces Premature Centrosome Separation and Centriole Disengagement in Human Lung Cells

    Science.gov (United States)

    Martino, Julieta; Holmes, Amie L.; Xie, Hong; Wise, Sandra S.; Wise, John Pierce

    2015-01-01

    Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. Lung tumors are characterized by structural and numerical chromosome instability. Centrosome amplification is a phenotype commonly found in solid tumors, including lung tumors, which strongly correlates with chromosome instability. Human lung cells exposed to Cr(VI) exhibit centrosome amplification but the underlying phenotypes and mechanisms remain unknown. In this study, we further characterize the phenotypes of Cr(VI)-induced centrosome abnormalities. We show that Cr(VI)-induced centrosome amplification correlates with numerical chromosome instability. We also show chronic exposure to particulate Cr(VI) induces centrosomes with supernumerary centrioles and acentriolar centrosomes in human lung cells. Moreover, chronic exposure to particulate Cr(VI) affects the timing of important centriolar events. Specifically, chronic exposure to particulate Cr(VI) causes premature centriole disengagement in S and G2 phase cells. It also induces premature centrosome separation in interphase. Altogether, our data suggest that chronic exposure to particulate Cr(VI) targets the protein linkers that hold centrioles together. These centriolar linkers are important for key events of the centrosome cycle and their premature disruption might underlie Cr(VI)-induced centrosome amplification. PMID:26293554

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

    Science.gov (United States)

    1979-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Haruka Tamura

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

  7. Acute and chronic effects from pulse exposure of D. magna to silver and copper oxide nanoparticles.

    Science.gov (United States)

    Sørensen, Sara Nørgaard; Holten Lützhøft, Hans-Christian; Rasmussen, Rose; Baun, Anders

    2016-11-01

    Aquatic toxicity testing of nanoparticles (NPs) is challenged by their dynamic behavior in test suspensions. The resulting difficulties in controlling and characterizing exposure concentrations are detrimental to the generation of concentration-response data needed for hazard identification of NPs. This study explores the applicability of short-term (1, 2 and 3h) pulse exposures as means to keep the exposure stable and at the same time disclose acute and chronic effects of AgNPs and CuONPs in D. magna. Dissolution, agglomeration and sedimentation were found to have less influence on exposure concentrations during 1-3h pulses than for 24-48h continuous exposures. For AgNPs, preparation of test suspensions in medium 24h before toxicity testing (aging) increased stability during the short-term pulses. In pulse tests, organisms were exposed to the test materials, AgNPs and CuONPs for 1, 2 and 3h, and afterwards transferred to clean medium and observed for 48h (post-exposure period) for acute effects and for 21 d for chronic effects. AgNO3 and CuCl2 were used as reference materials for dissolved silver and copper, respectively. For all test materials, a 3h pulse caused comparable immobility in D. magna (observed after 48h post-exposure) as 24h continuous exposure, as evidenced by overlapping 95% confidence intervals of EC50-values. In the 21 d post-exposure period, no trends in mortality or body length were identified. AgNP and AgNO3 pulses had no effect on the number of moltings, days to first live offspring or cumulated number of offspring, but the number of offspring increased for AgNPs (3h pulse only). In contrast, CuONP and CuCl2 pulses decreased the number of moltings and offspring, and for CuONPs the time to first live offspring was prolonged. After CuONP exposures, the offspring production decreased more with increasing concentrations than for CuCl2 exposures when taking the measured dissolved copper into account. This indicates a nanoparticle-specific effect

  8. Acute and Chronic Exposure to CO2 in Space Flight

    Science.gov (United States)

    Alexander, D.; Wu, J.; Barr, Y. R.; Watkins, S. D.

    2010-01-01

    Spacecraft and space stations, similar to other habitable confined spaces such as submarines, need to provide a breathable atmosphere for their inhabitants. The inevitable production of CO2 during respiration necessitates life support systems that "scrub" the atmosphere and lower CO2 levels. Due to operational limitations associated with space flight (limited mass, volume, power, and consumables) CO2 is not scrubbed down to its terrestrial equivalent of 0.03% CO2 (ppCO2 of 0.23 mmHg), but is kept below 0.7% (ppCO2 of 5.3 mmHg), a level established in NASA s 180-day mission Spacecraft Maximum Allowable Concentration (SMAC) to be safe and unlikely to cause symptoms. Reports of space flight crewmembers becoming symptomatic with headaches, fatigue, and malaise at levels below those known to cause such symptoms terrestrially has prompted studies measuring the levels of CO2 on both the space shuttle and the space station. Data from cabin atmosphere sampling were collected on space shuttle missions STS-113, STS-122, STS-123, and International Space Station Expeditions 12-15 and 17, and the measured CO2 levels were then correlated to symptoms reported by the crew. The results indicate that a correlation exists between CO2 levels and symptomatology, however causality cannot be established at this time. While the short-term effects of elevated CO2 exposure are well known terrestrially, less is known regarding potential long-term effects of prolonged exposure to a CO2-rich environment or how the physiological changes caused by microgravity may interact with such exposures. Other challenges include limitations in the CO2 monitors used, lack of convection in the microgravity environment, and formation of localized CO2 pockets. As it is unclear if the unique environment of space increases sensitivity to CO2 or if other confounding factors are present, further research is planned to elucidate these points. At the same time, efforts are underway to update the SMAC to a lower level

  9. Challenges Associated with Exposure to Chronic Trauma: Using a Public Health Framework to Foster Resilient Outcomes among Youth

    Science.gov (United States)

    Overstreet, Stacy; Mathews, Tara

    2011-01-01

    For many children, trauma exposure is a common and chronic experience. Chronic trauma exposure during childhood significantly increases the risk for emotional/behavioral disorders and academic failure. There is a critical need for school psychologists, and the schools in which they work, to understand the unique needs of students with or at risk…

  10. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

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

    Directory of Open Access Journals (Sweden)

    Saija Piiroinen

    2016-03-01

    Full Text Available 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.

  12. 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.

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

    Science.gov (United States)

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

  14. 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.

  15. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    Science.gov (United States)

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  16. 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.

  17. 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.

  18. Phosphorylation Regulates Removal of Synaptic N-Methyl-d-Aspartate Receptors after Withdrawal from Chronic Ethanol Exposure

    OpenAIRE

    Clapp, Peter; Gibson, Emily S.; Dell'Acqua, Mark L.; Hoffman, Paula L.

    2010-01-01

    Alterations in N-methyl-d-aspartate receptor (NMDAR) protein levels or subcellular localization in brain after chronic ethanol exposure may contribute to withdrawal-associated seizures and neurotoxicity. We have investigated synaptic localization of NMDARs in cultured hippocampal pyramidal neurons after prolonged (7 days) exposure to, and acute withdrawal from, 80 mM ethanol using fluorescence immunocytochemistry techniques. After chronic ethanol exposure, there was a significant increase in ...

  19. 21 CFR 182.3149 - Ascorbyl palmitate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ascorbyl palmitate. 182.3149 Section 182.3149 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives §...

  20. 21 CFR 582.3149 - Ascorbyl palmitate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ascorbyl palmitate. 582.3149 Section 582.3149 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives §...

  1. Chronic morphine exposure induces degradation of receptive field properties of LGN cells in cats

    Institute of Scientific and Technical Information of China (English)

    Li-hua HE; Guang-xing LI; Xiang-rui LI; Yi-feng ZHOU

    2005-01-01

    Aim: To investigate the effect of chronic morphine exposure on the receptive field properties of lateral geniculate nucleus (LGN) neurons in cats. Methods: Cats were injected with morphine (10 mg/kg) or saline twice daily, for 10 d. Subsequently,extracellular single-unit recording techniques were used to examine the sensitivity of LGN neurons to visual stimuli in chronic morphine-treated and saline-treated cats. Results: Compared with saline-treated cats (as controls), LGN neurons in morphine-treated cats had decreased signal-to-noise ratios (1.9 vs 3.1), and orientation and direction sensitivity (0.103 vs 0.135 and 0.074 vs 0.10, respectively),accompanied by significant increases in spontaneous (27.4 vs 17.5) and evoked activity (preferred: 42.2 vs 38.1; average: 28.1 vs 22.3). Conclusion: Chronic morphine exposure can lead to the functional degradation of LGN neurons in cats,which might result from the effects of chronic morphine exposure on inhibitory neurotransmission.

  2. Effects of chronic low level lead exposure on the physiology of individually identifiable neurons.

    Science.gov (United States)

    Audesirk, G; Audesirk, T

    1983-01-01

    Although chronic exposure to lead has been correlated with a variety of behavioral and neurochemical deficits in humans and other mammals, little is known of the mechanisms of action of chronic lead at the level of the individual nerve cell. We have used the individually identifiable neurons of the freshwater pond snail Lymnaea stagnalis as a model system to investigate the effects of chronic low level (5 microM) lead exposure on neuronal physiology. Thirteen neuronal parameters were measured with intracellular microelectrode recording in each of six different identifiable neurons or homogeneous neuron clusters. Results were analyzed by a multivariate analysis of variance (MANOVA). MANOVA analysis indicates that there is a significant overall effect of lead exposure (p = 0.0001) and a significant interaction between lead and neuron type (p = 0.01). In most neuron types, chronic lead causes an increase in the resting potential, a slowing of recovery of the membrane potential after the undershoot of a spike, a decrease in spontaneous spiking activity, and a decrease in the input resistance. Lead also has differential effects on identifiable neurons, depressing excitability in some neuron types while not altering excitability in others.

  3. 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...

  4. 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

  5. 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.

  6. 21 CFR 582.5936 - Vitamin A palmitate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin A palmitate. 582.5936 Section 582.5936 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5936 Vitamin A palmitate. (a) Product. Vitamin A palmitate. (b) Conditions of use....

  7. Acute and chronic cadmium exposure promotes E-cadherin degradation in MCF7 breast cancer cells.

    Science.gov (United States)

    Ponce, Esmeralda; Louie, Maggie C; Sevigny, Mary B

    2015-10-01

    Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure-both acute and chronic-contributes to breast cancer progression by interfering with the normal functional relationship between E-cadherin and β-catenin. An MCF7 breast cancer cell line (MCF7-Cd) chronically exposed to 10(-7)  M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10(-6)  M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E-cadherin protein via the ubiquitination pathway. This resulted in fewer E-cadherin/β-catenin complexes and the relocation of active β-catenin to the nucleus, where it interacted with transcription factor TCF-4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of β-catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down-regulating E-cadherin, thus decreasing the number of E-cadherin/β-catenin adhesion complexes, and (2) enhancing the nuclear translocation of β-catenin to increase expression of cancer-promoting proteins (i.e., c-Jun and cyclin D1).

  8. 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

  9. 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

  10. Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells.

    Science.gov (United States)

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2014-08-01

    Cigarette smoke (CS)-induced alveolar destruction and energy metabolism changes are known contributors to the pathophysiology of chronic obstructive pulmonary disease (COPD). This study examines the effect of CS exposure on metabolism in alveolar type II cells. Male A/J mice (8 wk old) were exposed to CS generated from a smoking machine for 4 or 8 weeks, and a recovery group was exposed to CS for 8 weeks and allowed to recover for 2 weeks. Alveolar type II cells were isolated from air- or CS- exposed mice. Acute CS exposure led to a reversible airspace enlargement in A/J mice as measured by the increase in mean linear intercept, indicative of alveolar destruction. The effect of CS exposure on cellular respiration was studied using the XF Extracellular Flux Analyzer. A decrease in respiration while metabolizing glucose was observed in the CS-exposed group, indicating altered glycolysis that was compensated by an increase in palmitate utilization; palmitate utilization was accompanied by an increase in the expression of CD36 and carnitine-palmitoyl transferase 1 in type II alveolar cells for the transport of palmitate into the cells and into mitochondria, respectively. The increase in palmitate use for energy production likely affects the surfactant biosynthesis pathway, as evidenced by the decrease in phosphatidylcholine levels and the increase in phospholipase A2 activity after CS exposure. These findings help our understanding of the mechanism underlying the surfactant deficiency observed in smokers and provide a target to delay the onset of COPD.

  11. Impact of acute and chronic inhalation exposure to CdO nanoparticles on mice

    OpenAIRE

    Lebedová, J.; Bláhová, L.; Večeřa, Z. (Zbyněk); P. Mikuška; Dočekal, B. (Bohumil); Buchtová, M. (Marcela); Míšek, I. (Ivan); Dumková, J.; Hampl, A.; Hilscherová, K.

    2016-01-01

    Cadmium nanoparticles can represent a risk in both industrial and environmental settings, but there is little knowledge on the impacts of their inhalation, especially concerning longer-term exposures. In this study, mice were exposed to cadmium oxide (CdO) nanoparticles in whole body inhalation chambers for 4 to 72 h in acute and 1 to 13 weeks (24 h/day, 7 days/week) in chronic exposure to investigate the dynamics of nanoparticle uptake and effects. In the acute experiment, mice were ...

  12. 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.

  13. Liver and kidney lesions and associated enzyme changes induced in rabbits by chronic cyanide exposure.

    Science.gov (United States)

    Okolie, N P; Osagie, A U

    1999-07-01

    The effect of prolonged chronic cyanide exposure on liver and kidney integrity, as well as some associated enzyme and metabolite changes, were investigated in New Zealand white rabbits (initial mean weight 1.52 kg) using a combination of colorimetric, spectrophotometric, enzymatic, gravimetric and histological procedures. Two groups of rabbits were fed for 40 weeks on either pure growers' mash or growers' mash containing 702 ppm inorganic cyanide. Results obtained indicate that the cyanide-fed rabbits had significantly decreased liver activities of alkaline phosphatase, glutamate pyruvate transaminase and sorbitol dehydrogenase relative to controls (Pactivities of these enzymes in the cyanide-treated group. Kidney alkaline phosphatase activity was significantly decreased (Pactivities of lactate dehydrogenase. In addition, liver and kidney rhodanese activities were significantly raised in the cyanide-fed group. There were marked degenerative changes in the liver and kidney sections from the cyanide-treated rabbits. These results suggest that chronic cyanide exposure may be deleterious to liver and kidney functions.

  14. Chronic effects of exposure to a pharmaceutical mixture and municipal wastewater in zebrafish.

    Science.gov (United States)

    Galus, Michal; Jeyaranjaan, Judy; Smith, Emily; Li, Hongxia; Metcalfe, Chris; Wilson, Joanna Y

    2013-05-15

    Pharmaceuticals and personal care products (PPCPs) are discharged in municipal wastewater. Effects in aquatic organisms exposed to individual pharmaceuticals in the laboratory have raised concerns regarding the environmental impacts of PPCPs, yet environmental exposures are always to complex mixtures. In this study, adult zebrafish (Danio rerio) showed significantly decreased embryo production after a 6 week exposure to a pharmaceutical mixture (MIX; 0.5 and 10μgL(-1)) of acetaminophen, carbamazepine, gemfibrozil and venlafaxine and to diluted wastewater effluent (WWE; 5% and 25%). Atretic oocytes and altered ovarian histology were significantly increased in female zebrafish exposed to both concentrations of MIX or WWE, which indicates a direct effect on oocyte development that may account for reduced embryo production. Apoptosis within the thecal and granulosa cell layers was identified in female zebrafish with atresia. Exposures to MIX or WWE at both concentrations severely altered kidney proximal tubule morphology, but no histological impacts on other organs were observed. Exposure of embryos to MIX or WWE at the high concentration significantly increased the incidence of developmental abnormalities. Embryo mortality was elevated with exposure to the high concentration of MIX. These studies indicate that chronic exposure of fish to pharmaceutical mixtures and wastewater impacts reproduction and induces histopathological changes, similar to what we have previously seen with single compound exposures. These data suggest that fish populations exposed to pharmaceuticals discharged in wastewater are at risk of negative impacts to reproductive capacity and health.

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

    Science.gov (United States)

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

    2016-01-01

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

  16. 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...

  17. 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.

  18. 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.

  19. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells.

    Science.gov (United States)

    Luo, Yi; Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients.

  20. 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.

  1. Lactobacillus rhamnosus GG Effect on Behavior of Zebrafish During Chronic Ethanol Exposure.

    Science.gov (United States)

    Schneider, Ana Claudia Reis; Rico, Eduardo Pacheco; de Oliveira, Diogo Losch; Rosemberg, Denis Broock; Guizzo, Ranieli; Meurer, Fábio; da Silveira, Themis Reverbel

    2016-01-01

    Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure.

  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. 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.

  4. 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

  5. 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.

  6. 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.

  7. Responses of subjects with chronic obstructive pulmonary disease after exposures to 0. 3 ppm ozone

    Energy Technology Data Exchange (ETDEWEB)

    Kehrl, H.R.; Hazucha, M.J.; Solic, J.J.; Bromberg, P.A.

    1985-05-01

    The authors previously reported 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 nonreversible COPD (9 current smokers; mean FEV1/FVC, 56%) were randomly exposed on 2 consecutive days for 2 h to air and 0.3 ppm ozone. During exposures, subjects exercised (minute ventilation, 26.4 +/- 3.0 L/min) for 7.5 min every 30 min; ventilation and gas exchange measured during exercise showed no difference between exposure days. Pulmonary function tests (spirometry, body plethysmography) obtained before and after exposures were unchanged on the air day. On the ozone day the mean airway resistance and specific airway resistance showed the largest (25 and 22%) changes (p = 0.086 and 0.058, respectively). Arterial oxygen saturation (SaO/sub 2/) obtained in 8 subjects during the last exercise interval showed a mean decrement of 0.95% on the ozone exposure day; this change did not attain significance (p = 0.074). Nevertheless, arterial oxygen desaturation may be a true consequence of low-level ozone exposure in this compromised patient group. As normal subjects undergoing exposures to ozone with slightly higher exercise intensities show a threshold for changes in their respiratory mechanics at approximately 0.3 ppm, these data indicate that persons with COPD are not unduly sensitive to the effects of low-level ozone exposure.

  8. Chronic myelogenous leukemia and benzene exposure: a systematic review and meta-analysis of the case-control literature.

    Science.gov (United States)

    Lamm, Steven H; Engel, Arnold; Joshi, Kiran P; Byrd, Daniel M; Chen, Rusan

    2009-12-10

    Benzene exposure is well demonstrated as a cause of acute myelogenous leukemia, but not of chronic myelogenous leukemia. Previous literature reviews based on case series and cohort studies have not shown an association. We have now conducted a literature search for case-control studies that examine the association between benzene exposure and chronic myelogenous leukemia. Six case-control studies have been found. These derive from occupational groups, cancer registries, and a clinical laboratory. Their exposure ascertainments are all based on job histories, job-exposure matricies, or industrial hygiene data. The odds ratios (ORs) for individual studies range from 0.73 to 1.2. The pooled OR is 1.003 with 95% confidence interval (CI) of 0.94-1.07 (p=0.98) for both a fixed effects model and a random effects model. The case-control literature indicates that chronic myelogenous leukemia does not appear to be related to benzene exposure.

  9. 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

  10. 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.

  11. Chronic exposure to aluminum and risk of Alzheimer's disease: A meta-analysis.

    Science.gov (United States)

    Wang, Zengjin; Wei, Xiaomin; Yang, Junlin; Suo, Jinning; Chen, Jingyi; Liu, Xianchen; Zhao, Xiulan

    2016-01-01

    A meta-analysis was performed to investigate whether chronic exposure to aluminum (Al) is associated with increased risk of Alzheimer's disease (AD). Eight cohort and case-control studies (with a total of 10567 individuals) that met inclusion criteria for the meta-analysis were selected after a thorough literature review of PubMed, Web of Knowledge, Elsevier ScienceDirect and Springer databases up to June, 2015. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. Q test and I(2) statistic were used to examine heterogeneity between selected studies. The overall odds ratio (OR) was calculated using a fixed-effect model because no significant heterogeneity between studies was found. No publication bias was observed based on a funnel plot and Egger's test. Results showed that individuals chronically exposed to Al were 71% more likely to develop AD (OR: 1.71, 95% confidence interval (CI), 1.35-2.18). The finding suggests that chronic Al exposure is associated with increased risk of AD.

  12. Effect of a chronic GSM 900 MHz exposure on glia in the rat brain.

    Science.gov (United States)

    Ammari, Mohamed; Brillaud, Elsa; Gamez, Christelle; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; de Seze, René

    2008-01-01

    Extension of the mobile phone technology raises concern about the health effects of 900 MHz microwaves on the central nervous system (CNS). In this study we measured GFAP expression using immunocytochemistry method, to evaluate glial evolution 10 days after a chronic exposure (5 days a week for 24 weeks) to GSM signal for 45 min/day at a brain-averaged specific absorption rate (SAR)=1.5 W/kg and for 15 min/day at a SAR=6 W/kg in the following rat brain areas: prefrontal cortex (PfCx), caudate putamen (Cpu), lateral globus pallidus of striatum (LGP), dentate gyrus of hippocampus (DG) and cerebellum cortex (CCx). In comparison to sham or cage control animals, rats exposed to chronic GSM signal at 6 W/kg have increased GFAP stained surface areas in the brain (pGSM at 1.5 W/kg did not increase GFAP expression. Our results indicated that chronic exposure to GSM 900 MHz microwaves (SAR=6 W/kg) may induce persistent astroglia activation in the rat brain (sign of a potential gliosis).

  13. 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.

  14. Central neurological abnormalities and multiple chemical sensitivity caused by chronic toluene exposure.

    Science.gov (United States)

    Lee, Y-L; Pai, M-C; Chen, J-H; Guo, Y L

    2003-10-01

    Multiple chemical sensitivity (MCS) is a syndrome in which multiple symptoms occur with low-level chemical exposure; whether it is an organic disease initiated by environmental exposure or a psychological disorder is still controversial. We report a 38-year-old male worker with chronic toluene exposure who developed symptoms such as palpitation, insomnia, dizziness with headache, memory impairment, euphoria while working, and depression during the weekend. Upon cessation of exposure, follow-up neurobehavioural tests, including the cognitive ability screening instrument and the mini-mental state examination, gradually improved and eventually became normal. Although no further toluene exposure was noted, non-specific symptoms reappeared whenever the subject smelled automotive exhaust fumes or paint, or visited a petrol station, followed by anxiety with sleep disturbance. During hospitalization for a toluene provocation test, there was no difference between pre-challenge and post-challenge PaCO(2), PaO(2), SaO(2) or pulmonary function tests, except some elevation of pulse rate. The clinical manifestations suggested that MCS was more relevant to psychophysiological than pathophysiological factors.

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

    Science.gov (United States)

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

    2016-10-01

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

  16. Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Madrid Univ. (Spain). Facultad de Medicina Complutense; Marquez, N.; Alvarez-Demanuel, E.; Lafuente, A. [Vigo Univ., Orense (Spain). Lab. de Toxicologia

    1998-07-01

    Cadmium increases or decreases prolactin secretion depending on the dose and duration of the exposure to the metal. However, whether there are cadmium effects on the episodic prolactin secretion is less well known. This study was undertaken to address whether chronic alternating exposure to two different doses of cadmium affects the episodic pattern of prolactin and to what extent the effects of cadmium are age-dependent. Male rats were treated s.c. with cadmium chloride (0.5 or 1.0 mg/kg) from day 30 to 60, or from day 60 to 90 of age, with alteration of the doses every 4 days, starting with the smaller dose. Controls received vehicle every 4 days. The last dose of cadmium was given 48 h prior to the pulsatility study. Prolactin secretion in the 4 experimental groups studied was episodic and changed significantly after cadmium exposure. Cadmium administration from day 30 to 60 of life significantly decreased the mean half-life of prolactin. On the other hand, when administered from day 60 to 90 cadmium significantly decreased the mean as well as serum prolactin levels and the absolute amplitude of the prolactin pulses, their duration, the relative amplitude or the mean half-life of the hormone. The frequency of prolactin peaks was not changed by cadmium administration. The results indicate that low intermittent doses of cadmium chronically administered change the episodic secretion pattern of prolactin in rats. The effects of cadmium on prolactin secretion were age dependent. (orig.)

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

    Science.gov (United States)

    Cruickshank-Quinn, Charmion I; Mahaffey, Spencer; Justice, Matthew J; Hughes, Grant; Armstrong, Michael; Bowler, Russell P; Reisdorph, Richard; Petrache, Irina; Reisdorph, Nichole

    2014-01-01

    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.

  18. 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.

  19. Chronic diclofenac (DCF) exposure alters both enzymatic and haematological profile of African catfish, Clarias gariepinus.

    Science.gov (United States)

    Ajima, Malachy N O; Ogo, Ogo A; Audu, Bala S; Ugwoegbu, Kyrian C

    2015-10-01

    Pharmaceuticals are used extensively in human and veterinary medicine to eradicate or prevent diseases. The residues of these drugs have been detected in aquatic ecosystem; nevertheless, their toxicological effects on Clarias gariepinus have not been critically investigated. In this study, the toxic effects of diclofenac (DCF), a non-steroid anti-inflammatory drug, were studied in C. gariepinus by acute and chronic static renewable bioassay. The 96 h LC50 of DCF to C. gariepinus was 25.12 mg/L. Exposure to acute toxicity resulted in abnormal behavior and mortality of some fish. Compared with the control, chronic exposure of the fish to concentration (1.57, 3.14 and 6.28 mg/L) showed significantly higher mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and white blood cell (WBC), with significantly lower haemoglobin (Hb), haematocrit, red blood cell (RBC) and mean corpuscular haemoglobin (MCH) with increase in the concentration of the drug. Furthermore, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and glucose values significantly increased while protein levels were reduced (p < 0.05) in serum and gills throughout the 42-day exposure period. The study reports that DCF-induced enzymatic and haematological changes in the fish and recommends that these parameters be used as potential biomarkers for assessing residual pharmaceuticals available in aquatic ecosystem.

  20. 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.

  1. Modeling hematopoietic system response caused by chronic exposure to ionizing radiation.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2011-05-01

    A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950-1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose-effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).

  2. 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...

  3. Nicotine improves working memory span capacity in rats following sub-chronic ketamine exposure.

    Science.gov (United States)

    Rushforth, Samantha L; Steckler, Thomas; Shoaib, Mohammed

    2011-12-01

    Ketamine, an NMDA-receptor antagonist, produces cognitive deficits in humans in a battery of tasks involving attention and memory. Nicotine can enhance various indices of cognitive performance, including working memory span capacity measured using the odor span task (OST). This study examined the effects of a sub-chronic ketamine treatment to model cognitive deficits associated with schizophrenia, and to evaluate the effectiveness of nicotine, antipsychotic clozapine, and the novel mGlu2/3 agonist, LY404039, in restoring OST performance. Male hooded Lister rats were trained in the OST, a working memory task involving detection of a novel odor from an increasing number of presented odors until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, administration of graded doses of nicotine (0.025-0.1 mg/kg) acutely restored the performance in ketamine-treated animals, while significant improvements in odor span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1-10 mg/kg) and LY404039 (0.3-10 mg/kg) failed to reverse ketamine-induced deficits in doses that were observed to impair performance in the control groups. These data suggest that sub-chronic ketamine exposure in the OST presents a valuable method to examine novel treatments to restore cognitive impairments associated with neuropsychiatric disorders such as schizophrenia. Moreover, it highlights a central role for neuronal nicotinic receptors as viable targets for intervention that may be useful adjuncts to the currently prescribed anti-psychotics.

  4. 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 < 0.05) when compared with the matched healthy control group. However, CYP2E1 was elevated in all the samples examined. Chronic exposure to alcohol has the potential to reduce the levels of pulmonary vitamin D and results in subsequent downregulation of the antimicrobial peptide, LL-37, in the human pulmonary system. PMID:27795667

  5. [Bioeffects of chronic exposure to radiofrequency electromagnetic fields of low intensity (standardization strategy)].

    Science.gov (United States)

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

    2003-01-01

    A retrospective analysis of the experimental researches on the effect of radio frequency electromagnetic fields (EMF) on human health, carried out in the USSR, is presented. The results of chronic exposure of laboratory animals to EMF have been considered. Apparently, EMF in the range of 1750-2750 MHz with power density up to 100-500 W/cm2 caused in immune globullin fractions, and a development of autoimmune processes. The changes in parameters of reproductive functions and posterity, the increase in embryo mortality were found. The standartization strategy used in the USSR and currently applied in Russia has been discussed.

  6. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD

    OpenAIRE

    Kitazawa, Masashi; Cheng, David; Frank M LaFerla

    2009-01-01

    Excess copper exposure is thought to be linked to the development of Alzheimer disease (AD) neuropathology. However, the mechanism by which copper affects the central nervous system remains unclear. To investigate the effect of chronic copper exposure on both beta-amyloid and tau pathologies, we treated young triple transgenic (3xTg-AD) mice with 250 ppm copper-containing water for the period of 3 or 9 months. Copper exposure resulted in altered APP processing; increased accumulation of the a...

  7. 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

  8. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    Directory of Open Access Journals (Sweden)

    Barfod Kenneth K

    2010-09-01

    exposures to commercial Bt based biopesticides can induce sub-chronic lung inflammation in mice, which may be the first step in the development of chronic lung diseases. Inhalation of Bt aerosols does not induce airway irritation, which could explain why workers may be less inclined to use a filter mask during the application process, and are thereby less protected from exposure to Bt spores.

  9. Growth Responses of Fish During Chronic Exposure of Metal Mixture under Laboratory Conditions

    Directory of Open Access Journals (Sweden)

    Saima Naz and Muhammad Javed

    2013-07-01

    Full Text Available Growth responses of five fish species viz. Catla catla, Labeo rohita, Cirrhina mrigala, Ctenopharyngodon idella and Hypophthalmichthys molitrix were determined, separately, under chronic exposure of binary mixture of metals (Zn+Ni at sub-lethal concentrations (1/3rd of LC50 for 12 weeks. Randomized complete block design (RCBD was followed to conduct this research work. The groups (10 fish each of Catla catla, Labeo rohita, Cirrhina mrigala, Ctenopharyngodon idella and Hypophthalmichthys molitrix having almost similar weights were investigated for their growth responses and metals bioaccumulation patterns in their body organs during chronic exposure of Zn+Ni mixture. The bioaccumulation of metals in the fish body organs viz. gills, liver, kidney, fins, bones, muscle and skin were also determined before and after growth trails under the stress of metals mixture. The exposure of fish to sub-lethal concentrations of mixture caused significant impacts on the average wet weight increments of five fish species. Ctenopharyngodon idella and Labeo rohita attained significantly higher weights, followed by that of Hypophthalmichthys molitrix, Cirrhina mrigala and Catla catla. However, the growth of metals mixture exposed fish species was significantly lesser than that of control fish (un-stressed. Significantly variable condition factor values reflected the degree of fish well-beings that correlated directly with fish growth and metal exposure concentration. Any significant change in feed intake, due to stress, is reflected in terms of fish growth showing the impacts of metal mixture on fish growth were either additive or antagonist / synergistic. Accumulation of all the metals in fish body followed the general order: liver>kidney>gills> skin >muscle> fins >bones.

  10. 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.

  11. Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, S., E-mail: up201208875@fc.up.pt [Departamento de Biologia da Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169–007 Porto (Portugal); Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Rua dos Bragas 289, 4050–123 Porto (Portugal); Antunes, S.C. [Departamento de Biologia da Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169–007 Porto (Portugal); Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Rua dos Bragas 289, 4050–123 Porto (Portugal); Correia, A.T. [Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Rua dos Bragas 289, 4050–123 Porto (Portugal); Faculdade de Ciências da Saúde da Universidade Fernando Pessoa (FCS-UFP), Rua Carlos da Maia, 296, 4200–150, Porto (Portugal); Nunes, B. [Centro de Estudos do Ambiente e do Mar (CESAM), Campus de Santiago, Universidade de Aveiro, 3810–193 Aveiro (Portugal); Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810–193 Aveiro (Portugal)

    2016-03-01

    Erythromycin (ERY) is a macrolide antibiotic used in human and veterinary medicine, and has been detected in various aquatic compartments. Recent studies have indicated that this compound can exert biological activity on non-target organisms environmentally exposed. The present study aimed to assess the toxic effects of ERY in Oncorhynchus mykiss after acute and chronic exposures. The here adopted strategy involved exposure to three levels of ERY, the first being similar to concentrations reported to occur in the wild, thus ecologically relevant. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by performing analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and of erythrocytic nuclear abnormalities (ENAs). The results suggest the occurrence of a mild, but significant, oxidative stress scenario in gills. For acutely exposed organisms, significant alterations were observed in CAT and GRed activities, and also in TBARS levels, which however are modifications with uncertain biological interpretation, despite indicating involvement of an oxidative effect and response. After chronic exposure, a significant decrease of CAT activity, increase of GPx activity and TBARS levels in gills was noticed. In liver, significant decrease in TBARS levels were observed in both exposures. Comet and ENAs assays indicated significant increases on genotoxic damage of O. mykiss, after erythromycin exposures. This set of data (acute and chronic) suggests that erythromycin has the potential to induce DNA strand breaks in blood cells, and demonstrate the induction of chromosome breakage and/or segregational abnormalities. Overall results indicate that both DNA damaging effects induced by

  12. 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.

  13. 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.

  14. Supernumerary Formation of Olfactory Glomeruli Induced by Chronic Odorant Exposure: A Constructivist Expression of Neural Plasticity

    Science.gov (United States)

    Valle-Leija, Pablo; Blanco-Hernández, Eduardo; Drucker-Colín, Rene; Gutiérrez-Ospina, Gabriel; Vidaltamayo, Roman

    2012-01-01

    It is accepted that sensory experience instructs the remodelling of neuronal circuits during postnatal development, after their specification has occurred. The story is less clear with regard to the role of experience during the initial formation of neuronal circuits, whether prenatal or postnatal, since this process is now supposed to be primarily influenced by genetic determinants and spontaneous neuronal firing. Here we evaluated this last issue by examining the effect that postnatal chronic exposure to cognate odorants has on the formation of I7 and M72 glomeruli, iterated olfactory circuits that are formed before and after birth, respectively. We took advantage of double knock-in mice whose I7 and M72 primary afferents express green fluorescent protein and β-galactosidase, correspondingly. Our results revealed that postnatal odorant chronic exposure led to the formation of permanent supernumerary I7 and M72 glomeruli in a dose and time dependent manner. Glomeruli in exposed mice were formed within the same regions of olfactory bulb and occupy small space volumes compared to the corresponding single circuits in non-exposed mice. We suggest that local reorganization of the primary afferents could participate in the process of formation of supernumerary glomeruli. Overall, our results support that sensory experience indeed instructs the permanent formation of specific glomeruli in the mouse olfactory bulb by means of constructivist processes. PMID:22511987

  15. The Effect of Chronic Exposure with Imidacloprid Insecticide on Fertility in Mature Male Rats

    Directory of Open Access Journals (Sweden)

    Golamreza Najafi

    2010-01-01

    Full Text Available Background: This study was conducted to evaluate the effect of chronic exposure to imidacloprid(IM insecticide on male testicular tissue, sperm morphology and testosterone levels in the serumof mature male rats.Materials and Methods: Animals were divided into and control-sham groups. The test group wassubdivided into two groups of rats which were administered doses of 225 and 112 mg/kg IM pergroup. Each test group received the designated oral dose of IM once daily, for 60 days while thecontrol-sham group received corn oil (0.2 ml/day for the same time period.Results: Clinical observations demonstrated decreased movement, staggering gait, occasionaltrembling, diarrhea and spasms in the test groups. No clinical signs were seen in control-shamrats. Light microscopic analyses revealed increased thickness of tunica albuginea, obvious edemain the sub-capsular and interstitial connective tissue, atrophied seminiferous tubules, arrestedspermatogenesis, negative tubular differentiation and repopulation indexes, decreased Leydig cells/mm2 of interstitial tissue, hypertrophy and cytoplasmic granulation of the Leydig cells, vasodilationand thrombosis, elevated death, as well as immature and decreased immotile sperm velocity.Hormonal investigations showed significant (p<0.05 decrease in serum testosterone levels. Nohormonal changes were seen in the testosterone levels of the control-sham group.Conclusion: The current data provide inclusive histological feature of chronic IM exposure intwo doses with an emphasis on reproductive disorders including a histological adverse effect ontesticular tissue, spermatogenesis, sperm viability, velocity and abnormality which potentially cancause infertility.

  16. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  18. Hair analysis used to assess chronic exposure to the organophosphate diazinon: a model study with rabbits.

    Science.gov (United States)

    Tutudaki, Maria; Tsakalof, Andreas K; Tsatsakis, Aristidis M

    2003-03-01

    The main purpose of the present study was to determine whether hair analysis would be a suitable method to assess chronic exposure of rabbits to the pesticide diazinon. A controlled study was designed, in which white rabbits of the New Zealand variety were systemically exposed to two dosage levels (15 mg/kg per day and 8 mg/kg per day) of the pesticide, through their drinking water, for a period of 4 months. Hair samples from the back of the rabbits were removed before commencing the experiment and at the end of the dosing period. Parallel experiments with spiked hair were carried out in order to design a simple and efficient method of extraction of diazinon from hair. The hair was pulverized in a ball mill homogenizer, incubated in methanol at 37 degrees C overnight, liquid-liquid extracted with ethyl acetate and measured by chromatography techniques (GC-NPD and GC-MS) for confirmation. The concentration of the diazinon in the hair of the exposed animals ranged from 0.11 to 0.26 ng/mg hair. It was concluded that there is a relationship between the administered dose and the detected pesticide concentration in hair. Finally, it seems that hair analysis may be used to investigate chronic exposure to the pesticide.

  19. Effects of a chronic lower range of triclosan exposure to a stream mesocosm community

    Science.gov (United States)

    Nietch, C.T.; Quinlan, E.L.; Lazorchak, J.; Impellitteri, C.; Raikow, D.; Walters, David M.

    2013-01-01

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicrobial found in consumer soaps and toothpaste. It is in treated wastewater effluents at low part per billion concentrations, representing a potentially chronic exposure condition for biota inhabiting receiving streams. A naturally colonized benthos was created using flow-through indoor mesocosms. Then the benthic communities were dosed to achieve different in-stream triclosan concentrations (Control, 0.1, 0.5, 1.0, 5.0, and 10 µg/L) for 56 days. Water quality parameters and endpoints from bacteria to macroinvertebrates plus interacting abiotic components were measured. Effects of triclosan on specific microbial endpoints were observed at all doses, including an effect on litter decomposition dynamics at doses 1.0 µg/L and higher. Resistance of periphytic bacteria to triclosan significantly increased in doses 0.5 µg/L and above. By the end of dosing, the antimicrobial appeared to stimulate the stream periphyton at the three lowest doses while the two highest doses exhibited decreased stocks of periphyton, including significantly lower bacteria cell densities, and cyanobacteria abundance compared to the control. Beside an effect on benthic ostracods, the changes that occurred in the periphyton did not translate to significant change in the colonizing nematodes, the macroinvertebrate community as a whole, or other measurements of stream function. The results shed light on the role a low, chronic exposure to triclosan may play in effluent dominated streams.

  20. 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.

  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. Oxidant/antioxidant effects of chronic exposure to predator odor in prefrontal cortex, amygdala, and hypothalamus.

    Science.gov (United States)

    Mejia-Carmona, G E; Gosselink, K L; Pérez-Ishiwara, G; Martínez-Martínez, A

    2015-08-01

    The incidence of anxiety-related diseases is increasing these days, hence there is a need to understand the mechanisms that underlie its nature and consequences. It is known that limbic structures, mainly the prefrontal cortex and amygdala, are involved in the processing of anxiety, and that projections from prefrontal cortex and amygdala can induce activity of the hypothalamic-pituitary-adrenal axis with consequent cardiovascular changes, increase in oxygen consumption, and ROS production. The compensatory reaction can include increased antioxidant enzymes activities, overexpression of antioxidant enzymes, and genetic shifts that could include the activation of antioxidant genes. The main objective of this study was to evaluate the oxidant/antioxidant effect that chronic anxiogenic stress exposure can have in prefrontal cortex, amygdala, and hypothalamus by exposition to predator odor. Results showed (a) sensitization of the HPA axis response, (b) an enzymatic phase 1 and 2 antioxidant response to oxidative stress in amygdala, (c) an antioxidant stability without elevation of oxidative markers in prefrontal cortex, (d) an elevation in phase 1 antioxidant response in hypothalamus. Chronic exposure to predator odor has an impact in the metabolic REDOX state in amygdala, prefrontal cortex, and hypothalamus, with oxidative stress being prevalent in amygdala as this is the principal structure responsible for the management of anxiety.

  3. Acute on chronic exposure to endotoxin is associated with enhanced chemoreflex responses in preterm fetal sheep.

    Science.gov (United States)

    Booth, Lindsea C; Drury, Paul P; Muir, Cameron; Jensen, Ellen C; Gunn, Alistair J; Bennet, Laura

    2013-05-15

    There is increasing evidence that exposure to infection can sensitize the fetus to subsequent hypoxic injury. However, it is unclear whether this involves compromise of the fetal cardiovascular adaptation to acute asphyxia. Chronically instrumented 103-day-old (0.7 gestational age, term is 147 days) fetal sheep in utero were randomized to receive either gram-negative lipopolysaccharide (LPS) as a continuous low-dose infusion for 120 h plus boluses of 1 μg LPS at 48, 72, and 96 h with asphyxia at 102 h (i.e., 6 h after the final LPS bolus) induced by umbilical cord occlusion for 15 min (LPS treated, n = 8), or the same volume of saline plus occlusion (saline treated, n = 7). Fetuses were killed 5 days after occlusion. LPS was associated with a more rapid fall in fetal heart rate at the onset of occlusion (P fall in CaBF to similar values as saline controls during occlusion. There were no differences between the groups in femoral blood flow before or during occlusion. Contrary to our initial hypothesis, acute on chronic exposure to LPS was associated with more rapid cardiovascular adaptation to umbilical cord occlusion.

  4. 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.

  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. 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.

  7. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation.

    Science.gov (United States)

    Rybkina, Valentina L; Azizova, Tamara V; Scherthan, Harry; Meineke, Viktor; Doerr, Harald; Adamova, Galina V; Teplyakova, Olga V; Osovets, Sergey V; Bannikova, Maria V; Zurochka, Alexander V

    2014-11-01

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  8. Chronic exposure to ozone and nitric acid vapor results in increased levels of rat pulmonary putrescine

    Energy Technology Data Exchange (ETDEWEB)

    Sindhu, R.K.; Kikkawa, Yutaka [Department of Pathology, College of Medicine, University of California at Irvine, Irvine (United States); Mautz, W.J. [Department of Community and Environmental Medicine, University of California at Irvine, Irvine, CA (United States)

    1998-06-01

    In the past decade, there has been growing public concern for the human health effects of exposure to environmental pollutants. Ozone (O{sub 3}) is one of the most reactive components of photochemical air pollution. Despite extensive investigations by many laboratories on the functional, biochemical, and cellular effects of O{sub 3} exposure in humans, animals, and in vitro systems, questions remain concerning the potential adverse effects to human health represented by chronic near-ambient exposure to this environmental pollutant. In the present investigation, the influence of inhalation of O{sub 3} and nitric acid (HNO{sub 3}) vapor on polyamine levels was examined in rat lungs. Male F344/N rats were exposed nose-only to 0.15 ppm O{sub 3} and 50 {mu}g/m{sup 3} HNO{sub 3} vapor alone and in combination for 4 hours/day, 3 days/week for a total of 40 weeks. At this time the animals were sacrificed and their lungs were examined for polyamine contents. Exposure to O{sub 3} and O{sub 3} plus HNO{sub 3} vapor caused a significant increase in the putrescine content of the lung compared to the air-exposed controls (P < 0.05). The concentrations of pulmonary spermidine and spermine were not significantly increased by exposure to either O{sub 3} or HNO{sub 3} vapor alone or in combination compared to the air-exposed controls. The role of polyamines in repair and anti-inflammatory processes has been discussed. (orig.) (orig.) With 1 fig., 1 tab., 30 refs.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Watson, Walter H. [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Zhong, Hai [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); States, J. Christopher [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2011-12-15

    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: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.

  10. Persistent Na+ and K+ channel dysfunctions after chronic exposure to insecticides and pyridostigmine bromide.

    Science.gov (United States)

    Nutter, T J; Jiang, N; Cooper, Brian Y

    2013-12-01

    Many soldiers that served in the 1991 Gulf War developed widespread chronic pain. Exposure to insecticides and the nerve gas prophylactic pyridostigmine bromide (PB) was identified as risk factors by the Research Advisory Committee on Gulf War Veterans' Illnesses (GWI). We examined whether a 60 day exposure to neurotoxicants/PB (NTPB) produced behavioral, molecular and cellular indices of chronic pain in the rat. Male rats were exposed to chlorpyrifos (120mg/kg; SC), permethrin (2.6mg/kg; topical), and PB (13.0mg/kg; oral) or their respective vehicles (corn oil, ethanol, and water). Permethrin can exert profound influences on voltage activated Na(+) channel proteins; while chlorpyrifos and PB can increase absorption and/or retard metabolism of permethrin as well as inhibit cholinesterases. During and after exposure to these agents, we assessed muscle pressure pain thresholds and activity (distance and rest time). Eight and 12 weeks after treatments ceased, we used whole cell patch electrophysiology to examine the physiology of tissue specific DRG nociceptor channel proteins expressed in muscle and putative vascular nociceptors (voltage dependent, activation, inactivation, and deactivation). Behavioral indices were unchanged after treatment with NTPB. Eight weeks after treatments ended, the peak and average conductance of Kv7 mediated K(+) currents were significantly increased in vascular nociceptors. When a specific Kv7 inhibitor was applied (linopirdine, 10μM) NTPB treated vascular nociceptors emitted significantly more spontaneous APs than vehicle treated neurons. Changes to Kv7 channel physiology were resolved 12 weeks after treatment. The molecular alterations to Kv7 channel proteins and the specific susceptibility of the vascular nociceptor population could be important for the etiology of GWI pain.

  11. Paliperidone Palmitate Intramuscular 3-Monthly Formulation: A Review in Schizophrenia.

    Science.gov (United States)

    Lamb, Yvette N; Keating, Gillian M

    2016-10-01

    A 3-monthly formulation of intramuscular paliperidone palmitate (3-monthly paliperidone palmitate) has recently been approved for the maintenance treatment of schizophrenia in adult patients in the EU (Trevicta(®)), following earlier approval in the USA (Invega Trinza(®)). This narrative review discusses the clinical use of 3-monthly paliperidone palmitate in the maintenance treatment of schizophrenia in adult patients and summarizes its pharmacological properties. The efficacy of the 3-monthly paliperidone palmitate formulation as a maintenance treatment for schizophrenia has been demonstrated in well designed, phase III trials. Three-monthly paliperidone palmitate was more effective than placebo in delaying time to relapse and reducing relapse rates, and was noninferior to 1-monthly paliperidone palmitate in the proportion of patients that remained relapse-free. The 3-monthly formulation was also more effective than placebo in controlling the symptoms of schizophrenia, whilst not differing significantly from the 1-monthly formulation in terms of symptomatic control. Three-monthly paliperidone palmitate was generally well tolerated in clinical trials, with a tolerability profile consistent with that of the 1-monthly formulation. In conclusion, 3-monthly paliperidone palmitate is a useful treatment option for adult patients with schizophrenia who are adequately treated with the 1-monthly formulation, particularly for those who would prefer, or may benefit from, longer dosing intervals.

  12. 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.

  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 parasite Nosema ceranae slightly impaired learning in honeybees, but no interactive effects were observed. Nosema did 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.

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

    Science.gov (United States)

    Liu, Qing; Spitsbergen, Jan M; Cariou, Ronan; Huang, Chun-Yuan; Jiang, Nan; Goetz, Giles; Hutz, Reinhold J; Tonellato, Peter J; Carvan, Michael J

    2014-01-01

    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.

  16. 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.

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

    Science.gov (United States)

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

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

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

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    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

  19. 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

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

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    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

  1. Chronic cadmium exposure: relation to male reproductive toxicity and subsequent fetal outcome

    Energy Technology Data Exchange (ETDEWEB)

    Zenick, H. (Univ. of Cincinnati, OH); Hastings, L.; Goldsmith, M.; Niewenhuis, R.J.

    1982-03-01

    Acute injections of high doses of Cd induced marked testicular necrosis. However, the effects of low-dose, oral Cd exposure on a chronic basis are not well documented. The present investigation was designed to examine the effects of such exposure as reflected in parameters of spermatotoxicity and histology. Moreover, the impact on fetal outcome was measured by evaluating teratological and postnatal neurobehavior endpoints. Male Long-Evans hooded rats (100 d of age) were exposed to 0, 17.2, 34.4, or 68.8 ppm Cd for 70 d. During this period, the animals were maintained on a semipurified diet to control for the contribution of Zn and other trace elements. Near the end of exposure the males were mated to three female rats. One was sacrificed on d 21 of pregnancy for teratological assessment, including fetal weight, and determination of preimplantation and postimplantation loss. The other two dams were allowed to deliver, and their offspring were tested on tasks of exploratory behavior (d 21) and learning (d 90). Subsequently, the male parent was sacrified and a variety of measures recorded including weights of testes and caudae epididymides, sperm count and sperm morphology, and Cd content of liver and kidney. One of the testes was also evaluated histologically. No significant effects were observed on any of the parameters of reproductive toxicity or fetal outcome. These findings suggest that, at the doses employed in this study, Cd did not have signficant deleterious effects on the male reproductive system. Morever, the traditional view of Cd-related testicular insult, based on acute exposure, injection protocols, needs to be reevaluated in terms of environmental relevance.

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

    Science.gov (United States)

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

    2015-09-22

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

  3. Chronic exposure to light reverses the effect of maternal separation on proteins in the prefrontal cortex.

    Science.gov (United States)

    Dimatelis, J J; Stein, D J; Russell, V A

    2013-11-01

    Animals subjected to maternal separation display behavioural and endocrine disturbances, as well as structural and functional changes in the prefrontal cortex and limbic areas. The aim of the present study was to determine the effect of maternal separation and treatment with either chronic constant light exposure or anti-depressant (escitalopram) on proteins in the prefrontal cortex. Four experimental groups of male Sprague-Dawley rats were subjected to (1) normal rearing, (2) maternal separation (3 h per day from postnatal day 2 (P2) to P14), (3) maternal separation followed by chronic light exposure (P42-P63) or (4) maternal separation followed by treatment with the anti-depressant drug, escitalopram (P68-P100). Groups 1-3 were treated with saline as vehicle control for the escitalopram-treated group. At P101, all rats were decapitated, and the prefrontal cortex was collected and stored at -80 °C. Tissue from three rats per group was pooled and proteins determined by isobaric tagging for relative and absolute quantification using matrix-assisted laser desorption/ionisation tandem mass spectrometry. Maternal separation led to disruptions in the prefrontal cortex that included hypometabolism by decreasing energy-related proteins (creatine kinase B, aconitate hydratase), decreased cell signalling (synapsin I, calmodulin, 14-3-3 protein epsilon) and impaired plasticity (spectrin, microtubule-associated protein). Maternal separation also increased dihydropyrimidinase-related protein/collapsin response mediator protein (CRMP) and myelin proteolipid protein. Exposure of maternally separated animals to constant light during adolescence reversed the hypometabolic state by increasing energy-related proteins in the prefrontal cortex and increasing cell signalling and cytoskeletal proteins and decreasing the expression of CRMP. Escitalopram had similar effects to light by increasing ATP synthase in maternally separated rats and dissimilar effects by increasing 2',3'-cyclic

  4. Chronic zinc exposure decreases the surface expression of NR2A-containing NMDA receptors in cultured hippocampal neurons.

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    Jia Zhu

    Full Text Available BACKGROUND: Zinc distributes widely in the central nervous system, especially in the hippocampus, amygdala and cortex. The dynamic balance of zinc is critical for neuronal functions. Zinc modulates the activity of N-methyl-D-aspartate receptors (NMDARs through the direct inhibition and various intracellular signaling pathways. Abnormal NMDAR activities have been implicated in the aetiology of many brain diseases. Sustained zinc accumulation in the extracellular fluid is known to link to pathological conditions. However, the mechanism linking this chronic zinc exposure and NMDAR dysfunction is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We reported that chronic zinc exposure reduced the numbers of NR1 and NR2A clusters in cultured hippocampal pyramidal neurons. Whole-cell and synaptic NR2A-mediated currents also decreased. By contrast, zinc did not affect NR2B, suggesting that chronic zinc exposure specifically influences NR2A-containg NMDARs. Surface biotinylation indicated that zinc exposure attenuated the membrane expression of NR1 and NR2A, which might arise from to the dissociation of the NR2A-PSD-95-Src complex. CONCLUSIONS: Chronic zinc exposure perturbs the interaction of NR2A to PSD-95 and causes the disorder of NMDARs in hippocampal neurons, suggesting a novel action of zinc distinct from its acute effects on NMDAR activity.

  5. 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.

  6. Responses of older men with and without chronic obstructive pulmonary disease to prolonged ozone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Gong, H. Jr.; Shamoo, D.A.; Anderson, K.R.; Linn, W.S. [Los Amigos Research and Education Institute, Inc., Downey, CA (United States)

    1997-01-01

    We tested responses to ozone (O{sub 3}) under simulated {open_quotes}worst-case{close_quotes} ambient exposure conditions. Subjects included 9 men who had severe chronic obstructive pulmonary disease (COPD) with subnormal carbon monoxide diffusing capacity (i.e., an emphysemic component) and 10 age-matched healthy men. Each subject was exposed to 0.24 ppm O{sub 3} and to clean air (control) in an environmentally controlled chamber at 24{degrees}C and 40% relative humidity. Exposures were randomized, they occurred 1 wk apart, and they lasted 4 h. During each half-hour interval, light exercise occurred (e.e., average ventilation 20 l/mm) for 15 min. during both control and O{sub 3} exposures, group mean symptom intensity and specific airway resistance (SRaw) increased, whereas forced expiratory performance decreased. The healthy subgroup`s mean arterial oxygen saturation (SaO{sub 2}) rose slightly, and the COPD subgroup`s mean SaO{sub 2} declined slightly, during exercise. Group mean forced expiratory volume in 1 s (FEV{sub 1.0}) declined significantly in O{sub 3} exposures, compared with controls (p {approx}.01). Mean excess FEV{sub 1.0} loss after 4 h in O{sub 3} (relative to control) was 8% of the preexposure value in the COPD subgroup, compared with 3% in the healthy subgroup (p > .05 [nonsignificant]). Overall FEV{sub 1.0} loss during O{sub 3} exposures, including exercise effects, averaged 19% in the COPD subgroup, compared with 2% in the healthy subgroup (p < .001). Symptoms, SRaw, and SaO{sub 2} responses, as well as healthy subjects` postexposure bronchial reactivity, differed little between O{sub 3}-exposed and control subjects. We therefore concluded that in older men with or without severe COPD, O{sub 3} causes lung dysfunction under {open_quotes}worst-case{close_quotes} ambient exposure conditions, despite older subjects` comparative unresponsiveness to O{sub 3}. 30 refs., 2 figs., 2 tabs.

  7. Association between chronic organochlorine exposure and immunotoxicity in the round stingray (Urobatis halleri).

    Science.gov (United States)

    Sawyna, Jillian M; Spivia, Weston R; Radecki, Kelly; Fraser, Deborah A; Lowe, Christopher G

    2017-04-01

    Chronic organochlorine (OC) exposure has been shown to cause immune impairment in numerous vertebrate species. To determine if elasmobranchs exhibited compromised immunity due to high OC contamination along the coastal mainland of southern California, innate immune function was compared in round stingrays (Urobatis halleri) collected from the mainland and Santa Catalina Island. Proliferation and phagocytosis of peripheral blood, splenic, and epigonal leukocytes were assessed. Percent phagocytosis and mean fluorescence intensity (MFI) were evaluated by quantifying % leukocytes positive for, and relative amounts of ingested fluorescent E. coli BioParticles. Total cell proliferation differed between sites, with mainland rays having a higher cell concentration in whole blood. ∑PCB load explained significantly higher % phagocytosis in blood of mainland rays, while ∑PCB and ∑pesticide loads described increased splenic % phagocytosis and MFI in the mainland population. Data provides evidence of strong OC-correlated immunostimulation; however, other site-specific environmental variables may be contributing to the observed effects.

  8. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Soo Lim

    Full Text Available There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ, is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48 were treated for 5 months with low concentrations (30 or 300 microg kg(-1 day(-1 of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent.

  9. Chronic intermittent high altitude exposure, occupation, and body mass index in workers of mining industry.

    Science.gov (United States)

    Esenamanova, Marina K; Kochkorova, Firuza A; Tsivinskaya, Tatyana A; Vinnikov, Denis; Aikimbaev, Kairgeldy

    2014-09-01

    The obesity and overweight rates in population exposed to chronic intermittent exposure to high altitudes are not well studied. The aim of the retrospective study was to evaluate whether there are differences in body mass index in different occupation groups working in intermittent shifts at mining industry at high altitude: 3800-4500 meters above sea level. Our study demonstrated that obesity and overweight are common in workers of high altitude mining industry exposed to chronic intermittent hypoxia. The obesity rate was lowest among miners as compared to blue- and white-collar employees (9.5% vs. 15.6% and 14.7%, p=0.013). Obesity and overweight were associated with older age, higher rates of increased blood pressure (8.79% and 5.72% vs. 1.92%), cholesterol (45.8% and 45.6% vs. 32.8%) and glucose (4.3% and 1.26% vs. 0.57%) levels as compared to normal body mass index category (pmining industry exposed to intermittent high-altitude hypoxia. Therefore, assessment and monitoring of body mass index seems to be essential in those who live and work at high altitudes to supply the correct nutrition, modify risk factors, and prevent related disorders.

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. 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.

  15. Occupational disease in dentistry and chronic exposure to trace anesthetic gases.

    Science.gov (United States)

    Cohen, E N; Gift, H C; Brown, B W; Greenfield, W; Wu, M L; Jones, T W; Whitcher, C E; Driscoll, E J; Brodsky, J B

    1980-07-01

    A mail survey of 30,650 dentists and 30,547 chairside assistants grouped according to occupational exposure to inhalation anesthetic and sedatives in the dental operatory indicated increased general health problems and reproductive difficulties among respondents exposed to anesthetics. For male dentists who were heavily exposed to anesthetics, the increase in liver disease was 1.7-fold, kidney disease was 1.2-fold, and neurological disease was 1.9-fold. For wives of male dentists who were heavily exposed to anesthetics, the increase in spontaneous abortion rate was 1.5-fold. Among female chairside assistants who were heavily exposed to anesthetics, the increase in liver disease was 1.6-fold, kidney disease was 1.7-fold, and neurological disease was 2.8-fold. The increase in spontaneous abortion rate among assistants who were heavily exposed was 2.3-fold. Cancer rates in women heavily exposed to inhalation anesthetics were increased 1.5-fold but this finding was not statistically significant (P = .06). Separate analysis of the data for disease rates and birth difficulties by type of inhalation anesthetic indicates that in both dentists and chairside assistants chronic exposure to nitrous oxide alone is associated with an increase rate of adverse response.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Palmitate impairs cytokinesis associated with RhoA inhibition

    Institute of Scientific and Technical Information of China (English)

    Jianhua Zhang; Ying Yang; Jiarui Wu

    2010-01-01

    @@ Dear Editor, Excess fatty acid accumulation in non-adipose tissues results in lipotoxicity, which has been implicated in the pathogenesis of metabolic diseases such as obesity and diabetes [1]. A number of tissue culture systems have been used to study lipotoxicity by supplementation of culture media with palmitate, which is a major saturated free fatty acid in human plasma and has been reported to induce apoptosis in various cell types [2]. Here we report that palmitate causes formation of binucleate cells as a consequence of cytokinetic impairment. Our results reveal a novel toxic effect of palmitate on cell division and extend the implication of lipotoxicity to cytokinetic failure.

  2. 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

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

    Science.gov (United States)

    Li, Miao

    2015-02-01

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

  4. 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...

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

    Science.gov (United States)

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

    2004-03-01

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

  6. 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.

  7. 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

  8. Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver

    Science.gov (United States)

    Schneider, Ana Claudia Reis; Gregório, Cleandra; Uribe-Cruz, Carolina; Guizzo, Ranieli; Malysz, Tais; Faccioni-Heuser, Maria Cristina; Longo, Larisse; da Silveira, Themis Reverbel

    2017-01-01

    AIM To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genes in zebrafish. METHODS Zebrafish (n = 104), wild type, adult, male and female, were divided into two groups: Control and ethanol (0.05 v/v). The ethanol was directly added into water; tanks water were changed every two days and the ethanol replaced. The animals were fed twice a day with fish food until satiety. After two and four weeks of trial, livers were dissected, histological analysis (hematoxilin-eosin and Oil Red staining) and gene expression assessment of adiponectin, adiponectin receptor 2 (adipor2), sirtuin-1 (sirt-1), tumor necrosis factor-alpha (tnf-a), interleukin-1b (il-1b) and interleukin-10 (il-10) were performed. Ultrastructural evaluations were conducted at fourth week. RESULTS Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks, as demonstrated by oil red staining. In ethanol-treated animals, the main ultrastructural changes were related to cytoplasmic lipid particles and droplets, increased number of rough endoplasmic reticulum cisterns and glycogen particles. Between two and four weeks, hepatic mRNA expression of il-1b, sirt-1 and adipor2 were upregulated, indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses. Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol, and il-10 did not show significant difference. CONCLUSION Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol. PMID:28357029

  9. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Lee-Chuan C.; Ford, Jeffery J. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); Lee, John C. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States); Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States)

    2014-07-18

    Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.

  10. Use of NHANES data to link chemical exposures to chronic diseases: a cautionary tale.

    Directory of Open Access Journals (Sweden)

    Judy S LaKind

    Full Text Available BACKGROUND: The National Health and Nutrition Examination Survey (NHANES is one example of cross-sectional datasets that have been used to draw causal inferences regarding environmental chemical exposures and adverse health outcomes. Our objectives were to analyze four NHANES datasets using consistent a priori selected methods to address the following questions: Is there a consistent association between urinary bisphenol A (BPA measures and diabetes, coronary heart disease (CHD, and/or heart attack across surveys? Is NHANES an appropriate dataset for investigating associations between chemicals with short physiologic half-lives such as BPA and chronic diseases with multi-factorial etiologies? Data on urinary BPA and health outcomes from 2003-2004, 2005-2006, 2007-2008, and 2009-2010 were available. METHODOLOGY AND FINDINGS: Regression models were adjusted for creatinine, age, gender, race/ethnicity, education, income, smoking, heavy drinking, BMI, waist circumference, calorie intake, family history of heart attack, hypertension, sedentary time, and total cholesterol. Urinary BPA was not significantly associated with adverse health outcomes for any of the NHANES surveys, with ORs (95% CIs ranging from 0.996 (0.951-1.04 to 1.03 (0.978-1.09 for CHD, 0.987 (0.941-1.04 to 1.04 (0.996-1.09 for heart attack, and 0.957 (0.899-1.02 to 1.01 (0.980-1.05 for diabetes. CONCLUSIONS: Using scientifically and clinically supportable exclusion criteria and outcome definitions, we consistently found no associations between urinary BPA and heart disease or diabetes. These results do not support associations and causal inferences reported in previous studies that used different criteria and definitions. We are not drawing conclusions regarding whether BPA is a risk factor for these diseases. We are stating the opposite--that using cross-sectional datasets like NHANES to draw such conclusions about short-lived environmental chemicals and chronic complex diseases is

  11. Chronic exposure to a neonicotinoid pesticide alters the interactions between bumblebees and wild plants.

    Science.gov (United States)

    Stanley, Dara A; Raine, Nigel E

    2016-07-01

    Insect pollinators are essential for both the production of a large proportion of world crops and the health of natural ecosystems. As important pollinators, bumblebees must learn to forage on flowers to feed both themselves and provision their colonies.Increased use of pesticides has caused concern over sublethal effects on bees, such as impacts on reproduction or learning ability. However, little is known about how sublethal exposure to field-realistic levels of pesticide might affect the ability of bees to visit and manipulate flowers.We observed the behaviour of individual bumblebees from colonies chronically exposed to a neonicotinoid pesticide (10 ppb thiamethoxam) or control solutions foraging for the first time on an array of morphologically complex wildflowers (Lotus corniculatus and Trifolium repens) in an outdoor flight arena.We found that more bees released from pesticide-treated colonies became foragers, and that they visited more L. corniculatus flowers than controls. Interestingly, bees exposed to pesticide collected pollen more often than controls, but control bees learnt to handle flowers efficiently after fewer learning visits than bees exposed to pesticide. There were also different initial floral preferences of our treatment groups; control bees visited a higher proportion of T. repens flowers, and bees exposed to pesticide were more likely to choose L. corniculatus on their first visit.Our results suggest that the foraging behaviour of bumblebees on real flowers can be altered by sublethal exposure to field-realistic levels of pesticide. This has implications for the foraging success and persistence of bumblebee colonies, but perhaps more importantly for the interactions between wild plants and flower-visiting insects and ability of bees to deliver the crucial pollination services to plants necessary for ecosystem functioning.

  12. Chronic cyclophosphamide exposure alters the profile of rat sperm nuclear matrix proteins.

    Science.gov (United States)

    Codrington, Alexis M; Hales, Barbara F; Robaire, Bernard

    2007-08-01

    Chronic exposure of male rats to the alkylating agent cyclophosphamide, a well-known male-mediated developmental toxicant, alters gene expression in male germ cells as well as in early preimplantation embryos sired by cyclophosphamide-exposed males. Sperm DNA is organized by the nuclear matrix into loop-domains in a sequence-specific manner. In somatic cells, loop-domain organization is involved in gene regulation. Various structural and functional components of the nuclear matrix are targets for chemotherapeutic agents. Consequently, we hypothesized that cyclophosphamide treatment would alter the expression of sperm nuclear matrix proteins. Adult male rats were treated for 4 wk with saline or cyclophosphamide (6.0 mg kg(-1) day(-1)), and the nuclear matrix was extracted from cauda epididymal sperm. Proteins were analyzed by two-dimensional gel electrophoresis. Identified proteins within the nuclear matrix proteome were mainly involved in cell structure, transcription, translation, DNA binding, protein processing, signal transduction, metabolism, cell defense, or detoxification. Interestingly, cyclophosphamide selectively induced numerous changes in cell defense and detoxification proteins, most notably, in all known forms of the antioxidant enzyme glutathione peroxidase 4, in addition to an uncharacterized 54-kDa form; an overall increase in glutathione peroxidase 4 immunoreactivity was observed in the nuclear matrix extracts from cyclophosphamide-exposed spermatozoa. An increase in glutathione peroxidase 4 expression suggests a role for this enzyme in maintaining nuclear matrix stability and function. These results led us to propose that a change in composition of the nuclear matrix in response to drug exposure was a factor in altered sperm function and embryo development.

  13. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

    Energy Technology Data Exchange (ETDEWEB)

    Saeed, Noha M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); El-Demerdash, Ebtehal [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Abdel-Rahman, Hanaa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); Algandaby, Mardi M. [Department of Biology (Botany), Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Al-Abbasi, Fahad A. [Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Abdel-Naim, Ashraf B., E-mail: abnaim@pharma.asu.edu.eg [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-10-01

    Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.

  14. Chronic exposure to nanosized, anatase titanium dioxide is not cyto- or genotoxic to Chinese hamster ovary cells.

    Science.gov (United States)

    Wang, Shuguang; Hunter, Lindsey A; Arslan, Zikri; Wilkerson, Michael G; Wickliffe, Jeffrey K

    2011-10-01

    Titanium dioxide nanoparticles (nano-TiO(2) ) are widely used in cosmetics, skin care products, paints, and water treatment processes. Disagreement remains regarding the safety of nano-TiO(2) , and little epidemiological data is available to provide needed resolution. Most studies have examined effects using acute exposure experiments with relatively few studies using a chronic exposure design. We examined cyto- and genotoxicity in CHO-K1 cells following 60 days of continuous exposure to defined levels of nano-TiO(2) (0, 10, 20, or 40 μg/ml). Oxidative stress increased in a concentration-dependent manner in short- (2 days) and long-term cultures, but long-term cultures had lower levels of oxidative stress. The primary reactive oxygen species appeared to be superoxide, and ROS indicators were lowered with the addition of superoxide dismutase (SOD). No cyto- or genotoxic effects were apparent using the XTT, trypan-blue exclusion, and colony-forming assays for viability and the Comet and Hprt gene mutation assays for genotoxicity. Nano-TiO(2) increased the percentage of cells in the G2/M phase of the cell cycle, but this effect did not appear to influence cell viability or cell division. Cellular Ti content was dose-dependent, but chronically exposed cells had lower amounts than acutely exposed cells. CHO cells appear to adapt to chronic exposure to nano-TiO(2) and detoxify excess ROS possibly through upregulation of SOD in addition to reducing particle uptake.

  15. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure.

    Science.gov (United States)

    Liu, Qing; Rise, Matthew L; Spitsbergen, Jan M; Hori, Tiago S; Mieritz, Mark; Geis, Steven; McGraw, Joseph E; Goetz, Giles; Larson, Jeremy; Hutz, Reinhold J; Carvan, Michael J

    2013-09-15

    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 (ngTCDD/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 (ngTCDD/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-regulated gene among each group based on microarray data, and their QPCR validations are consistent with microarray data for the 10 and 100 ppb TCDD treatment groups after 28 days exposure (pTCDD-responsive rainbow trout transcripts identified in the present study may lead to the development of new molecular biomarkers for assessing the potential impacts of

  16. Hair as a biological indicator of drug use, drug abuse or chronic exposure to environmental toxicants.

    Science.gov (United States)

    Boumba, Vassiliki A; Ziavrou, Kallirroe S; Vougiouklakis, Theodore

    2006-01-01

    In recent years hair has become a fundamental biological specimen, alternative to the usual samples blood and urine, for drug testing in the fields of forensic toxicology, clinical toxicology and clinical chemistry. Moreover, hair-testing is now extensively used in workplace testing, as well as, on legal cases, historical research etc. This article reviews methodological and practical issues related to the application of hair as a biological indicator of drug use/abuse or of chronic exposure to environmental toxicants. Hair structure and the mechanisms of drug incorporation into it are commented. The usual preparation and extraction methods as well as the analytical techniques of hair samples are presented and commented on. The outcomes of hair analysis have been reviewed for the following categories: drugs of abuse (opiates, cocaine and related, amphetamines, cannabinoids), benzodiazepines, prescribed drugs, pesticides and organic pollutants, doping agents and other drugs or substances. Finally, the specific purpose of the hair testing is discussed along with the interpretation of hair analysis results regarding the limitations of the applied procedures.

  17. 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.

  18. 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.

  19. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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.

  2. 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)

  3. 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.

  4. 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...

  5. Differential influences of Cu and Zn chronic exposure on Cd and Hg bioaccumulation in an estuarine oyster.

    Science.gov (United States)

    Liu, Fengjie; Wang, Wen-Xiong

    2014-03-01

    In this study, the effects of Cu and Zn exposure, alone and in combination, on the bioaccumulation of Cd and Hg were investigated in an estuarine oyster Crassostrea hongkongensis under different salinity gradients. We showed that Zn, but not Cu, exposure significantly enhanced the Cd bioaccumulation. In contrast, both Cu and Zn exposure significantly enhanced the Hg bioaccumulation. Combined exposure and salinity did not affect the metal interactions in oysters. The increased tissue concentrations of Cd or Hg were associated with their increased storage in inducible metal-binding ligands (e.g. metallothionein-like proteins, MTLP) by Cu/Zn exposure. The differential roles of Cu and Zn exposure in Cd and Hg bioaccumulation resulted from their contrasting ligand induction and affinities. Analysis of field collected oysters indicated that Cu/Zn exposure was a significant contributor to tissue concentrations of Cd, Cu and Hg. Overall, biochemical/physiological changes of the animals chronically exposed to metal stressors played a key role in affecting tissue concentrations of other metals. One metal's ability to enhance the bioaccumulation of other metals depended upon the relative affinities of the metals for MTLP.

  6. 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.

  7. 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

  8. 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.

  9. The Impact of Agent Orange Exposure on Presentation and Prognosis of Patients with Chronic Lymphocytic Leukemia (CLL)

    OpenAIRE

    Baumann Kreuziger, Lisa M.; Tarchand, Gobind; Morrison, Vicki A.

    2013-01-01

    Exposure to Agent Orange (AO) and the contaminating chemical 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) has been associated with the development of chronic lymphocytic leukemia (CLL). Of the195 veterans diagnosed with CLL from 2001–2010 in a retrospective cohort from the Minneapolis VA, 33 (17%) were exposed to AO. Prognostic factors including Rai stage, lymphocyte doubling time and cytogenetics did not differ between exposed and unexposed patients. Exposed patients were younger at diagnosis (61...

  10. Exposure-response analysis for beryllium sensitization and chronic beryllium disease among workers in a beryllium metal machining plant.

    Science.gov (United States)

    Madl, Amy K; Unice, Ken; Brown, Jay L; Kolanz, Marc E; Kent, Michael S

    2007-06-01

    The current occupational exposure limit (OEL) for beryllium has been in place for more than 50 years and was believed to be protective against chronic beryllium disease (CBD) until studies in the 1990s identified beryllium sensitization (BeS) and subclinical CBD in the absence of physical symptoms. Inconsistent sampling and exposure assessment methodologies have often prevented the characterization of a clear exposure-response relationship for BeS and CBD. Industrial hygiene (3831 personal lapel and 616 general area samples) and health surveillance data from a beryllium machining facility provided an opportunity to reconstruct worker exposures prior to the ascertainment of BeS or the diagnosis of CBD. Airborne beryllium concentrations for different job titles were evaluated, historical trends of beryllium levels were compared for pre- and postengineering control measures, and mean and upper bound exposure estimates were developed for workers identified as beryllium sensitized or diagnosed with subclinical or clinical CBD. Five approaches were used to reconstruct historical exposures of each worker: industrial hygiene data were pooled by year, job title, era of engineering controls, and the complete work history (lifetime weighted average) prior to diagnosis. Results showed that exposure metrics based on shorter averaging times (i.e., year vs. complete work history) better represented the upper bound worker exposures that could have contributed to the development of BeS or CBD. Results showed that beryllium-sensitized and CBD workers were exposed to beryllium concentrations greater than 0.2 microg/m3 (95th percentile), and 90% were exposed to concentrations greater than 0.4 microg/m3 (95th percentile) within a given year of their work history. Based on this analysis, BeS and CBD generally occurred as a result of exposures greater than 0.4 microg/m3 and maintaining exposures below 0.2 microg/m3 95% of the time may prevent BeS and CBD in the workplace.

  11. 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.

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

    Science.gov (United States)

    Huang, Chien-Yuan; Wu, Cheng-Long; Wu, Jin-Shang; Chang, Jung-Wei; Cheng, Ya-Yun; Kuo, Yau-Chang; Yang, Yi-Ching

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:26963719

  13. 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.

  14. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S. [Russian Inst. of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2000-05-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant <> for processing and temporary storage

  15. 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

  16. 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.

  17. 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

    2015-01-01

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

  18. Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol.

    Science.gov (United States)

    Crowley, Nicole A; Cody, Patrick A; Davis, Margaret I; Lovinger, David M; Mateo, Yolanda

    2014-02-01

    Dopamine (DA) plays an important role in integrative functions contributing to adaptive behaviors. In support of this essential function, DA modulates synaptic plasticity in different brain areas, including the striatum. Many drugs used for cognitive enhancement are psychostimulants, such as methylphenidate (MPH), which enhance DA levels. MPH treatment is of interest during adolescence, a period of enhanced neurodevelopment during which the DA system is in a state of flux. Recent epidemiological studies report the co-abuse of MPH and ethanol in adolescents and young adults. Although repeated MPH treatment produces enduring changes that affect subsequent behavioral responses to other psychostimulants, few studies have investigated the interactions between MPH and ethanol. Here we addressed whether chronic therapeutic exposure to MPH during adolescence predisposed mice to an altered response to ethanol and whether this was accompanied by altered DA release and striatal plasticity. C57BL/6J mice were administered MPH (3-6 mg/kg/day) via the drinking water between post-natal days 30 and 60. Voltammetry experiments showed that sufficient brain MPH concentrations were achieved during adolescence in mice to increase the DA clearance in adulthood. The treatment also increased long-term depression and reduced the effects of ethanol on striatal synaptic responses. Although the injection of 0.4 or 2 g/kg ethanol dose-dependently decreased locomotion in control mice, only the higher dose decreased locomotion in MPH-treated mice. These results suggested that the administration of MPH during development promoted long-term effects on synaptic plasticity in forebrain regions targeted by DA. These changes in plasticity might, in turn, underlie alterations in behaviors controlled by these brain regions into adulthood.

  19. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation.

    Science.gov (United States)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak

    2015-10-01

    A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100mGy and 1Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the level of mutation were found comparing different dose rates.

  20. 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...

  1. 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%.

  2. Patient-specific finite element analysis of chronic contact stress exposure after intraarticular fracture of the tibial plafond.

    Science.gov (United States)

    Li, Wendy; Anderson, Donald D; Goldsworthy, Jane K; Marsh, J Lawrence; Brown, Thomas D

    2008-08-01

    The role of altered contact mechanics in the pathogenesis of posttraumatic osteoarthritis (PTOA) following intraarticular fracture remains poorly understood. One proposed etiology is that residual incongruities lead to altered joint contact stresses that, over time, predispose to PTOA. Prevailing joint contact stresses following surgical fracture reduction were quantified in this study using patient-specific contact finite element (FE) analysis. FE models were created for 11 ankle pairs from tibial plafond fracture patients. Both (reduced) fractured ankles and their intact contralaterals were modeled. A sequence of 13 loading instances was used to simulate the stance phase of gait. Contact stresses were summed across loadings in the simulation, weighted by resident time in the gait cycle. This chronic exposure measure, a metric of degeneration propensity, was then compared between intact and fractured ankle pairs. Intact ankles had lower peak contact stress exposures that were more uniform and centrally located. The series-average peak contact stress elevation for fractured ankles was 38% (p = 0.0015; peak elevation was 82%). Fractured ankles had less area with low contact stress exposure than intact ankles and a greater area with high exposure. Chronic contact stress overexposures (stresses exceeding a damage threshold) ranged from near zero to a high of 18 times the matched intact value. The patient-specific FE models represent substantial progress toward elucidating the relationship between altered contact stresses and the outcome of patients treated for intraarticular fractures.

  3. 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.

  4. 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.

  5. 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

  6. Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar-endothelial co-cultures

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Jacobsen, Nicklas Raun;

    2016-01-01

    Free palmitic acid (PA) is a potential pro-atherogenic stimulus that may aggravate particle-mediated cardiovascular health effects. We hypothesized that the presence of PA can aggravate oxidative stress and endothelial activation induced by multi-walled carbon nanotube (MWCNT) exposure in vitro. We...

  7. Palmitate binding to serum albumin, measured by rate of dialysis

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B; Andersen, S

    1988-01-01

    with binding of the unsaturated acids is less pronounced. Chloride ions compete with binding of palmitate. Reserve albumin concentration in serum samples from 33 male adults was 420 +/- 59 microM (mean +/- SD), and in 33 females, 351 +/- 50 microM. Umbilical cord sera from ten newborn infants averaged 172......Dialysis experiments were performed with an acetylcellulose membrane between two identical sample solutions; a trace amount of radiolabelled palmitate was added on one side and the rate of dialytic equilibration of the label was measured. By comparison with rates measured in standard experiments......, using pure albumin solutions, we obtained the reserve albumin concentration for binding of palmitate, previously defined as the concentration of a pure standard albumin which binds the labelled ligand as tightly as it is bound in the sample. Two techniques were developed, one for 1-ml sample volumes...

  8. Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium.

    Science.gov (United States)

    Walker, Robert J; Leader, John P; Bedford, Jennifer J; Gobe, Glenda; Davis, Gerard; Vos, Frederiek E; deJong, Sylvia; Schollum, John B W

    2013-02-01

    There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-β(1) expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury in this model will provide a greater understanding of chronic interstitial fibrosis and allow the development of intervention strategies to prevent injury.

  9. Possible Involvement of Palmitate in Pathogenesis of Periodontitis.

    Science.gov (United States)

    Shikama, Yosuke; Kudo, Yasusei; Ishimaru, Naozumi; Funaki, Makoto

    2015-12-01

    Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been suggested to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. In this study, we showed that gingival fibroblasts have cell-surface expression of CD36, which is also known as FAT/fatty acid translocase. Moreover, CD36 expression was increased in gingival fibroblasts of high-fat diet-induced T2D model mice, compared with gingival fibroblasts of mice fed a normal diet. DNA microarray analysis revealed that palmitate increased mRNA expression of pro-inflammatory cytokines and chemokines in human gingival fibroblasts (HGF). Consistent with these results, we confirmed that palmitate-induced interleukin (IL)-6, IL-8, and CXCL1 secretion in HGF, using a cytokine array and ELISA. SFAs, but not an unsaturated fatty acid, oleate, induced IL-8 production. Docosahexaenoic acid (DHA), which is one of the omega-3 polyunsaturated fatty acids, significantly suppressed palmitate-induced IL-6 and IL-8 production. Treatment of HGF with a CD36 inhibitor also inhibited palmitate-induced pro-inflammatory responses. Finally, we demonstrated that Porphyromonas gingivalis (P.g.) lipopolysaccharide and heat-killed P.g. augmented palmitate-induced chemokine secretion in HGF. These results suggest a potential link between SFAs in plasma and the pathogenesis of periodontitis.

  10. 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.)

  11. 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

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

    Science.gov (United States)

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

    2010-07-01

    The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 microg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI 50 microg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1-3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20-45 years.

  13. Skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin A palmitate.

    Science.gov (United States)

    Gaspar, Lorena R; Tharmann, Julian; Maia Campos, Patricia M B G; Liebsch, Manfred

    2013-02-01

    The aim of this study was to evaluate the in vitro skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin A palmitate, assessed by two in vitro techniques: 3T3 Neutral Red Uptake Phototoxicity Test and Human 3-D Skin Model In Vitro Phototoxicity Test. For this, four different formulations containing vitamin A palmitate and different UV-filters combinations, two of them considered photostable and two of them considered photounstable, were prepared. Solutions of each UV-filter and vitamin under study and solutions of four different combinations under study were also prepared. The phototoxicity was assessed in vitro by the 3T3 NRU phototoxicity test (3T3-NRU-PT) and subsequently in a phototoxicity test on reconstructed human skin model (H3D-PT). Avobenzone presented a pronounced phototoxicity and vitamin A presented a tendency to a weak phototoxic potential. A synergistic effect of vitamin A palmitate on the phototoxicity of combinations containing avobenzone was observed. H3D-PT results did not confirm the positive 3T3-NRU-PT results. However, despite the four formulations studied did not present any acute phototoxicity potential, the combination 2 containing octyl methoxycinnamate (OMC), avobenzone (AVB) and 4-methylbenzilidene camphor (MBC) presented an indication of phototoxicity that should be better investigated in terms of the frequency of photoallergic or chronic phototoxicity in humans, once these tests are scientifically validated only to detect phototoxic potential with the aim of preventing phototoxic reactions in the general population, and positive results cannot predict the exact incidence of phototoxic reactions in humans.

  14. 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.

  15. 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.

  16. Chronic ZnO-NPs exposure at environmentally relevant concentrations results in metabolic and locomotive toxicities in Caenorhabditis elegans.

    Science.gov (United States)

    Huang, Chi-Wei; Li, Shang-Wei; Hsiu-Chuan Liao, Vivian

    2017-01-01

    ZnO nanoparticles (ZnO-NPs) are emerging contaminants that raise the concerns of potential risk in the aquatic environment. It has been estimated that the environmental ZnO-NPs concentration is 76 μg/l in the aquatic environment. Our aim was to determine the aquatic toxicity of ZnO-NPs with chronic exposure at environmentally relevant concentrations using the nematode Caenorhabditis elegans. Two simulated environmentally relevant mediums-moderately hard reconstituted water (EPA water) and simulated soil pore water (SSPW)-were used to represent surface water and pore water in sediment, respectively. The results showed that the ZnO-NPs in EPA water has a much smaller hydrodynamic diameter than that in SSPW. Although the ionic release of Zn ions increased time-dependently in both mediums, the Zn ions concentrations in EPA water increased two-fold more than that in SSPW at 48 h and 72 h. The ZnO-NPs did not induce growth defects or decrease head thrashes in C. elegans in either media. However, chronic exposure to ZnO-NPs caused a significant reduction in C. elegans body bends in EPA water even with a relatively low concentration (0.05 μg/l); similar results were not observed in SSPW. Moreover, at the same concentrations (50 and 500 μg/l), body bends in C. elegans were reduced more severely in ZnO-NPs than in ZnCl2 in EPA water. The ATP levels were consistently and significantly decreased, and ROS was induced after ZnO-NPs exposure (50 and 500 μg/l) in EPA water. Our results provide evidences that chronic exposure to ZnO-NPs under environmentally relevant concentrations causes metabolic and locomotive toxicities implicating the potential ecotoxicity of ZnO-NPs at low concentrations in aquatic environments.

  17. 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).

  18. 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

  19. Aflatoxin exposure may contribute to chronic hepatomegaly in Kenyan school children

    DEFF Research Database (Denmark)

    Gong, Yun Yun; Wilson, Shona; Mwatha, Joseph K;

    2012-01-01

    Presentation with a firm type of chronic hepatomegaly of multifactorial etiology is common among school-age children in sub-Saharan Africa.......Presentation with a firm type of chronic hepatomegaly of multifactorial etiology is common among school-age children in sub-Saharan Africa....

  20. 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.

  1. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    Science.gov (United States)

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

  7. 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.

  8. Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells.

    Science.gov (United States)

    Lubovac-Pilav, Zelmina; Borràs, Daniel M; Ponce, Esmeralda; Louie, Maggie C

    2013-01-01

    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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Biosysthesis of Corn Starch Palmitate by Lipase Novozym 435

    Directory of Open Access Journals (Sweden)

    Kai Lin

    2012-06-01

    Full Text Available Esterification of starch was carried out to expand the usefulness of starch for a myriad of industrial applications. Lipase B from Candida antarctica, immobilized on macroporous acrylic resin (Novozym 435, was used for starch esterification in two reaction systems: micro-solvent system and solvent-free system. The esterification of corn starch with palmitic acid in the solvent-free system and micro-solvent system gave a degree of substitution (DS of 1.04 and 0.0072 respectively. Esterification of corn starch with palmitic acid was confirmed by UV spectroscopy and IR spectroscopy. The results of emulsifying property analysis showed that the starch palmitate with higher DS contributes to the higher emulsifying property (67.6% and emulsion stability (79.6% than the native starch (5.3% and 3.9%. Modified starch obtained by esterification that possesses emulsifying properties and has long chain fatty acids, like palmitic acid, has been widely used in the food, pharmaceutical and biomedical applications industries.

  15. 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

  16. Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

    Directory of Open Access Journals (Sweden)

    Hovsepyan Meri

    2010-09-01

    Full Text Available Abstract Background Stearoyl-CoA desaturase 1 (SCD1 is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knockout of SCD1 in mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity. Inhibition of SCD1 has therefore been proposed as a potential therapy of the metabolic syndrome. Much of the work has focused on insulin target tissue and very little is known about how reduced levels of SCD1 would affect the insulin-producing β-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the β-cell. Results Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knockdown. When fatty acid oxidation was measured, no difference between cells with reduced levels of SCD1 and mock-transfected cells were found. Also, reducing levels of SCD1 did not affect insulin secretion in response to glucose. To investigate how SCD1 knockdown affected cellular mechanisms, differentially regulated proteins were identified by a proteomic approach. Cells with reduced levels of SCD1 had higher levels of ER chaperones and components of the proteasome. The higher amounts did not protect the β-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2α and CHOP after palmitate exposure was 2-fold higher in cells with reduced levels of SCD1 compared to mock-transfected cells. Accordingly, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells. Conclusions In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the β-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.

  17. 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...

  18. 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.

  19. Upregulation of CB₁ receptor binding in the ventromedial prefrontal cortex promotes proactive stress-coping strategies following chronic stress exposure.

    Science.gov (United States)

    McLaughlin, R J; Hill, M N; Dang, S S; Wainwright, S R; Galea, L A M; Hillard, C J; Gorzalka, B B

    2013-01-15

    Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB(1) receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB(1) receptor binding site density in the PFC. Our goal in these studies was to examine the effects of CUS on the density of CB(1) receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB(1) receptor maximal binding site density (B(max)) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB(1) receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB(1) receptor antagonist AM251 prior to swim stress. Moreover, local CB(1) receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB(1) receptor B(max) observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.

  20. Chronic Inorganic Arsenic Exposure In Vitro Induces a Cancer Cell Phenotype in Human Peripheral Lung Epithelial Cells

    Science.gov (United States)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J.

    2015-01-01

    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. PMID:25804888

  1. 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.

  2. 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.

  3. MRI characterization of structural mouse brain changes in response to chronic exposure to the glufosinate ammonium herbicide.

    Science.gov (United States)

    Meme, Sandra; Calas, André-Guilhem; Montécot, Céline; Richard, Oliver; Gautier, Hélène; Gefflaut, Thierry; Doan, Bich Thuy; Même, William; Pichon, Jacques; Beloeil, Jean-Claude

    2009-10-01

    Glufosinate ammonium (GLA) is the active component of herbicides widely used in agriculture, truck farming, or public domains. GLA acts by inhibiting the plant glutamine synthetase (GlnS). It also inhibits mammalian GlnS in vitro and ex vivo. In the central nervous system this enzyme is exclusively localized in glial cells. Whereas acute neurotoxic effects of GLA are well documented, long-term effects during chronic exposure at low doses remain largely undisclosed. In the present work, C57BL/6J mice were treated intraperitoneally with 2.5, 5, and 10 mg/kg of GLA three times a week during 10 weeks. Cerebral magnetic resonance imaging (MRI) experiments were performed at high field (9.4 T) and the images were analyzed with four texture analysis (TA) methods. TA highlighted structural changes in seven brain structures after chronic GLA treatments. Changes are dose dependent and can be seen at a dose as low as 2.5 mg/kg for two areas, namely hippocampus and somatosensorial cortex. Glial fibrillary acidic protein (GFAP) expression in the same seven brain structures and GlnS activity in the hippocampus and cortex areas were also studied. The number of GFAP-positive cells is modified in six out of the seven areas examined. GlnS activity was significantly increased in the hippocampus but not in the cortex. These results indicate some kind of suffering at the cerebral level after chronic GLA treatment. Changes in TA were compared with the modification of the number of GFAP-positive astrocytes in the studied brain areas after GLA treatment. We show that the noninvasive MRI-TA is a sensitive method and we suggest that it would be a very helpful tool that can efficiently contribute to the detection of cerebral alterations in vivo during chronic exposure to xenobiotics.

  4. Manipulating catalytic pathways: deoxygenation of palmitic acid on multifunctional catalysts.

    Science.gov (United States)

    Peng, Baoxiang; Zhao, Chen; Kasakov, Stanislav; Foraita, Sebastian; Lercher, Johannes A

    2013-04-08

    The mechanism of the catalytic reduction of palmitic acid to n-pentadecane at 260 °C in the presence of hydrogen over catalysts combining multiple functions has been explored. The reaction involves rate-determining reduction of the carboxylic group of palmitic acid to give hexadecanal, which is catalyzed either solely by Ni or synergistically by Ni and the ZrO2 support. The latter route involves adsorption of the carboxylic acid group at an oxygen vacancy of ZrO2 and abstraction of the α-H with elimination of O to produce the ketene, which is in turn hydrogenated to the aldehyde over Ni sites. The aldehyde is subsequently decarbonylated to n-pentadecane on Ni. The rate of deoxygenation of palmitic acid is higher on Ni/ZrO2 than that on Ni/SiO2 or Ni/Al2O3, but is slower than that on H-zeolite-supported Ni. As the partial pressure of H2 is decreased, the overall deoxygenation rate decreases. In the absence of H2, ketonization catalyzed by ZrO2 is the dominant reaction. Pd/C favors direct decarboxylation (-CO2), while Pt/C and Raney Ni catalyze the direct decarbonylation pathway (-CO). The rate of deoxygenation of palmitic acid (in units of mmol moltotal metal(-1) h(-1)) decreases in the sequence r(Pt black) ≈r(Pd black) >r(Raney Ni) in the absence of H2 . In situ IR spectroscopy unequivocally shows the presence of adsorbed ketene (C=C=O) on the surface of ZrO2 during the reaction with palmitic acid at 260 °C in the presence or absence of H2.

  5. NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

    Science.gov (United States)

    This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult rats were maintained on a chlorpyrifos-containing diet to p...

  6. 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.

    2016-01-01

    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, 10 mg/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 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/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 exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. PMID:26440580

  7. 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.

  8. Effects of chronic produced water exposure on the expression of some immune-related genes of juvenile Atlantic cod

    Energy Technology Data Exchange (ETDEWEB)

    Perez Casanova, J.; Hamoutene, D.; Samuelson, S.; Burt, K.; King, T. [Fisheries and Oceans Canada, St. John' s, NL (Canada); Lee, K. [Fisheries and Oceans Canada, Dartmouth, NS (Canada)

    2010-07-01

    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.

  9. 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.

  10. Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure.

    Science.gov (United States)

    Lear, Christopher A; Davidson, Joanne O; Booth, Lindsea C; Wassink, Guido; Galinsky, Robert; Drury, Paul P; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair J

    2014-08-15

    Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg(-1)·24 h(-1) for a further 96 h) or the same volume of saline (n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV.

  11. Transcriptome Profiling of the Lungs Reveals Molecular Clock Genes Expression Changes after Chronic Exposure to Ambient Air Particles

    Science.gov (United States)

    Song, Pengcheng; Li, Zhigang; Li, Xiaoqian; Yang, Lixin; Zhang, Lulu; Li, Nannan; Guo, Chen; Lu, Shuyu; Wei, Yongjie

    2017-01-01

    The symptoms of asthma, breathlessness, insomnia, etc. all have relevance to pulmonary rhythmic disturbances. Epidemiology and toxicology studies have demonstrated that exposure to ambient air particles can result in pulmonary dysfunction. However, there are no data directly supporting a link between air pollution and circadian rhythm disorder. In the present study, we found that breathing highly polluted air resulted in changes of the molecular clock genes expression in lung by transcriptome profiling analyses in a rodent model. Compared to those exposed to filtered air, in both pregnant and offspring rats in the unfiltered group, key clock genes (Per1, Per2, Per3, Rev-erbα and Dbp) expression level decreased and Bmal1 expression level increased. In both rat dams and their offspring, after continuous exposure to unfiltered air, we observed significant histologic evidence for both perivascular and peribronchial inflammation, increased tissue and systemic oxidative stress in the lungs. Our results suggest that chronic exposure to particulate matter can induce alterations of clock genes expression, which could be another important pathway for explaining the feedbacks of ambient particle exposure in addition to oxidative stress and inflammation. PMID:28106813

  12. 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.

  13. 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.

  14. 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.

  15. Transcriptome Profiling of the Lungs Reveals Molecular Clock Genes Expression Changes after Chronic Exposure to Ambient Air Particles

    Directory of Open Access Journals (Sweden)

    Pengcheng Song

    2017-01-01

    Full Text Available The symptoms of asthma, breathlessness, insomnia, etc. all have relevance to pulmonary rhythmic disturbances. Epidemiology and toxicology studies have demonstrated that exposure to ambient air particles can result in pulmonary dysfunction. However, there are no data directly supporting a link between air pollution and circadian rhythm disorder. In the present study, we found that breathing highly polluted air resulted in changes of the molecular clock genes expression in lung by transcriptome profiling analyses in a rodent model. Compared to those exposed to filtered air, in both pregnant and offspring rats in the unfiltered group, key clock genes (Per1, Per2, Per3, Rev-erbα and Dbp expression level decreased and Bmal1 expression level increased. In both rat dams and their offspring, after continuous exposure to unfiltered air, we observed significant histologic evidence for both perivascular and peribronchial inflammation, increased tissue and systemic oxidative stress in the lungs. Our results suggest that chronic exposure to particulate matter can induce alterations of clock genes expression, which could be another important pathway for explaining the feedbacks of ambient particle exposure in addition to oxidative stress and inflammation.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Cytobiologic and clinical aspects in a patient with chronic neutrophilic leukemia after thorotrast exposure

    Energy Technology Data Exchange (ETDEWEB)

    Boggs, D.R.; Kaplan, S.S.

    1986-11-01

    A patient with fairly typical chronic neutrophilic leukemia, as represented by some two dozen such reported cases, had been given Thorotrast more than 20 years before. Typical myeloblastic crisis developed with remarkable terminal leukocytosis. Mature blood neutrophils had normal function with respect to phagocytosis, bacterial killing, metabolic activation, and chemotactic response. The number of cells producing colonies of neutrophils and monocytes in in vitro semisolid cultures was normal in the blood and increased in marrow. Colony size was smaller than is usually observed in normal patients or in typical patients with chronic myeloid leukemia. Termination in blast crisis, also seen in a few other patients with chronic neutrophilic leukemia, indicates that this is indeed a form of leukemia and not a leukemoid reaction of obscure cause. The differential diagnosis of extreme neutrophilia is discussed.

  1. 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.

  2. Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

    Science.gov (United States)

    Virgolini, Miriam B; Chen, Kevin; Weston, Doug D; Bauter, Mark R; Cory-Slechta, Deborah A

    2005-10-01

    Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.

  3. Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

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    Golam Mohammod Mostakim

    2015-01-01

    Full Text Available Quinalphos (QP is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p<0.05 at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations.

  4. 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.

  5. 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.

  6. 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.

  7. Genotoxic and cell-transformation effects of multi-walled carbon nanotubes (MWCNT) following in vitro sub-chronic exposures.

    Science.gov (United States)

    Vales, Gerard; Rubio, Laura; Marcos, Ricard

    2016-04-05

    BEAS-2B cells were sub-chronically exposed (up to 4 weeks) to low doses of multi-walled carbon nanotubes (MWCNT, NM403). Genotoxic effects were evaluated using the comet and the micronucleus (MN) assays at three different time-points. The expression of different interleukins (IL) such as IL-1B, IL-6 and IL-8, as well as HO-1 as stress marker, was assessed after 3 weeks treatments. As a hallmark biomarker of cell-transforming ability we used the soft-agar assay, which detects anchorage-independent cell growth. Our results show high levels of intracellular reactive oxygen species (ROS) associated to MWCNT exposure. Nevertheless, an important proportion of these ROS levels seems to be associated to solubilized metals contaminants present in NM403, more than to the internalized MWCNT. No primary DNA damage was obtained in the Comet assay although significant levels of chromosome damage were detected using the micronucleus assay. A significant decrease in the expression of the studied cytokines was observed and significant increases in the number of induced colonies were obtained when the ability of induce anchorage-independent growth was determined. These results show that chromosome damage and reducing inflammatory signalling correlated with an increase in attachment-independent growth associated with sub-chronic MWCNT exposure.

  8. 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.

  9. Chronic toxicity of arsenic, cobalt, chromium and manganese to Hyalella azteca in relation to exposure and bioaccumulation

    Energy Technology Data Exchange (ETDEWEB)

    Norwood, W.P. [Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1 (Canada) and Aquatic Ecosystems Protection Research Division, Environment Canada, P.O. Box 5050, Burlington, ON L7R 4A6 (Canada)]. E-mail: warren.norwood@ec.gc.ca; Borgmann, U. [Aquatic Ecosystems Protection Research Division, Environment Canada, P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Dixon, D.G. [Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1 (Canada)

    2007-05-15

    Chronic toxicity of As, Co, Cr and Mn to Hyalella azteca can be described using a saturation-based mortality model relative to total-body or water metal concentration. LBC25s (total-body metal concentrations resulting in 25% mortality in 4 weeks) were 125, 103, 152 and 57,900 nmol g{sup -1} dry weight for As, Co, Cr and Mn respectively. LC50s (metal concentrations in water resulting in 25% mortality in 4 weeks) were 5600, 183, 731, and 197,000 nmol L{sup -1}, respectively. A hormesis growth response to As exposure was observed. Growth was a more variable endpoint than mortality for all four toxicants; however, confidence limits based on growth and mortality all overlapped, except Cr which had no effect on growth. Mn toxicity was greater in glass test containers compared to plastic. Bioaccumulation of As, Co, Cr, and Mn was strongly correlated with, and is useful for predicting, chronic mortality. - Chronic toxicity of As, Co, Cr and Mn to Hyalella azteca can be described using a saturation-based mortality model in relationship to total-body or water metal concentration.

  10. Biochemical Changes in the Serum of Patients with Chronic Toxigenic Mold Exposures: A Risk Factor for Multiple Renal Dysfunctions

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    Ebere Anyanwu

    2003-01-01

    Full Text Available This paper analyzes and presents the biochemical abnormalities in the sera of patients presenting with chronic mycosis in order to investigate the relationship with the risks of multiple renal disorders. The study population (n = 10 consisted of six females and four males (mean age 36.3 years exposed by toxic molds in their homes and offices for an average of 2.8 years. The control group comprised ten people, five males and five females (mean age 35.9 years without any known exposures to toxic molds. Blood samples were obtained from both the patients and the controls and were processed using specific biochemical methods that included enzyme-linked immunoabsorbent assay (ELISA. There were biochemical abnormal concentrations in creatinine, uric acid, phosphorus, alkaline phosphotase, cholesterol, HDH, SGOT/AST, segmented neutrophils, lymphocytes, total T3, IgG and IgA immunoglobulins with significant differences between patients and controls. These abnormalities were consistent with multiple renal disorders. The major complaints of the mycosis patients were headaches, pulmonary symptoms, allergic reactions, memory loss, skin rashes, blurred vision symptoms, fatigue, and runny nose. These findings were depictive of a strong association of chronic mycosis with abnormal renal indicators. It was concluded that, although this research was a pilot investigation, based on the overall results, people exposed to chronic indoor environmental toxic molds were at risk of multiple renal complications.

  11. 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.

  12. 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.

  13. Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

    NARCIS (Netherlands)

    Morissette, Mathieu C; Gao, Yang; Shen, Pamela; Thayaparan, Danya; Bérubé, Jean-Christophe; Paré, Peter D; Brandsma, Corry-Anke; Hao, Ke; Bossé, Yohan; Ettinger, Rachel; Herbst, Ronald; Humbles, Alison A; Kolbeck, Roland; Zhong, Nanshan; Chen, Rongchang; Stämpfli, Martin R

    2016-01-01

    Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and ma

  14. Renal effects of chronic exposure to organic solvents. A clinical controlled trial

    DEFF Research Database (Denmark)

    Krusell, Lars Romer; Nielsen, H K; Bælum, Jesper;

    1985-01-01

    Chronic effects of organic solvents on renal function were measured by creatinine clearances and urinary excretion rates of beta 2-microglobulin and albumin. Forty-three male printing trade workers occupationally exposed to different organic solvents for 9-25 years were compared with 43 age-match...

  15. The 73 kilodalton heat shock cognate protein purified from rat brain contains nonesterified palmitic and stearic acids.

    Science.gov (United States)

    Guidon, P T; Hightower, L E

    1986-08-01

    A protein related to the 71 kilodalton inducible rat heat shock protein was purified to electrophoretic homogeneity in milligram amounts from brain tissue of nonheat-stressed rats. The protein has been designated as a stress cognate protein based on previous studies and data presented herein that this protein cross-reacted with a monoclonal antibody originally raised against the Drosophila 70 kilodalton heat shock protein. The purified protein had an apparent molecular mass of 73 kilodaltons when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and an apparent mass of 150 kilodaltons as determined by nondissociative gel chromatography, suggesting that the purified protein is a homodimer. The purified protein had isoelectric points of 5.0 under nondissociative conditions and 5.6 when exposed to protein denaturants, suggesting loss of bound anionic molecules and/or net exposure of basic residues upon denaturation. Chloroform/methanol extraction of the purified protein and subsequent analyses by thin layer and gas-liquid chromatography resulted in the identification of palmitic and stearic acids noncovalently bound to the protein. Approximately four molecules of fatty acids were bound per dimer with palmitic and stearic acids present in a one-to-one ratio. The purified protein did not bind exogenously added radioactive palmitate, indicating that the fatty acid-binding sites of the cognate protein were fully occupied and that the associated fatty acids were too tightly bound to exchange readily. The possible significance of the fatty acids associated with the 73 kilodalton stress cognate protein is discussed.

  16. Mercury accumulation and its distribution to metallothionein in mouse brain after sub-chronic pulse exposure to mercury vapor

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Sawada, M.; Shimada, A. [Department of Veterinary Pathology, Tottori University, 4-101 Koyamacho, Minami, Tottori 680-0945 (Japan); Satoh, M. [Department of Hygienics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585 (Japan); Tohyama, C. [Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)

    2004-09-01

    Previously we found that exposure to mercury vapor effectively induced metallothionein (MT) biosynthesis in rat brain. Although the induction of not only MT-I/II but also MT-III was evident, the induction rate of the latter was much lower than that of the former. The brain of an MT-null mouse lacks MT-I/II, but has MT-III. Here we examined the effects of sub-chronic pulse exposure to mercury vapor on the brain MT in MT-null mice and their wild type controls. MT-null and wild type mice were preliminarily exposed to mercury vapor for 2 weeks at 0.1 mg Hg/m{sup 3} for 1 h/day for 3 days a week, and then exposed for 11 weeks at 4.1 mg Hg/m{sup 3} for 30 min/day for 3 days a week. This exposure caused no toxic signs such as abnormal behavior or loss of body weight gain in the mice of either strain throughout the experimental period. Twenty-four hours after the termination of the exposure, mice were sacrificed and brain samples were subjected to mercury analysis, MT assay, and pathological examination. The MT-null mice showed lower accumulation of mercury in the brain than the wild type mice. Mercury exposure resulted in a 70% increase of brain MT in the wild type mice, which was mostly accounted for by the increase in MT-I/II. On the other hand, the brain MT in the MT-null mice increased by 19%, suggesting less reactivity of the MT-III gene to mercury vapor. Although histochemical examination revealed silver-mercury grains in the cytoplasm of nerve cells and glial cells throughout the brains of both strains, no significant difference was observed between the two strains. (orig.)

  17. 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.

  18. 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.

  19. Effects from offshore oil production: chronic exposure of fish to produced water

    Energy Technology Data Exchange (ETDEWEB)

    Holth, Tor Fredrik

    2009-07-01

    The results of this study demonstrated that environmentally relevant levels of components of produced water may affect condition factor, maturation, biochemical processes and gene expression in fish. The usefulness of bile PAH and AP metabolite measurements to evaluate exposure was demonstrated in two fish species. The development of bio marker responses was shown to depend on exposure regime as well as exposure period. Lysosomal stability (LMS) in cod kidney was related to dose, the effects were observed early (within two weeks) and remained at a stable level throughout the exposure period in fish receiving both continuous and pulsed exposure. Thus, LMS appeared to be a useful marker for effects in Atlantic cod. Formation of DNA adducts in female cod liver was also related to dose, but in contrast to LMS, more than 16 weeks was required for formation of significant levels. This parameter may therefore be underestimated following short-term exposures, such as most offshore fish caging studies (often 4-6 weeks). Although a time-dependent increase was observed, it also required a continuous exposure regime, which is not often observed in the environment. Other bio markers were demonstrated either to adapt or appeared to be insensitive to the exposures. CYP1A activity (EROD) in female cod was responsive on occasion, but a reduction of activity over time was observed. Protein levels of vitellogenin and hepatic CYP1A in zebra fish, as well as AOX in cod kidneys, were not affected in the current study. Gene transcription of several distinct cellular mechanisms was clearly affected in both species, and a predominance of differentially expressed genes in zebra fish was down regulated. This indicated that down-regulation of responsive pathways may be as important or more important than up-regulation. As both presence and absence of effects following pulsed exposure were apparent (DNA adduct formation; oocyte maturation; condition factor), the effects of exposure regime on

  20. A case of paliperidone-palmitate-induced tardive dyskinesia.

    LENUS (Irish Health Repository)

    Lally, John

    2012-06-13

    OBJECTIVES: This is one of the first cases reported in the literature of paliperidone-palmitate-induced prolonged dyskinesia. METHOD: Case report. RESULTS: We report the case of a 49-year-old woman with paranoid schizophrenia who developed orofacial dyskinesia some 4 months after the commencement of paliperidone long-acting injection. CONCLUSION: This case serves as a clinical reminder that dyskinesia can occur with all antipsychotic medications.

  1. Recent and chronic exposure of wild ducks to lead in human-modified wetlands in Santa Fe Province, Argentina.

    Science.gov (United States)

    Ferreyra, Hebe; Romano, Marcelo; Uhart, Marcela

    2009-07-01

    Poisoning of waterfowl due to ingestion of lead pellets is a worldwide problem in areas that are subject to hunting. No studies have assessed exposure of waterbirds to this heavy metal in Argentina, in spite of intense hunting activity, and the fact that only lead ammunition is commercially available. The objective of this study was to evaluate duck exposure to lead by examining gizzard and bone samples collected from 30 wild ducks, 16 Rosy-billed Pochard (Netta peposaca), and 14 Fulvous Whistling-Duck (Dendrocygna bicolor), provided by hunters in northern Santa Fe Province, Argentina, in July 2007. Radiographs, followed by dissection of the gizzards, showed that 31% of the Rosy-billed Pochards and 29% of the Fulvous Whistling-Ducks had ingested lead pellets (between one and four per animal). Lead in bone was found at concentrations associated with detrimental health effects. In spite of the small number of samples in this project, these results indicate high levels of lead exposure (both recent and chronic) in these species. This is the first report of a problem in Argentina that could represent a threat to the health and conservation of native aquatic species, their predators, and the wetlands they inhabit.

  2. Acute cold- and chronic heat-exposure upregulate hepatic leptin and muscle uncoupling protein (UCP) gene expression in broiler chickens.

    Science.gov (United States)

    Dridi, Sami; Temim, Soraya; Derouet, Michel; Tesseraud, Sophie; Taouis, Mohammed

    2008-08-01

    Emerging evidence showed that variations in environmental temperature affect both leptin and uncoupling protein (UCP) gene expression in mammals, whereas a little is known about such interactions in birds. Thus, we conducted the present study to investigate the influence of acute (2 hours) cold (4 degrees C) and chronic (10 days) heat (32 degrees C) exposure on hepatic leptin and muscle UCP gene expression in 5-wk-old broiler chickens. Both cold- and heat-exposure significantly (P < 0.05 to P < 0.001) upregulated hepatic leptin (by 35 and 46%, respectively) and muscle UCP mRNA levels (by 71 and 71%, respectively) compared to the thermoneutrality (22 degrees C). This result suggests that leptin and UCP may be involved in the thermoregulation response of chickens to extreme climate (cold and hot temperatures). The upregulation of hepatic leptin gene expression was accompanied by an increase in plasma leptin levels, indicating that leptin may be regulated at transcriptional level. The increase of leptin and UCP mRNA abundance, and leptinemia we report here were not related to plasma glucose or insulin levels. In conclusion, the exposure of broiler chickens to extreme ambient temperatures (cold and heat) increases hepatic leptin and muscle UCP gene expression.

  3. The effect of chronic cocaine exposure throughout pregnancy on maternal and infant outcomes in the rhesus monkey.

    Science.gov (United States)

    Morris, P; Binienda, Z; Gillam, M P; Klein, J; McMartin, K; Koren, G; Duhart, H M; Slikker, W; Paule, M G

    1997-01-01

    To explore the effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were either treated (N = 10) with escalating doses of cocaine up to 7.5 mg/kg (IM), three times per day, 5 consecutive days per week, prior to conception and throughout gestation, or were not treated (N = 10) with cocaine at all. Substantial levels of both cocaine and its major metabolite, benzoylecgonine, were observed in samples of hair taken at birth from mothers and infants of the cocaine-treated group. Despite these differences in cocaine exposure, the experimental groups did not differ significantly with respect to maternal outcome, as measured by body weight again during pregnancy and length of pregnancy. On the other hand, the experimental groups did differ significantly with respect to infant outcome, as measured at birth by body weight, overall length, and crown circumference, all of which were decreased in the cocaine-treated group. A variety of reflexes tested at birth were normal in the cocaine-treated group. It was concluded that, in a rhesus monkey model, chronic cocaine exposure throughout pregnancy had no significant effect on maternal outcome, but did significantly affect infant outcome as assessed in this investigation.

  4. Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans

    Science.gov (United States)

    Gangemi, Silvia; Miozzi, Edoardo; Teodoro, Michele; Briguglio, Giusi; De Luca, Annamaria; Alibrando, Carmela; Polito, Irene; Libra, Massimo

    2016-01-01

    It is well known that pesticides are widely used compounds. In fact, their use in agriculture, forestry, fishery and the food industry has granted a huge improvement in terms of productive efficiency. However, a great number of epidemiological surveys have demonstrated that these toxic compounds can interact and exert negative effects not only with their targets (pests, herbs and fungi), but also with the rest of the environment, including humans. This is particularly relevant in the case of workers involved in the production, transportation, preparation and application of these toxicants. Accordingly, a growing body of evidence has demonstrated the correlation between occupational exposure to pesticides and the development of a wide spectrum of pathologies, ranging from eczema to neurological diseases and cancer. Pesticide exposure is often quite difficult to establish, as many currently used modules do not take into account all of the many variables that can occur in a diverse environment, such as the agricultural sector, and the assessment of the real risk for every single worker is problematic. Indeed, the use of personal protection equipment is necessary while handling these toxic compounds, but education of workers can be even more important: personal contamination with pesticides may occur even in apparently harmless situations. This review summarises the most recent findings describing the association between pesticide occupational exposure and the development of chronic diseases. PMID:27748877

  5. Effects of Paliperidone Palmitate on Coagulation: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Enver Demirel Yılmaz

    2014-01-01

    Full Text Available Objective. The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats. Materials and Methods. Experiments were performed on 22 female albino Wistar rats (8–12 weeks old. Control group was given drinking water as vehicle (0.3 mL. PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers. Results. Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control. Discussion. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.

  6. Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium

    Science.gov (United States)

    2011-03-01

    hippocampal slices in 10 mM HEPES-sucrose buffer ( pH 7.4). The stimulus-evoked increase in endogenous glutamate was significantly enhanced by...state by the reductase and NADPH (11). The oxidation of NADPH to NADP+ is accompanied by a decrease in absorbance. Catalase activity was determined...cerebellar catalase activity in chronically DU-exposed animals receiving only vehicle via osmotic minipump for two months. There are no changes in

  7. Chronic exposure to low dose bacterial lipopolysaccharide inhibits leptin signaling in vagal afferent neurons.

    Science.gov (United States)

    de La Serre, Claire B; de Lartigue, Guillaume; Raybould, Helen E

    2015-02-01

    Bacterially derived factors are implicated in the causation and persistence of obesity. Ingestion of a high fat diet in rodents and obesity in human subjects is associated with chronic elevation of low plasma levels of lipopolysaccharide (LPS), a breakdown product of Gram-negative bacteria. The terminals of vagal afferent neurons are positioned within the gut mucosa to convey information from the gut to the brain to regulate food intake and are responsive to LPS. We hypothesized that chronic elevation of LPS could alter vagal afferent signaling. We surgically implanted osmotic mini-pumps that delivered a constant, low-dose of LPS into the intraperitoneal cavity of rats (12.5 μg/kg/hr for 6 weeks). LPS-treated rats developed hyperphagia and showed marked changes in vagal afferent neuron function. Chronic LPS treatment reduced vagal afferent leptin signaling, characterized by a decrease in leptin-induced STAT3 phosphorylation. In addition, LPS treatment decreased cholecystokinin-induced satiety. There was no alteration in leptin signaling in the hypothalamus. These findings offer a mechanism by which a change in gut microflora can promote hyperphagia, possibly leading to obesity.

  8. 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.

  9. 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

    function due to CMS were observed. In the present experimental setting, there was no indication of the two exposures potentiating each other with respect to adverse effects on the nervous system. However, the effects of prenatal CMS indicate that stress during fetal life may interfere with the development...

  10. KIDNEY TOXICOGENOMICS OF CHRONIC POTASSIUM BROMATE EXPOSURE IN F344 MALE RAT

    Science.gov (United States)

    Potassium bromate (KBrO3), used in both the food and cosmetics industry, and a drinking water disinfection by-product, is a nephrotoxic compound and rodent carcinogen. To gain insight into the carcinogenic mechanism of action and provide possible biomarkers of KBrO3 exposure, the...

  11. The effect of chronic ammonia exposure on acute phase proteins, immunoglobulin and cytokines in laying hens

    Science.gov (United States)

    Ammonia is a potential health hazard to both humans and animals, causing systemic low-grade inflammation based on its levels and durations. The objective of this study was to examine the effect of 45 weeks of exposure to 30 ppm NH3 on the concentrations of acute phase proteins, immunoglobulins and c...

  12. Chronic morphine and tramadol re-exposure induced an anti-anxiety effect in prepubertal rats exposed neonatally to the same drugs.

    Science.gov (United States)

    Gholami, Morteza; Saboory, Ehsan; Khalkhali, Hamid Reza

    2014-10-01

    Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety-like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3-21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re-exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re-exposure to tramadol and this anxiolytic-like behaviour was more dominant in EPM re-exposure in rats that had received higher doses of tramadol. Re-exposure to tramadol elicited a stronger anxiolytic-like behaviour than re-exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re-exposure to these drugs at an immature stage produces considerable anxiolytic-like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long-term changes in the opioid response.

  13. 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.

  14. 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

  15. The Effect of Chronic Ozone Exposure on the Activation of Endoplasmic Reticulum Stress and Apoptosis in Rat Hippocampus

    Science.gov (United States)

    Rodríguez-Martínez, Erika; Nava-Ruiz, Concepcion; Escamilla-Chimal, Elsa; Borgonio-Perez, Gabino; Rivas-Arancibia, Selva

    2016-01-01

    The chronic exposure to low doses of ozone, like in environmental pollution, leads to a state of oxidative stress, which has been proposed to contribute to neurodegenerative disorders, including Alzheimer’s disease (AD). It induces an increase of calcium in the endoplasmic reticulum (ER), which produces ER stress. On the other hand, different studies show that, in diseases such as Alzheimer’s, there exist disturbances in protein folding where ER plays an important role. The objective of this study was to evaluate the state of chronic oxidative stress on ER stress and its relationship with apoptotic death in the hippocampus of rats exposed to low doses of ozone. We used 108 male Wistar rats randomly divided into five groups. The groups received one of the following treatments: (1) Control (air); (2) Ozone (O3) 7 days; (3) O3 15 days; (4) O3 30 days; (5) O3 60 days; and (6) O3 90 days. Two hours after each treatment, the animals were sacrificed and the hippocampus was extracted. Afterwards, the tissue was processed for western blot and immunohistochemistry using the following antibodies: ATF6, 78 kDa glucose-regulated protein (GRP78) and caspase 12. It was also subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and electronic microscopy. Our results show an increase in ATF6, GRP78 and caspase 12 as well as ER ultrastructural alterations and an increase of TUNEL positive cells after 60 and 90 days of exposure to ozone. With the obtained results, we can conclude that oxidative stress induced by chronic exposure to low doses of ozone leads to ER stress. ER stress activates ATF6 inducing the increase of GRP78 in the cytoplasm, which leads to the increase in the nuclear translocation of ATF6. Finally, the translocation creates a vicious cycle that, together with the activation of the cascade for apoptotic cell death, contributes to the maintenance of ER stress. These events potentially contribute in the neurodegeneration processes

  16. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Shrestha, Chandan [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Ito, Takashi [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kawahara, Ko-ichi [Department of Biomedical Engineering, Osaka Institute of Technology, Osaka (Japan); Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto [Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Maruyama, Ikuro, E-mail: rinken@m3.kufm.kagoshima-u.ac.jp [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

    2013-08-09

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis.

  17. Effects of chronic dietary selenomethionine exposure on repeat swimming performance, aerobic metabolism and methionine catabolism in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Thomas, Jith K; Wiseman, Steve; Giesy, John P; Janz, David M

    2013-04-15

    In a previous study we reported impaired swimming performance and greater stored energy in adult zebrafish (Danio rerio) after chronic dietary exposure to selenomethionine (SeMet). The goal of the present study was to further investigate effects of chronic exposure to dietary SeMet on repeat swimming performance, oxygen consumption (MO2), metabolic capacities (standard metabolic rate [SMR], active metabolic rate [AMR], factorial aerobic scope [F-AS] and cost of transport [COT]) and gene expression of energy metabolism and methionine catabolism enzymes in adult zebrafish. Fish were fed SeMet at measured concentrations of 1.3, 3.4, 9.8 or 27.5 μg Se/g dry mass (d.m.) for 90 d. At the end of the exposure period, fish from each treatment group were divided into three subgroups: (a) no swim, (b) swim, and (c) repeat swim. Fish from the no swim group were euthanized immediately at 90 d and whole body triglycerides, glycogen and lactate, and gene expression of energy metabolism and methionine catabolism enzymes were determined. Individual fish from the swim group were placed in a swim tunnel respirometer and swimming performance was assessed by determining the critical swimming speed (U(crit)). After both Ucrit and MO2 analyses, fish were euthanized and whole body energy stores and lactate were determined. Similarly, individual fish from the repeat swim group were subjected to two U(crit) tests (U(crit-1) and U(crit-2)) performed with a 60 min recovery period between tests, followed by determination of energy stores and lactate. Impaired swim performance was observed in fish fed SeMet at concentrations greater than 3 μg Se/g in the diet. However, within each dietary Se treatment group, no significant differences between single and repeat U(crits) were observed. Oxygen consumption, SMR and COT were significantly greater, and F-AS was significantly lesser, in fish fed SeMet. Whole body triglycerides were proportional to the concentration of SeMet in the diet. While

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

    Science.gov (United States)

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

    2011-09-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO(3) , pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72 µg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267 µg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61 µg Cu/L for survival; 8.8-38 µg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215 µg Cu/L) for survival or approximately fourfold (12-42 µg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

  19. Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs.

    Science.gov (United States)

    Hesterberg, T W; Miiller, W C; Thevenaz, P; Anderson, R

    1995-10-01

    Inhalation studies were conducted to determine the chronic biological effects in rodents of respirable fractions of different man-made vitreous fibres (MMVFs), including refractory ceramic fibre (RCF), fibrous glass, rock (stone) wool and slag wool. Animals were exposed nose-only, 6 h per day, 5 days per week, for 18 months (hamsters) or 24 months (rats). Exposure to 10 mg m-3 of crocidolite or chrysotile asbestos induced pulmonary fibrosis, lung tumours and mesothelioma in rats, thus validating the inhalation model with known human carcinogenic fibres. Exposure of rats to 30 mg m-3 of refractory ceramic fibres (RCF) also resulted in pulmonary fibrosis as well as significant increases in lung tumours and mesothelioma. In hamsters, 30 mg m-3 of RCF induced a 41% incidence of mesotheliomas. Exposure of rats to 30 mg m-3 of fibre glasses (MMVF 10 or 11) or of slag wool (MMVF 22) was associated with an inflammatory response, but no mesotheliomas or significant increase in the lung tumours were observed. Rock wool (stone wool: MMVF 21) at the same exposure level resulted in minimal lung fibrosis, but no mesotheliomas or significant increase in the lung tumours were observed. Fibre numbers (WHO fibres) and dimensions in the aerosols and lungs of exposed animals were comparable in this series of inhalation studies. Differences in lung fibre burdens and lung clearance rates could not explain the differences observed in the toxicologic effects of the MMVFs. These findings indicate that dose, dimension and durability may not be the only determinants of fibre toxicity. Chemical composition and the surface physico-chemical properties of the fibres may also play an important role.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Stress proteins and glial cell functions during chronic aluminium exposures: protective role of curcumin.

    Science.gov (United States)

    Sood, Pooja Khanna; Nahar, Uma; Nehru, Bimla

    2012-03-01

    Involved in the ongoing debate is the speculation that aluminium is somehow toxic for neurons. Glial cells cope up to protect neurons from this toxic insult by maintaining the glutathione homeostasis. Of late newer and newer roles of glial cells have been depicted. The present work looks into the other regulatory mechanisms that show the glial cells response to pro-oxidant effects of aluminium exposure. In the present investigation we have evaluated the inflammatory responses of the glial cells as well as HSP70-induction during aluminium exposure. Further, the protective role of curcumin is also evaluated. Aluminium was administered by oral gavage at a dose level of 100 mg/kg b.wt/day for a period of 8 weeks. Curcumin was administered i.p. at a dose of 50 mg/kg b.wt./day on alternate days. Enhanced gene and protein expression of HSP70 in the glial fractions of the aluminium exposed animals as compared to the corresponding neuronal population. Aluminium exposure resulted in a significant increase in the NF-κB and TNF-α expression suggesting inflammatory responses. In the conjunctive treatment group of aluminium and curcumin exposure marked reduction in the gene and protein expression of NF-κB and TNF-α was observed. This was further reflected in histopathological studies showing no evidence of inflammation in conjunctive group as compared to aluminium treatment. From the present study, it can be concluded that curcumin has a potential anti-inflammatory action and can be exploited in other toxicological conditions also.

  5. Metabonomic analysis of quercetin against the toxicity of chronic exposure to a mixture of four organophosphate pesticides in rat plasma.

    Science.gov (United States)

    Cao, Can; Zeng, Yan; Shi, Haidan; Yang, Shuang; Bao, Wei; Qi, Lei; Liu, Ying; Zhao, Xiujun

    2016-09-01

    1. A metabonomics approach was performed to investigate the effect of quercetin on the toxicity of chronic exposure to a mixture of four organophosphate pesticides (OPs) at their corresponding no-observed-adverse-effect level (NOAEL). The rats were divided into six groups (n = 10/group): control, two different doses of quercetin, OPs mixture and different doses of quercetin plus OPs mixture-treated groups. 2. Nine metabolites, including two quercetin metabolites and seven endogenous metabolites were identified in plasma. The intensities of metabolites significantly changed in the OP mixture-treated group compared with the control group (p quercetin-treated group compared with the OP mixture-treated group (p quercetin elicited partial protective effects against the toxicity induced by a mixture of OPs, which include regulation of lipid metabolism, improvement of tricarboxylic acid (TCA) cycle disorders, enhancement of antioxidant defence system to protect the liver.

  6. Chronic exposure to paclobutrazol causes hepatic steatosis in male rockfish Sebastiscus marmoratus and the mechanism involved

    Energy Technology Data Exchange (ETDEWEB)

    Sun Lingbin [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen (China); Li Jinshou [Department of Biological Engineering, Ningde Normal University, Ningde City, Fujian (China); Zuo Zhenghong [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen (China); Chen Meng [State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2013-01-15

    Paclobutrazol (PBZ) is a triazole-containing fungicide which is widely used in agriculture. Acute toxicity can follow its extensive use but it is generally weaker than traditional pesticides such as organochlorine and organophosphorus. However, its adverse effects on aquatic organisms need to be investigated. This study was conducted to investigate the effect of PBZ exposure on the hepatic lipid metabolism of Sebastiscus marmoratus. After PBZ exposure for 50 days, hepatic lipid droplets were enlarged and the hepatic total lipid, triglyceride, total cholesterol and free fatty acid content had increased in a dose dependent manner compared to the control. The mRNA expression of lipid metabolism associated genes such as peroxisome proliferator-activated receptors (PPARs), androgen receptor, acetyl-CoA carboxylase 1, fatty acid synthesis, fatty acid bing protein 4, liver X receptor {alpha} (LXR{alpha}) and stearoyl-CoA desaturase were up-regulated by PBZ exposure. These results indicated that triazole-containing fungicides might affect the metabolism and health of fish via the multi-signal pathways of nuclear receptors such as PPARs and LXR.

  7. Effects of chronic dietary exposure to trace elements on banded water snakes (Nerodia fasciata)

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, W.A.; Roe, J.H.; Snodgrass, J.W.; Staub, B.P.; Jackson, B.P.; Congdon, J.D. [University of Georgia, Aiken, SC (USA). Savannah River Ecology Lab.

    2002-07-01

    Little currently is known about the accumulation or effects of contaminants on reptiles. To date, most studies examining reptile exposure to trace elements report tissue burdens of field-captured animals. but seldom provide insight into the dose, duration, or mode of exposure involved. For two years, juvenile banded water snakes (Nerodia fasciata) were fed with prey items collected from a coal ash-contaminated site that contained elevated levels of As, Cd, Cu, Se, Sr, and V. With the exception of Cu, snakes accumulated significant concentrations of elements, usually in a dose-dependent manner. Accumulation varied significantly among liver, kidney, and gonads, and in most cases between sexes. Selenium accumulation was most notable, greatly exceeding established toxicity thresholds for other vertebrates. Despite the high concentrations of pollutants accumulated, snakes exposed to the contaminated diet survived through the study and exhibited normal food consumption, growth. condition factor, overwinter survival and mass loss, metabolic rate, and gonadosomatic index. The results of this study confirm that diet can be a significant route of exposure to trace elements in snakes and indicate that further studies on snakes are warranted to better understand their responses to contaminants.

  8. In Vitro Developmental Neurotoxicity Following Chronic Exposure to 50 Hz Extremely Low-Frequency Electromagnetic Fields in Primary Rat Cortical Cultures.

    Science.gov (United States)

    de Groot, Martje W G D M; van Kleef, Regina G D M; de Groot, Aart; Westerink, Remco H S

    2016-02-01

    Exposure to 50-60 Hz extremely low-frequency electromagnetic fields (ELF-EMFs) has increased considerably over the last decades. Several epidemiological studies suggested that ELF-EMF exposure is associated with adverse health effects, including neurotoxicity. However, these studies are debated as results are often contradictory and the possible underlying mechanisms are unknown. Since the developing nervous system is particularly vulnerable to insults, we investigate effects of chronic, developmental ELF-EMF exposure in vitro. Primary rat cortical neurons received 7 days developmental exposure to 50 Hz block-pulsed ELF-EMF (0-1000 μT) to assess effects on cell viability (Alamar Blue/CFDA assay), calcium homeostasis (single cell fluorescence microscopy), neurite outgrowth (β(III)-Tubulin immunofluorescent staining), and spontaneous neuronal activity (multi-electrode arrays). Our data demonstrate that cell viability is not affected by developmental ELF-EMF (0-1000 μT) exposure. Depolarization- and glutamate-evoked increases in intracellular calcium concentration ([Ca(2+)]i) are slightly increased at 1 μT, whereas both basal and stimulation-evoked [Ca(2+)]i show a modest inhibition at 1000 μT. Subsequent morphological analysis indicated that neurite length is unaffected up to 100 μT, but increased at 1000 μT. However, neuronal activity appeared largely unaltered following chronic ELF-EMF exposure up to 1000 μT. The effects of ELF-EMF exposure were small and largely restricted to the highest field strength (1000 μT), ie, 10 000 times above background exposure and well above current residential exposure limits. Our combined data therefore indicate that chronic ELF-EMF exposure has only limited (developmental) neurotoxic potential in vitro.

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

    Science.gov (United States)

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

    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 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.

  10. Effects of chronic exposure to crack cocaine on the respiratory tract of mice.

    Science.gov (United States)

    Herculiani, Percyleine P; Pires-Neto, Ruy C; Bueno, Heloisa M S; Zorzetto, Júlio C; Silva, Luiz C; Santos, Angela B G; Garcia, Raphael C T; Yonamine, Mauricio; Detregiachi, Cláudia R P; Saldiva, Paulo H N; Mauad, Thais

    2009-04-01

    Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

  11. Immune System Modifications Induced in a Mouse Model of Chronic Exposure to (90)Sr.

    Science.gov (United States)

    Synhaeve, Nicholas; Musilli, Stefania; Stefani, Johanna; Nicolas, Nour; Delissen, Olivia; Dublineau, Isabelle; Bertho, Jean-Marc

    2016-03-01

    Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown. In this study, we used a mouse model to evaluate the effects of (90)Sr ingestion on the immune system, the animals were chronically exposed to (90)Sr in drinking water at a concentration of 20 kBq/l, for a daily ingestion of 80-100 Bq/day. This resulted in a reduced number of CD19(+) B lymphocytes in the bone marrow and spleen in steady-state conditions. In contrast, the results from a vaccine experiment performed as a functional test of the immune system showed that in response to T-dependent antigens, there was a reduction in IgG specific to tetanus toxin (TT), a balanced Th1/Th2 response inducer antigen, but not to keyhole limpet hemocyanin (KLH), a strong Th2 response inducer antigen. This was accompanied by a reduction in Th1 cells in the spleen, consistent with the observed reduction in specific IgG concentration. The precise mechanisms by which (90)Sr acts on the immune system remain to be elucidated. However, our results suggest that (90)Sr ingestion may be responsible for some of the reported effects of internal contamination on the immune system in civilian populations exposed to the Chernobyl fallout.

  12. Mycotoxins and Antifungal Drug Interactions: Implications in the Treatment of Illnesses Due to Indoor Chronic Toxigenic Mold Exposures

    Directory of Open Access Journals (Sweden)

    Ebere C. Anyanwu

    2004-01-01

    Full Text Available Chronic exposure to toxigenic molds in water-damaged buildings is an indoor environmental health problem to which escalating health and property insurance costs are raising a statewide concern in recent times. This paper reviews the structural and functional properties of mycotoxins produced by toxigenic molds and their interactive health implications with antifungal drugs. Fundamental bases of pathophysiological, neurodevelopmental, and cellular mechanisms of mycotoxic effects are evaluated. It is most likely that the interactions of mycotoxins with antifungal drugs may, at least in part, contribute to the observable persistent illnesses, antifungal drug resistance, and allergic reactions in patients exposed to chronic toxigenic molds. Safe dose level of mycotoxin in humans is not clear. Hence, the safety regulations in place at the moment remain inconclusive, precautionary, and arbitrary. Since some of the antifungal drugs are derived from molds, and since they have structural and functional groups similar to those of mycotoxins, the knowledge of their interactions are important in enhancing preventive measures.

  13. Ethanol diversely alters palmitate, stearate and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer

    Science.gov (United States)

    Boros, Laszlo G.; Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu; Go, Vay Liang W.; Lee, Wai-Nang Paul

    2015-01-01

    Objective To determine tissue specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods Tissue fatty acid profile, and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and GC/MS. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results Fatty acid ratios in the liver indicated that there was an over two-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas there was a 17% decrease in the stearate to palmitate ratio, while oleate to palmitate ratio was increased by 30%. The fractions of deuterium labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas consistent with the oleate/stearate ratios in these tissues. Conclusions Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. PMID:19248221

  14. Aging and photo-aging DNA repair phenotype of skin cells-Evidence toward an effect of chronic sun-exposure

    Energy Technology Data Exchange (ETDEWEB)

    Prunier, Chloe; Masson-Genteuil, Gwenaeelle [Laboratoire Lesions des Acides Nucleiques, CEA, DSM, INAC, SCIB, UMR-E CEA/UJF-Grenoble 1, 17 Rue des Martyrs, F-38054 Grenoble Cedex 9 (France); Ugolin, Nicolas [Laboratoire de Cancerologie Experimentale, CEA, DSV, IRCM, SREIT, BP6, Fontenay-aux-Roses Cedex F-92265 (France); Sarrazy, Fanny [Laboratoire Lesions des Acides Nucleiques, CEA, DSM, INAC, SCIB, UMR-E CEA/UJF-Grenoble 1, 17 Rue des Martyrs, F-38054 Grenoble Cedex 9 (France); Sauvaigo, Sylvie, E-mail: sylvie.sauvaigo@cea.fr [Laboratoire Lesions des Acides Nucleiques, CEA, DSM, INAC, SCIB, UMR-E CEA/UJF-Grenoble 1, 17 Rue des Martyrs, F-38054 Grenoble Cedex 9 (France)

    2012-08-01

    Several studies have demonstrated the deleterious effect of aging on the capacity of cells to repair their DNA. However, current existing assays aimed at measuring DNA repair address only a specific repair step dedicated to the correction of a specific DNA lesion type. Consequently they provide no information regarding the repair pathways that handle other types of lesions. In addition to aging, consequences of photo-exposure on these repair processes remain elusive. In this study we evaluated the consequence of aging and of chronic and/or acute photo-exposure on DNA repair in human skin fibroblasts using a multiplexed approach, which provided detailed information on several repair pathways at the same time. The resulting data were analyzed with adapted statistics/bioinformatics tools. We showed that, irrespective of the repair pathway considered, excision/synthesis was less efficient in non-exposed cells from elderly compared to cells from young adults and that photo-exposure disrupted this very clear pattern. Moreover, it was evidenced that chronic sun-exposure induced changes in DNA repair properties. Finally, the identification of a specific signature at the level of the NER pathway in cells repeatedly exposed to sun revealed a cumulative effect of UVB exposure and chronic sun irradiation. The uses of bioinformatics tools in this study was essential to fully take advantage of the large sum of data obtained with our multiplexed DNA repair assay and unravel the effects of environmental exposure on DNA repair pathways.

  15. Postural disequilibrium quantification in children with chronic lead exposure: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, A.; Shukla, R.; Bornschein, R.; Dietrich, K.; Kopke, J.E.

    Previous studies reported that some children who survive acute lead encephalopathy suffer from ataxia and have difficulties maintaining postural equilibrium. More recent studies have failed to quantify postural imbalance in association with lower levels of lead exposures, perhaps due to the insensitivity of the clinical measure. In our study, we noninvasively measured postural disequilibrium with a microprocessor-based force platform. The test provides a real time quantification of the body's center of gravity movement pattern. Measurements were made in a cohort of 33 inner city children (mean age: six years +/- 0.4 SD) with well documented blood lead histories. The average maximum blood lead of these children during their first six years of life was 23.5 micrograms/dl (range = 8.5 to 49.4). The children performed four postural tests (i.e., standing eyes open (EO) and closed (EC), on firm surface and standing on a compliant foam surface with eyes open (FO) and closed (FC)). The results indicated that the maximum blood lead incurred during the second year of life was significantly positively related to postural sway, and the body balance was most affected in the EC test where visual cues were eliminated and proprioceptive feedback was not modified. Fetal Pb exposure levels as well as Pb exposures during the first year of life were not correlated with postural sway of six year olds. However, the maximum blood lead concentration beyond two years of life was significantly associated with the postural sway at six years of age.

  16. Risk of cataract in the context of acute and chronic exposure

    Directory of Open Access Journals (Sweden)

    Tukov A.R.

    2016-12-01

    Full Text Available Purpose: estimation of the risk of cataract using doses of different types of radiation. Material and methods. The study is carried out using the information database of the NP, recovery workers of the accident at the Chernobyl NP. Professional exposure and dose received during 30 km zone were used to calculate the risk. Results. The study shows the use of one of their parts of the total radiation dose of man, leads to obtaining of different levels of the risk of disease. Conclusion. Only use of a total radiation dose can lead to obtaining of the correct results of evaluating the risk of the emergence of the radiation- induced diseases.

  17. Chronic Electromagnetic Exposure at Occupational Safety Level Does Not Affect the Metabolic Profile nor Cornea Healing after LASIK Surgery.

    Science.gov (United States)

    Crouzier, David; Dabouis, Vincent; Gentilhomme, Edgar; Vignal, Rodolphe; Bourbon, Fréderic; Fauvelle, Florence; Debouzy, Jean-Claude

    2014-01-01

    LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m(2)), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, (1)H-NMR HRMAS metabolomics, (13)C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified.

  18. 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.

  19. Chronic Electromagnetic Exposure at Occupational Safety Level Does Not Affect the Metabolic Profile nor Cornea Healing after LASIK Surgery

    Directory of Open Access Journals (Sweden)

    David Crouzier

    2014-01-01

    Full Text Available LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m2, were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week. Neither clinical or histological examinations, nor experimental data, such as light scattering, 1H-NMR HRMAS metabolomics, 13C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy after eye surgery was not justified.

  20. Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Færgeman, Nils J.; Cole, Nelson B;

    2005-01-01

    . To better define a role for alpha-synuclein in brain fatty acid uptake and metabolism, we infused awake, wild-type, or alpha-synuclein gene-ablated mice with [1-(14)C]palmitic acid (16:0) and assessed fatty acid uptake and turnover kinetics in brain phospholipids. Alpha-synuclein deficiency decreased brain......Alpha-synuclein is an abundant protein in the central nervous system that is associated with a number of neurodegenerative disorders, including Parkinson's disease. Its physiological function is poorly understood, although recently it was proposed to function as a fatty acid binding protein...... 16:0 uptake 35% and reduced its targeting to the organic fraction. The incorporation coefficient for 16:0 entering the brain acyl-CoA pool was significantly decreased 36% in alpha-synuclein gene-ablated mice. Because incorporation coefficients alone are not predictive of fatty acid turnover...

  1. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  2. Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

    Science.gov (United States)

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

    2011-07-01

    Studies of nuclear workers make it possible to directly quantify the risks associated with ionizing radiation exposure at low doses and low dose rates. Studies of the CEA (Commissariat à l'Energie Atomique) and AREVA Nuclear Cycle (AREVA NC) cohort, currently the most informative such group in France, describe the long-term risk to nuclear workers associated with external exposure. Our aim is to assess the risk of mortality from solid cancers among CEA and AREVA NC nuclear workers and its association with external radiation exposure. Standardized mortality ratios (SMRs) were calculated and internal Poisson regressions were conducted, controlling for the main confounding factors [sex, attained age, calendar period, company and socioeconomic status (SES)]. During the period 1968-2004, there were 2,035 solid cancers among the 36,769 CEA-AREVA NC workers. Cumulative external radiation exposure was assessed for the period 1950-2004, and the mean cumulative dose was 12.1 mSv. Mortality rates for all causes and all solid cancers were both significantly lower in this cohort than in the general population. A significant excess of deaths from pleural cancer, not associated with cumulative external dose, was observed, probably due to past asbestos exposure. We observed a significant excess of melanoma, also unassociated with dose. Although cumulative external dose was not associated with mortality from all solid cancers, the central estimated excess relative risk (ERR) per Sv of 0.46 for solid cancer mortality was higher than the 0.26 calculated for male Hiroshima and Nagasaki A-bomb survivors 50 years or older and exposed at the age of 30 years or older. The modification of our results after stratification for SES demonstrates the importance of this characteristic in occupational studies, because it makes it possible to take class-based lifestyle differences into account, at least partly. These results show the great potential of a further joint international study of

  3. Chronic exposure to Tributyltin induces brain functional damage in juvenile common carp (Cyprinus carpio.

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Li

    Full Text Available The aim of the present study was to investigate the effect of Tributyltin (TBT on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase, Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters. The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

  4. Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Torres-Jardón, Ricardo; Henriquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Valencia-Salazar, Gildardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderón, Rafael; Reed, William

    2007-01-01

    Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

  5. Effects of chronic lead exposure on functions of nervous system in Chinese children and developmental rats.

    Science.gov (United States)

    Luo, Wenjing; Ruan, Diyun; Yan, Chonghuai; Yin, Shuting; Chen, Jingyuan

    2012-08-01

    Lead pollution is a very serious problem in China with the rapid economic development. A large amount of lead has been released into the environment due to mineral processing activities and has impacted water resources, soils, vegetables, and crops. The gasoline with lead has been banned in China since July 1, 2000. Though a noticeable decrease of lead poisoning rates has been evidenced, the children's blood lead levels are still significantly higher than those in developed countries. Therefore, lowering the lead exposure in childhood continues to be an important public health objective in China. There is also a lot that remains to be done to reduce children's exposure to lead. In this section, five scientists from China presented latest research results regarding the current situation of lead poisoning in China, the mechanisms involved in lead-induced neurotoxicity, and the new advances related to the potential therapy methods. Their researches may pave new way not only for the prevention of lead poisoning but also for the treatment of affected children in China and other countries.

  6. Chronic Exposure to Extremely Low Frequency Electromagnetic Field Induces Mild Renal Damages in Rats

    Directory of Open Access Journals (Sweden)

    T.S. Javadifar

    2011-01-01

    Full Text Available The kidney is a major potential route for the absorption of hazardous materials encountered in the environment. The aim of this study was to evaluate the influence of ELFEMF on function and structure of kidney in rats. Experimental adult male Wistar rats were exposed to a 50 Hz ELFEMF, 1 mT (emitted from solenoid for 24 h daily during 135 days. The sham rats were subjected to sham exposure and the control rats were kept in animal room. In final, blood samples collected for the determination of the creatinine, urea nitrogen, albumin, globulin and total protein concentration in the plasma. The kidney was examined using light microscopy. Results showed that in EMF exposed group plasma concentration of creatinine and urea nitrogen was increased (p<0.001 which was accompanied by marked vascular congestion in the renal cortex and reduction in red blood cell count in glomerular capillaries but there were no changes in total protein, albumin and globulin levels. In conclusion, long term exposure to ELFEMF impacts renal function by influencing the perfusion of kidney.

  7. Transcriptome comparison in the pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

    Science.gov (United States)

    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Nie, Qinghua

    2015-10-01

    Chronic stress can induce a series of maladjustments, and the response to stress is partly regulated by the hypothalamus-pituitary-adrenal axis. The aim of this study was to investigate the genetic mechanisms of this axis regulating stress responsiveness. The pituitary and adrenal cortex of Beagle and Chinese Field Dog (CFD) from a stress exposure group [including Beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), Beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)] and a control group [including Beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), Beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)], selected to perform RNA-seq transcriptome comparisons, showed that 40, 346, 376, 69, 70, 38, 57 and 71 differentially expressed genes were detected in BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1, BP2 vs. CFDP2, BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2 respectively. NPB was a gene common to BAC1 vs. BAC2 and CFDAC1 vs. CFDAC2, indicating it was a potential gene affecting response to chronic stress, regardless of the extent of chronic stress induced. PLP1 was a gene common to BP1 vs. CFDP1 and BP2 vs. CFDP2, suggesting its important roles in affecting the stress-tolerance difference between the two breeds, regardless of whether there was stress exposure or not. Pathway analysis found 12, 4, 11 and 1 enriched pathway in the comparisons of BP1 vs. CFDP1, BP2 vs. CFDP2, CFDP1 vs. CFDP2 and BAC1 vs. BAC2 respectively. Glutamatergic synapse, neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, GABAergic synapse, calcium signaling pathway and dopaminergic synapse were the most significantly enriched pathways in both CFDP1 vs. CFDP2 and BP1 vs. CFDP1. GO, KEGG pathway and gene network analysis demonstrated that GRIA3, GRIN2A, GRIN2B and NPY were important in regulating the stress response in CFD. Nevertheless, ADORA1, CAMK2A, GRM1, GRM7 and NR4A1 might be critical genes contributing to the stress

  8. Life-cycle chronic gamma exposure of Arabidopsis thaliana induces growth effects but no discernable effects on oxidative stress pathways.

    Science.gov (United States)

    Vandenhove, Hildegarde; Vanhoudt, Nathalie; Cuypers, Ann; van Hees, May; Wannijn, Jean; Horemans, Nele

    2010-09-01

    Arabidopsis thaliana was exposed to low-dose chronic gamma irradiation during a full life cycle (seed to seed) and several biological responses were investigated. Applied dose rates were 2336, 367 and 81 microGy h(-1). Following 24 days (inflorescence emergence), 34 days (approximately 50% of flowers open) and 54 days (silice ripening) exposure, plants were harvested and monitored for biometric parameters, capacities of enzymes involved in the antioxidative defence mechanisms (SOD, APOD, GLUR, GPOD, SPOD, CAT, ME), glutathione and ascorbate pool, lipid peroxidation products, altered gene expression of selected genes encoding for antioxidative enzymes or reactive oxygen species production, and DNA integrity. Root fresh weight was significantly reduced after gamma exposure compared to the control at all stages monitored but no significant differences in root weight for the different dose rates applied was observed. Leaf and stem fresh weight were significantly reduced at the highest irradiation level after 54 days exposure only. Also total plant fresh was significantly lower at silice riping and this for the highest and medium dose rate applied. The dose rate estimated to result in a 10% reduction in growth (EDR-10) ranged between 60 and 80 microGy h(-1). Germination of seeds from the gamma irradiated plants was not hampered. For several of the antioxidative defence enzymes studied, the enzyme capacity was generally stimulated towards flowering but generally no significant effect of dose rate on enzyme capacity was observed. Gene analysis revealed a significant transient and dose dependent change in expression of RBOHC indicating active reactive oxygen production induced by gamma irradiation. No effect of irradiation was observed on concentration or reduction state of the non-enzymatic antioxidants, ascorbate and glutathione. The level of lipid peroxidation products remained constant throughout the observation period and was not affected by dose rate. The comet assay

  9. Repeated Cycles of Chronic Intermittent Ethanol Exposure Increases Basal Glutamate in the Nucleus Accumbens of Mice without affecting glutamate transport

    Directory of Open Access Journals (Sweden)

    William C. Griffin

    2015-02-01

    Full Text Available Repeated cycles of chronic intermittent ethanol (CIE exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc is significantly elevated in ethanol dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na+ dependent and Na+ independent conditions to determine whether the function of excitatory amino acid transporters (EAATs; also known as system XAG or of system Xc- (Glial cysteine-glutamate exchanger was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (~2 –fold in the NAc of CIE exposed mice (i.e. ethanol-dependent compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na+ dependent nor Na+ independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical-striatal pathways underlies the increases in extracellular glutamate found in the nucleus accumbens of ethanol-dependent mice.

  10. Chronic exposure to volcanic air pollution and DNA damage in Furnas Volcano (São Miguel Island, Azores, Portugal) inhabitants

    Science.gov (United States)

    Linhares, Diana; Garcia, Patricia; Silva, Catarina; Ferreira, Teresa; Barroso, Joana; Camarinho, Ricardo; Rodrigues, Armindo

    2015-04-01

    Many studies in volcanic air pollution only have in consideration the acute toxic effects of gas or ash releases however the impact of chronic exposure to ground gas emissions in human health is yet poorly known. In the Azores archipelago (Portugal), São Miguel island has one of the most active and dangerous volcanoes: Furnas Volcano. Highly active fumarolic fields, hot springs and soil diffuse degassing phenomena are the main secondary volcanic phenomena that can be seen at the volcano surroundings. One of the main gases released in these diffuse degassing areas is radon (222Rn), which decay results in solid particles that readily settle within the airways. These decay particles emit alpha radiation that is capable of causing severe DNA damage that cumulatively can eventually cause cancer. Previous studies have established that chronic exposure to chromosome-damaging agents can lead to the formation of nuclear anomalies, such as micronuclei that is used for monitoring DNA damage in human populations. The present study was designed to evaluate whether chronic exposure to volcanic air pollution, associated to 222Rn, might result in DNA damage in human oral epithelial cells. A cross sectional study was performed in a study group of 142 individuals inhabiting an area where volcanic activity is marked by active fumarolic fields and soil degassing (hydrothermal area), and a reference group of 368 individuals inhabiting an area without these secondary manifestations of volcanism (non-hydrothermal area). For each individual, 1000 buccal epithelial cells were analyzed for the frequency of micronucleated cells (MNc) and the frequency of cells with other nuclear anomalies (ONA: pyknosis, karyolysis and karyorrhexis), by using the micronucleus assay. Information on lifestyle factors and an informed consent were obtained from each participant. Assessment of indoor radon was performed with the use of radon detectors. Data were analyzed with logistic regression models, adjusted

  11. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys

    DEFF Research Database (Denmark)

    Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M

    2005-01-01

    It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were...

  12. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

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

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Lundgren, Jens D; Ross, Michael

    2016-01-01

    of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). METHODS: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D...

  14. Kinetics studies on triacontanyl palmitate: a urease inhibitor.

    Science.gov (United States)

    Lodhi, Muhammad Arif; Abbasi, Muhammad Athar; Choudhary, Muhammad Iqbal; Ahmad, Viqar Uddin

    2007-07-10

    The mechanism of inhibition of jack bean and Bacillus pasteurii ureases was investigated by triacontanyl palmitate (1) which is a long-chain fatty ester and has been isolated from Symplocos racemosa Roxb. Lineweaver-Burk, Dixon plots, and their secondary replots showed that 1 is a non-competitive inhibitor of these enzymes. K(i) values were found to be 60.03 +/- 1.72 and 88.23 +/- 0.31 microM against jack bean and B. pasteurii ureases, respectively.

  15. The effect of chronic chromium exposure on the health of Chinook salmon (Oncorhynchus tshawytscha)

    Energy Technology Data Exchange (ETDEWEB)

    Farag, Aida M. [United States Geological Survey, Columbia Environmental Research Center, Jackson Field Research Station, P.O. Box 1089, Jackson, WY 83001 (United States)]. E-mail: aida_farag@usgs.gov; May, Thomas [United States Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201 (United States); Marty, Gary D. [Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, 1 Shields Ave., Davis, CA 95616-8732 (United States); Easton, Michael [International EcoGen Inc., 2015 McLallen Court, North Vancouver, BC, Canada V7P 3H6 (Canada); Harper, David D. [United States Geological Survey, Columbia Environmental Research Center, Jackson Field Research Station, P.O. Box 1089, Jackson, WY 83001 (United States); Little, Edward E. [United States Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201 (United States); Cleveland, Laverne [United States Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201 (United States)

    2006-03-10

    This study was designed to determine fish health impairment of Chinook salmon (Oncorhynchus tshawytscha) exposed to chromium. Juvenile Chinook salmon were exposed to aqueous chromium concentrations (0-266 {mu}g l{sup -1}) that have been documented in porewater from bottom sediments and in well waters near salmon spawning areas in the Columbia River in the northwestern United States. After Chinook salmon parr were exposed to 24 and 54 {mu}g Cr l{sup -1} for 105 days, neither growth nor survival of parr was affected. On day 105, concentrations were increased from 24 to 120 {mu}g Cr l{sup -1} and from 54 to 266 {mu}g Cr l{sup -1} until the end of the experiment on day 134. Weight of parr was decreased in the 24/120 {mu}g Cr l{sup -1} treatment, and survival was decreased in the 54/266 {mu}g Cr l{sup -1} treatment. Fish health was significantly impaired in both the 24/120 and 54/266 {mu}g Cr l{sup -1} treatments. The kidney is the target organ during chromium exposures through the water column. The kidneys of fish exposed to the greatest concentrations of chromium had gross and microscopic lesions (e.g. necrosis of cells lining kidney tububules) and products of lipid peroxidation were elevated. These changes were associated with elevated concentrations of chromium in the kidney, and reduced growth and survival. Also, variations in DNA in the blood were associated with pathological changes in the kidney and spleen. These changes suggest that chromium accumulates and enters the lipid peroxidation pathway where fatty acid damage and DNA damage (expressed as chromosome changes) occur to cause cell death and tissue damage. While most of the physiological malfunctions occurred following parr exposures to concentrations {>=}120 {mu}g Cr l{sup -1}, nuclear DNA damage followed exposures to 24 {mu}g Cr l{sup -1}, which was the smallest concentration tested. The abnormalities measured during this study are particularly important because they are associated with impaired growth

  16. Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, B.W.; Anderson, L.E.; Hilton, D.I.; Philips, R.D.

    1980-01-01

    As a component of studies to search for effects of 60-Hz electric field exposure on mammalian endocrine function, concentrations of melatonin, 5-methoxytryptophol, and serotonin-N-acetyl transferase activity were measured in the pineal glands of rats exposed or sham-exposed at 65 kV/m for 30 days.In two replicate experiments there were statistically significant differences between exposed and control rats in that the normal nocturnal increase in pineal melatonin content was depressed in the exposed animals. Concentrations of 5-methoxytryptophol were increased in the pineal glands of the exposed groups when compared to sham-exposed controls. An alteration was also observed in serotonin-N-acetyl transferase activity, with lower levels measured in pineal glands from exposed animals.

  17. Chronic Cadmium Exposure Lead to Inhibition of Serum and Hepatic Alkaline Phosphatase Activity in Wistar Rats.

    Science.gov (United States)

    Treviño, Samuel; Andrade-García, Alejandra; Herrera Camacho, Irma; León-Chavez, Bertha Alicia; Aguilar-Alonso, Patricia; Flores, Gonzalo; Brambila, Eduardo

    2015-12-01

    Alkaline phosphatase (ALP) activity in the serum and liver from rats administered with cadmium (Cd) in drinking water was studied. After metal administration, Cd showed a time-dependent accumulation in the liver, meanwhile metallothionein had a maximum increase at 1 month, remaining in this level until the end of the study. On the other hand, serum and liver ALP activity was decreased after 3 months exposure. To determine if Cd produced an inhibition on enzyme, apo-ALP prepared from both nonexposed and exposed rats was reactivated with Zn, showing 60% more activity as compared with the enzyme isolated from nonexposed rats. In vitro assays showed that Cd-ALP was partially reactivated with Zn; however, in the presence of cadmium, Zn-ALP was completely inhibited. Kinetic studies indicate a noncompetitive inhibition by Cd; these results suggest that Cd can substitute Zn, and/or Cd can interact with nucleophilic ligands essential for the enzymatic activity.

  18. Effects on auditory function of chronic exposure to electromagnetic fields from mobile phones.

    Science.gov (United States)

    Bhagat, Sanjeev; Varshney, Saurabh; Bist, Sampan Singh; Goel, Deepak; Mishra, Sarita; Jha, Vivek Kumar

    2016-08-01

    The widespread use of mobile phones has given rise to apprehension regarding the possible hazardous health effects of high-frequency electromagnetic fields (EMFs) on auditory function. We conducted a study to investigate the effects of long-term (>4 yr) exposure to EMFs emitted by mobile phones on auditory function. Our study population was made up of 40 healthy medical students-31 men and 9 women, aged 20 to 30 years (mean 22.7). Of this group, 31 subjects typically held their phone to the right ear and 9 to the left ear; the non-phone-using ear served as each subject's control ear. The phone-using subjects were also split into two groups of 20 based on the duration of their daily phone use (≤60 min vs. >60 min). All subjects underwent pure-tone audiometry, speech audiometry, impedance audiometry, and brainstem evoked response audiometry (BERA), and comparisons were made between the phone-using ear and the control ear and between the shorter and longer duration of daily use. We found no statistically significant differences in high-frequency pure-tone average between the phone-using ears and the control ears (p = 0.69) or between the shorter- and longer-duration phone-using ears (p = 0.85). Moreover, statistical analysis of BERA findings revealed no significant differences between the phone-using ears and the control ears in terms of wave I-III, III-V, and I-V interpeak latencies (p = 0.59, 0.74 and 0.44, respectively). None of the subjects reported any subjective symptoms, such as headache, tinnitus, or sensations of burning or warmth behind, around, or on the phone-using ear. We conclude that the long-term exposure to EMFs from mobile phones does not affect auditory function.

  19. Chronic nandrolone decanoate exposure during adolescence affects emotional behavior and monoaminergic neurotransmission in adulthood.

    Science.gov (United States)

    Rainer, Quentin; Speziali, Simona; Rubino, Tiziana; Dominguez-Lopez, Sergio; Bambico, Francis Rodriguez; Gobbi, Gabriella; Parolaro, Daniela

    2014-08-01

    Nandrolone decanoate, an anabolic androgen steroid (AAS) illicitly used by adult and adolescent athletes to enhance physical performance and body image, induces psychiatric side effects, such as aggression, depression as well as a spectrum of adverse physiological impairments. Since adolescence represents a neurodevelopmental window that is extremely sensitive to the detrimental effects of drug abuse, we investigated the long-term behavioral and neurophysiological consequences of nandrolone abuse during adolescence. Adolescent rats received daily injections of nandrolone decanoate (15 mg/kg, i.m.) for 14 days (PND 40-53). At early adulthood (PND 68), forced swim, sucrose preference, open field and elevated plus maze tests were performed to assess behavioral changes. In vivo electrophysiological recordings were carried out to monitor changes in electrical activity of serotonergic neurons of the dorsal raphe nucleus (DRN) and noradrenergic neurons of the locus coeruleus (LC). Our results show that after early exposure to nandrolone, rats display depression-related behavior, characterized by increased immobility in the forced swim test and reduced sucrose intake in the sucrose preference test. In addition, adult rats presented anxiety-like behavior characterized by decreased time and number of entries in the central zone of the open field and decreased time spent in the open arms of the elevated plus maze. Nandrolone decreased the firing rate of spontaneously active serotonergic neurons in the DRN while increasing the firing rate of noradrenergic neurons in the LC. These results provide evidence that nandrolone decanoate exposure during adolescence alters the emotional profile of animals in adulthood and significantly modifies both serotonergic and noradrenergic neurotransmission.

  20. Palmitic acid exerts pro-inflammatory effects on vascular smooth muscle cells by inducing the expression of C-reactive protein, inducible nitric oxide synthase and tumor necrosis factor-α.

    Science.gov (United States)

    Wu, Di; Liu, Juntian; Pang, Xiaoming; Wang, Shuyue; Zhao, Jingjing; Zhang, Xiaolu; Feng, Liuxin

    2014-12-01

    Atherosclerosis is a chronic inflammatory disease in the vessel, and inflammatory cytokines play an important role in the inflammatory process of atherosclerosis. A high level of free fatty acids (FFAs) produced in lipid metabolism disorders are known to participate in the formation of atherosclerosis through multiple bioactivities. As the main saturated fatty acid in FFAs, palmitic acid stimulates the expression of inflammatory cytokines in macrophages. However, it is unclear whether palmitic acid exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of palmitic acid on the expression of C-reactive protein (CRP), tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in VSMCs. Rat VSMCs were cultured, and palmitic acid was used as a stimulant for CRP, TNF-α and iNOS expression. mRNA expression was assayed with reverse transcription-polymerase chain reaction, and protein expression was detected with western blot analysis and immunocytochemistry. The results showed that palmitic acid significantly stimulated mRNA and protein expression of CRP, TNF-α and iNOS in VSMCs in time- and concentration-dependent manners, and therefore, palmitic acid is able to exert a pro-inflammatory effect on VSMCs via stimulating CRP, TNF-α and iNOS expression. The findings provide a novel explanation for the direct pro-inflammatory and atherogenic effects of palmitic acid, and for the association with metabolic syndrome, such as type 2 diabetes mellitus, obesity and atherosclerosis. Therefore, the intervention with anti-inflammatory agents may effectively delay the formation and progression of atherosclerosis in patients with metabolic syndrome.

  1. Chronic effects of temperature on mortality in the Southeastern USA using satellite-based exposure metrics

    Science.gov (United States)

    Shi, Liuhua; Liu, Pengfei; Wang, Yan; Zanobetti, Antonella; Kosheleva, Anna; Koutrakis, Petros; Schwartz, Joel

    2016-07-01

    Climate change may affect human health, particularly for elderly individuals who are vulnerable to temperature changes. While many studies have investigated the acute effects of heat, only a few have dealt with the chronic ones. We have examined the effects of seasonal temperatures on survival of the elderly in the Southeastern USA, where a large fraction of subpopulation resides. We found that both seasonal mean temperature and its standard deviation (SD) affected long-term survival among the 13 million Medicare beneficiaries (aged 65+) in this region during 2000-2013. A 1 °C increase in summer mean temperature corresponded to an increase of 2.5% in death rate. Whereas, 1 °C increase in winter mean temperature was associated with a decrease of 1.5%. Increases in seasonal temperature SD also influence mortality. We decomposed seasonal mean temperature and its temperature SD into long-term geographic contrasts between ZIP codes and annual anomalies within ZIP code. Effect modifications by different subgroups were also examined to find out whether certain individuals are more vulnerable. Our findings will be critical to future efforts assessing health risks related to the future climate change.

  2. Chronic Exposure to Static Magnetic Fields from Magnetic Resonance Imaging Devices Deserves Screening for Osteoporosis and Vitamin D Levels: A Rat Model

    Directory of Open Access Journals (Sweden)

    Harun R. Gungor

    2015-07-01

    Full Text Available Technicians often receive chronic magnetic exposures from magnetic resonance imaging (MRI devices, mainly due to static magnetic fields (SMFs. Here, we ascertain the biological effects of chronic exposure to SMFs from MRI devices on the bone quality using rats exposed to SMFs in MRI examining rooms. Eighteen Wistar albino male rats were randomly assigned to SMF exposure (A, sham (B, and control (C groups. Group A rats were positioned within 50 centimeters of the bore of the magnet of 1.5 T MRI machine during the nighttime for 8 weeks. We collected blood samples for biochemical analysis, and bone tissue samples for electron microscopic and histological analysis. The mean vitamin D level in Group A was lower than in the other groups (p = 0.002. The mean cortical thickness, the mean trabecular wall thickness, and number of trabeculae per 1 mm2 were significantly lower in Group A (p = 0.003. TUNEL assay revealed that apoptosis of osteocytes were significantly greater in Group A than the other groups (p = 0.005. The effect of SMFs in chronic exposure is related to movement within the magnetic field that induces low-frequency fields within the tissues. These fields can exceed the exposure limits necessary to deteriorate bone microstructure and vitamin D metabolism.

  3. Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

    Science.gov (United States)

    Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

    2015-06-01

    There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus.

  4. Population Pharmacokinetics of Obinutuzumab (GA101) in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma and Exposure-Response in CLL.

    Science.gov (United States)

    Gibiansky, E; Gibiansky, L; Carlile, D J; Jamois, C; Buchheit, V; Frey, N

    2014-10-29

    Treatment regimens involving obinutuzumab (GA101) demonstrated increased efficacy to rituximab in clinical trials for non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). However, the pharmacokinetic (PK) properties and the exposure-response relationships of obinutuzumab still need to be fully described. Data from four clinical trials of obinutuzumab were analyzed to describe the PK properties in patients with NHL or CLL and the pharmacodynamic (PD) properties in patients with CLL. A population PK model with linear time-dependent clearance described the obinutuzumab concentration-time course. Diagnosis, baseline tumor size (BSIZ), body weight, and gender were the main covariates affecting obinutuzumab exposure. In patients with CLL, exposure was not associated with safety but showed positive trends of correlation with efficacy. Although efficacy correlated positively with exposure, since both efficacy and exposure correlated negatively with BSIZ, it was not possible to determine with certainty whether it would be beneficial to adjust the dose according to BSIZ.

  5. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Yuan, Shuang-Shuang; Wu, Chang-Wen [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Li, Wei-Ye [Zhoushan fisheries research institute, Zhoushan 316022 (China)

    2016-08-15

    Highlights: • Zn and Cd induced some differences in oxidative damage in the liver of zebrafish. • Zn and Cd enhanced expression of Cu/Zn-SOD and CAT through Nrf2 pathway. • Zn and Cd did not affected protein levels of CAT. • Cd inhibited biological activities of Cu/Zn-SOD and CAT proteins. • Zn stimulated activity and protein levels of Cu/Zn-SOD. - Abstract: Based on the same toxic level of 0.6% LC{sub 50} for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180 μg L{sup −1}) and Cd exposures (30 μg L{sup −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

  6. Protection from palmitate-induced mitochondrial DNA damage prevents from mitochondrial oxidative stress, mitochondrial dysfunction, apoptosis, and impaired insulin signaling in rat L6 skeletal muscle cells.

    Science.gov (United States)

    Yuzefovych, Larysa V; Solodushko, Viktoriya A; Wilson, Glenn L; Rachek, Lyudmila I

    2012-01-01

    Saturated free fatty acids have been implicated in the increase of oxidative stress, mitochondrial dysfunction, apoptosis, and insulin resistance seen in type 2 diabetes. The purpose of this study was to determine whether palmitate-induced mitochondrial DNA (mtDNA) damage contributed to increased oxidative stress, mitochondrial dysfunction, apoptosis, impaired insulin signaling, and reduced glucose uptake in skeletal muscle cells. Adenoviral vectors were used to deliver the DNA repair enzyme human 8-oxoguanine DNA glycosylase/(apurinic/apyrimidinic) lyase (hOGG1) to mitochondria in L6 myotubes. After palmitate exposure, we evaluated mtDNA damage, mitochondrial function, production of mitochondrial reactive oxygen species, apoptosis, insulin signaling pathways, and glucose uptake. Protection of mtDNA from palmitate-induced damage by overexpression of hOGG1 targeted to mitochondria significantly diminished palmitate-induced mitochondrial superoxide production, restored the decline in ATP levels, reduced activation of c-Jun N-terminal kinase (JNK) kinase, prevented cells from entering apoptosis, increased insulin-stimulated phosphorylation of serine-threonine kinase (Akt) (Ser473) and tyrosine phosphorylation of insulin receptor substrate-1, and thereby enhanced glucose transporter 4 translocation to plasma membrane, and restored insulin signaling. Addition of a specific inhibitor of JNK mimicked the effect of mitochondrial overexpression of hOGG1 and partially restored insulin sensitivity, thus confirming the involvement of mtDNA damage and subsequent increase of oxidative stress and JNK activation in insulin signaling in L6 myotubes. Our results are the first to report that mtDNA damage is the proximal cause in palmitate-induced mitochondrial dysfunction and impaired insulin signaling and provide strong evidence that targeting DNA repair enzymes into mitochondria in skeletal muscles could be a potential therapeutic treatment for insulin resistance.

  7. Increased gut permeability and bacterial translocation after chronic chlorpyrifos exposure in rats.

    Directory of Open Access Journals (Sweden)

    Claire Joly Condette

    Full Text Available The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs, multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR and localization (using immunofluorescence of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs. In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning but not at day 60 (adulthood. At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal

  8. Canines as sentinel species for assessing chronic exposures to air pollutants: part 2. Cardiac pathology.

    Science.gov (United States)

    Calderón-Garcidueñas, L; Gambling, T M; Acuña, H; García, R; Osnaya, N; Monroy, S; Villarreal-Calderón, A; Carson, J; Koren, H S; Devlin, R B

    2001-06-01

    The principal objective of this study is to evaluate by light and electron microscopy (LM, EM) the heart tissues in stray southwest and northeast metropolitan Mexico City (SWMMC, NEMMC) dogs and compare their findings to those from 3 less polluted cities (Cuernavaca, Tlaxcala, and Tuxpam). Clinically healthy mongrel dogs, including 109 from highly polluted SWMMC and NEMMC, and 43 dogs from less polluted cities were studied. Dogs residing in cities with lower levels of pollutants showed little or no cardiac abnormalities. Mexico City and Cuernavaca dogs exhibited LM myocardial alterations including apoptotic myocytes, endothelial and immune effector cells, degranulated mast cells associated with scattered foci of mononuclear cells in left and right ventricles and interventricular septum, and clusters of adipocytes interspersed with mononuclear cells. Vascular changes included scattered polymorphonuclear leukocytes (PMN) margination and microthrombi in capillaries, and small venous and arteriolar blood vessels. Small veins exhibited smooth muscle cell hyperplasia, and arteriolar blood vessels showed deposition of particulate matter (PM) in the media and adventitia. Unmyelinated nerve fibers showed endoneural and epineural degranulated mast cells. EM examination of myocardial mast cells showed distended and abundant rough endoplasmic reticulum with few secretory granules. Myocardial capillaries exhibited fibrin deposition and their endothelial cells displayed increased luminal and abluminal pinocytic activity and the formation of anemone-like protrusions of the endothelium into the lumen. A close association between myocardial findings, lung epithelial and endothelial pathology, and chronic inflammatory lung changes was noted. The myocardial changes described in dogs exposed to ambient air pollutants may form the basis for developing hypothesis-driven mechanistic studies that might explain the epidemiological data of increased cardiovascular morbidity and mortality in

  9. Apocynin prevents vascular effects caused by chronic exposure to low concentrations of mercury.

    Directory of Open Access Journals (Sweden)

    Danize A Rizzetti

    Full Text Available UNLABELLED: Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS in the vasculature. Our aim was to investigate whether treatment with apocynin, an NADPH oxidase inhibitor, prevents the vascular effects caused by chronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a intramuscular injections (i.m. of saline; b HgCl(2 (i.m. 1(st dose: 4.6 µg/kg, subsequent doses: 0.07 µg/kg/day; c Apocynin (1.5 mM in drinking water plus saline i.m.; and d Apocynin plus HgCl(2. The mercury treatment resulted in 1 an increased aortic vasoconstrictor response to phenylephrine and reduced endothelium-dependent responses to acetylcholine; 2 the increased involvement of ROS and vasoconstrictor prostanoids in response to phenylephrine, whereas the endothelial NO modulation of such responses was reduced; and 3 the reduced activity of aortic superoxide dismutase (SOD and glutathione peroxidase (GPx and increased plasma malondialdehyde (MDA levels. Treatment with apocynin partially prevented the increased phenylephrine responses and reduced the endothelial dysfunction elicited by mercury treatment. In addition, apocynin treatment increased the NO modulation of vasoconstrictor responses and aortic SOD activity and reduced plasma MDA levels without affecting the increased participation of vasoconstrictor prostanoids observed in aortic segments from mercury-treated rats. CONCLUSIONS: Mercury increases the vasoconstrictor response to phenylephrine by reducing NO bioavailability and increasing the involvement of ROS and constrictor prostanoids. Apocynin protects the vessel from the deleterious effects caused by NADPH oxidase, but not from those

  10. Sampling strategies for estimating acute and chronic exposures of pesticides in streams

    Science.gov (United States)

    Crawford, Charles G.

    2004-01-01

    The Food Quality Protection Act of 1996 requires that human exposure to pesticides through drinking water be considered when establishing pesticide tolerances in food. Several systematic and seasonally weighted systematic sampling strategies for estimating pesticide concentrations in surface water were evaluated through Monte Carlo simulation, using intensive datasets from four sites in northwestern Ohio. The number of samples for the strategies ranged from 4 to 120 per year. Sampling strategies with a minimal sampling frequency outside the growing season can be used for estimating time weighted mean and percentile concentrations of pesticides with little loss of accuracy and precision, compared to strategies with the same sampling frequency year round. Less frequent sampling strategies can be used at large sites. A sampling frequency of 10 times monthly during the pesticide runoff period at a 90 km 2 basin and four times monthly at a 16,400 km2 basin provided estimates of the time weighted mean, 90th, 95th, and 99th percentile concentrations that fell within 50 percent of the true value virtually all of the time. By taking into account basin size and the periodic nature of pesticide runoff, costs of obtaining estimates of time weighted mean and percentile pesticide concentrations can be minimized.

  11. Chronic exposure to rifaximin causes hepatic steatosis in pregnane X receptor-humanized mice.

    Science.gov (United States)

    Cheng, Jie; Krausz, Kristopher W; Tanaka, Naoki; Gonzalez, Frank J

    2012-10-01

    Rifaximin, a nonsystemic antibiotic that exhibits low gastrointestinal absorption, is a potent agonist of human pregnane X receptor (PXR), which contributes to its therapeutic efficacy in inflammatory bowel disease. To investigate the effects of long-term administration of rifaximin on the liver, PXR-humanized mice were administered rifaximin for 6 months; wild-type and Pxr-null mice were treated in parallel as controls. Histological analysis revealed time-dependent intense hepatocellular fatty degeneration and increased hepatic triglycerides in PXR-humanized mice and not in wild-type and Pxr-null mice. After long-term treatment, PXR target genes were induced in small intestine and liver, with significant up-regulation in the expression of hepatic genes related to triglyceride synthesis and lipid accumulation. However, no significant hepatic accumulation of rifaximin was found, even after 6 months of treatment, in PXR-humanized mice. Genes in the small intestine that are involved in the uptake of fatty acids and triglycerides were induced along with increased triglyceride accumulation in intestinal epithelial cells of PXR-humanized mice; this was not observed in wild-type and Pxr-null mice. These findings suggest that long-term administration of rifaximin could lead to PXR-dependent hepatocellular fatty degeneration as a result of activation of genes involved in lipid uptake, thus indicating a potential adverse effect of rifaximin on liver function after long-term exposure.

  12. Lactate dehydrogenase isoenzyme patterns upon chronic exposure to cigarette smoke: Protective effect of bacoside A.

    Science.gov (United States)

    Anbarasi, Kothandapani; Sabitha, Kuruvimalai Ekambaram; Devi, Chennam Srinivasulu Shyamala

    2005-09-01

    Despite a strong association between cigarette smoking and alarming increase in mortality rate from smoking-related diseases, around 35-40% of the world's population continues to smoke and many more are being exposed to environmental tobacco smoke. Since the role of free radicals and oxidative damage in the pathogenesis of smoking-related diseases has been suggested, bacoside A, a potent antioxidant was tested for its ability to protect against cigarette smoking-induced toxicity in terms of lactate dehydrogenase (LDH) and its isoenzymes. Rats were exposed to cigarette smoke and simultaneously administered with bacoside A, for a period of 12 weeks. Total LDH activity was assayed in serum, lung, heart, brain, liver and kidney, and serum LDH isoforms were separated electrophoretically. Cigarette smoke exposure resulted in significant increase in serum LDH and its isoenzymes with a concomitant decrease in these organs. These alterations were prevented by administration of bacoside A. Excessive oxidants from cigarette smoke is known to cause peroxidation of membrane lipids leading to cellular damage, thereby resulting in the leakage of LDH into the circulation. Bacoside A could have rendered protection to the organs by stabilizing their cell membranes and prevented the release of LDH, probably through its free radical scavenging and anti-lipid peroxidative effect.

  13. Chronic exposure to pulsed low-intensity microwaves is carcinogenic and tumorogenic

    Science.gov (United States)

    Lundquist, Marjorie

    2004-03-01

    To study health effects of lifetime exposure to low-intensity pulsed radiation >890 MHz, one controlled laboratory study of SPF* rats[1-3] and two of mice[4,5] were conducted, but only one[4] reported that its data showed an association between irradiation and cancer; reports of the other two studies minimized or denied such association. Critical review of these identified data evaluation errors; their correction enables a conclusion of microwave carcinogenicity from each study (the rat study also shows an association with endocrine-system primary malignancies and with a benign tumor of the adrenal medulla), enhancing the credibility of an epidemiological study[6] reporting a brain cancer risk for users of both analog and digital cellular phones. [1] J. Raloff. Science News 126(7):103(1984). [2] K. R. Foster & A. W. Guy. Sci Am 255(3):32-39(1986). [3] C.-K. Chou et al. Bioelectromagnetics 13:469-496(1992). [4] M. H. Repacholi et al. Radiat Res 147:631-640(1990)SPF\\. [5] T. D. Utteridge et al. Radiat Res 158:357-364(2002)non-SPF\\. [6] L. Hardell et al. Int J Oncol 22:399-407(2003). * SPF = specific-pathogen-free

  14. Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability

    Science.gov (United States)

    Lowen, Steven B.; Rohan, Michael L.; Gillis, Timothy E.; Thompson, Britta S.; Wellons, Clara B.W.; 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 applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral-mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue-induced neural response and may form the basis for habit-forming vulnerability. PMID:27006904

  15. Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability

    Directory of Open Access Journals (Sweden)

    Steven B. Lowen

    2015-01-01

    Full Text Available 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 applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral-mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue-induced neural response and may form the basis for habit-forming vulnerability.

  16. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    Directory of Open Access Journals (Sweden)

    Cristan Herbert

    2013-03-01

    Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC. We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These

  17. Acute and chronic toxicity of imidacloprid to the aquatic invertebrates Chironomus tentans and Hyalella azteca under constant- and pulse-exposure conditions.

    Science.gov (United States)

    Stoughton, Sarah J; Liber, Karsten; Culp, Joseph; Cessna, Allan

    2008-05-01

    The toxicity of imidacloprid, a nicotinic mimic insecticide, to the aquatic invertebrates Chironomus tentans and Hyalella azteca, was first evaluated in static 96-hour tests using both technical material (99.2% pure) and Admire, a commercially available formulated product (240 g a.i. L(-1)). The 96-h lethal concentration (LC)50 values for technical imidacloprid and Admire were 65.43 and 17.44 microg/L, respectively, for H. azteca, and 5.75 and 5.40 microg/L, respectively, for C. tentans. Admire was subsequently used in 28-day chronic tests with both species. Exposure scenarios consisted of a constant- and a pulse-exposure regime. The pulse exposure lasted for four days, after which time the animals were transferred to clean water for the remaining 24 days of the study. Assessments were made on both day 10 and day 28. In the C. tentans under constant exposure, larval growth on day 10 was significantly reduced at 3.57 microg/L imidacloprid, the lowest-observed-effect concentration (LOEC). The no-observed-effect concentration (NOEC) and LOEC for the 28-day exposure duration (adult survival and emergence) were 1.14 and greater than 1.14 mug/L, respectively; the associated LC50 and LC25 were 0.91 and 0.59 microg/L, respectively. The LOEC for the pulse treatment was greater than 3.47 microg/L, but the day 10 LC25 was 3.03 microg/L. In the H. azteca tests, the day 10 and 28 constant exposure, as well as the day 28 pulse exposure, LOEC (survival) values were similar at 11.95, 11.46, and 11.93 microg/L, respectively. The day 10 and 28 constant exposure effective concentration (EC)25s (dry weight) were also similar, at 6.22 and 8.72 microg/L, respectively, but were higher than the pulse-exposure day 10 LOEC and EC25 (dry weight) values of 3.53 and 2.22 microg/L, respectively. Overall, C. tentans was more sensitive to acute and chronic imidacloprid exposure, but less sensitive to a single pulse, than H. azteca. Chronic, low-level exposure to imidacloprid may therefore reduce

  18. Chronic homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons.

    Science.gov (United States)

    Schaub, Christina; Uebachs, Mischa; Beck, Heinz; Linnebank, Michael

    2013-04-01

    Homocystinuria is an inborn error of metabolism characterized by plasma homocysteine levels up to 500 μM, premature vascular events and mental retardation. Mild elevations of homocysteine plasma levels up to 25 μM, which are common in the general population, are associated with vascular disease, cognitive impairment and neurodegeneration. Several mechanisms of homocysteine neurotoxicity have been investigated. However, information on putative effects of hyperhomocysteinemia on the electrophysiology of neurons is limited. To screen for such effects, we examined primary cultures of mouse hippocampal neurons with the whole-cell patch-clamp technique. Homocysteine was applied intracellularly (100 μM), or cell cultures were incubated with 100 μM homocysteine for 24 h. Membrane voltage was measured in current-clamp mode, and action potential firing was induced with short and prolonged current injections. Single action potentials induced by short current injections (5 ms) were not altered by acute application or incubation of homocysteine. When we elicited trains of action potentials with prolonged current injections (200 ms), a broadening of action potentials during repetitive firing was observed in control neurons. This spike broadening was unaltered by acute application of homocysteine. However, it was significantly diminished when incubation with homocysteine was extended to 24 h prior to recording. Furthermore, the number of action potentials elicited by low current injections was reduced after long-term incubation with homocysteine, but not by the acute application. After 24 h of homocysteine incubation, the input resistance was reduced which might have contributed to the observed alterations in membrane excitability. We conclude that homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons as a mechanism of neurological symptoms of hyperhomocysteinemia.

  19. Chronic lead exposure decreases the vascular reactivity of rat aortas: the role of hydrogen peroxide.

    Directory of Open Access Journals (Sweden)

    Karolini Zuqui Nunes

    Full Text Available We investigated whether exposure to small concentrations of lead alters blood pressure and vascular reactivity. Male Wistar rats were sorted randomly into the following two groups: control (Ct and treatment with 100 ppm of lead (Pb, which was added to drinking water, for 30 days. Systolic blood pressure (BP was measured weekly. Following treatment, aortic ring vascular reactivity was assessed. Tissue samples were properly stored for further biochemical investigation. The lead concentration in the blood reached approximately 8 μg/dL. Treatment increased blood pressure and decreased the contractile responses of the aortic rings to phenylephrine (1 nM-100 mM. Following N-nitro-L arginine methyl ester (L-NAME administration, contractile responses increased in both groups but did not differ significantly between them. Lead effects on Rmax were decreased compared to control subjects following superoxide dismutase (SOD administration. Catalase, diethyldithiocarbamic acid (DETCA, and apocynin increased the vasoconstrictor response induced by phenylephrine in the aortas of lead-treated rats but did not increase the vasoconstrictor response in the aortas of untreated rats. Tetraethylammonium (TEA potentiated the vasoconstrictor response induced by phenylephrine in aortic segments in both groups, but these effects were greater in lead-treated rats. The co-incubation of TEA and catalase abolished the vasodilatory effect noted in the lead group. The present study is the first to demonstrate that blood lead concentrations well below the values established by international legislation increased blood pressure and decreased phenylephrine-induced vascular reactivity. The latter effect was associated with oxidative stress, specifically oxidative stress induced via increases in hydrogen peroxide levels and the subsequent effects of hydrogen peroxide on potassium channels.

  20. Hepatic and renal trace element concentrations in American alligators (Alligator mississippiensis) following chronic dietary exposure to coal fly ash contaminated prey.

    Science.gov (United States)

    Tuberville, Tracey D; Scott, David E; Metts, Brian S; Finger, John W; Hamilton, Matthew T

    2016-07-01

    Little is known about the propensity of crocodilians to bioaccumulate trace elements as a result of chronic dietary exposure. We exposed 36 juvenile alligators (Alligator mississippiensis) to one of four dietary treatments that varied in the relative frequency of meals containing prey from coal combustion waste (CCW)-contaminated habitats vs. prey from uncontaminated sites, and evaluated tissue residues and growth rates after 12 mo and 25 mo of exposure. Hepatic and renal concentrations of arsenic (As), cadmium (Cd) and selenium (Se) varied significantly among dietary treatment groups in a dose-dependent manner and were higher in kidneys than in livers. Exposure period did not affect Se or As levels but Cd levels were significantly higher after 25 mo than 12 mo of exposure. Kidney As and Se levels were negatively correlated with body size but neither growth rates nor body condition varied significantly among dietary treatment groups. Our study is among the first to experimentally examine bioaccumulation of trace element contaminants in crocodilians as a result of chronic dietary exposure. A combination of field surveys and laboratory experiments will be required to understand the effects of different exposure scenarios on tissue residues, and ultimately link these concentrations with effects on individual health.

  1. Triglyceride accumulation in long-term cultures of adult rat hepatocytes by chronic exposure to Aroclor 1254.

    Science.gov (United States)

    Mendoza-Figueroa, T; Hernández, A; López, M L

    1989-01-01

    The effect of chronic exposure to micromolar concentrations of Aroclor 1254 (Aro) on the hepatic lipid metabolism was studied in long-term cultures of adult rat hepatocytes. Hepatocytes were cocultivated with mitomycin C-treated 3T3 cells and exposed for 2 wk to Aroclor 1254 concentrations ranging from 0.01 to 20 micrograms/ml. The Aro-exposed cultures showed intracytoplasmic lipid droplets and a maximum increase of 55% in the triglyceride (TG) content and of 4.4-fold in the cytochrome P-450 content. Labeling studies with [14C]acetic and [14C]oleic acid showed no changes in the uptake of fatty acid and TG precursors by the Aro-treated cultures; the synthesis of cellular lipids from [14C]acetic acid was slightly inhibited by Aroclor 1254, but that from [14C]oleic acid was increased, specially for TG (37%). The secretion of total lipids and TG was 2.1- and 2.7-fold lower, respectively, in the cultures treated with 20 micrograms/ml of Aroclor 1254, resulting in an increase of 1.9-fold in the intracellular content of TG. The synthesis of cellular proteins labeled with [3H]leucine was unchanged in the Aro-treated cultures, but the secretion of exportable proteins was 1.7-fold lower in the cultures treated with 20 micrograms/ml of Aroclor 1254. Our results showed that long-term exposure to in vivo relevant concentrations of Aroclor 1254 produced morphological and biochemical changes in cultured hepatocytes, like those described in vivo, and intracellular TG accumulation due mostly to impaired secretion of TG by the hepatocytes. Our results also suggest that this culture system could be useful for the screening of toxic agents producing fatty liver and the study of the involved mechanism(s).

  2. Triglyceride accumulation in long-term cultures of adult rat hepatocytes by chronic exposure to Aroclor 1254

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza-Figueroa, T.; Hernandez, A.; de Lourdes Lopez, M. (Instituto Politecnico Nacional, Mexico City (Mexico))

    1989-01-01

    The effect of chronic exposure to micromolar concentrations of Aroclor 1254 (Aro) on the hepatic lipid metabolism was studied in long-term cultures of adult rat hepatocytes. Hepatocytes were cocultivated with mytomicin C-treated 3T3 cells and exposed for 2 wk to Aroclor 1254 concentrations ranging from 0.01 to 20 {mu}g/ml. The Aro-exposed cultures showed intracytoplasmic lipid droplets and a maximum increase of 55% in the triglyceride (TG) content and of 4.4-fold in the cytochrome P-450 content. Labeling studies with ({sup 14}C)acetic and ({sup 14}C)oleic acid showed no changes in the uptake of fatty acid and TG precursors by the Aro-treated cultures; the synthesis of cellular lipids from ({sup 14}C)acetic acid was slightly inhibited by Aroclor 1254, but that from ({sup 14}C)oleic acid was increased, specially for TF (37%). The secretion of total lipids and TG was 2.1- and 2.7-fold lower, respectively, in the cultures treated with 20 {mu}g/ml of Aroclor 1254, resulting in an increase of 1.9-fold in the intracellular content of TG. The synthesis of cellular proteins labeled with ({sup 3}H)leucine was unchanged in the Aro-treated cultures, but the secretion of exportable proteins was 1.7-fold lower in the cultures treated with 20 {mu}g/ml of Aroclor 1254. Our results showed that long-term exposure to in vivo relevant concentrations of Aroclor 1254 produced morphological and biochemical changes in cultured hepatocytes, like those described in vivo, and intracellular TG accumulation due mostly to impaired secretion of TG by the hepatocytes. Our results also suggest that this culture system could be useful for the screening of toxic agents producing fatty liver and the study of the involved mechanism(s).

  3. Physiological Predictors of Response to Exposure, Relaxation, and Rescripting Therapy for Chronic Nightmares in a Randomized Clinical Trial

    Science.gov (United States)

    Davis, Joanne L.; Rhudy, Jamie L.; Pruiksma, Kristi E.; Byrd, Patricia; Williams, Amy E.; McCabe, Klanci M.; Bartley, Emily J.

    2011-01-01

    Study Objectives: Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy(ERRT) and extended prior research by including broad measures of mental health difficulties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined. Methods: Forty-seven individuals were randomized to treatment or waitlist control. Results: The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, significant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health. Conclusions: Findings provide additional support for the use of ERRT in treating nightmares and related difficulties and improving sleep. Citation: Davis JL; Rhudy JL; Pruiksma KE; Byrd P; Williams AE; McCabe KM; Bartley EJ. Physiological predictors of response to exposure, relaxation, and rescripting therapy for chronic nightmares in a randomized clinical trial. J Clin Sleep Med 2011;7(6):622-631. PMID:22171201

  4. Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea.

    Directory of Open Access Journals (Sweden)

    Yunji Hwang

    Full Text Available This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC.The Thyroid Cancer Longitudinal Study (T-CALOS included 2,258 DTC patients (449 men and 1,809 women and 22,580 healthy participants (4,490 men and 18,090 women who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs and 95% confidence intervals (95%CI were estimated using conditional regression models.While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion was associated with increased risks in men (OR = 2.22, 95%CI = 1.27-3.87 and women (OR = 3.61, 95%CI = 1.52-8.58 compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31-40 years: OR = 1.58, 95%CI = 1.10-2.28; 41+ years: OR = 3.46, 95%CI = 2.06-5.80 and women (31-40 years: OR = 2.18, 95%CI = 1.62-2.92; 41+ years: OR = 2.71, 95%CI = 1.36-5.05 compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage.The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.

  5. ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure.

    Directory of Open Access Journals (Sweden)

    Jingchun Chen

    Full Text Available Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS sample showed similar pattern of association with number of cigarettes smoked per day (numCIG for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000 for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions.

  6. EROD activity and antioxidant defenses of sea bass (Dicentrarchus labrax) after an in vivo chronic hydrocarbon pollution followed by a post-exposure period.

    Science.gov (United States)

    Danion, Morgane; Le Floch, Stéphane; Lamour, François; Quentel, Claire

    2014-12-01

    Chronic concentrations of polycyclic aromatic hydrocarbons (PAHs) have been commonly detected in international estuaries ecosystems. Reliable indicators still need to be found in order to properly assess the impact of PAHs in fish. After an in vivo chronic exposure to hydrocarbons, the enzymatic activity of 7-ethoxyresorufin O-deethylase (EROD) and the antioxidant defense system were assessed in sea bass, Dicentrarchus labrax. A total of 45 fish were exposed to the water-soluble fraction of Arabian crude oil, similar to a complex pollution by hydrocarbons chronically observed in situ, while 45 other control fish sustained the same experimental conditions in clean seawater. Fish samples were made after a 21-day exposure period and after a 15-day recovery period in clean fresh water. Throughout the experiment, liver EROD activity was significantly higher in contaminated fish than in control fish. In addition, nonenzymatic (total glutathione) and enzymatic (GPx, SOD, and CAT) antioxidant defense parameters measured in liver were not significantly different in fish. Furthermore, in gills, glutathione content had significantly increased while SOD activity had significantly decreased in contaminated fish compared to controls. On the other hand, CAT and GPx activities were not affected. Chronic exposure to PAHs disturbing the first step (SOD) and inhibiting the second step (GPx and CAT) could induce oxidative stress in tissues by the formation of oxygen radicals. After the postexposure period, there was no significant difference between control and contaminated fish in any of the antioxidant defense parameters measured in gills, attesting to the reversibility of the effects.

  7. Role of orexin A signaling in dietary palmitic acid-activated microglial cells.

    Science.gov (United States)

    Duffy, Cayla M; Yuan, Ce; Wisdorf, Lauren E; Billington, Charles J; Kotz, Catherine M; Nixon, Joshua P; Butterick, Tammy A

    2015-10-08

    Excess dietary saturated fatty acids such as palmitic acid (PA) induce peripheral and hypothalamic inflammation. Hypothalamic inflammation, mediated in part by microglial activation, contributes to metabolic dysregulation. In rodents, high fat diet-induced microglial activation results in nuclear translocation of nuclear factor-kappa B (NFκB), and increased central pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The hypothalamic neuropeptide orexin A (OXA, hypocretin 1) is neuroprotective in brain. In cortex, OXA can also reduce inflammation and neurodegeneration through a microglial-mediated pathway. Whether hypothalamic orexin neuroprotection mechanisms depend upon microglia is unknown. To address this issue, we evaluated effects of OXA and PA on inflammatory response in immortalized murine microglial and hypothalamic neuronal cell lines. We demonstrate for the first time in microglial cells that exposure to PA increases gene expression of orexin-1 receptor but not orexin-2 receptor. Pro-inflammatory markers IL-6, TNF-α, and inducible nitric oxide synthase in microglial cells are increased following PA exposure, but are reduced by pretreatment with OXA. The anti-inflammatory marker arginase-1 is increased by OXA. Finally, we show hypothalamic neurons exposed to conditioned media from PA-challenged microglia have increased cell survival only when microglia were pretreated with OXA. These data support the concept that OXA may act as an immunomodulatory regulator of microglia, reducing pro-inflammatory cytokines and increasing anti-inflammatory factors to promote a favorable neuronal microenvironment.

  8. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Science.gov (United States)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  9. Palmitic acid and linoleic acid metabolism in Caco-2 cells: Different triglyceride synthesis and lipoprotein secretion

    NARCIS (Netherlands)

    van Greevenbroek, M.M.J.; Voorhout, W.F.; Erkelens, D.W.; van Meer, G.; de Bruin, T.W.A.

    1995-01-01

    Polarized monolayers of intestinal Caco-2 cells were used to study the effects of saturated palmitic acid (16:0) and polyunsaturated linoleic acid (18:2) on triglyceride synthesis and lipoprotein secretion. Monolayers were incubated for 24 h, at the apical or lumenal side, with palmitic acid (16:0)

  10. 21 CFR 178.3450 - Esters of stearic and palmitic acids.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Esters of stearic and palmitic acids. 178.3450 Section 178.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... SANITIZERS Certain Adjuvants and Production Aids § 178.3450 Esters of stearic and palmitic acids. The...

  11. Global burden of mortalities due to chronic exposure to ambient PM2.5 from open combustion of domestic waste

    Science.gov (United States)

    Kodros, John K.; Wiedinmyer, Christine; Ford, Bonne; Cucinotta, Rachel; Gan, Ryan; Magzamen, Sheryl; Pierce, Jeffrey R.

    2016-12-01

    Uncontrolled combustion of domestic waste has been observed in many countries, creating concerns for air quality; however, the health implications have not yet been quantified. We incorporate the Wiedinmyer et al (2014 Environ. Sci. Technol. 48 9523-30) emissions inventory into the global chemical-transport model, GEOS-Chem, and provide a first estimate of premature adult mortalities from chronic exposure to ambient PM2.5 from uncontrolled combustion of domestic waste. Using the concentration-response functions (CRFs) of Burnett et al (2014 Environ. Health Perspect. 122 397-403), we estimate that waste-combustion emissions result in 270 000 (5th-95th: 213 000-328 000) premature adult mortalities per year. The confidence interval results only from uncertainty in the CRFs and assumes equal toxicity of waste-combustion PM2.5 to all other PM2.5 sources. We acknowledge that this result is likely sensitive to choice of chemical-transport model, CRFs, and emission inventories. Our central estimate equates to 9% of adult mortalities from exposure to ambient PM2.5 reported in the Global Burden of Disease Study 2010. Exposure to PM2.5 from waste combustion increases the risk of premature mortality by more than 0.5% for greater than 50% of the population. We consider sensitivity simulations to uncertainty in waste-combustion emission mass, the removal of waste-combustion emissions, and model resolution. A factor-of-2 uncertainty in waste-combustion PM2.5 leads to central estimates ranging from 138 000 to 518 000 mortalities per year for factors-of-2 reductions and increases, respectively. Complete removal of waste combustion would only avoid 191 000 (5th-95th: 151 000-224 000) mortalities per year (smaller than the total contributed premature mortalities due to nonlinear CRFs). Decreasing model resolution from 2° × 2.5° to 4° × 5° results in 16% fewer mortalities attributed to waste-combustion PM2.5, and over Asia, decreasing resolution from 0.5° × 0.666° to 2° × 2

  12. Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.

    Science.gov (United States)

    Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J

    We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.

  13. Effects of chronic exposure to diluted automotive exhaust gas on the CNS of normotensive and hypertensive rats.

    Science.gov (United States)

    Roggendorf, W; Thron, N L; Ast, D; Köhler, P R

    1981-01-01

    Regarding the potential impact of traffic-born air pollutants on public health, attention during the last years has been increasingly focused on the possible effects in high-risk groups of the population. In order to evaluated this point further, the combined influence of both, chronic arterial hypertension and long-time exhaust gas exposure on the CNS has been studied. Both, normotensive Wistar) and spontaneously hypertensive rats (SHR) of either sex were exposed 5 X 8 hours per week for up to 18 months to atmospheres polluted by the emissions of an idling Otto engine with CO concentrations held constant at about 0,90 and 250 ppm, respectively. Biochemical data, body weight, and blood pressure were checked regularly. Characteristic histomorphological findings in the non-exposed SHR brains were hyalinosis and hyperplasia of intracerebral arterioles and -- in some cases -- small focal hemorrhages and infarcts. In the exposed SHR brains, large infarcts of the hemisphere and in the basal ganglia were found, which possibly corresponds to the increase of the mortality rate in SHR. We assume that the increase hematocrit plays an important role in the disturbance of microcirculation of the CNS.

  14. Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.

    Science.gov (United States)

    Antunes, S C; Nunes, B; Rodrigues, S; Nunes, R; Fernandes, J; Correia, A T

    2016-07-01

    Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here.

  15. DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry.

    Science.gov (United States)

    Savina, Natalya V; Smal, Marharyta P; Kuzhir, Tatyana D; Ershova-Pavlova, Alla A; Goncharova, Roza I

    2012-10-09

    The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored.

  16. Nitrogen inputs and losses in response to chronic CO2 exposure in a sub-tropical oak woodland

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    B. A. Hungate

    2014-01-01

    Full Text Available Rising atmospheric CO2 concentrations could alter the nitrogen (N content of ecosystems by changing N inputs and N losses, but responses vary in field experiments, possibly because multiple mechanisms are at play. We measured N fixation and N losses in a subtropical oak woodland exposed to 11 yr of elevated atmospheric CO2 concentrations. We also explored the role of herbivory, carbon limitation, and competition for light and nutrients in shaping response of N fixation to elevated CO2. Elevated CO2 did not significantly alter gaseous N losses, but lower recovery and deeper distribution in the soil of a long-term 15N tracer indicated that elevated CO2 increased leaching losses. Elevated CO2 had no effect on asymbiotic N fixation, and had a transient effect on symbiotic N fixation by the dominant legume. Elevated CO2 tended to reduce soil and plant concentrations of iron, molybdenum, phosphorus, and vanadium, nutrients essential for N fixation. Competition for nutrients and herbivory likely contributed to the declining response N fixation to elevated CO2. These results indicate that positive responses of N fixation to elevated CO2 may be transient, and that chronic exposure to elevated CO2 can increase N leaching. Models that assume increased fixation or reduced N losses with elevated CO2 may overestimate future N accumulation in the biosphere.

  17. Effects of chronic exposure to air pollution from Sao Paulo city on coronary of Swiss mice, from birth to adulthood.

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    Akinaga, Lícia Mioko Yoshizaki; Lichtenfels, Ana Julia; Carvalho-Oliveira, Regiani; Caldini, Elia Garcia; Dolhnikoff, Marisa; Silva, Luiz Fernando Ferraz; Bueno, Heloisa Maria De Siqueira; Pereira, Luiz Alberto Amador; Saldiva, Paulo Hilário Nascimento; Garcia, Maria Lúcia Bueno

    2009-04-01

    To explore the hypothesis that air pollution promotes cardiovascular changes, Swiss mice were continuously exposed, since birth, in two open-top chambers (filtered and nonfiltered for airborne particles chronic exposure to urban air since birth induces mild but significant vascular structural alterations in normal individuals, presented as coronary arteriolar fibrosis and elastosis. These results might contribute to altered vascular response and ischemic events in the adulthood.

  18. Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.

    Science.gov (United States)

    Ince, S; Avdatek, F; Demirel, H H; Arslan-Acaroz, D; Goksel, E; Kucukkurt, I

    2016-06-01

    Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100 mg l(-1) , approximately 1/50 of oral LD50 ) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg(-1) for 60 days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic-treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200 mg kg(-1) , reversed arsenic-induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic-induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats.

  19. Chronic exposure to broadband noise at moderate sound pressure levels spatially shifts tone-evoked responses in the rat auditory midbrain.

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    Lau, Condon; Pienkowski, Martin; Zhang, Jevin W; McPherson, Bradley; Wu, Ed X

    2015-11-15

    Noise-induced hearing disorders are a significant public health concern. One cause of such disorders is exposure to high sound pressure levels (SPLs) above 85 dBA for eight hours/day. High SPL exposures occur in occupational and recreational settings and affect a substantial proportion of the population. However, an even larger proportion is exposed to more moderate SPLs for longer durations. Therefore, there is significant need to better understand the impact of chronic, moderate SPL exposures on auditory processing, especially in the absence of hearing loss. In this study, we applied functional magnetic resonance imaging (fMRI) with tonal acoustic stimulation on an established broadband rat exposure model (65 dB SPL, 30 kHz low-pass, 60 days). The auditory midbrain response of exposed subjects to 7 kHz stimulation (within exposure bandwidth) shifts dorsolaterally to regions that typically respond to lower stimulation frequencies. This shift is quantified by a region of interest analysis that shows that fMRI signals are higher in the dorsolateral midbrain of exposed subjects and in the ventromedial midbrain of control subjects (pmidbrain regions above the exposure bandwidth spatially expand due to exposure. This expansion shifts lower frequency regions dorsolaterally. Similar observations have previously been made in the rat auditory cortex. Therefore, moderate SPL exposures affect auditory processing at multiple levels, from the auditory cortex to the midbrain.

  20. Beta-palmitate - a natural component of human milk in supplemental milk formulas.

    Science.gov (United States)

    Havlicekova, Zuzana; Jesenak, Milos; Banovcin, Peter; Kuchta, Milan

    2016-03-17

    The composition and function of human milk is unique and gives a basis for the development of modern artificial milk formulas that can provide an appropriate substitute for non-breastfed infants. Although human milk is not fully substitutable, modern milk formulas are attempting to mimic human milk and partially substitute its complex biological positive effects on infants. Besides the immunomodulatory factors from human milk, research has been focused on the composition and structure of human milk fat with a high content of β-palmitic acid (sn-2 palmitic acid, β-palmitate). According to the available studies, increasing the content of β-palmitate added to milk formulas promotes several beneficial physiological functions. β-palmitate positively influences fatty acid metabolism, increases calcium absorption, improves bone matrix quality and the stool consistency, and has a positive effect on the development of the intestinal microbiome.

  1. Cytoprotective Effect of Hispidin against Palmitate-Induced Lipotoxicity in C2C12 Myotubes

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    Jun Myoung Park

    2015-03-01

    Full Text Available It is well known that Phellinus linteus, which produces hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in C2C12 myotubes increased ROS generation and cell death as compared with the control. However, pretreatment of hispidin for 8 h improved the survival of C2C12 myotubes against palmitate-induced oxidative stress via inhibition of intracellular ROS production. Hispidin also inhibited palmitate-induced apoptotic nuclear condensation in C2C12 myotubes. In addition, we found that hispidin can suppress cleavage of caspase-3, expression of Bax, and NF-κB translocation. Therefore, these results suggest that hispidin is capable of protecting C2C12 myotubes against palmitate-induced oxidative stress.

  2. Effects of chronic exposure to dietary selenomethionine on the physiological stress response in juvenile white sturgeon (Acipenser transmontanus).

    Science.gov (United States)

    Patterson, Sarah; Zee, Jenna; Wiseman, Steve; Hecker, Markus

    2017-02-03

    dose WS. Exposure to an acute handling stressor elicited a typical cortisol response, but the magnitude of the response appeared to be significantly lower than those typically observed in teleosts. SeMeth also did not appear to modulate the cortisol response to a secondary stressor. However, WS exposed to 22.4μg Se/g dm and sampled 2h post-stressor, had significantly higher concentrations of muscle glycogen compared to controls, indicating effects on their ability to utilize muscle glycogen for energy. Overall, the results indicate that chronic exposure to dietary SeMeth concentrations >22.4μg/g can affect cortisol dynamics and mobilization of energy substrates in juvenile WS.

  3. Behavioral effects of D3 receptor inhibition and 5-HT4 receptor activation on animals undergoing chronic cannabinoid exposure during adolescence.

    Science.gov (United States)

    Abboussi, Oualid; Said, Nadia; Fifel, Karim; Lakehayli, Sara; Tazi, Abdelouahhab; El Ganouni, Soumaya

    2016-04-01

    Chronic exposure to cannabinoids during adolescence results in long-lasting behavioral deficits that match some symptomatologic aspects of schizophrenia. The aim of this study was to investigate the reversibility of the emotional and the cognitive effects of chronic exposure to cannabinoids during adolescence, via subsequent modulation of the serotoninergic 5-HT4 and dopaminergic D3 receptors. RS67333 as a 5-HT4 agonist and U-99194A as a D3 antagonist were administered separately at 1 mg/kg and 20 mg/kg, and in combination at 0.5 mg/kg and 10 mg/kg to adult animals undergoing chronic treatment with the synthetic cannabinoid receptor agonist WIN55,212-2 (1 mg/kg) during adolescence. Animals were tested for anxiety-like behavior and episodic-like memory in the open field and novel object recognition tests respectively 30 minutes after the last drug administration. Chronic WIN55,212-2 treated animals exhibited a lasting disruption of episodic memory and increased anxiety levels. The effect on episodic-like memory were partially restored by acute administration of RS67333 and U-99194A and completely by administration of both drugs in combination at lower doses. However, only RS67333 (20 mg/kg) improved the anxiogenic-like effect of WIN55,212-2. These findings give further support that chronic exposure to cannabinoids during adolescence may be used as an animal model for schizophrenia, and highlight D3 and 5-HT4 receptors as potential targets for an enhanced treatment of the cognitive aspect of this disease.

  4. Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air

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    Lopez Ivan A

    2009-05-01

    Full Text Available Abstract Background The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO exposure (25 parts per million subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5 to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO. At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS, neuronal (nNOS, and endothelial (eNOS nitric oxide synthases. Results Superoxide dismutase-1 (SOD1, SOD2, and hemeoxygenase-1 (HO-1 immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein, synapsin-1 (functional protein, and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA, were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained

  5. Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

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    Cabrera R.J.

    1999-01-01

    Full Text Available Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS during pregnancy (prenatal stress; PS group. Control pregnant rats (C group were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36 while the other PS pups were cross-fostered with C dams (PSF group, N = 47 and the other C pups were cross-fostered with PS dams (CF group, N = 58. Pups were undisturbed until weaning (postnatal day 28. The male offspring underwent motor activity tests (day 28, enriched environment tests (day 37 and social interaction tests (day 42 in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, P<0.05. The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; c2 test, P<0.05 and lower body weight than controls at days 28 and 60 (Duncan's test, P<0.05 and P<0.01, respectively. The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, P<0.01 for PS group and P<0.05 for CF and PSF groups. In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, P<0.05. Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, P<0.05. In fact, CVS treatment during gestation plus

  6. The effect of oleic and palmitic acid on induction of steatosis and cytotoxicity on rat hepatocytes in primary culture.

    Science.gov (United States)

    Moravcová, A; Červinková, Z; Kučera, O; Mezera, V; Rychtrmoc, D; Lotková, H

    2015-01-01

    In vitro models serve as a tool for studies of steatosis. Palmitic and oleic acids can induce steatosis in cultured hepatocytes. The aim of our study was to verify steatogenic and cytotoxic effects of palmitic acid (PA), oleic acid (OA) and their combinations as well as their impact on functional capacity of rat primary hepatocytes. Hepatocytes were exposed to OA or PA (0.125-2 mmol/l) or their combination at ratios of 3:1, 2:1 or 1:1 at the final concentrations of 0.5-1 mmol/l. Both OA and PA caused a dose-dependent increase in triacylglycerol content in hepatocytes. PA was more steatogenic at 0.25 and 0.5 mmol/l while OA at 0.75 and 1 mmol/l. PA exhibited a dose-dependent cytotoxic effect associated with ROS production, present markers of apoptosis and necrosis and a decrease in albumin production. OA induced a damage of the cytoplasmic membrane from 1 mM concentration. Mixture of OA and PA induced lower cytotoxicity with less weakened functional capacity than did PA alone. Extent of steatosis was comparable to that after exposure to OA alone. In conclusion, OA or combination of OA with PA is more suitable for simulation of simple steatosis than PA alone.

  7. Chronic exposure to triclosan sustains microbial community shifts and alters antibiotic resistance gene levels in anaerobic digesters.

    Science.gov (United States)

    Carey, Daniel E; Zitomer, Daniel H; Kappell, Anthony D; Choi, Melinda J; Hristova, Krassimira R; McNamara, Patrick J

    2016-08-10

    Triclosan, an antimicrobial chemical found in consumer personal care products, has been shown to stimulate antibiotic resistance in pathogenic bacteria. Although many studies focus on antibiotic resistance pertinent to medical scenarios, resistance developed in natural and engineered environments is less studied and has become an emerging concern for human health. In this study, the impacts of chronic triclosan (TCS) exposure on antibiotic resistance genes (ARGs) and microbial community structure were assessed in lab-scale anaerobic digesters. TCS concentrations from below detection to 2500 mg kg(-1) dry solids were amended into anaerobic digesters over 110 days and acclimated for >3 solid retention time values. Four steady state TCS concentrations were chosen (30-2500 mg kg(-1)). Relative abundance of mexB, a gene coding for a component of a multidrug efflux pump, was significantly higher in all TCS-amended digesters (30 mg kg(-1) or higher) relative to the control. TCS selected for bacteria carrying tet(L) and against those carrying erm(F) at concentrations which inhibited digester function; the pH decrease associated with digester failure was suspected to cause this selection. Little to no impact of TCS was observed on intI1 relative abundance. Microbial communities were also surveyed by high-throughput 16S rRNA gene sequencing. Compared to the control digesters, significant shifts in community structure towards clades containing commensal and pathogenic bacteria were observed in digesters containing TCS. Based on these results, TCS should be included in studies and risk assessments that attempt to elucidate relationships between chemical stressors (e.g. antibiotics), antibiotic resistance genes, and public health.

  8. The Efficacy of Syzygium aromaticum Essential Oil in Cognitive Disorders against Manganese Chronic Exposure in Rats during Development

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    Djallal Eddine Houari ADLI

    2014-06-01

    Full Text Available The essential oil of Syzygium aromaticum has been widely used in traditional medicine to treat a variety of diseases, including some neurological disorders. This study aims at testing, in vivo, the possible anxiolytic and antidepressant effects, of the Syzygium aromaticum essential oil against chronic manganese chloride (4.79 mg/l intoxication during the gestation and lactation period, in Wistar rat pups. Wistar rat pups were exposed to manganese via their dams’ drinking water from postnatal day (PND 1 to (PND 21. After their weaning, the rats exposed to manganese received injections of essential oil of Syzygium aromaticum (0.1 ml/kg for 18 days. The level of anxiety, depression and locomotor activity were studied. Locomotor activity (open field test, anxiety (elevated plus maze tests, and depression (forced swimming test were evaluated. The results of the present study indicate that Manganese exposure induces, on the one hand, impairments of body (p<0.001 and of brain weight (p<0.05. On the other hand, it increases level of anxiety (p<0.05, depression (p<0.001 and locomotor hyporactivity (p<0.001, when compared to control rats. Administration of essential oil of Syzygium aromaticum leads to a reduction in the level of anxiety (p<0.05, of depression (p<0.001 and corrects locomotor hyporactivity (p<0.05 in rats exposed to manganese beforehand. These results suggest that essential oil of Syzygium aromaticum can employ as a natural, protective agent against neuro-toxicity induced by manganese chloride during the gestation and lactation periods.

  9. Chronic exposure of imidacloprid and clothianidin reduce queen survival, foraging, and nectar storing in colonies of Bombus impatiens.

    Science.gov (United States)

    Scholer, Jamison; Krischik, Vera

    2014-01-01

    In an 11-week greenhouse study, caged queenright colonies of Bombus impatiens Cresson, were fed treatments of 0 (0 ppb actual residue I, imidacloprid; C, clothianidin), 10 (14 I, 9 C), 20 (16 I, 17C), 50 (71 I, 39 C) and 100 (127 I, 76 C) ppb imidacloprid or clothianidin in sugar syrup (50%). These treatments overlapped the residue levels found in pollen and nectar of many crops and landscape plants, which have higher residue levels than seed-treated crops (less than 10 ppb, corn, canola and sunflower). At 6 weeks, queen mortality was significantly higher in 50 ppb and 100 ppb and by 11 weeks in 20 ppb-100 ppb neonicotinyl-treated colonies. The largest impact for both neonicotinyls starting at 20 (16 I, 17 C) ppb was the statistically significant reduction in queen survival (37% I, 56% C) ppb, worker movement, colony consumption, and colony weight compared to 0 ppb treatments. Bees at feeders flew back to the nest box so it appears that only a few workers were collecting syrup in the flight box and returning the syrup to the nest. The majority of the workers sat immobilized for weeks on the floor of the flight box without moving to fed at sugar syrup feeders. Neonicotinyl residues were lower in wax pots in the nest than in the sugar syrup that was provided. At 10 (14) ppb I and 50 (39) ppb C, fewer males were produced by the workers, but queens continued to invest in queen production which was similar among treatments. Feeding on imidacloprid and clothianidin can cause changes in behavior (reduced worker movement, consumption, wax pot production, and nectar storage) that result in detrimental effects on colonies (queen survival and colony weight). Wild bumblebees depending on foraging workers can be negatively impacted by chronic neonicotinyl exposure at 20 ppb.

  10. Chronic exposure of imidacloprid and clothianidin reduce queen survival, foraging, and nectar storing in colonies of Bombus impatiens.

    Directory of Open Access Journals (Sweden)

    Jamison Scholer

    Full Text Available In an 11-week greenhouse study, caged queenright colonies of Bombus impatiens Cresson, were fed treatments of 0 (0 ppb actual residue I, imidacloprid; C, clothianidin, 10 (14 I, 9 C, 20 (16 I, 17C, 50 (71 I, 39 C and 100 (127 I, 76 C ppb imidacloprid or clothianidin in sugar syrup (50%. These treatments overlapped the residue levels found in pollen and nectar of many crops and landscape plants, which have higher residue levels than seed-treated crops (less than 10 ppb, corn, canola and sunflower. At 6 weeks, queen mortality was significantly higher in 50 ppb and 100 ppb and by 11 weeks in 20 ppb-100 ppb neonicotinyl-treated colonies. The largest impact for both neonicotinyls starting at 20 (16 I, 17 C ppb was the statistically significant reduction in queen survival (37% I, 56% C ppb, worker movement, colony consumption, and colony weight compared to 0 ppb treatments. Bees at feeders flew back to the nest box so it appears that only a few workers were collecting syrup in the flight box and returning the syrup to the nest. The majority of the workers sat immobilized for weeks on the floor of the flight box without moving to fed at sugar syrup feeders. Neonicotinyl residues were lower in wax pots in the nest than in the sugar syrup that was provided. At 10 (14 ppb I and 50 (39 ppb C, fewer males were produced by the workers, but queens continued to invest in queen production which was similar among treatments. Feeding on imidacloprid and clothianidin can cause changes in behavior (reduced worker movement, consumption, wax pot production, and nectar storage that result in detrimental effects on colonies (queen survival and colony weight. Wild bumblebees depending on foraging workers can be negatively impacted by chronic neonicotinyl exposure at 20 ppb.

  11. Paliperidone palmitate injection for the acute and maintenance treatment of schizophrenia in adults

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    Kim S

    2012-07-01

    Full Text Available Shiyun Kim,1 Hugo Solari,2 Peter J Weiden,2 Jeffrey R Bishop11Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, 2Department of Psychiatry, University of Illinois at Chicago College of Medicine, Chicago, IL, USAPurpose: To review the use of paliperidone palmitate in treatment of patients with schizophrenia.Methods: Published clinical trial data for the development and utilization of paliperidone palmitate for the treatment of schizophrenia were assessed in this review. Four short-term, randomized, double-blind, placebo-controlled trials investigated the efficacy of paliperidone palmitate in acute exacerbation of schizophrenia. Paliperidone palmitate was also studied as a maintenance treatment to prevent or delay relapse in stable schizophrenia. In addition, paliperidone palmitate was compared to risperidone long-acting injection for noninferiority in three studies.Results: Paliperidone palmitate has been shown to be effective in reducing symptoms as measured by the Positive and Negative Syndrome Scale total scores in the four acute treatment studies. In the maintenance treatment studies, paliperidone palmitate was found to be more effective than placebo in preventing or delaying the time to first relapse in stable schizophrenia patients. In addition, paliperidone palmitate was shown to be noninferior to risperidone long-acting injection in two studies. It was shown to be reasonably well tolerated in all clinical trials. Acute treatment phase should be initiated with a dose of 234 mg on day one and 156 mg on day eight, followed by a recommended monthly maintenance dose of 39–234 mg based on efficacy and tolerability results from the clinical studies.Conclusion: Providing an optimal long-term treatment can be challenging. Paliperidone palmitate can be used as an acute treatment even in outpatient setting, and it has shown to be well tolerated by patients. Also, it does not require overlapping oral

  12. Chronic Lead Exposure and Mixed Factors of Gender×Age×Brain Regions Interactions on Dendrite Growth, Spine Maturity and NDR Kinase.

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    Yang Du

    Full Text Available NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender×age×brain regions remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender×age×brain regions, as well as the NDR1/2 kinase expression. Sprague-Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real-time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender×age×brain regions effects and related to NDR1/2 signal expression.

  13. Investigation of the interaction of naringin palmitate with bovine serum albumin: spectroscopic analysis and molecular docking.

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    Xia Zhang

    Full Text Available BACKGROUND: Bovine serum albumin (BSA contains high affinity binding sites for several endogenous and exogenous compounds and has been used to replace human serum albumin (HSA, as these two compounds share a similar structure. Naringin palmitate is a modified product of naringin that is produced by an acylation reaction with palmitic acid, which is considered to be an effective substance for enhancing naringin lipophilicity. In this study, the interaction of naringin palmitate with BSA was characterised by spectroscopic and molecular docking techniques. METHODOLOGY/PRINCIPAL FINDINGS: The goal of this study was to investigate the interactions between naringin palmitate and BSA under physiological conditions, and differences in naringin and naringin palmitate affinities for BSA were further compared and analysed. The formation of naringin palmitate-BSA was revealed by fluorescence quenching, and the Stern-Volmer quenching constant (KSV was found to decrease with increasing temperature, suggesting that a static quenching mechanism was involved. The changes in enthalpy (ΔH and entropy (ΔS for the interaction were detected at -4.11 ± 0.18 kJ·mol(-1 and -76.59 ± 0.32 J·mol(-1·K(-1, respectively, which indicated that the naringin palmitate-BSA interaction occurred mainly through van der Waals forces and hydrogen bond formation. The negative free energy change (ΔG values of naringin palmitate at different temperatures suggested a spontaneous interaction. Circular dichroism studies revealed that the α-helical content of BSA decreased after interacting with naringin palmitate. Displacement studies suggested that naringin palmitate was partially bound to site I (subdomain IIA of the BSA, which was also substantiated by the molecular docking studies. CONCLUSIONS/SIGNIFICANCE: In conclusion, naringin palmitate was transported by BSA and was easily removed afterwards. As a consequence, an extension of naringin applications for use in food, cosmetic

  14. Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion.

    Science.gov (United States)

    Mickley, G Andrew; Remus, Jennifer L; Ramos, Linnet; Wilson, Gina N; Biesan, Orion R; Ketchesin, Kyle D

    2012-01-18

    opportunity to drink saccharin was provided (spontaneous recovery test). Saline-treated control rats that went through the EU-EXT procedure achieved asymptotic extinction more quickly than did the CSO-EXT rats and did not exhibit a spontaneous recovery of the CTA. Chronic DCS treatments did not significantly reduce the time to achieve asymptotic CTA extinction in rats exposed to either CSO or EU extinction methods. Further, animals treated with DCS throughout EU-EXT exhibited a spontaneous recovery of the CTA whereas the saline-treated, EU-EXT rats did not. Thus, chronic DCS treatment did not shorten the time to extinguish a CTA and this treatment eliminated the ability of EU-EXT to block spontaneous recovery of the CTA. Acute DCS treatments were more effective in reducing the time required to extinguish a CTA than were chronic drug treatments. Moreover, the timing of these acute DCS treatments affected spontaneous recovery of the CTA depending on the extinction method employed. Acute DCS administrations later in extinction were more effective in reducing spontaneous recovery than were early administrations if the rats went through the CSO-EXT procedure. However, late-in-extinction administrations of DCS facilitated spontaneous recovery of the CTA in rats that experienced the EU-EXT method. These data agree with other findings suggesting that DCS treatments are more effective when administered a limited number of times. Our data extend these findings to the CTA paradigm and further suggest that, depending on the extinction paradigm employed, acute exposure to DCS can speed up CTA extinction and reduce spontaneous recovery of the aversion. The timing of the acute DCS treatment during extinction is generally less important than its duration in predicting the rate of CTA extinction. However, the timing of acute DCS treatments during extinction and the method of extinction employed can interact to affect spontaneous recovery of a CTA.

  15. Insights antifibrotic mechanism of methyl palmitate: Impact on nuclear factor kappa B and proinflammatory cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Mantawy, Eman M.; Tadros, Mariane G. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Awad, Azza S. [Department of Pharmacology and Toxicology, Faulty of Pharmacy, Al-Azhar University, Cairo (Egypt); Hassan, Dina A.A. [Department of Histology, Faculty of Medicine, Al-Azhar University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-01-01

    Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment is evident. The present study was designed to assess the potential antifibrotic effect of MP and whether MP can attenuate the severity of oxidative stress and inflammatory response in chronic liver injury. Male albino rats were treated with either CCl{sub 4} (1 ml/kg, twice a week) and/or MP (300 mg/kg, three times a week) for six weeks. CCl{sub 4}-intoxication significantly increased liver weight, serum aminotransferases, total cholesterol and triglycerides while decreased albumin level and these effects were prevented by co-treatment with MP. As indicators of oxidative stress, CCl{sub 4}-intoxication caused significant glutathione depletion and lipid peroxidation while MP co-treatment preserved them within normal values. As markers of fibrosis, hydroxyproline content and α-SMA expression increased markedly in the CCl{sub 4} group and MP prevented these alterations. Histopathological examination by both light and electron microscope further confirmed the protective efficacy of MP. To elucidate the antifibrotic mechanisms of MP, the expression of NF-κB, iNOS and COX-2 and the tissue levels of TNF-α and nitric oxide were assessed; CCl{sub 4} increased the expression of NF-κB and all downstream inflammatory cascade while MP co-treatment inhibited them. Collectively these findings indicate that MP possesses a potent antifibrotic effect which may be partly a consequence of its antioxidant and anti-inflammatory properties. -- Highlights: ► Methyl palmitate is free fatty acid methyl ester. ► It possesses a strong antifibrotic effect. ► It inhibits NF-κB and the consequent proinflammatory and oxidative stress response.

  16. Nerve growth factor protects against palmitic acid-induced injury in retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    Pan-shi Yan; Shu Tang; Hai-feng Zhang; Yuan-yuan Guo; Zhi-wen Zeng; Qiang Wen

    2016-01-01

    Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of dia-betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF signiifcantly attenuated the levels of reactive oxygen species (ROS) and malondialde-hyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 sig-naling pathways.

  17. Fetal exposure to a diabetic intrauterine environment resulted in a failure of cord blood endothelial progenitor cell adaptation against chronic hypoxia

    Science.gov (United States)

    Dincer, U Deniz

    2015-01-01

    Gestational diabetes mellitus (GDM) has long-term health consequences, and fetal exposure to a diabetic intrauterine environment increases cardiovascular risk for her adult offspring. Some part of this could be related to their endothelial progenitor cells (EPCs). Understanding the vessel-forming ability of human umbilical cord blood (HUCB)-derived endothelial colony-forming cells (ECFCs) against pathological stress such as GDM response to hypoxia could generate new therapeutic strategies. This study aims to investigate the role of chronic hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC was expressed in endothelial and pro-angiogenic specific markers, namely endothelial nitric oxide synthase (eNOS), platelet (PECAM-1) endothelial cell adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell adhesion molecule), vascular endothelial growth factor A, (VEGFA) and insulin-like growth factor 1 (IGF1). Chronic hypoxia did not affect CdH5, but PECAM1 MRNA expressions were increased in control and GDM subjects. Control hypoxic and GDM normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1α) protein expressions were significantly increased in HUCB ECFCs. GDM resulted in most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs’ proliferative ability due to reduction of clonogenic capacity and diminished vessel formation. Furthermore, GDM also resulted in most failure of cord blood ECFC adaptation against chronic hypoxic environment. PMID:25565870

  18. CHRONIC EXPOSURE TO DIBROMOACETIC ACID, A WATER DISINFECTION BY-PRODUCT, DIMINISHES PRIMORDIAL FOLLICLES IN THE RABBIT

    Science.gov (United States)

    Exposure to dibromoacetic acid (DBA), a commonly occurring water disinfection by-product, has detrimental effects on spermatogenesis and fertility in rats and rabbits. Despite indications of important reproductive consequences of DBA exposure in males, reproductive sequelae follo...

  19. Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yunxia, E-mail: wwwdluyx@sina.com [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Cheng, Jingjing [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Chen, Li [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Department of Medical Laboratory, Anhui Provincial Hospital, Hefei, Anhui 230001 (China); Li, Chaofei; Chen, Guanjun [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Gui, Li [The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Shen, Bing [Department of Physiology, Anhui Medical University, Hefei, Anhui 230032 (China); Zhang, Qiu [Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022 (China)

    2015-02-27

    Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS. - Highlights: • Fenofibrate treatment improved pathological changes in thoracic aorta by chronic high-fat-diet feeding. • Fenofibrate pretreatment improved endothelium-dependent vasodilation impaired by different concentrations of palmitic acid. • The inhibition of proliferation in endothelial cells by palmitic acid were inverted by fenofibric

  20. Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle During Adulthood

    Directory of Open Access Journals (Sweden)

    Fiona B Mcdonald

    2016-03-01

    Full Text Available Intermittent hypoxia is a feature of apnea of prematurity, chronic lung disease and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH during postnatal development (pCIH causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 hours of delivery, pups and their respective dams were exposed to CIH: 90s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 hrs per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH, where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  1. Early life exposure to chronic intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during adulthood.

    LENUS (Irish Health Repository)

    McDonald, Fiona B

    2016-03-01

    Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and\\/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  2. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  3. Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures

    Science.gov (United States)

    Wang, Ning; Ingersoll, Christopher G.; Dorman, Rebecca A.; Brumbaugh, William G.; Mebane, Christopher A.; Kunz, James L.; Hardesty, Douglas K.

    2014-01-01

    Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water-only exposures started with newly hatched larvae or approximately 1-mo-old juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon tests was higher than the EC20 from the trout tests, whereas the EC20 for copper, lead, or zinc for the sturgeon were lower than those EC20s for the trout. When the EC20s from the present study were included in compiled toxicity databases for all freshwater species, species mean chronic value for white sturgeon was in a relatively low percentile of the species sensitivity distribution for copper (9th percentile) and in the middle percentile for cadmium (55th percentile), zinc (40th percentile), or lead (50th percentile). However, the species mean chronic value for rainbow trout was in a high percentile for copper, lead, and zinc (∼68th–82nd percentile), but in a low percentile for cadmium (23rd percentile). The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or lead were above US Environmental Protection Agency chronic ambient water quality criteria (AWQC) or Washington State chronic water quality standards (WQS), whereas the sturgeon EC20s for copper or zinc were approximately equal to or below the chronic AWQC and WQS. In addition, acute 50% effect concentrations (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were below the final acute value used to derive acute AWQC and below acute WQS for copper.

  4. Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures.

    Science.gov (United States)

    Wang, Ning; Ingersoll, Christopher G; Dorman, Rebecca A; Brumbaugh, William G; Mebane, Christopher A; Kunz, James L; Hardesty, Doug K

    2014-10-01

    Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water-only exposures started with newly hatched larvae or approximately 1-mo-old juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon tests was higher than the EC20 from the trout tests, whereas the EC20 for copper, lead, or zinc for the sturgeon were lower than those EC20s for the trout. When the EC20s from the present study were included in compiled toxicity databases for all freshwater species, species mean chronic value for white sturgeon was in a relatively low percentile of the species sensitivity distribution for copper (9th percentile) and in the middle percentile for cadmium (55th percentile), zinc (40th percentile), or lead (50th percentile). However, the species mean chronic value for rainbow trout was in a high percentile for copper, lead, and zinc (∼68th-82nd percentile), but in a low percentile for cadmium (23rd percentile). The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or lead were above US Environmental Protection Agency chronic ambient water quality criteria (AWQC) or Washington State chronic water quality standards (WQS), whereas the sturgeon EC20s for copper or zinc were approximately equal to or below the chronic AWQC and WQS. In addition, acute 50% effect concentrations (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were below the final acute value used to derive acute AWQC and below acute WQS for copper.

  5. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability.

    Science.gov (United States)

    Morris, Gerwyn; Berk, Michael; Walder, Ken; Maes, Michael

    2016-05-01

    Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

  6. Heterogeneous OH oxidation of palmitic acid in single component and internally mixed aerosol particles: vaporization and the role of particle phase

    Directory of Open Access Journals (Sweden)

    C. B. Stipe

    2008-09-01

    Full Text Available We studied the OH oxidation of submicron aerosol particles consisting of pure palmitic acid (PA or thin (near monolayer coatings of PA on aqueous and effloresced inorganic salt particles. Experiments were performed as a function of particle size and OH exposure using a continuous-flow photochemical reaction chamber coupled to a chemical ionization mass spectrometer (CIMS system, for detection of gas and particle-bound organics, and a DMA/CPC for monitoring particle size distributions. The loss rate of PA observed for pure PA aerosols and PA on crystalline NaCl aerosols indicates that the OH oxidation of PA at the gas-aerosol interface is efficient. The pure PA oxidation data are well represented by a model consisting of four main processes: 1 surface-only reactions between OH and palmitic acid, 2 secondary reactions between palmitic acid and OH oxidation products, 3 volatilization of condensed-phase mass, and 4 a surface renewal process. Using this model we infer a value of γOH between 0.8 and 1. The oxidation of palmitic acid in thin film coatings of salt particles is also efficient, though the inferred γOH is lower, ranging from ~0.3+0.1/−0.05 for coatings on solid NaCl and ~0.05 (±0.01 on aqueous NaCl particles. These results, together with simultaneous data on particle size change and volatilized oxidation products, provide support for the ideas that oxidative aging of aliphatic organic aerosol is a source of small oxidized volatile organic compounds (OVOCs, and that OH oxidation may initiate secondary condensed-phase reactions.

  7. The heterogeneous OH oxidation of palmitic acid in single component and internally mixed aerosol particles: vaporization, secondary chemistry, and the role of particle phase

    Directory of Open Access Journals (Sweden)

    V. F. McNeill

    2008-03-01

    Full Text Available We studied the OH oxidation of submicron aerosol particles consisting of pure palmitic acid (PA or thin (near monolayer coatings of PA on aqueous and effloresced inorganic salt particles. Experiments were performed as a function of particle size and OH exposure using a continuous-flow photochemical reaction chamber coupled to a chemical ionization mass spectrometer (CIMS system, for detection of gas and particle-bound organics, and a DMA/CPC for monitoring particle size distributions. The loss rate of PA observed for pure PA aerosols and PA on crystalline NaCl aerosols indicates that the OH oxidation of PA at the gas-aerosol interface is efficient. The pure PA oxidation data are well represented by a model consisting of four main processes: 1 surface-only reactions between OH and palmitic acid, 2 secondary reactions between palmitic acid and OH oxidation products, 3 volatilization of condensed-phase mass, and 4 a surface renewal process. Using this model we infer a value of γOH between 0.8 and 1. The oxidation of palmitic acid in thin film coatings of salt particles is also efficient, though the inferred γOH is lower, ranging from ~0.3 (+0.1/−0.05 for coatings on solid NaCl and ~0.05 (±0.01 on aqueous NaCl particles. These results, together with simultaneous data on particle size change and volatilized oxidation products, provide support for the ideas that oxidative aging of aliphatic organic aerosol is a source of small oxidized volatile organic compounds (OVOCs, and that OH oxidation may initiate secondary condensed-phase reactions.

  8. The effects of chronic cadmium exposure on repeat swimming performance and anaerobic metabolism in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis)

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, Jessie L.; McGeer, James C., E-mail: jmcgeer@wlu.ca

    2016-04-15

    Highlights: • Exposure to 18 nM waterborne Cd induced plasma Ca loss that recovered by day 30 for lake whitefish but not brown trout. • Ucrit measured after an initial swim to 85% of Ucrit and a 30 min rest period was reduced in 18 nM Cd exposed fish compared to controls. • Swimming to 85% of Ucrit resulted in decreased muscle glycogen and increased lactate that was not recovered in the 30 min recovery period. • Second swim impairment is not related to metabolic processes in white muscle. - Abstract: This study investigates the effect of chronic Cd exposure on the ability to perform repeat swim challenges in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). Fish were exposed to waterborne Cd (18 nM) in moderately hard water (120 mg L{sup −1} CaCO{sub 3}) for 30 days. This level of exposure has been shown to cause sublethal physiological disruption and acclimation responses but no impairment of sustained swimming capacity (U{sub crit}) in single swim challenges. Swim trials were done over the course of the exposure and each one consisted of an initial swim to 85% of the U{sub crit} of control fish, a 30 min recovery period and finally a second swim challenge to determine U{sub crit}. Plasma and tissue samples were collected before and after each of the swim periods. As expected from previous studies, Cd exposure resulted in significant accumulation of Cd in gills, liver and kidney but not in white muscle. Exposure also induced a loss of plasma Ca followed by subsequent recovery (in lake whitefish but not brown trout) with few mortalities (100% survival for lake whitefish and 93% for brown trout). Both control and exposed fish swam to 85% of the single swim U{sub crit} and no differences in performance were seen. The Ucrit of unexposed controls in the second swim challenges were not different from the single swim Ucrit. However, second swim performance was significantly reduced in Cd exposed fish, particularly after a week of exposure

  9. Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Health.

    Science.gov (United States)

    Mancini, Annamaria; Imperlini, Esther; Nigro, Ersilia; Montagnese, Concetta; Daniele, Aurora; Orrù, Stefania; Buono, Pasqualina

    2015-09-18

    A growing body of evidence highlights the close association between nutrition and human health. Fat is an essential macronutrient, and vegetable oils, such as palm oil, are widely used in the food industry and highly represented in the human diet. Palmitic acid, a saturated fatty acid, is the principal constituent of refined palm oil. In the last few decades, controversial studies have reported potential unhealthy effects of palm oil due to the high palmitic acid content. In this review we provide a concise and comprehensive update on the functional role of palm oil and palmitic acid in the development of obesity, type 2 diabetes mellitus, cardiovascular diseases and cancer. The atherogenic potential of palmitic acid and its stereospecific position in triacylglycerols are also discussed.

  10. Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Health

    Directory of Open Access Journals (Sweden)

    Annamaria Mancini

    2015-09-01

    Full Text Available A growing body of evidence highlights the close association between nutrition and human health. Fat is an essential macronutrient, and vegetable oils, such as palm oil, are widely used in the food industry and highly represented in the human diet. Palmitic acid, a saturated fatty acid, is the principal constituent of refined palm oil. In the last few decades, controversial studies have reported potential unhealthy effects of palm oil due to the high palmitic acid content. In this review we provide a concise and comprehensive update on the functional role of palm oil and palmitic acid in the development of obesity, type 2 diabetes mellitus, cardiovascular diseases and cancer. The atherogenic potential of palmitic acid and its stereospecific position in triacylglycerols are also discussed.

  11. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Science.gov (United States)

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  12. Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

    Energy Technology Data Exchange (ETDEWEB)

    Bugel, Sean M., E-mail: Sean.Bugel@oregonstate.edu [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Bonventre, Josephine A. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); White, Lori A. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States); Tanguay, Robert L. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Cooper, Keith R. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States)

    2014-07-01

    Highlights: • Reproductive biomarker genes in Newark Bay killifish are desensitized to estrogen. • Gene desensitization indicates pre-transcriptional effects on estrogen signaling. • Desensitization does not have a metabolic or epigenetic basis (gene methylation). • Modulation of vitellogenin and choriogenin genes correlates with reproductive impacts. • Choriogenin L appears less prone to false negatives and may be a sensitive biomarker. - Abstract: Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen-responsive genes in this model population. First, a dose–response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β-estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β-estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi-chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng

  13. Free fatty acid palmitate impairs the vitality and function of cultured human bladder smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Andreas Oberbach

    Full Text Available BACKGROUND: Incidence of urinary tract infections is elevated in patients with diabetes mellitus. Those patients show increased levels of the saturated free fatty acid palmitate. As recently shown metabolic alterations induced by palmitate include production and secretion of the pro-inflammatory cytokine interleukine-6 (IL-6 in cultured human bladder smooth muscle cells (hBSMC. Here we studied the influence of palmitate on vital cell properties, for example, regulation of cell proliferation, mitochondrial enzyme activity and antioxidant capacity in hBSMC, and analyzed the involvement of major cytokine signaling pathways. METHODOLOGY/PRINCIPAL FINDINGS: HBSMC cultures were set up from bladder tissue of patients undergoing cystectomy and stimulated with palmitate. We analyzed cell proliferation, mitochondrial enzyme activity, and antioxidant capacity by ELISA and confocal immunofluorescence. In signal transduction inhibition experiments we evaluated the involvement of NF-κB, JAK/STAT, MEK1, PI3K, and JNK in major cytokine signaling pathway regulation. We found: (i palmitate decreased cell proliferation, increased mitochondrial enzyme activity and antioxidant capacity; (ii direct inhibition of cytokine receptor by AG490 even more strongly suppressed cell proliferation in palmitate-stimulated cells, while counteracting palmitate-induced increase of antioxidant capacity; (iii in contrast knockdown of the STAT3 inhibitor SOCS3 increased cell proliferation and antioxidant capacity; (iv further downstream JAK/STAT3 signaling cascade the inhibition of PI3K or JNK enhanced palmitate induced suppression of cell proliferation; (v increase of mitochondrial enzyme activity by palmitate was enhanced by inhibition of PI3K but counteracted by inhibition of MEK1. CONCLUSIONS/SIGNIFICANCE: Saturated free fatty acids (e.g., palmitate cause massive alterations in vital cell functions of cultured hBSMC involving distinct major cytokine signaling pathways. Thereby

  14. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  15. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    INTRODUCTION: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  16. Sublethal and Reproductive Effects of Acute and Chronic Exposure to Flowback and Produced Water from Hydraulic Fracturing on the Water Flea Daphnia magna.

    Science.gov (United States)

    Blewett, Tamzin A; Delompré, Perrine L M; He, Yuhe; Folkerts, Erik J; Flynn, Shannon L; Alessi, Daniel S; Goss, Greg G

    2017-02-13

    Hydraulic fracturing is an industrial process allowing for the extraction of gas or oil. To fracture the rocks, a proprietary mix of chemicals is injected under high pressure, which later returns to the surface as