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Sample records for abnormal acid exposure

  1. Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium

    PubMed Central

    2012-01-01

    Abstract Barrett’s esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence. However the genetic basis of this process is poorly understood. It is conceived that preclinical models of BE may facilitate discovery of molecular markers due to ease of longitudinal sampling. Clinical markers to stratify the patients at higher risk are vital to institute appropriate therapeutic intervention since EAC has very poor prognosis. We developed a dynamic in-vitro BE carcinogenesis (BEC) model by exposing naïve Barrett’s epithelium cell line (BAR-T) to acid and bile at pH4 (B4), 5min/day for a year. The BEC model acquired malignant characteristics after chronic repeated exposure to B4 similar to the sequential progression of BE to EAC in vivo. Aim To study cytogenetic changes during progressive transformation in the BEC model. Results We observed that the BAR-T cells progressively acquired several chromosomal abnormalities in the BEC model. Evidence of chromosomal loss (-Y) rearrangements [t(10;16) and dup (11q)] and clonal selection appeared during the early stages of the BEC model. Clonal selection resulted in a stabilized monoclonal population of cells that had a changed morphology and formed colony in soft agar. BAR-T cells grown in parallel without any exposure did not show any of these abnormalities. Conclusions Prolonged acid and bile exposure induced chromosomal aberrations and clonal selection in benign BAR-T cells. Since aneuploidy preceded morphological/dysplastic changes in the BEC model, chromosomal aberrations may be an early predictor of BE progression. The [t(10;16) and dup(11q)] aberrations identified in this study harbor several genes associated with cancer

  2. Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

    PubMed

    Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

    2011-06-01

    Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism.

  3. Solar retinopathy without abnormal exposure: case report.

    PubMed

    Stock, Ricardo Alexandre; Savaris, Simone Louise; de Lima Filho, Erasmo Carlos Rodrigues; Bonamigo, Elcio Luiz

    2013-01-01

    Solar retinopathy is photochemical damage to the retina, usually caused, by direct or indirect solar observation resulting from the use of hallucinogenic drugs, mental disorders or during eclipses. There may be a loss of visual acuity. We report the case of a 38-year-old patient who presented with a clinical diagnosis of solar retinopathy in the left eye, no prior history of sun exposure, normal visual acuity and complaints of metamorphopsia. Optical coherence tomography showed a rupture of the retinal pigment epithelium, confirming class II solar retinopathy. Visual acuity tends to normalize after 3 to 9 months, but not always. Thus, there is a real need to educate people about using eye protection during sun exposure especially given that some people may be highly susceptible to retinal damage, which was presumably the case for this patient. Finally, we note the importance of optical coherence tomography in diagnosing solar retinopathy. PMID:23828473

  4. Solar retinopathy without abnormal exposure: case report.

    PubMed

    Stock, Ricardo Alexandre; Savaris, Simone Louise; de Lima Filho, Erasmo Carlos Rodrigues; Bonamigo, Elcio Luiz

    2013-01-01

    Solar retinopathy is photochemical damage to the retina, usually caused, by direct or indirect solar observation resulting from the use of hallucinogenic drugs, mental disorders or during eclipses. There may be a loss of visual acuity. We report the case of a 38-year-old patient who presented with a clinical diagnosis of solar retinopathy in the left eye, no prior history of sun exposure, normal visual acuity and complaints of metamorphopsia. Optical coherence tomography showed a rupture of the retinal pigment epithelium, confirming class II solar retinopathy. Visual acuity tends to normalize after 3 to 9 months, but not always. Thus, there is a real need to educate people about using eye protection during sun exposure especially given that some people may be highly susceptible to retinal damage, which was presumably the case for this patient. Finally, we note the importance of optical coherence tomography in diagnosing solar retinopathy.

  5. Radiographic abnormalities and mortality in subjects with exposure to crocidolite.

    PubMed

    de Klerk, N H; Musk, A W; Cookson, W O; Glancy, J J; Hobbs, M S

    1993-10-01

    Plain chest radiographs from a one in six random sample of the workforce of the asbestos industry at Wittenoom, Western Australia between 1943 and 1966 have been classified for degree of profusion and pleural thickening by two independent observers according to the 1980 UICC-ILO Classification of Radiographs for the pneumoconioses to clarify the effect of degree of radiological abnormality on survival. A total of 1106 subjects were selected. Each subject's age, cumulative exposure to crocidolite, and time since first exposure were determined from employment records, the results of a survey of airborne concentrations of fibres > 5 mu in length conducted in 1966, and an exposure rating by an industrial hygienist and an ex-manager of the mine and mill at Wittenoom. By the end of 1986 193 subjects had died. Conditional logistic regression was used to model the relative risk of death in five separate case-control analyses in which the outcomes were deaths from: (1) all causes, (2) malignant mesothelioma, (3) lung cancer, (4) asbestosis, and (5) other causes excluding cancer and asbestosis. Up to 20 controls per case were randomly chosen from all men of the same age who were not known to have died before the date of death of the index case. After adjustment for exposure and time since first exposure, there were significant and independent effects of radiographic profusion and pleural thickening on all cause mortality. The effect of profusion was largely a result of the effect on mortality from malignant mesothelioma and asbestosis but not lung cancer. The effect of pleural thickening was greatest on mortality from other causes, mainly ischaemic heart disease. This study has shown that degree of radiographic abnormality has an independent effect on mortality from malignant mesothelioma, asbestosis, and all causes even after allowing for the effects of age, degree of exposure, and time since first exposure.

  6. Gait abnormalities, ADHD, and environmental exposure to nitrous oxide.

    PubMed

    Fluegge, Keith

    2016-08-30

    Papadopoulos et al. (2014) investigated gait profiles of children with attention-deficit hyperactivity disorder-combined type (ADHD-CT) compared to typical developing (TD) controls. The authors reported differences in the gait profile of ADHD-CT in the self-selected fast speed category. Additionally, others have proposed a maturational delay hypothesis in gait, demonstrating that gait variability decreases with age in ADHD children. It has been previously suggested that the cognitive impairment seen in conditions like ADHD may result from chronic, environmental exposure to the air pollutant, nitrous oxide (N2O). Exposure to N2O is thought to exert its antinociceptive properties by stimulating release of dynorphin peptides in the central nervous system which act upon kappa opioid receptors (KOR). Opioid-mediated gait abnormalities in ADHD are supported with evidence that prodynorphin mutations in mice lead to cytotoxic levels of dynorphin A (DYN A) and contribute to abnormal gait profiles and gradual loss of motor coordination. Interestingly, constitutive activity of the KOR receptor in rat brain has been recently shown to undergo maturational alterations, suggesting that while altered gait profiles in ADHD may be a function of the enhanced opioidergic activity attributable to chronic exposure to the environmental air pollutant, N2O, age-attenuated constitutive activity of KOR in brain may explain the normalization of these altered gait profiles in older ADHD subjects. PMID:27285951

  7. CHRONIC PERCHLORATE EXPOSURE CAUSES MORPHOLOGICAL ABNORMALITIES IN DEVELOPING STICKLEBACK

    PubMed Central

    Bernhardt, Richard R.; Von Hippel, Frank A.; O’Hara, Todd M.

    2011-01-01

    Few studies have examined the effects of chronic perchlorate exposure during growth and development, and fewer still have analyzed the effects of perchlorate over multiple generations. We describe morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (G1,2003) and for their offspring (G2,2004) that were not directly treated with perchlorate. The G1,2003 displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G2,2004) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites PMID:21465539

  8. Autism and developmental abnormalities in children with perinatal cocaine exposure.

    PubMed Central

    Davis, E.; Fennoy, I.; Laraque, D.; Kanem, N.; Brown, G.; Mitchell, J.

    1992-01-01

    Cocaine in all forms is the number one illicit drug of choice among pregnant women. Records of 70 children with cocaine exposure in utero who were referred for developmental evaluation at a large inner-city hospital were reviewed in an effort to determine whether a specific pattern of abnormalities could be discerned. Patients received physical examinations, neurological screenings, and behavioral and developmental assessments based on the Gesell Developmental Inventory, and the Denver Developmental Screening Test. Documentation of specified drug use was obtained by history. Mean age (SEM) at referral was 19.2 (1.7) months. All mothers used cocaine in one of its forms, although polydrug use was common. Growth parameters were low (median = 15th percentile). Significant neurodevelopmental abnormalities were observed, including language delay in 94% of the children and an extremely high frequency of autism (11.4%). The high rate of autistic disorders not known to occur in children exposed to alcohol or opiates alone suggests specific cocaine effects. PMID:1380564

  9. Exposures to acidic aerosols.

    PubMed

    Spengler, J D; Keeler, G J; Koutrakis, P; Ryan, P B; Raizenne, M; Franklin, C A

    1989-02-01

    Ambient monitoring of acid aerosols in four U.S. cities and in a rural region of southern Ontario clearly show distinct periods of strong acidity. Measurements made in Kingston, TN, and Steubenville, OH, resulted in 24-hr H+ ion concentrations exceeding 100 nmole/m3 more than 10 times during summer months. Periods of elevated acidic aerosols occur less frequently in winter months. The H+ determined during episodic conditions in southern Ontario indicates that respiratory tract deposition can exceed the effects level reported in clinical studies. Observed 12-hr H+ concentrations exceeded 550 nmole/m3 (approximately 27 micrograms/m3 H2SO4). The maximum estimated 1-hr concentration exceeded 1500 nmole/m3 for H+ ions. At these concentrations, an active child might receive more than 2000 nmole of H+ ion in 12 hr and in excess of 900 nmole during the hour when H2SO4 exceeded 50 micrograms/m3.

  10. Abnormalities in the male reproductive system after exposure to diesel and biodiesel blend.

    PubMed

    Kisin, Elena R; Yanamala, Naveena; Farcas, Mariana T; Gutkin, Dmitriy W; Shurin, Michael R; Kagan, Valerian E; Bugarski, Aleksandar D; Shvedova, Anna A

    2015-03-01

    Altering the fuel source from petroleum-based ultralow sulfur diesel to biodiesel and its blends is considered by many to be a sustainable choice for controlling exposures to particulate material. As the exhaust of biodiesel/diesel blends is composed of a combination of combustion products of polycyclic aromatic hydrocarbons and fatty acid methyl esters, we hypothesize that 50% biodiesel/diesel blend (BD50) exposure could induce harmful outcomes because of its ability to trigger oxidative damage. Here, adverse effects were compared in murine male reproductive organs after pharyngeal aspiration with particles generated by engine fueled with BD50 or neat petroleum diesel (D100). When compared with D100, exposure to BD50 significantly altered sperm integrity, including concentration, motility, and morphological abnormalities, as well as increasing testosterone levels in testes during the time course postexposure. Serum level of luteinizing hormone was significantly depleted only after BD50 exposure. Moreover, we observed that exposure to BD50 significantly increased sperm DNA fragmentation and the upregulation of inflammatory cytokines in the serum and testes on Day 7 postexposure when compared with D100. Histological evaluation of testes sections from BD50 exposure indicated more noticeable interstitial edema, degenerating spermatocytes, and dystrophic seminiferous tubules with arrested spermatogenesis. Significant differences in the level of oxidative stress assessed by accumulation of lipid peroxidation products and depletion of glutathione were detected on exposure to respirable BD50 and D100. Taken together, these results indicate that exposure of mice to inhalable BD50 caused more pronounced adverse effects on male reproductive function than diesel.

  11. Abnormalities in the male reproductive system after exposure to diesel and biodiesel blend.

    PubMed

    Kisin, Elena R; Yanamala, Naveena; Farcas, Mariana T; Gutkin, Dmitriy W; Shurin, Michael R; Kagan, Valerian E; Bugarski, Aleksandar D; Shvedova, Anna A

    2015-03-01

    Altering the fuel source from petroleum-based ultralow sulfur diesel to biodiesel and its blends is considered by many to be a sustainable choice for controlling exposures to particulate material. As the exhaust of biodiesel/diesel blends is composed of a combination of combustion products of polycyclic aromatic hydrocarbons and fatty acid methyl esters, we hypothesize that 50% biodiesel/diesel blend (BD50) exposure could induce harmful outcomes because of its ability to trigger oxidative damage. Here, adverse effects were compared in murine male reproductive organs after pharyngeal aspiration with particles generated by engine fueled with BD50 or neat petroleum diesel (D100). When compared with D100, exposure to BD50 significantly altered sperm integrity, including concentration, motility, and morphological abnormalities, as well as increasing testosterone levels in testes during the time course postexposure. Serum level of luteinizing hormone was significantly depleted only after BD50 exposure. Moreover, we observed that exposure to BD50 significantly increased sperm DNA fragmentation and the upregulation of inflammatory cytokines in the serum and testes on Day 7 postexposure when compared with D100. Histological evaluation of testes sections from BD50 exposure indicated more noticeable interstitial edema, degenerating spermatocytes, and dystrophic seminiferous tubules with arrested spermatogenesis. Significant differences in the level of oxidative stress assessed by accumulation of lipid peroxidation products and depletion of glutathione were detected on exposure to respirable BD50 and D100. Taken together, these results indicate that exposure of mice to inhalable BD50 caused more pronounced adverse effects on male reproductive function than diesel. PMID:25327512

  12. Abnormalities in the Male Reproductive System After Exposure to Diesel and Biodiesel Blend

    PubMed Central

    Kisin, Elena R.; Yanamala, Naveena; Farcas, Mariana T.; Gutkin, Dmitriy W.; Shurin, Michael R.; Kagan, Valerian E.; Bugarski, Aleksandar D.; Shvedova, Anna A.

    2016-01-01

    Altering the fuel source from petroleum-based ultra-low sulfur diesel to biodiesel and its blends is considered by many to be a sustainable choice for controlling exposures to particulate material. As the exhaust of biodiesel/diesel blends is composed of a combination of combustion products of polycyclic aromatic hydrocarbons and fatty acid methyl esters, we hypothesize that 50% biodiesel/diesel blend (BD50) exposure could induce harmful outcomes because of its ability to trigger oxidative damage. Here, adverse effects were compared in murine male reproductive organs after pharyngeal aspiration with particles generated by engine fueled with BD50 or neat petroleum diesel (D100). When compared with D100, exposure to BD50 significantly altered sperm integrity, including concentration, motility, and morphological abnormalities, as well as increasing testosterone levels in testes during the time course postexposure. Serum level of luteinizing hormone was significantly depleted only after BD50 exposure. Moreover, we observed that exposure to BD50 significantly increased sperm DNA fragmentation and the upregulation of inflammatory cytokines in the serum and testes on Day 7 postexposure when compared with D100. Histological evaluation of testes sections from BD50 exposure indicated more noticeable interstitial edema, degenerating spermatocytes, and dystrophic seminiferous tubules with arrested spermatogenesis. Significant differences in the level of oxidative stress assessed by accumulation of lipid peroxidation products and depletion of glutathione were detected on exposure to respirable BD50 and D100. Taken together, these results indicate that exposure of mice to inhalable BD50 caused more pronounced adverse effects on male reproductive function than diesel. PMID:25327512

  13. Abnormal Canine Bone Development Associated with Hypergravity Exposure

    NASA Technical Reports Server (NTRS)

    Morgan, J. P.; Fisher, G. L.; McNeill, K. L.; Oyama, J.

    1979-01-01

    Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 x g and 2.6 x g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.

  14. Lead exposure causes thyroid abnormalities in diabetic rats.

    PubMed

    Zadjali, Salah Al; Nemmar, Abderrahim; Fahim, Mohamed Abdelmonem Ay; Azimullah, Sheikh; Subramanian, Dhanasekaran; Yasin, Javed; Amir, Naheed; Hasan, Mohammed Yousif; Adem, Abdu

    2015-01-01

    Lead is a widely-spread environmental pollutant and a commonly-used industrial chemical that can cause multisystemic adverse health effects. However, the effects of lead exposure on diabetic animals have not been reported so far. The aim of this study is to evaluate the effects of lead exposure on thyroid, renal and oxidative stress markers in diabetic Wistar rats. Diabetes was induced with an intraperitoneal (i.p.) injection of streptozocin (STZ). Six weeks later, rats were exposed i.p. to either distilled water (control group) or 25, 50 and 100 mg/kg of lead acetate (treatment groups). We found a positive relationship between the administered doses of lead acetate and its measured levels in blood samples (P < 0.01). Treatment of diabetic animals with lead acetate resulted in significant weight loss (P < 0.001). It also caused an increase in thyroid stimulating hormone levels (P < 0.05) and reductions in thyroxine (P < 0.05) and triiodothyronine levels (P < 0.01), a clinical picture consistent with hypothyroidism. Lead acetate exposure increased urea levels (P < 0.05) and caused a significant decrease in creatinine (P < 0.05). Besides, while the concentrations of malondialdehyde were not affected, glutathione stores were depleted (P < 0.01); in response to lead exposure. In conclusion, exposure of diabetic rats to lead acetate resulted in weight loss, clinical hypothyroidism, renal damage and oxidative stress. PMID:26221254

  15. Abnormal cardiovascular responses induced by localized high power microwave exposure

    SciTech Connect

    Lu, S.-T; Brown, D.O.; Johnson, C.E.; Mathur, S.P. ); Elson, E.C. )

    1992-05-01

    A hypothesis of microwave-induced circulatory under perfusion was tested in ketamine anesthetized rats whose heart rate, mean arterial pressure, pulse pressure, respiration rate, and body temperatures were monitored continuously. Fifty-eight ventral head and neck exposures in a waveguide consisted of sham-exposure and exposure to continuous wave (CW) and pulsed 1.25 GHz microwaves for 5 min. The 0.5 Hz and 16 Hz pulsemodulated microwaves were delivered at 400 kW peak power. The CW microwaves were 2 and 6.4 W. The average specific absorption rate was 4.75 W/kg per watt transmitted in the brain and 17.15 W/kg per watt transmitted in the neck. Respiration rate and mean arterial pressure were not altered. Changes in heart rate and pulse pressure were observed in rats exposed to higher power but not to the lower average power microwaves. Depression of pulse pressure, an indication of a decrease in stroke volume, and increased or decreased heart rate were noted in presence of whole-body hyperthermia. The cardiac output of those animals exposed to higher average power microwaves was considered to be below normal as hypothesized. Decreased cardiac output and normal mean arterial pressure resulted in an increase in the total peripheral resistance which was contrary to the anticipated thermal response of animals.

  16. Abnormal cardiovascular responses induced by localized high power microwave exposure.

    PubMed

    Lu, S T; Brown, D O; Johnson, C E; Mathur, S P; Elson, E C

    1992-05-01

    A hypothesis of microwave-induced circulatory under perfusion was tested in ketamine anesthetized rats whose heart rate, mean arterial pressure, pulse pressure, respiration rate, and body temperatures were monitored continuously. Fifty-eight ventral head and neck exposures in a waveguide consisted of sham-exposure and exposure to continuous wave (CW) and pulsed 1.25 GHz microwaves for 5 min. The 0.5 Hz (10 microseconds, 2 W average) and 16 Hz (1 microsecond, 6.4 W average) pulse-modulated microwaves were delivered at 400 kW peak power. The CW microwaves were 2 and 6.4 W. The average specific absorption rate was 4.75 W/kg per watt transmitted in the brain and 17.15 W/kg per watt transmitted in the neck. Respiration rate and mean arterial pressure were not altered. Changes in heart rate and pulse pressure were observed in rats exposed to higher power (16 Hz pulses and 6.4 W CW) but not to the lower average power microwaves (0.5 Hz pulses and 2 W CW). Depression of pulse pressure, an indication of a decrease in stroke volume, and increased (tachycardia) or decreased (bradycardia) heart rate were noted in presence of whole-body hyperthermia. The cardiac output of those animals exposed to higher average power microwaves was considered to be below normal as hypothesized. Decreased cardiac output and normal mean arterial pressure resulted in an increase in the total peripheral resistance which was contrary to the anticipated thermal response of animals. PMID:1388133

  17. Radiographic abnormalities and exposure to asbestos-contaminated vermiculite in the community of Libby, Montana, USA.

    PubMed Central

    Peipins, Lucy A; Lewin, Michael; Campolucci, Sharon; Lybarger, Jeffrey A; Miller, Aubrey; Middleton, Dan; Weis, Christopher; Spence, Michael; Black, Brad; Kapil, Vikas

    2003-01-01

    Mining, handling, processing, and personal or commercial use of asbestos-contaminated vermiculite have led to widespread contamination of the Libby, Montana, area. We initiated a medical testing program in response to reports of respiratory illness in the community. The purpose of this analysis was to identify and quantify asbestos-related radiographic abnormalities among persons exposed to vermiculite in Libby and to examine associations between these outcomes and participants' self-reported exposures. A cross-sectional interview and medical testing were conducted in Libby from July through November 2000 and from July through September 2001. A total of 7,307 persons who had lived, worked, or played in Libby for at least 6 months before 31 December 1990 completed the interview. Of those, 6,668 participants > or = 18 years of age received chest radiographs to assess the prevalence of pleural and interstitial abnormalities. We observed pleural abnormalities in 17.8% of participants and interstitial abnormalities in < 1% of participants undergoing chest radiography. We examined 29 occupational, recreational, household, and other exposure pathways in the analysis. The prevalence of pleural abnormalities increased with increasing number of exposure pathways, ranging from 6.7% for those who reported no apparent exposures to 34.6% for those who reported > or = 12 pathways. The factors most strongly associated with pleural abnormalities were being a former W.R. Grace worker, being older, having been a household contact of a W.R. Grace worker, and being a male. In addition to being a former W.R. Grace worker, environmental exposures and other nonoccupational risk factors were also important predictors of asbestos-related radiographic abnormalities. PMID:14594627

  18. Exposure of C. elegans eggs to a glyphosate-containing herbicide leads to abnormal neuronal morphology.

    PubMed

    McVey, Kenneth A; Snapp, Isaac B; Johnson, Megan B; Negga, Rekek; Pressley, Aireal S; Fitsanakis, Vanessa A

    2016-01-01

    Recent data demonstrate that chronic exposure of Caenorhabditis elegans (C. elegans) to a high-use glyphosate-containing herbicide, Touchdown (TD), potentially damages the adult nervous system. It is unknown, however, whether unhatched worms exposed to TD during the egg stage show abnormal neurodevelopment post-hatching. Therefore, we investigated whether early treatment with TD leads to aberrant neuronal or neurite development in C. elegans. Studies were completed in three different worm strains with green fluorescent protein (GFP)-tagged neurons to facilitate visual neuronal assessment. Initially, eggs from C. elegans with all neurons tagged with GFP were chronically exposed to TD. Visual inspection suggested decreased neurite projections associated with ventral nerve cord neurons. Data analysis showed a statistically significant decrease in overall green pixel numbers at the fourth larval (L4) stage (*p<0.05). We further investigated whether specific neuronal populations were preferentially vulnerable to TD by treating eggs from worms that had all dopaminergic (DAergic) or γ-aminobutyric acid (GABAergic) neurons tagged with GFP. As before, green pixel number associated with these discrete neuronal populations was analyzed at multiple larval stages. Data analysis indicated statistically significant decreases in pixel number associated with DAergic, but not GABAergic, neurons (***p<0.001) at all larval stages. Finally, statistically significant decreases (at the first larval stage, L1) or increases (at the fourth larval stage, L4) in superoxide levels, a developmental signaling molecule, were detected (*p<0.05). These data suggest that early exposure to TD may impair neuronal development, perhaps through superoxide perturbation. Since toxic insults during development may late render individuals more vulnerable to neurodegenerative diseases in adulthood, these studies provide some of the first evidence in this model organism that early exposure to TD may adversely

  19. Exposure of C. elegans eggs to a glyphosate-containing herbicide leads to abnormal neuronal morphology.

    PubMed

    McVey, Kenneth A; Snapp, Isaac B; Johnson, Megan B; Negga, Rekek; Pressley, Aireal S; Fitsanakis, Vanessa A

    2016-01-01

    Recent data demonstrate that chronic exposure of Caenorhabditis elegans (C. elegans) to a high-use glyphosate-containing herbicide, Touchdown (TD), potentially damages the adult nervous system. It is unknown, however, whether unhatched worms exposed to TD during the egg stage show abnormal neurodevelopment post-hatching. Therefore, we investigated whether early treatment with TD leads to aberrant neuronal or neurite development in C. elegans. Studies were completed in three different worm strains with green fluorescent protein (GFP)-tagged neurons to facilitate visual neuronal assessment. Initially, eggs from C. elegans with all neurons tagged with GFP were chronically exposed to TD. Visual inspection suggested decreased neurite projections associated with ventral nerve cord neurons. Data analysis showed a statistically significant decrease in overall green pixel numbers at the fourth larval (L4) stage (*p<0.05). We further investigated whether specific neuronal populations were preferentially vulnerable to TD by treating eggs from worms that had all dopaminergic (DAergic) or γ-aminobutyric acid (GABAergic) neurons tagged with GFP. As before, green pixel number associated with these discrete neuronal populations was analyzed at multiple larval stages. Data analysis indicated statistically significant decreases in pixel number associated with DAergic, but not GABAergic, neurons (***p<0.001) at all larval stages. Finally, statistically significant decreases (at the first larval stage, L1) or increases (at the fourth larval stage, L4) in superoxide levels, a developmental signaling molecule, were detected (*p<0.05). These data suggest that early exposure to TD may impair neuronal development, perhaps through superoxide perturbation. Since toxic insults during development may late render individuals more vulnerable to neurodegenerative diseases in adulthood, these studies provide some of the first evidence in this model organism that early exposure to TD may adversely

  20. Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality.

    PubMed

    Liao, Ya-Tang; Li, Wan-Fen; Chen, Chien-Jen; Prineas, Ronald J; Chen, Wei J; Zhang, Zhu-Ming; Sun, Chien-Wen; Wang, Shu-Li

    2009-09-01

    Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure >14.7 ppm-year or drinking artesian well water >21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful

  1. Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality

    SciTech Connect

    Liao, Y.-T.; Li, W.-F.; Chen, C.-J.; Prineas, Ronald J.; Chen, Wei J.; Zhang Zhuming; Sun, C.-W.; Wang, S.-L.

    2009-09-01

    Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure > 14.7 ppm-year or drinking artesian well water > 21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful

  2. Acidic sulfate aerosols: characterization and exposure.

    PubMed

    Lioy, P J; Waldman, J M

    1989-02-01

    Exposures to acidic aerosol in the atmosphere are calculated from data reported in the scientific literature. The majority of date was not derived from studies necessarily designed to examine human exposures. Most of the studies were designed to investigate the characteristics of the atmosphere. However, the measurements were useful in defining two potential exposure situations: regional stagnation and transport conditions and local plume impacts. Levels of acidic aerosol in excess of 20 to 40 micrograms/m3 (as H2SO4) have been observed for time durations ranging from 1 to 12 hr. These were associated with high, but not necessarily the highest, atmospheric SO4(2)- levels. Exposures of 100 to 900 micrograms/m3/hr were calculated for the acid events that were monitored. In contrast, earlier London studies indicated that apparent acidity in excess of 100 micrograms/m3 (as H2SO4) was present in the atmosphere, and exposures less than 2000 micrograms/m3/hr were possible. Our present knowledge about the frequency, magnitude, and duration of acidic sulfate aerosol events and episodes is insufficient. Efforts must be made to gather more data, but these should be done in such a way that evaluation of human exposure is the focus of the research. In addition, further data are required on the mechanisms of formation of H2SO4 and on what factors can be used to predict acidic sulfate episodes.

  3. Acidic sulfate aerosols: characterization and exposure.

    PubMed Central

    Lioy, P J; Waldman, J M

    1989-01-01

    Exposures to acidic aerosol in the atmosphere are calculated from data reported in the scientific literature. The majority of date was not derived from studies necessarily designed to examine human exposures. Most of the studies were designed to investigate the characteristics of the atmosphere. However, the measurements were useful in defining two potential exposure situations: regional stagnation and transport conditions and local plume impacts. Levels of acidic aerosol in excess of 20 to 40 micrograms/m3 (as H2SO4) have been observed for time durations ranging from 1 to 12 hr. These were associated with high, but not necessarily the highest, atmospheric SO4(2)- levels. Exposures of 100 to 900 micrograms/m3/hr were calculated for the acid events that were monitored. In contrast, earlier London studies indicated that apparent acidity in excess of 100 micrograms/m3 (as H2SO4) was present in the atmosphere, and exposures less than 2000 micrograms/m3/hr were possible. Our present knowledge about the frequency, magnitude, and duration of acidic sulfate aerosol events and episodes is insufficient. Efforts must be made to gather more data, but these should be done in such a way that evaluation of human exposure is the focus of the research. In addition, further data are required on the mechanisms of formation of H2SO4 and on what factors can be used to predict acidic sulfate episodes. PMID:2651103

  4. Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis.

    PubMed

    Katsuta, Yuji; Iida, Toshii; Inomata, Shinji; Denda, Mitsuhiro

    2005-05-01

    Abnormal follicular keratinization is involved in comedogenesis in acne vulgaris. We recently demonstrated that calcium influx into epidermal keratinocytes is associated with impaired skin barrier function and epidermal proliferation. Based on these results, we hypothesized that sebum components affect calcium dynamics in the keratinocyte and consequently induce abnormal keratinization. To test this idea, we first observed the effects of topical application of sebum components, triglycerides (triolein), saturated fatty acids (palmitic acid and stearic acid), and unsaturated fatty acids (oleic acid and palmitoleic acid) on hairless mouse skin. Neither triglyceride nor saturated fatty acids affected the skin surface morphology or epidermal proliferation. On the other hand, application of unsaturated fatty acids, oleic acid, and palmitoleic acid induced scaly skin, abnormal keratinization, and epidermal hyperplasia. Application of triglycerides and saturated fatty acids on cultured human keratinocytes did not affect the intracellular calcium concentration ([Ca(2+)](i)), whereas unsaturated fatty acids increased the [Ca(2+)](i) of the keratinocytes. Moreover, application of oleic acid on hairless mouse skin induced an abnormal calcium distribution in the epidermis. These results suggest that unsaturated fatty acids in sebum alter the calcium dynamics in epidermal keratinocytes and induce abnormal follicular keratinization.

  5. Acidic sulfate aerosols: characterization and exposure

    SciTech Connect

    Lioy, P.J.; Waldman, J.M.

    1989-02-01

    Exposures to acidic aerosol in the atmosphere are calculated from data reported in the scientific literature. The majority of date was not derived from studies necessarily designed to examine human exposures. Most of the studies were designed to investigate the characteristics of the atmosphere. However, the measurements were useful in defining two potential exposure situations: regional stagnation and transport conditions and local plume impacts. Levels of acidicaerosol in excess of 20 to 40 micrograms/m/sup 3/ (as H/sub 2/SO/sub 4/) have been observed for time durations ranging from 1 to 12 hr. These were associated with high, but not necessarily the highest, atmospheric SO/sub 4/(2)- levels. Exposures of 100 to 900 micrograms/m/sup 3//hr were calculated for the acid events that were monitored. In contrast, earlier London studies indicated that apparent acidity in excess of 100 micrograms/m/sup 3/ (as H/sub 2/SO/sub 4/) was present in the atmosphere, and exposures less than 2000 micrograms/m/sup 3//hr were possible. Our present knowledge about the frequency, magnitude, and duration of acidic sulfate aerosol events and episodes is insufficient. Efforts must be made to gather more data, but these should be done in such a way that evaluation of human exposure is the focus of the research. In addition, further data are required on the mechanisms of formation of H/sub 2/SO/sub 4/ and on what factors can be used to predict acidic sulfate episodes. 96 references.

  6. Estrogen receptor subtypes selectively mediate female mouse reproductive abnormalities induced by neonatal exposure to estrogenic chemicals.

    PubMed

    Nakamura, Takeshi; Katsu, Yoshinao; Watanabe, Hajime; Iguchi, Taisen

    2008-11-20

    Perinatal exposure to estrogens such as diethylstilbestrol (DES), and to estrogenic chemicals, induces persistent anovulation caused by alteration of hypothalamic-pituitary-gonadal (HPG) axis, polyovular follicles, uterine abnormalities and persistent vaginal changes in mice. Most activities of estrogenic chemicals are mediated through estrogen receptor alpha (ERalpha) and/or ERbeta. However, little was known about the relative contribution of the individual ER subtypes in induction of abnormalities. We tested the effects of neonatal exposure to ER selective ligands and DES on female mice. Transactivation assays using mouse ERalpha and ERbeta showed that 10(-10)M DES activated both ER subtypes and that the ERalpha agonist (propyl pyrazole triol, PPT) and the ERbeta agonist (diarylpropionitrile, DPN) selectively activated their respective ERs at 10(-9)M. Neonatal female mice were injected subcutaneously with DES, PPT or DPN and the animals were examined at 13 and 15 weeks of age, respectively. Persistent estrous smears and anovulation were induced in all mice by 0.025-2.5 microg DES and 2.5-25 microg PPT, but not by DPN, suggesting that the observed anovulation was primarily mediated through ERalpha. Disorganization of uterine musculature and ovary-independent vaginal epithelial cell proliferation accompanied by persistent expression of EGF-related genes and interleukin-1-related genes were also mediated through ERalpha. In contrast, polyovular follicles were induced by neonatal treatment with both ERalpha and ERbeta ligands, suggesting that ovarian abnormalities are mediated through both ER subtypes.

  7. Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat

    PubMed Central

    Zhao, Tianyun; Li, Chuanxiang; Wei, Wei; Zhang, Haixing; Ma, Daqing; Song, Xingrong; Zhou, Libing

    2016-01-01

    Ketamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings. PMID:27226073

  8. Exposure to sulfuric acid in zinc production.

    PubMed

    Bråtveit, Magne; Haaland, Inger Margrethe; Moen, Bente E; Målsnes, Agnar

    2004-03-01

    This study characterized workers' exposure to sulfuric acid in two cell houses of a zinc production plant. We also aimed at estimating previous exposure to sulfuric acid by simulating the process conditions from before 1975 to produce exposure data for an epidemiological study on cancer in this industry. Further, we compared different sampling methods for aerosols in the cell houses. Personal sampling with a 37 mm Millipore cassette showed that the geometric means of the exposure levels for the workers in the two cell houses were 0.07 mg/m3 (range 0.01-0.48 mg/m3) and 0.04 mg/m3 (range 0.01-0.15 mg/m3). Norway's newly revised limit value of 0.1 mg/m3 was exceeded in 39.0 and 12.9% of the samples in the two cell houses. After the foam layer was removed from the electrolyte surface to simulate the production process from before 1975, the concentration of sulfuric acid increased from 0.11 to 6.04 mg/m3 in stationary measurement by the Millipore sampler. Stationary sampling showed that the Millipore sampler and the inhalable fraction of the Respicon impactor underestimated the sulfuric acid concentration by factors of 1.5 and 2.1 compared with the Institute of Occupational Medicine (IOM) sampler. Sampling with the Respicon impactor showed that the respirable, tracheobronchial and extrathoracic fractions constituted 3.0, 18.7 and 71.7% of the inhalable sulfuric acid aerosol, respectively. Today's exposure levels are lower than those reported to be associated with an increased prevalence of laryngeal cancer in other industries, but the levels prior to 1975 seem to have been much higher. By mass, most of the inhalable aerosol was in the size fractions considered to be highly relevant for the effects of sulfuric acid on the respiratory system. The risk of cancer among the cell house workers should be investigated in an epidemiological study.

  9. In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice.

    PubMed

    Ling, Wenting; Endo, Toshihiro; Kubo, Ken-Ichiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2016-01-01

    Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA-40), or 400 (BPA-400) μg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner. PMID:26869994

  10. In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice

    PubMed Central

    Ling, Wenting; Endo, Toshihiro; Kubo, Ken-ichiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2016-01-01

    Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA-40), or 400 (BPA-400) μg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner. PMID:26869994

  11. In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice.

    PubMed

    Ling, Wenting; Endo, Toshihiro; Kubo, Ken-Ichiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2016-01-01

    Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA-40), or 400 (BPA-400) μg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner.

  12. Prenatal exposure to phencyclidine produces abnormal behaviour and NMDA receptor expression in postpubertal mice.

    PubMed

    Lu, Lingling; Mamiya, Takayoshi; Lu, Ping; Toriumi, Kazuya; Mouri, Akihiro; Hiramatsu, Masayuki; Kim, Hyoung-Chun; Zou, Li-Bo; Nagai, Taku; Nabeshima, Toshitaka

    2010-08-01

    Several studies have shown the disruptive effects of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists on neurobehavioural development. Based on the neurodevelopment hypothesis of schizophrenia, there is growing interest in animal models treated with NMDA antagonists at developing stages to investigate the pathogenesis of psychological disturbances in humans. Previous studies have reported that perinatal treatment with phencyclidine (PCP) impairs the development of neuronal systems and induces schizophrenia-like behaviour. However, the adverse effects of prenatal exposure to PCP on behaviour and the function of NMDA receptors are not well understood. This study investigated the long-term effects of prenatal exposure to PCP in mice. The prenatal PCP-treated mice showed hypersensitivity to a low dose of PCP in locomotor activity and impairment of recognition memory in the novel object recognition test at age 7 wk. Meanwhile, the prenatal exposure reduced the phosphorylation of NR1, although it increased the expression of NR1 itself. Furthermore, these behavioural changes were attenuated by atypical antipsychotic treatment. Taken together, prenatal exposure to PCP produced long-lasting behavioural deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors in postpubertal mice. It is worth investigating the influences of disrupted NMDA receptors during the prenatal period on behaviour in later life.

  13. Hydrofluoric acid exposure: a case report and review on the clinical presentation and management.

    PubMed

    Strausburg, Matthew; Travers, Jeffrey; Mousdicas, Nico

    2012-01-01

    Exposure to hydrofluoric acid can cause severe skin damage via both corrosive and chemical means. Dermatologists should be aware of the various clinical presentations and knowledgeable of how to manage such patients. A case of a man with exposure of the hands after use of a consumer product containing hydrofluoric acid is presented. The presentation may vary depending on the concentration and duration of exposure. Patients experiencing exposure are at risk of serious complications, including death, resulting from electrolyte abnormalities. Information regarding the source of exposure will allow the physician to better predict the patient's course. The use of immediate flushing with water and the use of topical calcium gluconate can prevent extensive damage to the area of exposure and potentially fatal complications that may occur. More extensive burns may necessitate more invasive therapies. The treatment and the management and monitoring of such cases will allow for more optimal outcomes.

  14. Causes and mechanisms of acid-base and electrolyte abnormalities in cancer patients.

    PubMed

    Miltiadous, George; Christidis, Dimitrios; Kalogirou, Michalis; Elisaf, Moses

    2008-01-01

    Patients with cancer frequently exhibit acid-base and electrolyte disturbances that complicate their management and prolong their hospitalization. The mechanisms encountered for these abnormalities are multifactorial in origin. Both the underlying disease and the therapeutic interventions can contribute to the development of these disturbances. An understanding of the mechanisms involved in their pathogenesis is of paramount importance for their prevention and treatment in cancer patients. This article briefly reviews the causes and the pathophysiology of acid-base and electrolyte abnormalities observed in cancer patients. PMID:18206594

  15. Transmission of clonal chromosomal abnormalities in human hematopoietic stem and progenitor cells surviving radiation exposure.

    PubMed

    Kraft, Daniela; Ritter, Sylvia; Durante, Marco; Seifried, Erhard; Fournier, Claudia; Tonn, Torsten

    2015-07-01

    In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal abnormalities are often observed in bone marrow cells of patients, suggesting that their formation is crucial in the development of the disease. Since rAML is considered to originate from hematopoietic stem and progenitor cells (HSPC), we investigated the frequency and spectrum of radiation-induced chromosomal abnormalities in human CD34(+) cells. We then measured stable chromosomal abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared two radiation qualities used in radiotherapy, sparsely ionizing X-rays and densely ionizing carbon ions (29 and 60-85 keV/μm, doses between 0.5 and 4 Gy). Only a negligible number of de novo arising, unstable aberrations (≤ 0.05 aberrations/cell, 97% breaks) were measured in the descendants of irradiated HSPC. However, stable aberrations were detected in colonies formed by irradiated HSPC. All cells of the affected colonies exhibited one or more identical aberrations, indicating their clonal origin. The majority of the clonal rearrangements (92%) were simple exchanges such as translocations (77%) and pericentric inversions (15%), which are known to contribute to the development of rAML. Carbon ions were more efficient in inducing cell killing (maximum of ∼ 30-35% apoptotic cells for 2 Gy carbon ions compared to ∼ 25% for X-rays) and chromosomal aberrations in the first cell-cycle after exposure (∼ 70% and ∼ 40% for 1 Gy of carbon ions and X-rays, respectively), with a higher fraction of non-transmissible aberrations. In contrast, for both radiation qualities the percentage of clones with chromosomal abnormalities was similar (40%). Using the frequency of colonies with clonal aberrations as a surrogate marker for the leukemia risk following radiotherapy of solid tumors, charged particle therapy is not expected to lead to an increased risk of

  16. Transmission of clonal chromosomal abnormalities in human hematopoietic stem and progenitor cells surviving radiation exposure.

    PubMed

    Kraft, Daniela; Ritter, Sylvia; Durante, Marco; Seifried, Erhard; Fournier, Claudia; Tonn, Torsten

    2015-07-01

    In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal abnormalities are often observed in bone marrow cells of patients, suggesting that their formation is crucial in the development of the disease. Since rAML is considered to originate from hematopoietic stem and progenitor cells (HSPC), we investigated the frequency and spectrum of radiation-induced chromosomal abnormalities in human CD34(+) cells. We then measured stable chromosomal abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared two radiation qualities used in radiotherapy, sparsely ionizing X-rays and densely ionizing carbon ions (29 and 60-85 keV/μm, doses between 0.5 and 4 Gy). Only a negligible number of de novo arising, unstable aberrations (≤ 0.05 aberrations/cell, 97% breaks) were measured in the descendants of irradiated HSPC. However, stable aberrations were detected in colonies formed by irradiated HSPC. All cells of the affected colonies exhibited one or more identical aberrations, indicating their clonal origin. The majority of the clonal rearrangements (92%) were simple exchanges such as translocations (77%) and pericentric inversions (15%), which are known to contribute to the development of rAML. Carbon ions were more efficient in inducing cell killing (maximum of ∼ 30-35% apoptotic cells for 2 Gy carbon ions compared to ∼ 25% for X-rays) and chromosomal aberrations in the first cell-cycle after exposure (∼ 70% and ∼ 40% for 1 Gy of carbon ions and X-rays, respectively), with a higher fraction of non-transmissible aberrations. In contrast, for both radiation qualities the percentage of clones with chromosomal abnormalities was similar (40%). Using the frequency of colonies with clonal aberrations as a surrogate marker for the leukemia risk following radiotherapy of solid tumors, charged particle therapy is not expected to lead to an increased risk of

  17. Radiation exposure and chromosome abnormalities. Human cytogenetic studies at the National Institute of Radiological Sciences, Japan, 1963-1988

    SciTech Connect

    Ishihara, T.; Kohno, S.; Minamihisamatsu, M. )

    1990-03-01

    The results of human cytogenetic studies performed at the National Institute of Radiological Sciences (NIRS), Chiba, Japan for about 25 years are described. The studies were pursued primarily under two major projects: one involving people exposed to radiation under various conditions and the other involving patients with malignant diseases, especially leukemias. Whereas chromosome abnormalities in radiation-exposed people are excellent indicators of radiation exposure, their behavior in bone marrow provide useful information for a better understanding of chromosome abnormalities in leukemias and related disorders. The role of chromosome abnormalities in the genesis and development of leukemia and related disorders is considered, suggesting a view for future studies in this field.

  18. Abnormal lead exposure in globally threatened Cinereous vultures (Aegypius monachus) wintering in South Korea.

    PubMed

    Nam, Dong-Ha; Lee, Doo-Pyo

    2009-02-01

    Globally threatened Cinereous vultures (Aegypius monachus) regularly over-winter in South Korea, and they have frequently been found dead in their natural habitats. As one possible factor for their mortality, we investigated tissues for heavy metal contaminants along with necropsies on 20 dead Cinereous vultures. Severe emaciation was found in the survey, being associated with 19 of the deaths. Two of the 19 showed lesions suggestive of lead poisoning in the tissues; there was no indication of trauma, embedded shot, lead bullets in the stomach, or signs of electrocution in the specimens. Of 20 vultures, two showed lesions compatible with death from lead poisoning with 19.7 ppm dry weight (6.9 ppm wet weight) and 34.1 ppm dry weight (11.1 ppm wet weight), and 14 individuals had a potentially toxic level of lead with >6 ppm dry weight (about 2 ppm wet weight) in liver or kidney. The ingestion of lead-contaminated carcasses probably occurs along their migratory route. The possibility of lead exposure from the breeding site (Mongolia) or stopover area (China) should also be considered because some individuals are likely to die at or upon arrival. Our results suggest that most of the dead Cinereous vultures may be suffering from abnormally high lead exposure, indicating a potentially important cause of mortality in this endangered species.

  19. Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer.

    PubMed Central

    Baró, L.; Hermoso, J. C.; Núñez, M. C.; Jiménez-Rios, J. A.; Gil, A.

    1998-01-01

    We evaluated total plasma fatty acid concentrations and percentages, and the fatty acid profiles for the different plasma lipid fractions and red blood cell lipids, in 17 patients with untreated colorectal cancer and 12 age-matched controls with no malignant diseases, from the same geographical area. Cancer patients had significantly lower total plasma concentrations of saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives than healthy controls; when the values were expressed as relative percentages, cancer patients had significantly higher proportions of oleic acid and lower levels of linoleic acid than controls. With regard to lipid fractions, cancer patients had higher proportions of oleic acid in plasma phospholipids, triglycerides and cholesterol esters, and lower percentages of linoleic acid and its derivatives. On the other hand, alpha-linolenic acid was significantly lower in triglycerides from cancer patients and tended to be lower in phospholipids. Its derivatives also tended to be lower in phospholipids and triglycerides from cancer patients. Our findings suggest that colorectal cancer patients present abnormalities in plasma and red blood cell fatty acid profiles characterized by lower amounts of most saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives, especially members of the n-6 series, than their healthy age-matched counterparts. These changes are probably due to metabolic changes caused by the illness per se but not to malnutrition. PMID:9667678

  20. Microheterogeneity of antithrombin III: effect of single amino acid substitutions and relationship with functional abnormalities.

    PubMed

    De Stefano, V; Leone, G; Mastrangelo, S; Lane, D A; Girolami, A; de Moerloose, P; Sas, G; Abildgaard, U; Blajchman, M; Rodeghiero, F

    1994-02-01

    Microheterogeneity of antithrombin III (AT-III) was investigated by crossed immunoelectrofocusing (CIEF) on eleven molecular variants. A normal pattern was found in five variants while two different abnormal CIEF patterns were found in the other four and two variants, respectively. Point mutations causing a major pI change (exceeding 4.0) of the amino acid substituted lead to alterations in the overall microheterogeneity. The variants thus substituted share a first type of abnormal CIEF pattern with alterations throughout the pH range, regardless of the location of the mutation (reactive site and adjacent regions or heparin binding region). Minor amino acid pI changes in these regions do not alter the AT-III overall microheterogeneity, whatever the resulting functional defect. However, if the mutation is placed in the region around positions 404 or 429, then even minor changes of the amino acid pI seem able to alter the overall charge, leading to a second type of abnormal CIEF pattern with the main alteration at pH 4.8-4.6. Neuraminidase treatment leads to disappearance of microheterogeneity except for the variants with the Arg393 to Cys substitution. Addition of thrombin induces CIEF modifications specifically related to the functional defect. A normal formation of thrombin-antithrombin complexes induces a shift towards the more acid pH range, whereas in the variants substituted at the reactive site the CIEF pattern is substantially unaffected by thrombin; variants substituted at positions 382-384 show a maximal thrombin-induced increase of the isoforms at pI 4.8-4.6. Therefore mutant antithrombins with different functional abnormalities but sharing a common CIEF pattern were well distinguished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8180341

  1. Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

    PubMed Central

    Roussotte, Florence; Soderberg, Lindsay

    2010-01-01

    Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

  2. Factors affecting the response of lung clearance systems to acid aerosols: role of exposure concentration, exposure time, and relative acidity.

    PubMed

    Schlesinger, R B

    1989-02-01

    The ability of the lungs to clear deposited material is essential for maintenance of lung homeostasis. Acid aerosols have been shown to alter the efficiency of this process. This paper assesses the role of acid aerosol exposure concentration (C), exposure time (T), and relative acidity in producing changes in clearance from both the tracheobronchial tree and respiratory region of the lungs of rabbits. The response was found to be due to total exposure, i.e., some combination form of C x T, and was also related to relative acidity.

  3. Exposure to asbestiform minerals and radiographic chest abnormalities in a talc mining region of upstate New York

    SciTech Connect

    Fitzgerald, E.F.; Stark, A.D.; Vianna, N.; Hwang, S.A. )

    1991-05-01

    A radiologist in New York reported a high prevalence of pulmonary fibrosis in St. Lawrence and Jefferson counties. The New York State Department of Health responded by conducting a case history study of radiographic abnormalities found in the lung parenchyma and pleura of residents in Lawrence and Jefferson counties, where tremolitic talc has been mined for many years. During a 1-y period, all radiographs from 6 hospitals in the region were reviewed. A B-reader confirmed that 355 of 9,442 patients who were at least 40 y of age (3.8%) had a relevant abnormality; 60% of them reported occupational exposure to asbestiform minerals, and another 15% had a chest condition or injury that could have accounted for the abnormal radiograph. The results should be interpreted cautiously, but there was no evidence of widespread radiographic abnormalities resulting from ambient dust exposure. The data, however, support earlier studies that indicate that talc miners and millers experience excess parenchymal fibrosis and pleural changes. The data also suggest that individuals in the paper industry and construction trades may be at risk.

  4. Prenatal valproic acid exposure disrupts tonotopic c-Fos expression in the rat brainstem.

    PubMed

    Dubiel, A; Kulesza, R J

    2016-06-01

    Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions characterized by difficulties in communication and social interactions, restricted, repetitive behaviors and sensory abnormalities. Notably, the vast majority of individuals with ASD experience some degree of auditory dysfunction and we have recently reported consistent hypoplasia and dysmorphology in auditory brainstem centers in individuals with ASD. Prenatal exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of ASD. In rodents, prenatal exposure to VPA is employed as an animal model of ASD and is associated with a number of anatomical, physiological and behavioral deficits, including hypoplasia and dysmorphology of auditory brainstem centers. Based on these observations, we hypothesized that such dysmorphology in VPA-exposed animals would translate into abnormal neuronal activity in brainstem circuits and irregular tonotopic maps. Herein, we have subjected control and VPA-exposed animals to 4- or 16-kHz tones and examined neuronal activation with immunohistochemistry for c-Fos. After these exposures, we identified significantly more c-Fos-positive neurons in the auditory brainstem of VPA-exposed animals. Additionally, we observed a larger dispersion of c-Fos-positive neurons and shifted tonotopic bands in VPA-exposed rats. We interpret these findings to suggest hyper-responsiveness to sounds and disrupted mapping of sound frequencies after prenatal VPA exposure. Based on these findings, we suggest that such abnormal patterns of activation may play a role in auditory processing deficits in ASD. PMID:27094734

  5. Serendipity in Technetium-99m dimethyl iminodiacetic acid cholescintigraphy. [Visualization of nonbiliary incidental abnormalities

    SciTech Connect

    Weissmann, H.S.; Sugarman, L.A.; Frank, M.S.; Freeman, L.M.

    1980-05-01

    Technetium-99m dimethyl iminodiacetic acid cholescintigraphy has contributed significantly to the diagnosis of acute and chronic biliary tract disorders. Yet attention should also be focused on the other structres visualized during the blood pool, hepatocyte, renal excretory, and intestinal phases of the study. Nonbiliary pathology was detected in 42 of 294 patients (14.3%) studied for suspected acute cholecystitis. The serendipitous detection of previously unsuspected abnormalities assisted in directing further work-up away from suspected biliary disease and towards the real source of the patient's acute problem in 28 cases (9.5%).

  6. Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

    2011-02-14

    Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.

  7. Abnormal incorporation of amino acids into the gas hydrate crystal lattice.

    PubMed

    Sa, Jeong-Hoon; Kwak, Gye-Hoon; Lee, Bo Ram; Ahn, Docheon; Lee, Kun-Hong

    2014-12-28

    Gas hydrates are crystalline ice-like solid materials enclosing gas molecules inside. The possibility of the presence of gas hydrates with amino acids in the universe is of interest when revealing the potential existence of life as they are evidence of a source of water and organic precursors, respectively. However, little is known about how they can naturally coexist, and their crystallization behavior would become far more complex as both crystallize with formation of hydrogen bonds. Here, we report abnormal incorporation of amino acids into the gas hydrate crystal lattice that is contrary to the generally accepted crystallization mode, and this resulted in lattice distortion and expansion. The present findings imply the potential for their natural coexistence by sharing the crystal lattice, and will be helpful for understanding the role of additives in the gas hydrate crystallization.

  8. Radiographic abnormalities in long-tenure Vermont granite workers and the permissible exposure limit for crystalline silica.

    PubMed

    Graham, W G; Vacek, P M; Morgan, W K; Muir, D C; Sisco-Cheng, B

    2001-04-01

    This study was undertaken to assess the prevalence of radiographic abnormalities consistent with silicosis in a group of 600 retired granite workers who were receiving pensions. Files of regional clinics and hospitals were searched for chest radiographs taken on these men, and 470 x-ray films suitable for interpretation were located. After exclusions (women, and men who had worked in the granite industry elsewhere), 408 x-ray films were independently read by three experienced readers using the 1980 International Labour Office scheme. Dust exposures were estimated for workers hired after 1940, when the dust-control standard of 10 million particles per cubic foot (mppcf) (equivalent to 0.1 mg/m3) was put in place and monitored by the Vermont Division of Industrial Hygiene. Dust levels were initially high but were gradually reduced from 1940 to 1954, after which average quartz exposures stabilized to a mean of approximately 0.05 to 0.06 mg/m3; however, about 10% to 15% of samples after 1954 exceeded 0.1 mg/m3. Of the 408 x-ray films, 58 were taken on workers hired before dust controls were instituted in 1940, and 25.9% showed abnormalities (a profusion score of 1/0 or greater). A total of 350 x-ray films were taken on workers hired in 1940 or after, and the prevalence in this group was 5.7%. The radiographic changes in workers hired after 1940 are likely due to excessive exposures during the first 15 years of dust control. We conclude that if the exposure standard of 0.1 mg/m3 is rigorously observed in the workplace, radiographic abnormalities caused by quartz dust in long-term workers will be rare.

  9. Perfluorooctanoic Acid Exposure Suppresses T-independent Antibody Responses

    EPA Science Inventory

    Exposure to  3.75mg/kg of perfluoroocatnoic acid (PFOA) for 15d suppresses T-dependent antibody responses (TDAR), suggesting that T helper cells and/or B cells/plasma cells may be impacted. This study evaluated effects of PFOA exposure on the T cell-independent antibody response...

  10. Human health effects of exposure to airborne acid.

    PubMed

    Folinsbee, L J

    1989-02-01

    This paper summarizes and critiques a series of reports on the health effects of acid aerosol exposure, presented at the Symposium on the Health Effects of Acid Aerosols and compares these data to selected previous studies. The role of the two major defenses against acid aerosols, the conversion of acid to the ammonium salts by respiratory ammonia and buffering of acid by airway surface liquid are discussed in relation to airway acid burdens expected from typical inhalation exposures. The roles of particle size and hygroscopicity on airway deposition of aerosol are also included. The major health effects studied were the effects of acid aerosol on mucociliary clearance in healthy individuals and changes in lung function in asthmatics, an important sensitive subpopulation. The broad range of response in asthmatics suggests the need for further study.

  11. Morphological abnormalities in frogs from a rice-growing region in NSW, Australia, with investigations into pesticide exposure.

    PubMed

    Spolyarich, Nicholas; Hyne, Ross V; Wilson, Scott P; Palmer, Carolyn G; Byrne, Maria

    2011-02-01

    Three frog species (Limnodynastes tasmaniensis, Limnodynastes fletcheri and Litoria raniformis) were surveyed in rice bays of the Coleambally Irrigation Area (CIA), NSW, Australia, during the rice-growing seasons of 2005/2006 and 2006/2007. A total external morphological abnormality index of 7.0% was observed in frogs of the CIA (n=1,209). The types and frequencies of abnormalities were typical of reports from agricultural areas with ectrodactyly being the most common aberration. A relatively low abnormality index of 1.2% was observed in L. raniformis (n=87) compared to indices of 7.1% and 8.2% observed in L. fletcheri (n=694) and L. tasmaniensis (n=428), respectively. No conclusive evidence was found of unnaturally high rates of intersex, gonadal maldevelopment or unbalanced sex ratios in any species. Rice bay surface waters differed significantly in mean pesticide concentrations of atrazine and metolachlor on farms growing rice and corn compared to farms with rice as the sole crop. However, the similar abnormality indices observed in recent metamorphs emerging from these two farm types provided no evidence to suggest a link between larval exposure to the measured pesticides and developmental malformations.

  12. Characterisation of acid-base abnormalities in pigs experimentally infected with Chlamydia suis.

    PubMed

    Reinhold, Petra; Hartmann, Helmut; Constable, Peter D

    2010-05-01

    This study characterises the acid-base abnormalities in pigs experimentally infected with Chlamydia suis (Henderson-Hasselbalch equation and Constable's simplified strong ion equation). Eight pigs were challenged with the respiratory pathogen C. suis and four pigs served as non-infected controls. Pigs were monitored from 7 days before challenge to 8 days post-inoculation. Clinical examination was performed twice daily and venous blood samples were collected every two days. Blood-gas analysis, haemoxymetry, serum biochemical analysis and electrophoresis were performed in order to characterise the acid-base derangement. Aerosol challenge with C. suis resulted in severe acid-base disturbance characterised by acute respiratory acidosis and strong ion (metabolic) acidosis secondary to anaerobic metabolism and hyper L-lactataemia. Maximal changes were seen at day 3 post-inoculation when severe clinical signs of respiratory dysfunction were evident. The results of the study provide new information regarding the pathophysiology of respiratory infection caused by C. suis and the applicability and diagnostic utility of different approaches for assessing acid-base status in pigs.

  13. Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

    PubMed Central

    Cervera, José; Montesinos, Pau; Hernández-Rivas, Jesús M.; Calasanz, María J.; Aventín, Anna; Ferro, María T.; Luño, Elisa; Sánchez, Javier; Vellenga, Edo; Rayón, Chelo; Milone, Gustavo; de la Serna, Javier; Rivas, Concha; González, José D.; Tormo, Mar; Amutio, Elena; González, Marcos; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2010-01-01

    Background Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter. Design and Methods Based on cytogenetic data available for 495 patients with acute promyelocytic leukemia enrolled in two consecutive PETHEMA trials (LPA96 and LPA99), we analyzed the incidence, characteristics, and outcome of patients with acute promyelocytic leukemia with and without additional chromosomal abnormalities who had been treated with all-trans retinoic acid plus anthracycline monochemotherapy for induction and consolidation. Results Additional chromosomal abnormalities were observed in 140 patients (28%). Trisomy 8 was the most frequent abnormality (36%), followed by abn(7q) (5%). Patients with additional chromosomal abnormalities more frequently had coagulopathy (P=0.03), lower platelet counts (P=0.02), and higher relapse-risk scores (P=0.02) than their counterparts without additional abnormalities. No significant association with FLT3/ITD or other clinicopathological characteristics was demonstrated. Patients with and without additional chromosomal abnormalities had similar complete remission rates (90% and 91%, respectively). Univariate analysis showed that additional chromosomal abnormalities were associated with a lower relapse-free survival in the LPA99 trial (P=0.04), but not in the LPA96 trial. However, neither additional chromosomal abnormalities overall nor any specific abnormality was identified as an independent risk factor for relapse in multivariate analysis. Conclusions The lack of independent prognostic value of additional chromosomal abnormalities in acute promyelocytic leukemia does not support the use of alternative therapeutic strategies when such abnormalities are found. PMID:19903674

  14. Airborne acidity: estimates of exposure and human health effects.

    PubMed Central

    Lippmann, M

    1985-01-01

    Human health effects have resulted from the inhalation of ambient acidic aerosols, and there is suggestive evidence that current North American levels of exposure are producing excesses in respiratory morbidity. Annual mean mortality rates have been correlated with ambient aerosol concentration indices, with SO4(2-), FP, IP, and TSP having a descending order as predictive coefficients. These pollutant indices also contain H+ in descending mass ratios, and may all be surrogates for H+ as an active agent. Controlled exposure studies in humans and animals provide evidence that acidic aerosols produce greater changes in respiratory mechanical function and rates of particle clearance than other constituents of ambient particulate matter. The strong acid content of the ambient aerosol has not been measured in any of the population based pollutant effects studies in which it is a likely causal factor. The absence of direct measurement data on acidic aerosol in these studies, and their reliance on surrogate indices such as SO2 and SO4(2-), precludes firm conclusions about exposure-response relationships. High priority areas for further investigation include systematic investigation of the spatial and temporal distribution of population exposures; extension and refinement of population response studies in relation to acid aerosol exposures; responses of normal healthy and asthmatic human volunteers to mixtures of acidic aerosols and oxidant vapors under controlled conditions of exposure and exercise intensity; and progression of changes in lung epithelia during repetitive daily exposures of experimental animals to acidic aerosols, oxidants, and their mixtures, with concurrent measurements of particle clearance and respiratory function. PMID:4076095

  15. Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age

    PubMed Central

    Ostrea, Enrique M.; Reyes, Alexis; Villanueva-Uy, Esterlita; Pacifico, Rochelle; Benitez, Bernadette; Ramos, Essie; Bernardo, Rommel C.; Bielawski, Dawn M.; Delaney-Black, Virginia; Chiodo, Lisa; Janisse, James J.; Ager, Joel W.

    2012-01-01

    Objective Our aim was to determine the effects of fetal exposure to propoxur and pyrethroids, on child neurodevelopment at 2 years of age. Patients and Methods Mothers were prospectively recruited during mid-pregnancy in Bulacan, Philippines where multiple pesticides including propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin are used. To detect prenatal exposure to these pesticides, maternal hair and blood, infant’s hair, cord blood, and meconium were analyzed for the pesticides by gas chromatography/mass spectrometry. Infants were examined at 2 years of age with 95.1% follow up rate and their neurodevelopment outcome was assessed by the Griffiths Mental Developmental Scale (N=754). Results Meconium analysis was the most sensitive method to detect fetal exposure to pesticides and exposure was highest for propoxur (21.3%) and the grouped pyrethroids (2.5% - bioallethrin, transfluthrin, cyfluthrin and cypermethrin). Path analysis modeling was performed to determine the effects of fetal exposure to propoxur and pyrethroids on the child’s neurodevelopment at 24 months of age while controlling for confounders. Only singletons and those with complete data for the path analysis were included (N=696). Using a path analysis model, there was a significant negative (β= −0.14, p<0.001) relationship between prenatal pesticide exposure to propoxur and motor development at 2 years of age after controlling for confounders, e.g., infant gender, socioeconomic status, maternal intelligence, home stimulation (HOME), postnatal exposure to propoxur and blood lead level at 2 years of age. Conclusion At 2 years of age, prenatal exposure to propoxur was associated with poorer motor development in children. PMID:22155319

  16. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    SciTech Connect

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  17. Effects of nitrous acid exposure on human mucous membranes.

    PubMed

    Rasmussen, T R; Brauer, M; Kjaergaard, S

    1995-05-01

    Nitrous acid (HONO) is formed both indirectly from the reaction of nitrogen dioxide (NO2) with water on indoor surfaces, and directly during combustion. This gaseous pollutant may be a previously unrecognized causal factor in assessments of nitrogen oxide exposure effects. The present study is the first attempt to evaluate exposure effects of HONO on the human airways and the mucous membranes of the eyes and nose. Fifteen healthy adult nonsmokers were exposed for 3.5 h in a double-blind, balanced protocol to clean air, 77, and 395 ppb HONO. Each exposure was preceded by a 1-h baseline measurement period, and exposures were separated by 1 wk. There was a 10-min exercise period during exposure. Effects measurements included assessment of bronchial reactivity, measurement of specific airway conductance, spirometry, acoustic rhinometry, nasal lavage, tear-fluid cytology, a CO2 eye-provocation test, evaluation of eye redness, and subjective sensations. Effects of HONO exposure on the eyes were found as exposure-related changes in tear-fluid cytology. In particular, the number of squamous cells increased by 20, 67, and 80% following exposure to clean air, 77, and 395 ppb HONO, respectively (p = 0.004). Possible indications of exposure effects on sensitivity to CO2 eye provocation and on specific airway conductance were also measured. For specific airway conductance there was an approximate 10% decrease in conductance following exercise in association with HONO exposure, compared with a 2% decrease with clean air (p = 0.038).

  18. Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.

    PubMed

    Otsuki, Noriyuki; Homma, Takujiro; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Shichiri, Mototada; Takashima, Mizuki; Ito, Junitsu; Konno, Tasuku; Kurahashi, Toshihiro; Yoshida, Yasukazu; Goto, Kaoru; Fujii, Satoshi; Fujii, Junichi

    2016-08-01

    Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity. PMID:27166294

  19. Reversible Brain Abnormalities in People Without Signs of Mountain Sickness During High-Altitude Exposure

    PubMed Central

    Fan, Cunxiu; Zhao, Yuhua; Yu, Qian; Yin, Wu; Liu, Haipeng; Lin, Jianzhong; Yang, Tianhe; Fan, Ming; Gesang, Luobu; Zhang, Jiaxing

    2016-01-01

    A large proportion of lowlanders ascending to high-altitude (HA) show no signs of mountain sickness. Whether their brains have indeed suffered from HA environment and the persistent sequelae after return to lowland remain unknown. Thirty-one sea-level college students, who had a 30-day teaching on Qinghai-Tibet plateau underwent MRI scans before, during, and two months after HA exposure. Brain volume, cortical structures, and white matter microstructure were measured. Besides, serum neuron-specific enolase (NSE), C-reactive protein, and interleukin-6 and neuropsychiatric behaviors were tested. After 30-day HA exposure, the gray and white matter volumes and cortical surface areas significantly increased, with cortical thicknesses and curvatures changed in a wide spread regions; Anisotropy decreased with diffusivities increased in multiple sites of white matter tracts. Two months after HA exposure, cortical measurements returned to basal level. However, increased anisotropy with decreased diffusivities was observed. Behaviors and serum inflammatory factor did not significant changed during three time-point tests. NSE significantly decreased during HA but increased after HA exposure. Results suggest brain swelling occurred in people without neurological signs at HA, but no negative sequelae in cortical structures and neuropsychiatric functions were left after the return to lowlands. Reoxygenation changed white matter microstructure. PMID:27633944

  20. Reversible Brain Abnormalities in People Without Signs of Mountain Sickness During High-Altitude Exposure.

    PubMed

    Fan, Cunxiu; Zhao, Yuhua; Yu, Qian; Yin, Wu; Liu, Haipeng; Lin, Jianzhong; Yang, Tianhe; Fan, Ming; Gesang, Luobu; Zhang, Jiaxing

    2016-01-01

    A large proportion of lowlanders ascending to high-altitude (HA) show no signs of mountain sickness. Whether their brains have indeed suffered from HA environment and the persistent sequelae after return to lowland remain unknown. Thirty-one sea-level college students, who had a 30-day teaching on Qinghai-Tibet plateau underwent MRI scans before, during, and two months after HA exposure. Brain volume, cortical structures, and white matter microstructure were measured. Besides, serum neuron-specific enolase (NSE), C-reactive protein, and interleukin-6 and neuropsychiatric behaviors were tested. After 30-day HA exposure, the gray and white matter volumes and cortical surface areas significantly increased, with cortical thicknesses and curvatures changed in a wide spread regions; Anisotropy decreased with diffusivities increased in multiple sites of white matter tracts. Two months after HA exposure, cortical measurements returned to basal level. However, increased anisotropy with decreased diffusivities was observed. Behaviors and serum inflammatory factor did not significant changed during three time-point tests. NSE significantly decreased during HA but increased after HA exposure. Results suggest brain swelling occurred in people without neurological signs at HA, but no negative sequelae in cortical structures and neuropsychiatric functions were left after the return to lowlands. Reoxygenation changed white matter microstructure. PMID:27633944

  1. Sulfuric acid aerosol exposure in humans assessed by bronchoalveolar lavage

    SciTech Connect

    Frampton, M.W.; Voter, K.Z.; Morrow, P.E.; Roberts, N.J. Jr.; Culp, D.J.; Cox, C.; Utell, M.J. )

    1992-09-01

    Epidemiologic and experimental evidence suggests that exposure to acidic aerosols may affect human health. Brief exposures to acidic aerosols alter mucociliary clearance and increase airway responsiveness, but effects on host defense mechanisms at the alveolar level have not been studied in humans. Twelve healthy, nonsmoking volunteers between 20 and 39 yr of age were exposed for 2 h to aerosols of approximately 1,000 micrograms/m3 sulfuric acid (H2SO4) or sodium chloride (NaCl (control)), with intermittent exercise, in a randomized, double-blind fashion. Each subject received both exposures, separated by at least 2 wk. Bronchoalveolar lavage (BAL) was performed 18 h after exposure in order to detect evidence of an inflammatory response, changes in alveolar cell subpopulations, or changes in alveolar macrophage (AM) function, which is important in host defense. When compared with NaCl, exposure to H2SO4 did not increase polymorphonuclear leukocytes in BAL fluid. The percentage of T lymphocytes decreased in association with H2SO4 exposure, but the difference was not statistically significant (14.9% after NaCl, 11.5% after H2SO4; p = 0.14). Antibody-mediated cytotoxicity of AM increased in association with H2SO4 exposure (percent lysis 19.1 after NaCl, 23.6 after H2SO4; p = 0.16). No significant change was seen in release of superoxide anion or inactivation of influenza virus in vitro. Brief exposures to H2SO4 aerosol at 1,000 micrograms/m3 do not cause an influx of inflammatory cells into the alveolar space, and no evidence was found for alteration in antimicrobial defense 18 h after exposure.

  2. Pulmonary function and clearance after prolonged sulfuric acid aerosol exposure

    SciTech Connect

    Ives, P.J. ); Gerrity, T.R.; DeWitt, P.; Folinsbee, L.J. )

    1991-03-15

    The authors studied pulmonary function and clearance responses after a 4 H exposure to 75-100 {mu}g/m{sup 3} sulfuric acid aerosol (SAA). Healthy subjects, who exercised for 30 min/H at ventilation of about 25 L/min, were exposed once to clean air and once to SAA. Oral hygiene and acidic juice gargle were used to minimize oral ammonia. Lung function tests, including spirometry, plethysmography, and partial flow-volume (PEFV) curves were performed before and after exposure. Clearance of 99m-Technetium labeled iron oxide was assessed after each exposure. The first moment of fractional tracheobronchial retention (M1TBR), after correcting for 24 H retention and normalizing to time zero, was used as an index of clearance. There were no significant changes in lung volumes, airways resistance, or maximum expiratory flows after SAA exposure. Flow at 40% of total lung capacity on PEFV curves decreased 17% (NS) after SAA exposure. Tracheobronchial clearance was accelerated after a single exposure to SAA; M1TBR decreased from 73 {plus minus} 5 min (air) to 69 {plus minus} 5 min (SAA). These results suggest that acute prolonged exposure to low levels of SAA has minimal effects on lung mechanics in healthy subjects but does produce a modest acceleration of particle clearance.

  3. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    NASA Astrophysics Data System (ADS)

    Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  4. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    SciTech Connect

    Hunt, W.A.; Joseph, J.A.; Rabin, B.M.

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  5. Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

    PubMed

    Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

    2012-12-01

    Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery.

  6. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    PubMed

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage.

  7. Ultrastructural analysis of reorganization of the periodontium in simulated torsion abnormality and its correction with succinic acid.

    PubMed

    Karasulova, E L; Khloponin, P A; Popkov, V L; Galenko-Yaroshevskii, P A

    2003-11-01

    Morphological study confirmed the positive effect of succinic acid on tissue ultrastructure, energy metabolism in cells of fibroblastic differon, reorganization and neogenesis of intercellular substance of the periodontal connective tissue during the retention period after correction of simulated dental torsion abnormality in dogs.

  8. Cerebral cortical abnormalities seen in a non-human primate model of prenatal cocaine exposure are not related to vasoconstriction.

    PubMed

    He, Na; Lidow, Michael S

    2004-03-01

    In our previous studies [J. Comp. Neurol. 435 (2001) 263] we demonstrated that rhesus monkeys born to mothers receiving cocaine orally during the period of pregnancy when neurons destined for the cerebral neocortex were generated displayed inappropriate positioning of neocortical neurons, loss of normal neocortical lamination, and reduction in neocortical volume, density and total number of neocortical neurons. In the present paper, we examined whether these cytoarchitectural abnormalities were related to the relatively high blood levels of the cocaine metabolite, benzoylecgonine, associated with oral cocaine administration. We also evaluated the role of vasoconstriction of the uteroumbilical and fetal brain vessels in the generation of these abnormalities. For these purposes, we compared cerebral neocortical cytoarchitecture in 2-month-old monkeys from five groups of mothers: (1). a drug-naïve group, (2). a cocaine-treated group, (3). a group treated with benzoylecgonine at doses producing higher blood levels of this metabolite and stronger vasoconstriction that those in the cocaine-treated group, (4). a group treated with cocaine plus the vasodilator, isosorbide dinitrate, which counteracted the vasoconstrictive actions of cocaine, and (5). a group exposed to isosorbide dinitrate alone. All treatments were carried out from the 45 th through 102 nd day of pregnancy. We found that the general appearance of the neocortex and the position and number of neocortical neurons in the offspring of benzoylecgonine- and isosorbide dinitrate-treated mothers were indistinguishable from those in the offspring of drug-naïve mothers. In contrast, significant alterations in these parameters (similar to those seen in our previous studies) were observed in the offspring of cocaine and cocaine + isosorbide dinitrate-treated mothers. These findings suggest that it is unlikely that either benzoylecgonine or vasoconstriction are responsible for the abnormalities seen in the

  9. Reproductive abnormalities in adult male mice following preimplantation exposures to estradiol or pesticide methoxychlor.

    PubMed

    Amstislavsky, Sergei Ya; Amstislavskaya, Tamara G; Amstislavsky, Vjacheslav S; Tibeikina, Marina A; Osipov, Kiril V; Eroschenko, Victor P

    2006-02-01

    Adult females of ICR strain of mice were bred, separated into different experimental groups, and treated as follows. On Days 2-4 of pregnancy, the mice received daily subcutaneous injections of either 0.05 ml sesame oil (vehicle) or same volume of 5.0mg of purified methoxychlor (MXC) suspended in the vehicle. Another group received a single subcutaneous injection of 1.0 microg of estradiol-17beta (E) on Day 2 of pregnancy only. Male offspring were tested at 3 and 6 months of age. At 3 months, E or MXC did not alter the weights of seminal vesicles, preputial glands, or testes, although after exposure for 30 min to a female in estrus behind a partition, testosterone levels were significantly reduced in treated males in comparison to control males exposed to the same partition test. At 6 months, the preputial glands and testes weight remained unchanged, while the seminal vesicles were significantly heavier in E- and MXC-treated males. Same partition tests again revealed that in E and MXC groups, testosterone levels remained significantly lower in comparison to control males. MXC or E exposures during preimplantation appear to induce long-term effects on the sexual development in 3 and 6 month-old-males by compromising their sexual arousal and altering seminal vesicles weights in the older group.

  10. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats.

    PubMed

    Huang, Hui; Morisseau, Christophe; Wang, JingFeng; Yang, Tianxin; Falck, John R; Hammock, Bruce D; Wang, Mong-Heng

    2007-07-01

    Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats.

  11. Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a Huntington disease mouse model.

    PubMed

    Naseri, Nima N; Xu, Hui; Bonica, Joseph; Vonsattel, Jean Paul G; Cortes, Etty P; Park, Larry C; Arjomand, Jamshid; Gibson, Gary E

    2015-06-01

    Glucose metabolism is reduced in the brains of patients with Huntington disease (HD). The mechanisms underlying this deficit, its link to the pathology of the disease, and the vulnerability of the striatum in HD remain unknown. Abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase complex (PDHC) and the tricarboxylic acid (TCA) cycle, may contribute to these deficits. Here, activities for these enzymes and select protein levels were measured in human postmortem cortex and in striatum and cortex of an HD mouse model (Q175); mRNA levels encoding for these enzymes were also measured in the Q175 mouse cortex. The activities of PDHC and nearly all of the TCA cycle enzymes were dramatically lower (-50% to 90%) in humans than in mice. The activity of succinate dehydrogenase increased with HD in human (35%) and mouse (23%) cortex. No other changes were detected in the human HD cortex or mouse striatum. In Q175 cortex, there were increased activities of PDHC (+12%) and aconitase (+32%). Increased mRNA levels for succinyl thiokinase (+88%) and isocitrate dehydrogenase (+64%) suggested an upregulation of the TCA cycle. These patterns of change differ from those reported in other diseases, which may offer unique metabolic therapeutic opportunities for HD patients.

  12. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    SciTech Connect

    Perna, A.F.; Smogorzewski, M.; Massry, S.G.

    1988-12-01

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and /sup 45/Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in /sup 45/Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker.

  13. Pre-administration of curcumin prevents neonatal sevoflurane exposure-induced neurobehavioral abnormalities in mice.

    PubMed

    Ji, Mu-Huo; Qiu, Li-Li; Yang, Jiao-Jiao; Zhang, Hui; Sun, Xiao-Ru; Zhu, Si-Hai; Li, Wei-Yan; Yang, Jian-Jun

    2015-01-01

    Sevoflurane, a commonly used inhaled anesthetic, can induce neuronal apoptosis in the developing rodent brain and correlate with functional neurological impairment later in life. However, the mechanisms underlying these deleterious effects of sevoflurane remain unclear and no effective treatment is currently available. Herein, the authors investigated whether curcumin can prevent the sevoflurane anesthesia-induced cognitive impairment in mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane 2h daily for 3 consecutive days and were treated with curcumin at the dose of 20 mg/kg or vehicle 30 min before the sevoflurane anesthesia from postnatal days 6 (P6) to P8. Cognitive functions were evaluated by open field, Morris water maze, and fear conditioning tests on P61, P63-69, and P77-78, respectively. In another separate experiment, mice were killed on day P8 or P78, and the brain tissues were harvested and then subjected to biochemistry studies. Our results showed that repeated neonatal sevoflurane exposure led to significant cognitive impairment later in life, which was associated with increased neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, and decreased memory related proteins. By contrast, pre-administration of curcumin ameliorated early neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, memory related proteins, and later cognitive dysfunction. In conclusion, our data suggested that curcumin pre-administration can prevent the sevoflurane exposure-induced cognitive impairment later in life, which may be partly attributed to its ability to attenuate the neural apoptosis, inflammation, and oxidative nitrosative stress in mouse brain. PMID:25447320

  14. Exposure assessment of oxidant gases and acidic aerosols

    SciTech Connect

    Lioy, P.J.

    1989-01-01

    Clearly the presence of high ozone and acidic species in North America is primarily dependent upon photochemical air pollution. Evidence shows, however, that high acid exposures may occur in specific types of areas of high sulfur fuel use during the winter. At the present time, our concerns about exposure to local populations and regional populations should be directed primarily toward the outdoor activity patterns of individuals in the summer, and how those activity patterns relate to the location, duration, and concentrations of ozone and acid aerosol in photochemical air pollution episodes. Lioy Dyba and Mage et al have examined the activity patterns of children in summer camps. Because they spend more time outside than the normal population, these children form an important group of exercising individuals subject to photochemical pollution exposures. The dose of ozone inhaled by the children in the two camps was within 50% and 25% of the dose inhaled by adults in controlled clinical situations that produced clinically significant decrements in pulmonary function and increased the symptoms after 6.6 hr exposure in a given day. The chamber studies have used only ozone, whereas in the environment this effect may be enhanced by the presence of a complex mixture. The work of Lioy et al in Mendham, New Jersey found that hydrogen ion seemed to play a role in the inability of the children to return immediately to their normal peak expiratory flow rate after exposure. The camp health study conducted in Dunsville, Ontario suggested that children participating in a summer camp where moderate levels of ozone (100 ppb) but high levels of acid (46 micrograms/m3) occurred during an episode had a similar response. Thus, for children or exercising adults who are outdoors for at least one hour or more during a given day, the presence and persistence of oxidants in the environment are of particular concern. 63 references.

  15. A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals

    PubMed Central

    Zhao, Linjing; Ni, Yan; Ma, Xiaojing; Zhao, Aihua; Bao, Yuqian; Liu, Jiajian; Chen, Tianlu; Xie, Guoxiang; Panee, Jun; Su, Mingming; Yu, Herbert; Wang, Congrong; Hu, Cheng; Jia, Weiping; Jia, Wei

    2016-01-01

    Increasing evidences support that metabolically healthy obese (MHO) is a transient state. However, little is known about the early markers associated with the development of metabolic abnormalities in MHO individuals. Serum free fatty acids (FFAs) profile is highlighted in its association with obesity-related insulin resistance, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). To examine the association of endogenous fatty acid metabolism with future development of metabolic abnormalities in MHO individuals, we retrospectively analyzed 24 [product FFA]/[precursor FFA] ratios in fasting sera and clinical data from 481 individuals who participated in three independent studies, including 131 metabolic healthy subjects who completed the 10-year longitudinal Shanghai Diabetes Study (SHDS), 312 subjects cross-sectionally sampled from the Shanghai Obesity Study (SHOS), and 38 subjects who completed an 8-week very low carbohydrate diet (VLCD) intervention study. Results showed that higher baseline level of oleic acid/stearic acid (OA/SA), and lower levels of stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with higher rate of MHO to MUO conversion in the longitudinal SHDS. Further, the finding was validated in the cross-sectional and interventional studies. This panel of FFA ratios could be used for identification and early intervention of at-risk obese individuals. PMID:27344992

  16. A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals.

    PubMed

    Zhao, Linjing; Ni, Yan; Ma, Xiaojing; Zhao, Aihua; Bao, Yuqian; Liu, Jiajian; Chen, Tianlu; Xie, Guoxiang; Panee, Jun; Su, Mingming; Yu, Herbert; Wang, Congrong; Hu, Cheng; Jia, Weiping; Jia, Wei

    2016-01-01

    Increasing evidences support that metabolically healthy obese (MHO) is a transient state. However, little is known about the early markers associated with the development of metabolic abnormalities in MHO individuals. Serum free fatty acids (FFAs) profile is highlighted in its association with obesity-related insulin resistance, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). To examine the association of endogenous fatty acid metabolism with future development of metabolic abnormalities in MHO individuals, we retrospectively analyzed 24 [product FFA]/[precursor FFA] ratios in fasting sera and clinical data from 481 individuals who participated in three independent studies, including 131 metabolic healthy subjects who completed the 10-year longitudinal Shanghai Diabetes Study (SHDS), 312 subjects cross-sectionally sampled from the Shanghai Obesity Study (SHOS), and 38 subjects who completed an 8-week very low carbohydrate diet (VLCD) intervention study. Results showed that higher baseline level of oleic acid/stearic acid (OA/SA), and lower levels of stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with higher rate of MHO to MUO conversion in the longitudinal SHDS. Further, the finding was validated in the cross-sectional and interventional studies. This panel of FFA ratios could be used for identification and early intervention of at-risk obese individuals. PMID:27344992

  17. [Alpha-lipoic acid triggers elimination of cells with abnormal nuclei in human carcinoma epidermoid cell line].

    PubMed

    Kisurina-Evgen'eva, O P; Onishchenko, G E

    2010-01-01

    The skin is usually exposed to adverse environmental conditions that may cause pathological cell proliferation and cellular transformations leading to the formation of malignant cells. Antioxidants may affect these processes and induce the elimination of transformed cell. The purpose of this work was to investigate the effect of alfa-lipoic acid on human carcinoma epidermoid cell line A431. Our results showed that alfa-lipoic acid induced inhibition of cell proliferation or stimulated apoptotic cell death. Cells with abnormal nuclei were eliminated by apoptosis. Electron microscopy showed that survived cells had typical for control cells shape and organization of the nuclei, organization of the cytoplasm and organelles. Thus, alfa-lipoic acid not only triggered apoptosis of carcinoma cells, but it may also activate the mechanism of elimination of cells with abnormal chromosome number.

  18. Mode of action: developmental thyroid hormone insufficiency--neurological abnormalities resulting from exposure to propylthiouracil.

    PubMed

    Zoeller, R Thomas; Crofton, Kevin M

    2005-01-01

    Because thyroid hormone is essential for normal brain development before and after birth, environmental chemicals that interfere with thyroid hormone signaling can adversely affect brain development. Adverse consequences of thyroid hormone insufficiency depend both on severity and developmental timing, indicating that environmental antithyroid factors may produce different effects at different developmental windows of exposure. Mechanistic studies can provide important insight into the potential impact of chemicals on human thyroid function, but relevance to humans must be systematically evaluated. This kind of analysis depends on data sets that include information about animals and humans. The drug 6-n-propyl-2-thiouracil (PTU) is used in animals to experimentally manipulate serum thyroid hormone levels, and in humans to treat patients, including pregnant women, with Graves' disease. A systematic analysis of the mode of action (MOA) of PTU in rats and in humans discloses similar modes of action. While the analysis predicts that PTU doses that produce thyroid hormone insufficiency in humans would adversely affect the developing brain, careful monitoring of PTU administration in pregnant and lactating humans keeps infant serum thyroid hormone levels within the normal range.

  19. Abnormal urinary bile acids in a patient suffering from cerebrotendinous xanthomatosis during oral administration of ursodeoxycholic acid.

    PubMed

    Koopman, B J; Wolthers, B G; van der Molen, J C; Nagel, G T; Kruizinga, W

    1987-02-14

    The urinary bile acid profile, obtained by capillary gas chromatography, of a patient suffering from cerebrotendinous xanthomatosis and treated with ursodeoxycholic acid demonstrated, besides the occurrence of 23-norcholic acid and (23R)-hydroxycholic acid (as a consequence of this disease), six additional unknown bile acids and three known bile acids, viz. ursodeoxycholic acid, hyocholic acid and omega-muricholic acid. The structure of two of the unknown bile acids were elucidated and proven by organic syntheses. These were 23-norursodeoxycholic acid and 3 beta-ursodeoxycholic acid. The structures of three bile acids were tentatively elucidated as being 1 beta-hydroxyursodeoxycholic acid, 21-hydroxyursodeoxycholic acid and 22-hydroxyursodeoxycholic acid, and the possibility that the structure of the remaining bile acid is that of 5-hydroxyursodeoxycholic acid is discussed. Two of these bile acids (1 beta-hydroxyursodeoxycholic acid and 5-hydroxyursodeoxycholic acid) also occurred in urine of a healthy individual during oral ursodeoxycholic acid treatment, whereas 23-norcholic acid, 23-norursodeoxycholic acid, (23R)-hydroxycholic acid, 21-hydroxyursodeoxycholic acid and 22-hydroxyursodeoxycholic acid were only present in urine of the patient suffering from cerebrotendinous xanthomatosis. The metabolism of ursodeoxycholic acid, both in the normal state and in the cerebrotendinous xanthomatosis, is discussed.

  20. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

    PubMed Central

    Ghosh, P; Bitsanis, D; Ghebremeskel, K; Crawford, M A; Poston, L

    2001-01-01

    Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood. PMID:11410637

  1. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

    PubMed

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming.

  2. Acid exposure induces multiplication of Salmonella enterica serovar Typhi.

    PubMed

    Ahirwar, Suneel Kumar; Pratap, Chandra Bhan; Patel, Saurabh Kumar; Shukla, Vijay K; Singh, Indarjeet Gambhir; Mishra, Om Prakash; Kumar, Kailash; Singh, Tej Bali; Nath, Gopal

    2014-12-01

    Salmonella enterica serovar Typhi faces several environmental stresses while going through the stomach (acidic pH) to the small intestine (basic pH) and intracellularly in macrophages (acidic pH) in humans. The acidic pH followed by alkaline pH in the small intestine might be responsible for expression of certain stress-induced genes, resulting in not only better survival but also induction of multiplication and invasion of the bacterium in the small intestine. Based on this hypothesis, we developed a process wherein we exposed the blood, urine, and stool specimens from 90 acute typhoid fever patients and 36 chronic typhoid carriers to acidic pH to see the effect on isolation rate of S. Typhi. About 5 g of freshly passed unpreserved stool, a centrifuged deposit of 15 ml of urine, and 5 ml of blood clot were subjected to 5 ml of Luria-Bertani (LB) broth (pH 3.5) for 20 min, followed by enrichment in bile broth-selenite F broth. When the combined isolation from all 3 specimens, i.e., blood, urine, and stool, after acid exposure was considered, a total of 77.7% of the acute typhoid patients were observed to be positive for the isolation of the S. Typhi serotype, compared to 8.8% by the conventional method. Similarly, 42% (15/36) of chronic carriers yielded positive for S. Typhi growth after acid exposure, compared to 5.5% (2/36) by the conventional method. It therefore can be concluded that acid shock triggers the multiplication of the bacteria, resulting in better isolation rates from blood clot, stool, and urine specimens.

  3. Accelerated Fatigue of Dentin with Exposure to Lactic Acid

    PubMed Central

    Majd, H.; Ryou, H.; Mutluay, M. M.; Xu, Hockin H. K.; Arola, D.

    2013-01-01

    Composite restorations accumulate more biofilm than other dental materials. This increases the likelihood for the hard tissues supporting a restoration (i.e. dentin and enamel) to be exposed to acidic conditions beyond that resulting from dietary variations. In this investigation the fatigue strength and fatigue crack growth resistance of human coronal dentin were characterized within a lactic acid solution (with pH=5) and compared to that of controls evaluated in neutral conditions (pH=7). A comparison of the fatigue life distributions showed that the lactic acid exposure resulted in a significant reduction in the fatigue strength (p≤0.001), and nearly 30% reduction in the apparent endurance limit (from 44 MPa to 32 MPa). The reduction in pH also caused a significant decrease (p≤0.05) in the threshold stress intensity range required for the initiation of cyclic crack growth, and significant increase in the incremental rate of crack extension. Exposure of tooth structure to lactic acid may cause demineralization, but it also increases the likelihood of restored tooth failures via fatigue, and after short time periods. PMID:23948166

  4. Accelerated fatigue of dentin with exposure to lactic acid.

    PubMed

    Do, Dominic; Orrego, Santiago; Majd, Hessam; Ryou, Heonjune; Mutluay, Mustafa M; Xu, Hockin H K; Arola, Dwayne D

    2013-11-01

    Composite restorations accumulate more biofilm than other dental materials. This increases the likelihood for the hard tissues supporting a restoration (i.e. dentin and enamel) to be exposed to acidic conditions beyond that resulting from dietary variations. In this investigation the fatigue strength and fatigue crack growth resistance of human coronal dentin were characterized within a lactic acid solution (with pH = 5) and compared to that of controls evaluated in neutral conditions (pH = 7). A comparison of the fatigue life distributions showed that the lactic acid exposure resulted in a significant reduction in the fatigue strength (p ≤ 0.001), and nearly 30% reduction in the apparent endurance limit (from 44 MPa to 32 MPa). The reduction in pH also caused a significant decrease (p ≤ 0.05) in the threshold stress intensity range required for the initiation of cyclic crack growth, and significant increase in the incremental rate of crack extension. Exposure of tooth structure to lactic acid may cause demineralization, but it also increases the likelihood of restored tooth failures via fatigue, and after short time periods.

  5. Exposure of acid aerosol for schoolchildren in metropolitan Taipei

    NASA Astrophysics Data System (ADS)

    Mao, I.-Fang; Lin, Chih-Hung; Lin, Chun-Ji; Chen, Yi-Ju; Sung, Fung-Chang; Chen, Mei-Lien

    Metropolitan Taipei, which is located in the subtropical area, is characterized by high population and automobile densities. For convenience, most primary schools are located near major roads. This study explores the exposure of acid aerosols for schoolchildren in areas in Taipei with different traffic densities. Acid aerosols were collected by using a honeycomb denuder filter pack sampling system (HDS). Experimental results indicated that the air pollutants were significantly correlated with traffic densities. The ambient air NO 2, SO 2, HNO 3, NO 3-, SO 42-, and aerosol acidity concentrations were 31.3 ppb, 4.7 ppb, 1.3 ppb, 1.9 μg m -3, 18.5 μg m -3, and 49.5 nmol m -3 in high traffic density areas, and 6.1 ppb, 1.8 ppb, 0.9 ppb, 0.7 μg m -3, 8.8 μg m -3 and 14.7 nmol m -3 in low traffic density areas. The exposure levels of acid aerosols for schoolchildren would be higher than the measurements because the sampling height was 5 m above the ground. The SO 2 levels were low (0.13-8.03 ppb) in the metropolitan Taipei. However, the SO 42- concentrations were relatively high, and might be attributed to natural emissions of sulfur-rich geothermal sources. The seasonal variations of acid aerosol concentrations were also observed. The high levels of acidic particles in spring time may be attributed to the Asian dust storm and low height of the mixture layer. We conclude that automobile contributed not only the primary pollutants but also the secondary acid aerosols through the photochemical reaction. Schoolchildren were exposed to twice the acid aerosol concentrations in high traffic density areas compared to those in low traffic density areas. The incidence of allergic rhinitis of schoolchildren in the high traffic density areas was the highest in spring time. Accompanied by high temperature variation and high levels of air pollution in spring, the health risk of schoolchildren had been observed.

  6. Dietary combination of sucrose and linoleic acid causes skeletal muscle metabolic abnormalities in Zucker fatty rats through specific modification of fatty acid composition

    PubMed Central

    Ohminami, Hirokazu; Amo, Kikuko; Taketani, Yutaka; Sato, Kazusa; Fukaya, Makiko; Uebanso, Takashi; Arai, Hidekazu; Koganei, Megumi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Takeda, Eiji

    2014-01-01

    A dietary combination of sucrose and linoleic acid strongly contributes to the development of metabolic disorders in Zucker fatty rats. However, the underlying mechanisms of the metabolic disorders are poorly understood. We hypothesized that the metabolic disorders were triggered at a stage earlier than the 8 weeks we had previously reported. In this study, we investigated early molecular events induced by the sucrose and linoleic acid diet in Zucker fatty rats by comparison with other combinations of carbohydrate (sucrose or palatinose) and fat (linoleic acid or oleic acid). Skeletal muscle arachidonic acid levels were significantly increased in the sucrose and linoleic acid group compared to the other dietary groups at 4 weeks, while there were no obvious differences in the metabolic phenotype between the groups. Expression of genes related to arachidonic acid synthesis was induced in skeletal muscle but not in liver and adipose tissue in sucrose and linoleic acid group rats. In addition, the sucrose and linoleic acid group exhibited a rapid induction in endoplasmic reticulum stress and abnormal lipid metabolism in skeletal muscle. We concluded that the dietary combination of sucrose and linoleic acid primarily induces metabolic disorders in skeletal muscle through increases in arachidonic acid and endoplasmic reticulum stress, in advance of systemic metabolic disorders. PMID:25147427

  7. Abnormal White Matter Integrity Related to Head Impact Exposure in a Season of High School Varsity Football

    PubMed Central

    Davenport, Elizabeth M.; Urban, Jillian E.; Espeland, Mark A.; Jung, Youngkyoo; Rosenbaum, Daryl A.; Gioia, Gerard A.; Powers, Alexander K.; Stitzel, Joel D.; Maldjian, Joseph A.

    2014-01-01

    Abstract The aim of this study was to determine whether the cumulative effects of head impacts from a season of high school football produce magnetic resonance imaging (MRI) measureable changes in the brain in the absence of clinically diagnosed concussion. Players from a local high school football team were instrumented with the Head Impact Telemetry System (HITS™) during all practices and games. All players received pre- and postseason MRI, including diffusion tensor imaging (DTI). Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was also conducted. Total impacts and risk-weighted cumulative exposure (RWE), including linear (RWELinear), rotational (RWERotational), and combined components (RWECP), were computed from the sensor data. Fractional, linear, planar, and spherical anisotropies (FA, CL, CP, and CS, respectively), as well as mean diffusivity (MD), were used to determine total number of abnormal white matter voxels defined as 2 standard deviations above or below the group mean. Delta (post-preseason) ImPACT scores for each individual were computed and compared to the DTI measures using Spearman's rank correlation coefficient. None of the players analyzed experienced clinical concussion (N=24). Regression analysis revealed a statistically significant linear relationship between RWECP and FA. Secondary analyses demonstrated additional statistically significant linear associations between RWE (RWECP and RWELinear) and all DTI measures. There was also a strong correlation between DTI measures and change in Verbal Memory subscore of the ImPACT. We demonstrate that a single season of football can produce brain MRI changes in the absence of clinical concussion. Similar brain MRI changes have been previously associated with mild traumatic brain injury. PMID:24786802

  8. Abnormal white matter integrity related to head impact exposure in a season of high school varsity football.

    PubMed

    Davenport, Elizabeth M; Whitlow, Christopher T; Urban, Jillian E; Espeland, Mark A; Jung, Youngkyoo; Rosenbaum, Daryl A; Gioia, Gerard A; Powers, Alexander K; Stitzel, Joel D; Maldjian, Joseph A

    2014-10-01

    The aim of this study was to determine whether the cumulative effects of head impacts from a season of high school football produce magnetic resonance imaging (MRI) measureable changes in the brain in the absence of clinically diagnosed concussion. Players from a local high school football team were instrumented with the Head Impact Telemetry System (HITS™) during all practices and games. All players received pre- and postseason MRI, including diffusion tensor imaging (DTI). Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was also conducted. Total impacts and risk-weighted cumulative exposure (RWE), including linear (RWELinear), rotational (RWERotational), and combined components (RWECP), were computed from the sensor data. Fractional, linear, planar, and spherical anisotropies (FA, CL, CP, and CS, respectively), as well as mean diffusivity (MD), were used to determine total number of abnormal white matter voxels defined as 2 standard deviations above or below the group mean. Delta (post-preseason) ImPACT scores for each individual were computed and compared to the DTI measures using Spearman's rank correlation coefficient. None of the players analyzed experienced clinical concussion (N=24). Regression analysis revealed a statistically significant linear relationship between RWECP and FA. Secondary analyses demonstrated additional statistically significant linear associations between RWE (RWECP and RWELinear) and all DTI measures. There was also a strong correlation between DTI measures and change in Verbal Memory subscore of the ImPACT. We demonstrate that a single season of football can produce brain MRI changes in the absence of clinical concussion. Similar brain MRI changes have been previously associated with mild traumatic brain injury.

  9. Etiology, pathogenesis, and treatment of seasonal and non-seasonal mood disorders: possible role of circadian rhythm abnormalities related to developmental alcohol exposure.

    PubMed

    Sher, Leo

    2004-01-01

    Developmental alcohol exposure adversely influences the developing brain. Alcohol exposure during rapid brain growth causes cell loss, alters connections between brain regions, and lowers the production of biological substances responsible for the communication among neurons. It is reasonable to suggest that alcohol may adversely affect the development of suprachiasmatic nuclei (SCN), the master circadian pacemaker. Multiple research reports suggest that abnormalities in circadian rhythms are involved in the etiopathogenesis of seasonal affective disorder (SAD), a syndrome in which depression develops during autumn or winter and remits the following spring or summer. Several lines of evidence suggest that changes in the circadian system are also involved in the development of nonseasonal mood disorders, such as major depression and bipolar disorder. Thus, developmental alcohol exposure produces subtle abnormalities in circadian rhythms that may contribute to the development of seasonal and nonseasonal mood disorders. Pharmacological, psychological, and light treatments of mood disorders have multiple effects on circadian function. The state of the circadian system may affect a response to treatment. Circadian rhythms have been reported for neurotransmitters, receptors, enzymes, and the second messenger system in the brain that are involved in the effects of treatments. Some of these rhythms have amplitudes as large as several 100%. Effects of many psychotropic medications depend on the time of administration in relation to body rhythmicity. Therefore, subtle circadian rhythm abnormalities related to developmental alcohol exposure may affect treatment response in patients with mood disorders.

  10. Metabolic inflexibility of white and brown adipose tissues in abnormal fatty acid partitioning of type 2 diabetes.

    PubMed

    Grenier-Larouche, T; Labbé, S M; Noll, C; Richard, D; Carpentier, A C

    2012-12-01

    Type 2 diabetes (T2D) is characterized by a general dysregulation of postprandial energy substrate partitioning. Although classically described in regard to glucose metabolism, it is now evident that metabolic inflexibility of plasma lipid fluxes is also present in T2D. The organ that is most importantly involved in the latter metabolic defect is the white adipose tissue (WAT). Both catecholamine-induced nonesterified fatty acid mobilization and insulin-stimulated storage of meal fatty acids are impaired in many WAT depots of insulin-resistant individuals. Novel molecular imaging techniques now demonstrate that these defects are linked to increased dietary fatty acid fluxes toward lean organs and myocardial dysfunction in humans. Recent findings also demonstrate functional abnormalities of brown adipose tissues in T2D, thus suggesting that a generalized adipose tissue dysregulation of energy storage and dissipation may be at play in the development of lean tissue energy overload and lipotoxicity. PMID:27152152

  11. Early life perfluorooctanesulphonic acid (PFOS) exposure impairs zebrafish organogenesis

    PubMed Central

    Chen, Jiangfei; Tanguay, Robert L.; Tal, Tamara L.; Bai, Chenglian; Tilton, Susan C.; Jin, Daqing; Yang, Dongren; Huang, Changjiang; Dong, Qiaoxiang

    2014-01-01

    As a persistent organic contaminant, perfluorooctanesulphonic acid (PFOS) has been widely detected in the environment, wildlife, and humans. The present study revealed that zebrafish embryos exposed to 16 µM PFOS during a sensitive window of 48–96 hour post-fertilization (hpf) disrupted larval morphology at 120 hpf. Malformed zebrafish larvae were characterized by uninflated swim bladder, less developed gut, and curved spine. Histological and ultrastructural examination of PFOS-exposed larvae showed structural alterations in swim bladder and gut. Whole genome microarray was used to identify the early transcripts dysregulated following exposure to 16 µM PFOS at 96 hpf. In total, 1,278 transcripts were significantly misexpressed (p < 0.05) and 211 genes were changed at least two-fold upon PFOS exposure in comparison to the vehicle exposed control group. A PFOS-induced network of perturbed transcripts relating to swim bladder and gut development revealed that misexpression of genes were involved in organogenesis. Taken together, early life stage exposure to PFOS perturbs various molecular pathways potentially resulting in observed defects in swim bladder and gut development. PMID:24667235

  12. Relationship between long-term exposure to low-level arsenic in drinking water and the prevalence of abnormal blood pressure.

    PubMed

    Zhang, Chuanwu; Mao, Guangyun; He, Suxia; Yang, Zuopeng; Yang, Wei; Zhang, Xiaojing; Qiu, Wenting; Ta, Na; Cao, Li; Yang, Hui; Guo, Xiaojuan

    2013-11-15

    Arsenic increases the risk and incidence of cardiovascular disease. To explore the impact of long-term exposure to low-level arsenic in drinking water on blood pressure including pulse pressure (PP) and mean arterial blood pressure (MAP), a cross-sectional study was conducted in 2010 in which the blood pressure of 405 villagers was measured, who had been drinking water with an inorganic arsenic content <50 μg/L. A multivariate logistic regression model was used to estimate odds ratios and 95% confidence intervals. After adjusting for age, gender, Body Mass Index (BMI), alcohol consumption and smoking, the odds ratios showed a 1.45-fold (95%CI: 0.63-3.35) increase in the group with >30-50 years of arsenic exposure and a 2.95-fold (95%CI: 1.31-6.67) increase in the group with >50 years exposure. Furthermore, the odds ratio for prevalence of abnormal PP and MAP were 1.06 (95%CI: 0.24-4.66) and 0.87 (95%CI: 0.36-2.14) in the group with >30-50 years of exposure, and were 2.46 (95%CI: 0.87-6.97) and 3.75 (95%CI: 1.61-8.71) for the group with >50 years exposure, compared to the group with arsenic exposure ≤ 30 years respectively. Significant trends for Hypertension (p<0.0001), PP (p<0.0001) and MAP (p=0.0016) were found. The prevalence of hypertension and abnormal PP as well as MAP is marked among a low-level arsenic exposure population, and significantly increases with the duration of arsenic exposure.

  13. Abnormalities in the fatty-acid composition of the serum phospholipids of stroke patients.

    PubMed Central

    Glew, Robert H.; Okolie, Henry; Huang, Yung-Sheng; Chuang, Lu-Te; Suberu, Ojo; Crossey, Michael; VanderJagt, Dorothy J.

    2004-01-01

    The incidence of cardiovascular diseases, stroke, and myocardial infarction is increasing in sub-Saharan Africa. Since dietary polyunsaturated fatty acids (PUFA) are protective of the cardiovascular system in humans, we were interested in the question of the PUFA status of adults in northern Nigeria who had experienced a recent stroke. We collected blood from 21 consecutive admissions for stroke (15 male patients, mean age 39.3 years and six females, mean age 40.7 years) to the Federal Medical Centre in Gombe, Nigeria and analyzed the fatty-acid composition of the serum phospholipids. Blood was collected from 30 healthy controls for comparison. The contribution palmitic acid made to the fatty-acid total was greatly decreased in the phospholipids of the stroke patients (29.2% versus 37.2 %, p < 0.001). However, the phospholipids of the stroke patients had significantly higher percentages of 20-, 22-, and 24-carbon saturated fatty acids, as well as higher proportions of the omega-6 fatty-acid, arachidonic acid (11.4 versus 8.14%, p < 0.001), and the omega-3 fatty-acid, docosahexaenoic acid (3.21 versus 1.80%, p < 0.001). Using the percentages and melting points of the individual fatty acids, we estimated that the acyl chains of the serum phospholipids of the stroke patients had a lower mean melting point than the controls (27.8 versus 34.6 degrees C, p < 0.001). Assuming that serum phospholipids are surrogates for tissue phospholipids, we conclude that the tissue membranes of the stroke patients may be considerably more fluid than those of the controls. PMID:15233494

  14. Abnormal Fatty Acid Pattern in the Superior Temporal Gyrus Distinguishes Bipolar Disorder from Major Depression and Schizophrenia and Resembles Multiple Sclerosis

    PubMed Central

    McNamara, Robert K.; Rider, Therese; Jandacek, Ronald; Tso, Patrick

    2014-01-01

    This study investigated the fatty acid composition of the postmortem superior temporal gyrus (STG), a cortical region implicated in emotional processing, from normal controls (n=15) and patients with bipolar disorder (BD, n=15), major depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative purposes, STG fatty acid composition was determined in a separate cohort of multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and 18:1/18:0 ratios were lower in the STG of BD patients and were inversely correlated with total PUFA composition. MS patients exhibited a pattern of fatty acid abnormalities similar to that observed in BD patients including elevated PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD patients exhibit a pattern of fatty acid abnormalities in the STG that is not observed in MDD and SZ patients and closely resembles MS patients. PMID:24439517

  15. Acute exposure to acid fog. Effects on mucociliary clearance

    SciTech Connect

    Laube, B.L.; Bowes, S.M. III; Links, J.M.; Thomas, K.K.; Frank, R. )

    1993-05-01

    Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min).

  16. Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

    PubMed

    Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

    2015-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects.

  17. Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

    PubMed Central

    Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

  18. Chronic exposure to environmentally-relevant concentrations of fluoxetine (Prozac) decreases survival, increases abnormal behaviors, and delays predator escape responses in guppies.

    PubMed

    Pelli, Marco; Connaughton, Victoria P

    2015-11-01

    This study evaluates the impact of fluoxetine, an antidepressant drug and common pollutant in aquatic environments, on growth, survival, and behavior in juvenile guppies and on predator escape responses in adult guppies (Poecilia reticulata). In juveniles, the effects of acute (4d) and chronic (35d) exposure on growth and survival were examined, and behavioral changes were noted throughout the chronic experiment. In adults, escape responses to a mock predator during chronic (28d) fluoxetine exposure were videotaped to determine the overall speed of response in treated vs. control fish. The effects of fish gender and the presence of a group/school on escape responses were also determined. Our results show that acute exposure to nominal concentrations of 0.03 and 0.5μg/L, levels within the environment, did not adversely impact juvenile guppy survival. However, chronic exposure significantly reduced weight, length, and belly width/girth measurements compared to controls. Chronic exposure also resulted in abnormal swimming behavior and reduced survival in juveniles. In adults, fluoxetine exposure significantly delayed predator escape responses in both males and females. Escape responses were also reduced when adults were tested either individually or in a group, with significantly more delayed responses seen in individually tested fish. Taken together, these findings suggest that fluoxetine can impact guppy populations, during both juvenile and adult stages, with chronic exposure resulting in decreased survival and growth and altered behavioral responses. PMID:26126230

  19. Exposure of two upland plant species to acidic fogs.

    PubMed

    Ashenden, T W; Rafarel, C R; Bell, S A

    1991-01-01

    A system is described for exposing large numbers of plants to acidic fogs. The system allows low volumes of treatment solutions to be provided at particle sizes chiefly in the 5-30 microm range (equivalent to fog/cloud droplets). Plants of Poa alpina L. and Epilobium brunnescens were propagated from material collected in Snowdonia, North Wales and exposed to fog treatments at pH values of 2.5, 3.5, 4.5 and 5.6. There were 3 x 4 h exposures per week which provided a total of 6 mm deposition. Supplementary watering was with pH 4.5 simulated acid rain (24 mm per week). After 21 weeks, there was increased lowering and a greater dry weight for plants of E. brunnescens exposed to the pH 2.5 fog in comparison with other treatments. Also, the plants used assimilated material to form shoots rather than roots. A similar increase in dry weight accumulation in the pH 2.5 treatment was found in P. alpina after 63 weeks but this was not associated with changes in assimilate partitioning.

  20. The risk of menstrual abnormalities after preconceptional use of folic acid or a folic acid-containing multivitamin in Chinese women.

    PubMed

    Shen, Lianlian; Chu, Zhiping; Yang, Jian; Wang, Yubang

    2016-01-01

    The associations of preconceptional folic acid use with menstruation-related changes were examined by a retrospective study through 219 questionnaires. The kind of folic acid (alone or with other vitamins), the using time and frequency, the menstrual regularity, the cycle length before and after use, and other menstruation-related changes after use were obtained. Two hundred of 219 participants were users, and menstruation-related changes occurred in 32 women, with abnormalities of involvement being longer cycles (increase of 3-20 days, 7.7 ± 4.8 days), shorter cycles (decrease of 3-7 days, 5.7 ± 2.3 days), irregular cycles, less blood loss, bleeding or spotting between cycles, and algomenorrhea. Seventeen women stopped using folic acid or folic acid-containing multivitamin, and sixteen of the seventeen women experienced at least one menstruation before conception. Fifteen of sixteen women found complete recovery, indicating the high possibility that these changes were attributed to the use of folic acid or folic acid-containing multivitamin.

  1. Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

    PubMed

    Gómez-Meda, B C; Zamora-Perez, A L; Muñoz-Magallanes, T; Sánchez-Parada, M G; García Bañuelos, J J; Guerrero-Velázquez, C; Sánchez-Orozco, L V; Vera-Cruz, J M; Armendáriz-Borunda, J; Zúñiga-González, G M

    2016-02-01

    Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients.

  2. Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

    PubMed

    Gómez-Meda, B C; Zamora-Perez, A L; Muñoz-Magallanes, T; Sánchez-Parada, M G; García Bañuelos, J J; Guerrero-Velázquez, C; Sánchez-Orozco, L V; Vera-Cruz, J M; Armendáriz-Borunda, J; Zúñiga-González, G M

    2016-02-01

    Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients. PMID:26921015

  3. Identifiability of PBPK models with applications to dimethylarsinic acid exposure.

    PubMed

    Garcia, Ramon I; Ibrahim, Joseph G; Wambaugh, John F; Kenyon, Elaina M; Setzer, R Woodrow

    2015-12-01

    Any statistical model should be identifiable in order for estimates and tests using it to be meaningful. We consider statistical analysis of physiologically-based pharmacokinetic (PBPK) models in which parameters cannot be estimated precisely from available data, and discuss different types of identifiability that occur in PBPK models and give reasons why they occur. We particularly focus on how the mathematical structure of a PBPK model and lack of appropriate data can lead to statistical models in which it is impossible to estimate at least some parameters precisely. Methods are reviewed which can determine whether a purely linear PBPK model is globally identifiable. We propose a theorem which determines when identifiability at a set of finite and specific values of the mathematical PBPK model (global discete identifiability) implies identifiability of the statistical model. However, we are unable to establish conditions that imply global discrete identifiability, and conclude that the only safe approach to analysis of PBPK models involves Bayesian analysis with truncated priors. Finally, computational issues regarding posterior simulations of PBPK models are discussed. The methodology is very general and can be applied to numerous PBPK models which can be expressed as linear time-invariant systems. A real data set of a PBPK model for exposure to dimethyl arsinic acid (DMA(V)) is presented to illustrate the proposed methodology. PMID:26194069

  4. Lead exposure among lead-acid battery workers in Jamaica.

    PubMed

    Matte, T D; Figueroa, J P; Burr, G; Flesch, J P; Keenlyside, R A; Baker, E L

    1989-01-01

    To assess lead exposure in the Jamaican lead-acid battery industry, we surveyed three battery manufacturers (including 46 production workers) and 10 battery repair shops (including 23 battery repair workers). Engineering controls and respiratory protection were judged to be inadequate at battery manufacturers and battery repair shops. At manufacturers, 38 of 42 air samples for lead exceeded a work-shift time-weighted average concentration of 0.050 mg/m3 (range 0.030-5.3 mg/m3), and nine samples exceeded 0.50 mg/m3. Only one of seven air samples at repair shops exceeded 0.050 mg/m3 (range 0.003-0.066 mg/m3). Repair shop workers, however, had higher blood lead levels than manufacturing workers (65% vs. 28% with blood lead levels above 60 micrograms/dl, respectively). Manufacturing workers had a higher prevalence of safe hygienic practices and a recent interval of minimal production had occurred at one of the battery manufacturers. Workers with blood lead levels above 60 micrograms/dl tended to have higher prevalences of most symptoms of lead toxicity than did workers with lower blood lead levels, but this finding was not consistent or statistically significant. The relationship between zinc protoporphyrin concentrations and increasing blood lead concentrations was consistent with that described among workers in developed countries. The high risk of lead toxicity among Jamaican battery workers is consistent with studies of battery workers in other developing countries. PMID:2773946

  5. Lead exposure among lead-acid battery workers in Jamaica.

    PubMed

    Matte, T D; Figueroa, J P; Burr, G; Flesch, J P; Keenlyside, R A; Baker, E L

    1989-01-01

    To assess lead exposure in the Jamaican lead-acid battery industry, we surveyed three battery manufacturers (including 46 production workers) and 10 battery repair shops (including 23 battery repair workers). Engineering controls and respiratory protection were judged to be inadequate at battery manufacturers and battery repair shops. At manufacturers, 38 of 42 air samples for lead exceeded a work-shift time-weighted average concentration of 0.050 mg/m3 (range 0.030-5.3 mg/m3), and nine samples exceeded 0.50 mg/m3. Only one of seven air samples at repair shops exceeded 0.050 mg/m3 (range 0.003-0.066 mg/m3). Repair shop workers, however, had higher blood lead levels than manufacturing workers (65% vs. 28% with blood lead levels above 60 micrograms/dl, respectively). Manufacturing workers had a higher prevalence of safe hygienic practices and a recent interval of minimal production had occurred at one of the battery manufacturers. Workers with blood lead levels above 60 micrograms/dl tended to have higher prevalences of most symptoms of lead toxicity than did workers with lower blood lead levels, but this finding was not consistent or statistically significant. The relationship between zinc protoporphyrin concentrations and increasing blood lead concentrations was consistent with that described among workers in developed countries. The high risk of lead toxicity among Jamaican battery workers is consistent with studies of battery workers in other developing countries.

  6. Indoor exposures to fine aerosols and acid gases.

    PubMed

    Koutrakis, P; Brauer, M; Briggs, S L; Leaderer, B P

    1991-11-01

    Indoor exposures to aerosols and gases are associated with both indoor and outdoor air pollution sources. The identification of sources and the assessment of their relative contribution can be a complicated process due to a) the presence of numerous indoor sources, which can vary from building to building; b) the uncertainties associated with the estimation of the impact of outdoor sources on indoor air quality; c) the interactions between pollutants; and d) the importance of reactions between pollutants and indoor surfaces. It is well established that fine particles (diameter less than or equal to 2.5 microns) originating from outdoor sources such as automobiles, oil and coal combustion, incineration, and diverse industrial activities can penetrate into the indoor environment. Indoor/outdoor ratios, usually varying between 0.4 and 0.8, depend on parameters such as particle size and density, air exchange rate, and the surface-to-volume ratio of the indoor environment. Determining fine particle elemental composition makes it possible to identify the contribution of different outdoor sources. This paper focuses on the origin and the concentration of indoor aerosols and acid gases by highlighting the results from two indoor air quality studies. PMID:1821374

  7. Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

    PubMed Central

    Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

    2016-01-01

    Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

  8. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

    PubMed Central

    Bártfai, Zoltán; Bánhidy, Ferenc

    2011-01-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’). PMID:25083211

  9. Short antisense-locked nucleic acids (all-LNAs) correct alternative splicing abnormalities in myotonic dystrophy

    PubMed Central

    Wojtkowiak-Szlachcic, Agnieszka; Taylor, Katarzyna; Stepniak-Konieczna, Ewa; Sznajder, Lukasz J.; Mykowska, Agnieszka; Sroka, Joanna; Thornton, Charles A.; Sobczak, Krzysztof

    2015-01-01

    Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by expansion of CTG triplet repeats in 3′-untranslated region of DMPK gene. The pathomechanism of DM1 is driven by accumulation of toxic transcripts containing expanded CUG repeats (CUGexp) in nuclear foci which sequester several factors regulating RNA metabolism, such as Muscleblind-like proteins (MBNLs). In this work, we utilized very short chemically modified antisense oligonucleotides composed exclusively of locked nucleic acids (all-LNAs) complementary to CUG repeats, as potential therapeutic agents against DM1. Our in vitro data demonstrated that very short, 8- or 10-unit all-LNAs effectively bound the CUG repeat RNA and prevented the formation of CUGexp/MBNL complexes. In proliferating DM1 cells as well as in skeletal muscles of DM1 mouse model the all-LNAs induced the reduction of the number and size of CUGexp foci and corrected MBNL-sensitive alternative splicing defects with high efficacy and specificity. The all-LNAs had low impact on the cellular level of CUGexp-containing transcripts and did not affect the expression of other transcripts with short CUG repeats. Our data strongly indicate that short all-LNAs complementary to CUG repeats are a promising therapeutic tool against DM1. PMID:25753670

  10. Roles of retinoic acid signaling in normal and abnormal development of the palate and tongue.

    PubMed

    Okano, Junko; Udagawa, Jun; Shiota, Kohei

    2014-05-01

    Palatogenesis involves various developmental events such as growth, elevation, elongation and fusion of opposing palatal shelves. Extrinsic factors such as mouth opening and subsequent tongue withdrawal are also needed for the horizontal elevation of palate shelves. Failure of any of these steps can lead to cleft palate, one of the most common birth defects in humans. It has been shown that retinoic acid (RA) plays important roles during palate development, but excess RA causes cleft palate in fetuses of both rodents and humans. Thus, the coordinated regulation of retinoid metabolism is essential for normal palatogenesis. The endogenous RA level is determined by the balance of RA-synthesizing (retinaldehyde dehydrogenases: RALDHs) and RA-degrading enzymes (CYP26s). Cyp26b1 is a key player in normal palatogenesis. In this review, we discuss recent progress in the study of the pathogenesis of RA-induced cleft palate, with special reference to the regulation of endogenous RA levels by RA-degrading enzymes.

  11. Postnatal Isoflurane Exposure Induces Cognitive Impairment and Abnormal Histone Acetylation of Glutamatergic Systems in the Hippocampus of Adolescent Rats.

    PubMed

    Liang, Bing; Fang, Jie

    2016-09-01

    Isoflurane can elicit cognitive impairment. However, the pathogenesis in the brain remains inconclusive. The present study investigated the mechanism of glutamate neurotoxicity in adolescent male rats that underwent postnatal isoflurane exposure and the role of sodium butyrate (NaB) in cognitive impairment induced by isoflurane exposure. Seven-day-old rats were exposed to 1.7 % isoflurane for 35 min every day for four consecutive days, and then glutamate neurotoxicity was examined in the hippocampus. Morris water maze analysis showed cognitive impairments in isoflurane-exposed rats. High-performance liquid chromatography found higher hippocampal glutamate concentrations following in vitro and in vivo isoflurane exposure. The percentage of early apoptotic hippocampal neurons was markedly increased after isoflurane exposure. Decreased acetylation and increased HDAC2 activity were observed in the hippocampus of isoflurane-exposed rats and hippocampal neurons. Furthermore, postnatal isoflurane exposure decreased histone acetylation of hippocampal neurons in the promoter regions of GLT-1 and mGLuR1/5, but not mGLuR2/3. Treatment with NaB not only restored the histone acetylation of the GLT-1 and mGLuR1/5 promoter regions and glutamate excitatory neurotoxicity in hippocampal neurons, but also improved cognitive impairment in vivo. Moreover, NaB may be a potential therapeutic drug for cognitive impairment caused by isoflurane exposure. These results suggest that postnatal isoflurane exposure contributes to cognitive impairment via decreasing histone acetylation of glutamatergic systems in the hippocampus of adolescent rats. PMID:27307148

  12. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    SciTech Connect

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert; Volz, Cornelia; Jägle, Herbert; Liebisch, Gerhard; Utermöhlen, Olaf; Langmann, Thomas

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  13. Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington's Disease Patients.

    PubMed

    Naseri, Nima N; Bonica, Joseph; Xu, Hui; Park, Larry C; Arjomand, Jamshid; Chen, Zhengming; Gibson, Gary E

    2016-01-01

    Metabolic dysfunction is well-documented in Huntington's disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD. The experiments utilize the advantages of lymphoblasts to reveal new insights about HD. The large quantity of homogeneous cell populations permits multiple dynamic measures to be made on exactly comparable tissues. The activities of nine enzymes related to the TCA cycle and the expression of twenty-nine mRNAs encoding for these enzymes and enzyme complexes were measured. Cells were studied under baseline conditions and during metabolic stress. The results support our recent findings that the activities of the pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected depression in MDH activities. Furthermore, message levels for isocitrate dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were responsive to treatments. The use of lymphoblasts allowed us to clarify that the reported decrease in aconitase activity in HD autopsy brains is likely due to secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the TCA cycle are critical therapeutic targets that have been understudied in HD. PMID:27611087

  14. Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

    PubMed Central

    Banerjee, Anwesha; Engineer, Crystal T.; Sauls, Bethany L.; Morales, Anna A.; Kilgard, Michael P.; Ploski, Jonathan E.

    2014-01-01

    Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning. PMID:25429264

  15. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures

    PubMed Central

    Rossignol, D A; Frye, R E

    2012-01-01

    Recent studies have implicated physiological and metabolic abnormalities in autism spectrum disorders (ASD) and other psychiatric disorders, particularly immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures (‘four major areas'). The aim of this study was to determine trends in the literature on these topics with respect to ASD. A comprehensive literature search from 1971 to 2010 was performed in these four major areas in ASD with three objectives. First, publications were divided by several criteria, including whether or not they implicated an association between the physiological abnormality and ASD. A large percentage of publications implicated an association between ASD and immune dysregulation/inflammation (416 out of 437 publications, 95%), oxidative stress (all 115), mitochondrial dysfunction (145 of 153, 95%) and toxicant exposures (170 of 190, 89%). Second, the strength of evidence for publications in each area was computed using a validated scale. The strongest evidence was for immune dysregulation/inflammation and oxidative stress, followed by toxicant exposures and mitochondrial dysfunction. In all areas, at least 45% of the publications were rated as providing strong evidence for an association between the physiological abnormalities and ASD. Third, the time trends in the four major areas were compared with trends in neuroimaging, neuropathology, theory of mind and genetics (‘four comparison areas'). The number of publications per 5-year block in all eight areas was calculated in order to identify significant changes in trends. Prior to 1986, only 12 publications were identified in the four major areas and 51 in the four comparison areas (42 for genetics). For each 5-year period, the total number of publications in the eight combined areas increased progressively. Most publications (552 of 895, 62%) in the four major areas were published in the last 5 years (2006–2010). Evaluation

  16. Phenotypic Dichotomy Following Developmental Exposure to Perfluorooctanic Acid (PFOA) Exposure in CD-1 Mice: Low Doses Induce Elevated Serum, Leptin, Insulin, and Overweight in Mid-Life.

    EPA Science Inventory

    The synthetic surfactant, perfluorooctanoic acid (PFOA) is a proven developmental toxicant in mice, causing prenatal pregnancy loss, increased neonatal mortality, delayed eye opening, and abnormal mammary gland growth in animals exposed during fetal life. PFOA is found in the ser...

  17. Heat exposure in female rats elicits abnormal fear expression and cellular changes in prefrontal cortex and hippocampus.

    PubMed

    Gruene, Tina M; Lipps, Jennifer; Rey, Colin D; Bouck, Anna; Shansky, Rebecca M

    2014-11-01

    Despite a twofold higher prevalence of fear-related disorders in women, the neurobiological factors that modulate and drive fear expression are rarely studied in female animals. Fear conditioning and extinction are useful tools for dissecting these mechanisms, and here we tested the effects of environmental manipulations - four days of exposure to 31°C temperatures in the animal housing facility - on fear learning and memory exclusively in female rats. We found that heat exposure disrupted freezing to tone during fear conditioning, and elicited enhanced freezing during extinction and extinction retrieval. We also performed immunohistochemistry for c-fos expression in the infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex during extinction retrieval, and found that heat exposure induced a switch from IL-dominated activity to PL-dominated activity. Finally, morphological analysis of spines in hippocampal CA3 neurons revealed an increase in spine head diameter in heat-exposed animals, which may partly underlie the persistent freezing observed in these animals. Together, our data show that heat exposure can induce changes at behavioral, physiological, and structural levels, and add to a woefully lacking body of literature on fear processes in female animals.

  18. An outbreak of illness after occupational exposure to ozone and acid chlorides.

    PubMed Central

    Ng, T P; Tsin, T W; O'Kelly, F J

    1985-01-01

    New labelling processes installed without adequate ventilation control in an electric motor factory exposed production line workers to toxic gases. Symptoms of eye and respiratory tract irritation together with complaints of headache, fever, chills, dizziness, malaise, general weakness, nausea, and vomiting were widespread. Chest signs, radiographic abnormalities, reduction in ventilatory function, and blood gas abnormalities were found in some cases. Epidemiological analysis of the spatial and temporal distribution of cases supported an exposure effect relationship. Investigations suggested ozone and possibly phosgene and associated trichloroacetyl chlorides as the toxic agents that were generated by an ultraviolet print curing arrangement and perchloroethylene used as a cleaning solvent. PMID:4041387

  19. Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice.

    PubMed

    Koseki, Takenao; Mouri, Akihiro; Mamiya, Takayoshi; Aoyama, Yuki; Toriumi, Kazuya; Suzuki, Shizuka; Nakajima, Azusa; Yamada, Takuma; Nagai, Taku; Nabeshima, Toshitaka

    2012-11-01

    Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP-induced decrease of acetylated Lys9 in histone H3-positive cells and increase of the histone deacetylase (HDAC)5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys9 in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia.

  20. Chronic Dietary Exposure to Aristolochic Acid and Kidney Function in Native Farmers from a Croatian Endemic Area and Bosnian Immigrants

    PubMed Central

    Jelaković, Bojan; Karanović, Sandra; Dika, Živka; Kos, Jelena; Dickman, Kathleen; Šekoranja, Maja; Poljičanin, Tamara; Mišić, Maja; Premužić, Vedran; Abramović, Mirta; Matijević, Vesna; Miletić Medved, Marica; Cvitković, Ante; Edwards, Karen; Fuček, Mirjana; Leko, Ninoslav; Teskera, Tomislav; Laganović, Mario; Čvorišćec, Dubravka; Grollman, Arthur P.

    2015-01-01

    Background and objectives Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15–30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. Design, setting, participants, & measurements In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m2 were considered to be abnormal. Results CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15–30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage

  1. Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin.

    PubMed

    El Sheikh Saad, H; Meduri, G; Phrakonkham, P; Bergès, R; Vacher, S; Djallali, M; Auger, J; Canivenc-Lavier, M C; Perrot-Applanat, M

    2011-07-01

    The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland.

  2. Chronic exposure of mutant DISC1 mice to lead produces sex-dependent abnormalities consistent with schizophrenia and related mental disorders: a gene-environment interaction study.

    PubMed

    Abazyan, Bagrat; Dziedzic, Jenifer; Hua, Kegang; Abazyan, Sofya; Yang, Chunxia; Mori, Susumu; Pletnikov, Mikhail V; Guilarte, Tomas R

    2014-05-01

    The glutamatergic hypothesis of schizophrenia suggests that hypoactivity of the N-methyl-D-aspartate receptor (NMDAR) is an important factor in the pathophysiology of schizophrenia and related mental disorders. The environmental neurotoxicant, lead (Pb(2+)), is a potent and selective antagonist of the NMDAR. Recent human studies have suggested an association between prenatal Pb(2+) exposure and the increased likelihood of schizophrenia later in life, possibly via interacting with genetic risk factors. In order to test this hypothesis, we examined the neurobehavioral consequences of interaction between Pb(2+) exposure and mutant disrupted in schizophrenia 1 (mDISC1), a risk factor for major psychiatric disorders. Mutant DISC1 and control mice born by the same dams were raised and maintained on a regular diet or a diet containing moderate levels of Pb(2+). Chronic, lifelong exposure of mDISC1 mice to Pb(2+) was not associated with gross developmental abnormalities but produced sex-dependent hyperactivity, exaggerated responses to the NMDAR antagonist, MK-801, mildly impaired prepulse inhibition of the acoustic startle, and enlarged lateral ventricles. Together, these findings support the hypothesis that environmental toxins could contribute to the pathogenesis of mental disease in susceptible individuals.

  3. Effects of ascorbic acid supplementation on male reproductive system during exposure to hypoxia

    NASA Astrophysics Data System (ADS)

    Havazhagan, G.; Riar, S. S.; Kain, A. K.; Bardhan, Jaya; Thomas, Pauline

    1989-09-01

    Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.

  4. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    PubMed

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus. PMID:21315145

  5. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    PubMed

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus.

  6. TOXICOGENOMIC DISSECTION OF RODENT LIVER TRANSCRIPT PROFILES AFTER EXPOSURE TO PERFLUOROALKYL ACIDS

    EPA Science Inventory

    Exposure to peroxisome proliferator chemicals (PPC) leads to alterations in the balance between hepatocyte growth and apoptosis, increases in liver to body weight ratios and liver tumors. The perfluoroalkyl acids including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (...

  7. Examination of age-related epigenetic changes following early-life exposure to dichloroacetic acid

    EPA Science Inventory

    Recent studies have shown that transient early-life exposure to dichloroacetic acid (DCA), a pyruvate analog and metabolic reprogramming agent, increases liver cancer incidence in older mice. This carcinogenic effect is not associated with direct mutagenicity, persistent cytotoxi...

  8. Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice.

    PubMed

    Yang, Eun-Jeong; Ahn, Sangzin; Lee, Kihwan; Mahmood, Usman; Kim, Hye-Sun

    2016-01-01

    Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life.

  9. Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice

    PubMed Central

    Yang, Eun-Jeong; Ahn, Sangzin; Lee, Kihwan; Mahmood, Usman; Kim, Hye-Sun

    2016-01-01

    Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life. PMID:27071011

  10. Sperm abnormalities induced by pre-pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract.

    PubMed

    Nayak, G; Vadinkar, A; Nair, S; Kalthur, S G; D'Souza, A S; Shetty, P K; Mutalik, S; Shetty, M M; Kalthur, G; Adiga, S K

    2016-03-01

    Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy. PMID:25904411

  11. Sperm abnormalities induced by pre-pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract.

    PubMed

    Nayak, G; Vadinkar, A; Nair, S; Kalthur, S G; D'Souza, A S; Shetty, P K; Mutalik, S; Shetty, M M; Kalthur, G; Adiga, S K

    2016-03-01

    Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy.

  12. Acute lung injury following exposure to nitric acid

    PubMed Central

    Jayalakshmi, T. K.; Shah, Samir; Lobo, Ivona; Uppe, Abhay; Mehta, Ankur

    2009-01-01

    We present a series of three cases of survival following inhalation of nitric acid fumes, which resulted in acute respiratory distress. Inhalation of nitric acid fumes and its decomposition gases such as nitrogen dioxide results in delayed onset of acute respiratory distress syndrome. Intensive respiratory management, ventilatory support, and steroids can help in survival. PMID:20532002

  13. EFFECTS OF PERFLUOROOCTANOIC ACID EXPOSURE DURING PREGNANCY IN THE MOUSE

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, has recently been detected in humans and wildlife. The current study characterizes the developmental toxicity of PFOA in the mouse. Timed pregnant CD-1 mice were given 1,...

  14. Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat

    EPA Science Inventory

    Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in...

  15. Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes

    PubMed Central

    Vu, Bao G.; Stach, Christopher S.; Kulhankova, Katarina; Salgado-Pabón, Wilmara; Klingelhutz, Aloysius J.

    2015-01-01

    ABSTRACT Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among S. aureus virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to S. aureus superantigens facilitates the development of DMII, which may lead to therapeutic targeting of S. aureus and its superantigens. PMID:25714716

  16. The Exposure Experience: Ohio River Valley Residents Respond to Local Perfluorooctanoic Acid (PFOA) Contamination.

    PubMed

    Judge, J Matthew; Brown, Phil; Brody, Julia Green; Ryan, Serena

    2016-09-01

    This article explores the "exposure experience" of participants who received their personal results in a biomonitoring study for perfluorooctanoic acid. Exposure experience is the process of identifying, understanding, and responding to chemical contamination. When biomonitoring studies report results to participants, those participants generate an exposure experience that identifies hidden contaminants and helps level informational imbalances between polluters and affected communities. Participants welcomed the opportunity to learn their exposure results, reporting no psychological harm following report-back. They wove health, economic, and political considerations into their interpretation of results and their present views of past impact. Participants framed their experiences by a half-century of dependence on the chemical industry's economic benefits, leading them to considerable acceptance of chemical exposure as a tradeoff for jobs and the local economy. Our findings show that the exposure experience is an ongoing process that influences social action, with new activism being generated by exposure and health studies. PMID:27601409

  17. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass.

    PubMed

    Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O C; Chun, Jerold; Salles, Jean Pierre

    2011-09-01

    Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1-LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1 may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1((-/-)) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1((-/-)) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1((-/-)) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology.

  18. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass☆,☆☆

    PubMed Central

    Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O. C.; Chun, Jerold; Salles, Jean Pierre

    2013-01-01

    Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1–LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1(−/−) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1(−/−) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1(−/−) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology. PMID:21569876

  19. A MULTISTAGE BIOLOGICALLY BASED MODEL FOR MOUSE LIVER TUMORS RESULTING FROM EXPOSURE TO DICHLOROACETIC ACID

    EPA Science Inventory

    Dichloroacetic Acid (DCA) is a major byproduct of the chlorine disinfection of humic acid containing drinking water sources. It is a hepatocarcinogen in mice and rats at exposure concentrations in drinking water that are at least 4 orders of magnitude above the concentrations in ...

  20. Understanding Potential Exposure Sources of Perfluorinated Carboxylic Acids in the Workplace

    PubMed Central

    Kaiser, Mary A.; Dawson, Barbara J.; Barton, Catherine A.; Botelho, Miguel A.

    2010-01-01

    This paper integrates perspectives from analytical chemistry, environmental engineering, and industrial hygiene to better understand how workers may be exposed to perfluorinated carboxylic acids when handling them in the workplace in order to identify appropriate exposure controls. Due to the dramatic difference in physical properties of the protonated acid form and the anionic form, this family of chemicals provides unique industrial hygiene challenges. Workplace monitoring, experimental data, and modeling results were used to ascertain the most probable workplace exposure sources and transport mechanisms for perfluorooctanoic acid (PFOA) and its ammonium salt (APFO). PFOA is biopersistent and its measurement in the blood has been used to assess human exposure since it integrates exposure from all routes of entry. Monitoring suggests that inhalation of airborne material may be an important exposure route. Transport studies indicated that, under low pH conditions, PFOA, the undissociated (acid) species, actively partitions from water into air. In addition, solid-phase PFOA and APFO may also sublime into the air. Modeling studies determined that contributions from surface sublimation and loss from low pH aqueous solutions can be significant potential sources of workplace exposure. These findings suggest that keeping surfaces clean, preventing accumulation of material in unventilated areas, removing solids from waste trenches and sumps, and maintaining neutral pH in sumps can lower workplace exposures. PMID:20974675

  1. Using tensor-based morphometry to detect structural brain abnormalities in rats with adolescent intermittent alcohol exposure

    NASA Astrophysics Data System (ADS)

    Paniagua, Beatriz; Ehlers, Cindy; Crews, Fulton; Budin, Francois; Larson, Garrett; Styner, Martin; Oguz, Ipek

    2011-03-01

    Understanding the effects of adolescent binge drinking that persist into adulthood is a crucial public health issue. Adolescent intermittent ethanol exposure (AIE) is an animal model that can be used to investigate these effects in rodents. In this work, we investigate the application of a particular image analysis technique, tensor-based morphometry, for detecting anatomical differences between AIE and control rats using Diffusion Tensor Imaging (DTI). Deformation field analysis is a popular method for detecting volumetric changes analyzing Jacobian determinants calculated on deformation fields. Recent studies showed that computing deformation field metrics on the full deformation tensor, often referred to as tensor-based morphometry (TBM), increases the sensitivity to anatomical differences. In this paper we conduct a comprehensive TBM study for precisely locating differences between control and AIE rats. Using a DTI RARE sequence designed for minimal geometric distortion, 12-directional images were acquired postmortem for control and AIE rats (n=9). After preprocessing, average images for the two groups were constructed using an unbiased atlas building approach. We non-rigidly register the two atlases using Large Deformation Diffeomorphic Metric Mapping, and analyze the resulting deformation field using TBM. In particular, we evaluate the tensor determinant, geodesic anisotropy, and deformation direction vector (DDV) on the deformation field to detect structural differences. This yields data on the local amount of growth, shrinkage and the directionality of deformation between the groups. We show that TBM can thus be used to measure group morphological differences between rat populations, demonstrating the potential of the proposed framework.

  2. Hepatic mitochondrial alteration in CD1 mice associated with prenatal exposures to low doses of perfluorooctanoic acid (PFOA)

    PubMed Central

    Quist, Erin M.; Filgo, Adam J.; Cummings, Connie A.; Kissling, Grace E.; Hoenerhoff, Mark J.; Fenton, Suzanne E.

    2014-01-01

    Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3 and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number, but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA. PMID:25326589

  3. Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by 1H-NMR-based metabonomics

    PubMed Central

    Dan Yue; Zhang, Yuwei; Cheng, Liuliu; Ma, Jinhu; Xi, Yufeng; Yang, Liping; Su, Chao; Shao, Bin; Huang, Anliang; Xiang, Rong; Cheng, Ping

    2016-01-01

    Hepatitis B virus X protein (HBx) plays an important role in HBV-related hepatocarcinogenesis; however, mechanisms underlying HBx-mediated carcinogenesis remain unclear. In this study, an NMR-based metabolomics approach was applied to systematically investigate the effects of HBx on cell metabolism. EdU incorporation assay was conducted to examine the effects of HBx on DNA synthesis, an important feature of nucleic acid metabolism. The results revealed that HBx disrupted metabolism of glucose, lipids, and amino acids, especially nucleic acids. To understand the potential mechanism of HBx-induced abnormalities of nucleic acid metabolism, gene expression profiles of HepG2 cells expressing HBx were investigated. The results showed that 29 genes involved in DNA damage and DNA repair were differentially expressed in HBx-expressing HepG2 cells. HBx-induced DNA damage was further demonstrated by karyotyping, comet assay, Western blotting, immunofluorescence and immunohistochemistry analyses. Many studies have previously reported that DNA damage can induce abnormalities of nucleic acid metabolism. Thus, our results implied that HBx initially induces DNA damage, and then disrupts nucleic acid metabolism, which in turn blocks DNA repair and induces the occurrence of hepatocellular carcinoma (HCC). These findings further contribute to our understanding of the occurrence of HCC. PMID:27075403

  4. Phenolic acid metabolites as biomarkers for tea- and coffee-derived polyphenol exposure in human subjects.

    PubMed

    Hodgson, Jonathan M; Chan, Shin Yee; Puddey, Ian B; Devine, Amanda; Wattanapenpaiboon, Naiyana; Wahlqvist, Mark L; Lukito, Widjaja; Burke, Valerie; Ward, Natalie C; Prince, Richard L; Croft, Kevin D

    2004-02-01

    Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4-O-methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual (r 0.50, P<0.001) and current (r 0.57, P<0.001) tea intake, and isoferulic acid was related to usual (r 0.26, P=0.008) and current (r 0.18, P<0.001) coffee intake. Overall, our present results are consistent with the proposal that 4OMGA is a good biomarker for black tea-derived polyphenol exposure, but isoferulic acid may be of limited usefulness as a biomarker for coffee-derived polyphenol exposure.

  5. PHARMACOKINETIC PROFILES OF PERFLUOROOCTANOIC ACID IN MICE AFTER CHRONIC EXPOSURE

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is highly persistent in humans, with serum half-life estimates of 2.3 to 3.8 years. In the mouse, elimination of PFOA appears to be first-order after a single oral administration, with serum half-life estimates of 16 days for females and 22 days for ...

  6. ALTERED GENE EXPRESSION IN MOUSE LIVERS AFTER DICHLOROACETIC ACID EXPOSURE

    EPA Science Inventory

    Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated that DCA exhibits hepatocarcinogenic effects in rodents when administered in drinking water. The mechanism(s) involved in DCA induction of cancer are not clear...

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

    EPA Science Inventory

    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...

  8. Effects of Perfluorooctanoic Acid on Mouse Mammary Gland Development and Differentiation Resulting from Cross-Foster and Restricted Gestational Exposures

    EPA Science Inventory

    The adverse consequences of developmental exposures to perfluorooctanoic acid (PFOA) have been established, and include impaired development of the offspring mammary gland (MG). However, the relationship between the timing or route of exposure, and the phenotypic consequences in ...

  9. Effect of acute nitrogen dioxide exposure on the composition of fatty acid associated with phospholipids in alveolar lavage

    SciTech Connect

    Kobayashi, T.; Noguchi, T.; Kikuno, M.; Kubota, K.

    1984-01-01

    In vivo exposure of rats to 10 ppm nitrogen dioxide (NO/sub 2/) for 12 h caused changes in fatty acids composition of alveolar lavage phospholipids. Among the fatty acid species, the relative ratio of palmitic acid, myristic acid and palmitoleic acid increased significantly. While the relative ratio of stearic acid, oleic acid, linoleic acid and arachidonic acid decreased significantly. Both the increase in the incorporation of palmitic acid in phosphatidylcholine which would be released into the alveoli and the increase in the release of phosphatidylcholine into the alveoli may account for the changes in the fatty acid composition of the present findings.

  10. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  11. Dietary exposure estimates for the food preservatives benzoic acid and sorbic acid in the total diet in Taiwan.

    PubMed

    Ling, Min-Pei; Lien, Keng-Wen; Wu, Chiu-Hua; Ni, Shih-Pei; Huang, Hui-Ying; Hsieh, Dennis P H

    2015-02-25

    The purpose was to assess the health risk to general consumers in Taiwan associated with dietary intake of benzoic acid and sorbic acid by conducting a total diet study (TDS). The hazard index (HI) in percent acceptable daily intake (%ADI) of benzoic acid and sorbic acid for eight exposure groups classified by age were calculated. In high-intake consumers, the highest HI of benzoic acid was 54.1%ADI for males aged 1-2 years old at the 95th percentile, whereas for females, the HI was 61.7%ADI for aged over 66 years old. The highest HI of sorbic acid for male and female consumers aged 3-6 years old at the 95th percentile were 14.0%ADI and 12.2%ADI, respectively. These results indicate that the use of benzoic acid and sorbic acid as preservatives at the current level of use in the Taiwanese diet does not constitute a public health and safety concern.

  12. Ascorbic Acid Ameliorates Nicotine Exposure Induced Impaired Spatial Memory Performance in Rats

    PubMed Central

    Sirasanagandla, SR; Rooben, RK; Rajkumar; Narayanan, SN; Jetti, R

    2014-01-01

    Introduction: The long lasting behavioural and cognitive impairments in offspring prenatally exposed to nicotine have been confirmed in animal models. In the present study, we investigated the effect of ascorbic acid on prenatal nicotine exposure induced behavioural deficits in male offspring of rats. Methods: The pregnant Wistar dams were divided into four groups of six rats: control, vehicle control, nicotine and nicotine+ascorbic acid groups. The nicotine group received daily dose of subcutaneous injections of 0.96 mg/kg body weight (bw) nicotine free base throughout gestation. Pregnant dams in nicotine+ascorbic acid group were first given nicotine free base (0.96 mg/kg bw/day; subcutaneous route) followed by ascorbic acid (50 mg/kg bw/day, orally) daily throughout gestation. The cognitive function of male offspring of all the experimental groups was studied using Morris water maze test at postnatal day 40. Results: Prenatal nicotine exposure altered spatial learning and memory in male offspring. However, treatment with ascorbic acid ameliorated these changes in rats. Conclusion: Ascorbic acid supplementation was found to be effective in preventing the prenatal nicotine exposure induced cognitive deficits in rat offspring to some extent. PMID:25429474

  13. Biomarker-Based Calibration of Retrospective Exposure Predictions of Perfluorooctanoic Acid

    PubMed Central

    2015-01-01

    Estimated historical exposures and serum concentrations of perfluorooctanoic acid (PFOA) have been extensively used in epidemiologic studies that examined associations between PFOA exposures and adverse health outcomes among residents in highly exposed areas in the Mid-Ohio Valley. Using measured serum PFOA levels in 2005–2006, we applied two calibration methods to these retrospective exposure predictions: (1) multiplicative calibration and (2) Bayesian pharmacokinetic calibration with larger adjustments to more recent exposure estimates and smaller adjustments to exposure estimates for years farther in the past. We conducted simulation studies of various hypothetical exposure scenarios and compared hypothetical true historical intake rates with estimates based on mis-specified baseline exposure and pharmacokinetic models to find the method with the least bias. The Bayesian method outperformed the multiplicative method if a change to bottled water consumption was not reported or if the half-life of PFOA was mis-specified. On the other hand, the multiplicative method outperformed the Bayesian method if actual tap water consumption rates were systematically overestimated. If tap water consumption rates gradually decreased over time because of substitution with bottled water or other liquids, neither method clearly outperformed another. Calibration of retrospective exposure estimates using recently collected biomarkers may help reduce uncertainties in environmental epidemiologic studies. PMID:24730513

  14. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  15. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  16. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  17. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  18. Effects of ozone and acid aerosol exposures on surfactant-associated protein A in the lung

    SciTech Connect

    Su, W.Y.

    1993-01-01

    This study examined the effect of ozone and/or acid aerosol exposure on the level of surfactant associated protein A (SP-A), its gene expression and functionality in the lung. Guinea pigs were exposed to (1) a single exposure to 0.2 to 0.8 ppm ozone for 6 hr and sacrificed at 0 to 120 hr postexposure, (2) 0.8 ppm ozone, 6 hr/day for 3 to 5 days and sacrificed immediately postexposure, or (3) 0.8 ppm ozone, 600 [mu]g/m[sup 3] sulfuric acid, or ozone plus acid for 6 hr and sacrificed at 72 hr postexposure. The concentration of SP-A was determined by ELISA in lavage fluid, lavage cell pellets, and lung tissue compartments. SP-A gene expression was examined in lung tissue by Northern and slot blot analysis. Effect of ozone exposure on functionality of surfactant was tested by its ability to modulate phagocytic cell respiratory burst in a luminol-amplified chemiluminescence (CL) assay of phagocytic cells simulated by PMA or opsonized-zymosan. There were isolated, but significant, changes in SP-A concentrations in the lavage cell and the lavage fluid compartments at 24 and 48 hr after single exposure to 0.8 ppm ozone, respectively. Exposure to ozone and ozone plus acid also slightly increased total SP-A level in the lung. No change in SP-A gene expression was detected under the exposure conditions examined. However, surfactant from ozone exposed animals significantly enhanced CL response of phagocytic cells stimulated by either PMA or opsonized-zymosan. Blocking of the enhancement of CL by a rabbit anti-human SP-A antibody strongly suggested that SP-A may contribute in the altered respiratory burst of phagocytic cells induced by surfactant from ozone exposed animals.

  19. Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure.

    PubMed

    Trommer, Hagen; Böttcher, Rolf; Huschka, Christoph; Wohlrab, Wolfgang; Neubert, Reinhard H H

    2005-08-01

    This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid. PMID:16102251

  20. Acute effects of chlorinated resin acid exposure on juvenile rainbow trout, Oncorhynchus mykiss

    SciTech Connect

    Kennedy, C.J.; Sweeting, R.M.; Farrell, A.P.; McKeown, B.A.; Johansen, J.A.

    1995-06-01

    The effects of an acute exposure to either 14-monochlorodehydroabietic acid (MCDHAA) or 12,14-dichlorodehydroabietic acid (DCDHAA) were examined in juvenile rainbow trout, Oncorhynchus mykiss. The experimentally determined 96-h LC50 values (and their 95% confidence limits) were 1.03 (0.72, 1.48) and 0.91 (0.70, 1.21) mg/L, for MCDHAA and DCDHAA, respectively. To measure effects on several biochemical parameters, swimming performance, and disease resistance, juvenile trout were exposed for 24 h to sublethal concentrations of one or the other resin acid in an intermittent-flow respirometer. Hematocrit, plasma lactate, and liver protein were significantly affected by exposure to the highest dose (80% of the 96-h LC50 value) of either of the resin acids. Plasma cortisol levels were 14- and 3-fold higher than were controls. Resistance to infection by Aeromonas salmonicida was significantly reduced; the cumulative percent mortalities due to furunculosis in fish exposed to MCDHAA or DCDHAA reached 20 and 26%, respectively. Swimming performance, measured as critical swimming speed (mean values 6.32 {+-} 0.20 and 5.93 {+-} 0.15 body lengths per second for MCDHAA and DCDHAA, respectively), was not significantly affected by resin acid exposure.

  1. Evaluation of a chlorous acid-chlorine dioxide teat dip under experimental and natural exposure conditions.

    PubMed

    Drechsler, P A; Wildman, E E; Pankey, J W

    1990-08-01

    A postmilking teat dip containing chlorous acid-chlorine dioxide was evaluated by experimental challenge and in two herds under natural exposure. The test product had an efficacy of 78.9% against Staphylococcus aureus and 52.5% against Streptococcus agalactiae in the experimental challenge trial. The product was compared with a 1% iodine product in a 15-mo natural exposure study. Post-dipping with chlorous acid-chlorine dioxide reduced incidence of udder infection by major mastitis pathogens 36.1% when data were combined from the two herds. The 1% iodine and the chlorous acid-chlorine dioxide products were not equivalent for major mastitis pathogens; the test product was more effective. Incidence of udder infection by environmental mastitis pathogens was reduced 36.8% in both herds combined. Efficacy of the two teat dips was equivalent for environmental pathogens. PMID:2229601

  2. Serum metabolomics reveals that arsenic exposure disrupted lipid and amino acid metabolism in rats: a step forward in understanding chronic arsenic toxicity.

    PubMed

    Wang, Xiaoxue; Mu, Xiaoli; Zhang, Jie; Huang, Qingyu; Alamdar, Ambreen; Tian, Meiping; Liu, Liangpo; Shen, Heqing

    2015-03-01

    Chronic arsenic exposure through drinking water threatens public health worldwide. Although its multiorgan toxicity has been reported, the impact of chronic arsenic exposure on the metabolic network remains obscure. In this study, male Sprague Dawley rats were exposed to 0.5, 2 or 10 ppm sodium arsenite for three months. An ultra-high performance liquid chromatography/mass spectrometry based metabolomics approach was utilized to unveil the global metabolic response to chronic arsenic exposure in rats. Distinct serum metabolome profiles were found to be associated with the doses. Eighteen differential metabolites were identified, and most of them showed dose-dependent responses to arsenic exposure. Metabolic abnormalities mainly involved lipid metabolism and amino acid metabolism. The metabolic alterations were further confirmed by hepatic gene expression. Expressions of cpt2, lcat, cact, crot and mtr were significantly elevated in high dose groups. This study provides novel evidence to support the association between arsenic exposure and metabolic disruption, and it contributes to understanding the mechanism of chronic arsenic toxicity.

  3. Serum metabolomics reveals that arsenic exposure disrupted lipid and amino acid metabolism in rats: a step forward in understanding chronic arsenic toxicity.

    PubMed

    Wang, Xiaoxue; Mu, Xiaoli; Zhang, Jie; Huang, Qingyu; Alamdar, Ambreen; Tian, Meiping; Liu, Liangpo; Shen, Heqing

    2015-03-01

    Chronic arsenic exposure through drinking water threatens public health worldwide. Although its multiorgan toxicity has been reported, the impact of chronic arsenic exposure on the metabolic network remains obscure. In this study, male Sprague Dawley rats were exposed to 0.5, 2 or 10 ppm sodium arsenite for three months. An ultra-high performance liquid chromatography/mass spectrometry based metabolomics approach was utilized to unveil the global metabolic response to chronic arsenic exposure in rats. Distinct serum metabolome profiles were found to be associated with the doses. Eighteen differential metabolites were identified, and most of them showed dose-dependent responses to arsenic exposure. Metabolic abnormalities mainly involved lipid metabolism and amino acid metabolism. The metabolic alterations were further confirmed by hepatic gene expression. Expressions of cpt2, lcat, cact, crot and mtr were significantly elevated in high dose groups. This study provides novel evidence to support the association between arsenic exposure and metabolic disruption, and it contributes to understanding the mechanism of chronic arsenic toxicity. PMID:25697676

  4. Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population-based case-control study.

    PubMed

    Bánhidy, Ferenc; Dakhlaoui, Abdallah; Puhó, Erzsébet H; Czeizel, Andrew A E

    2011-06-01

    The objective of the present study was to estimate the preventive effect of folic acid for structural birth defects (i.e. congenital abnormalities [CAs]) in the offspring of pregnant women with diabetes mellitus type 1 (DM-1). The occurrence of medically recorded DM-1 in pregnant women who had malformed fetuses/newborns (cases) and delivered healthy babies (controls) with or without folic acid supplementation was compared in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. The case group included 22,843 offspring, and there were 79 (0.35%) pregnant women with DM-1, while the control group comprised of 38,151 newborns, and 88 (0.23%) had mothers with DM-1. Case mothers with DM-1 associated with a higher risk of total rate of CAs in their offspring (OR with 95% CI: 1.5, 1.1-2.0) compared to the total rate of CAs in the offspring of non-diabetic case mothers. This higher risk can be explained by four specific types/groups of CAs: isolated renal a/dysgenesis; obstructive CA of the urinary tract; cardiovascular CAs; and multiple CAs, namely caudal dysplasia sequence. However, there was no higher rate of total CAs in the children of pregnant women with DM-1 after folic acid supplementation; in addition, neural-tube defect and renal a/dysgenesis did not occur. However, this benefit cannot be explained by the CA reduction effect of folic acid during the critical period of major CAs. In conclusion, there was a certain reduction in maternal teratogenic effect of DM-1 after folic acid supplementation during pregnancy, but the explanation of this effect requires further study.

  5. Exposure assessment of boron in Bandırma boric acid production plant.

    PubMed

    Duydu, Yalçin; Başaran, Nurşen; Bolt, Hermann M

    2012-06-01

    Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL of 17.5mg B/kg-bw/day (corresponds to ∼2020 ng boron/g blood) has been identified for the (male) reproductive effects of boron in a multigenerational study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day (corresponds to 1270 ng boron/g blood). These values are being taken as the basis of current EU safety assessments. The present study was conducted to assess the boron exposure under extreme exposure conditions in a boric acid production plant located in Bandırma, Turkey. The mean blood boron concentrations of low and high exposure groups were 72.94 ± 15.43 (48.46-99.91) and 223.89 ± 60.49 (152.82-454.02)ng/g respectively. The mean blood boron concentration of the high exposure group is still ≈ 6 times lower than the highest no effect level of boron in blood with regard to the developmental effects in rats and ≈ 9 times lower than the highest no effect level of boron in blood with regard to the reprotoxic effects in male rats. In this context, boric acid and sodium borates should not be considered as toxic to reproduction for humans in daily life.

  6. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    NASA Astrophysics Data System (ADS)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  7. Controlled exposures of volunteers to respirable carbon and sulfuric acid aerosols

    SciTech Connect

    Anderson, K.R.; Avol, E.L.; Edwards, S.A.; Shamoo, D.A.; Ruchuan Peng; Linn, W.S.; Hackney, J.D. )

    1992-06-01

    Respirable carbon or fly ash particles are suspected to increase the respiratory toxicity of coexisting acidic air pollutants, by concentrating acid on their surfaces and so delivering it efficiently to the lower respiratory tract. To investigate this issue, the authors exposed 15 healthy and 15 asthmatic volunteers in a controlled-environment chamber to four test atmospheres: (1) clean air; (2) 0.5-{mu}m H{sub 2}SO{sub 4} aerosol at {approx}100 {mu}g/m{sup 3}, generated from water solution; (3) 0.5-{mu}m carbon aerosol at {approx}250 {mu}g/m{sup 3}, generated from highly pure carbon black with specific surface area comparable to ambient pollution particles; and (4) carbon as in (3) plus {approx}100 {mu}g/m{sup 3} of ultrafine H{sub 2}SO{sub 4} aerosol generated from fuming sulfuric acid. Electron microscopy showed that nearly all acid in (4) became attached to carbon particle surfaces, and that most particles remained in the sub-{mu}m size range. Exposures were performed double-blind, 1 week apart. They lasted 1 hr each, with alternate 10-min periods of heavy exercise (ventilation {approx}50 L/min) and rest. Subjects gargled citrus juice before exposure to suppress airway ammonia. Lung function and symptoms were measured pre-exposure, after initial exercise, and at end-exposure. Bronchial reactivity to methacholine was measured after exposure. Statistical analyses tested for effects of H{sub 2}SO{sub 4} or carbon, separate or interactive, on health measures.

  8. The effect of ozone exposure on rat alveolar macrophage arachidonic acid metabolism

    SciTech Connect

    Madden, M.C.; Eling, T.E.; Dailey, L.A.; Friedman, M. )

    1991-01-01

    Rat alveolar macrophages were prelabeled with {sup 3}H-arachidonic acid ({sup 3}H-AA) and exposed to air or O3 (0.1-1.0 ppm) in vitro for 2 h. Alveolar macrophages released 3.6-fold more tritium at the 1.0 ppm exposure concentration compared with air-exposed macrophages. A significantly increased production of several {sup 3}H-AA metabolites, including 6-keto-PGF1 alpha, thromboxane B2, 12-hydroxy-5,8,10-heptadecatrienoic acid, prostaglandins E2 and D2, leukotrienes B4 and D4, and 15-hydroxyeicosatetraenoic acid was formed by macrophages exposed to 1.0 ppm O3 compared with air-exposed macrophages as determined by high performance liquid chromatography (HPLC) analysis. O3 exposure did not alter macrophage {sup 3}H-AA metabolism in response to calcium ionophore A23187. The largest tritiated peak observed in the HPLC chromatograms of O{sub 3}-exposed cells was a polar complex of products that contained various phospholipids and neutral lipids (including diacylglycerol) and possibly degradation products of {sup 3}H-AA and some of its metabolites. These changes in macrophage arachidonic acid metabolism may play an important role in the lung response to O{sub 3} exposure in vivo.

  9. Abnormal concentrations of B vitamins and amino acids in plasma and B vitamins in bile of rabbits with aflatoxicosis.

    PubMed Central

    Viogt, M N; Clarke, J D; Jain, A V; Ayres, J C; Koehler, P E; Hatch, R C

    1981-01-01

    The dosages of aflatoxin B1 (AFB1) required to produce significant changes in concentrations of B vitamins in plasma and bile and of amino acids in plasma of rabbits were determined. Folate increased by 98% in plasma, whereas concentration of thiamine, vitamin B6, and biotin decreased by more than 50%. In bile, choline and biotin increased 14- and 18-fold, respectively, whereas folate and niacin decreased by more than 50%. All amino acids in plasma increased between 76 and 155%. The dosages of AFB1 required to induce these changes were usually between 12.5 and 37.5 microgram/kg of body weight per day. Except for changes in biliary concentrations of pantothenic acid, folic acid, and biotin, lower threshold dosages of aflatoxin were required to produce weight loss and anorexia (5.0 and 8.5 microgram of AFB1/kg per day, respectively) than for changes in vitamins and amino acids (approximately 25 to 50 microgram of AFB1/kg per day). The data indicated that AFB1 interfered with the metabolism of B vitamins and amino acids in rabbits. PMID:6786221

  10. Prenatal arachidonic acid exposure and selected immune-related variables in childhood.

    PubMed

    Dirix, Chantal E H; Hogervorst, Janneke G F; Rump, Patrick; Hendriks, Johannes J E; Bruins, Maaike; Hornstra, Gerard

    2009-08-01

    Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely.

  11. Prenatal arachidonic acid exposure and selected immune-related variables in childhood.

    PubMed

    Dirix, Chantal E H; Hogervorst, Janneke G F; Rump, Patrick; Hendriks, Johannes J E; Bruins, Maaike; Hornstra, Gerard

    2009-08-01

    Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely. PMID:19173768

  12. Atlantic salmon (Salmo salar L.) smolts require more than two weeks to recover from acidic water and aluminium exposure.

    PubMed

    Nilsen, Tom O; Ebbesson, Lars O E; Handeland, Sigurd O; Kroglund, Frode; Finstad, Bengt; Angotzi, Anna R; Stefansson, Sigurd O

    2013-10-15

    The detrimental effects of acid rain and aluminium (Al) on salmonids have been extensively studied, yet knowledge about the extent and rate of potential recovery after exposures to acid and Al episodes is limited. Atlantic salmon smolts in freshwater (FW) were exposed for 2 and 7-day episodes (ACID2 and ACID7, respectively) to low pH (5.7±0.2) and inorganic aluminium (Ali; 40±4 μg) and then transferred to good water quality, control water (CW; pH 6.8±0.1; <14±2 μg Ali). Al accumulation on gills after 2 and 7 days of acid/Al exposure was 35.3±14.1 and 26.6±1.8 μg g(-1) dry weight, respectively. These elevated levels decreased 2 days post transfer to CW and remained higher than in control (CON; 5-10 μg Ali) for two weeks. Plasma Na(+) levels in ACID2 and ACID7 smolts decreased to 141±0.8 and 138.6±1.4mM, respectively, and remained significantly lower than CON levels for two weeks post transfer to CW. Similarly, plasma Cl(-) levels in ACID7 smolts (124.3±2.8mM) were significantly lower than in CON, with Cl(-) levels remaining significantly lower in ACID7 (126.2±4.8 mM) and ACID2 (127.6±3.7 mM) than in CON following 9 and 14 days post-transfer to CW, respectively. ACID2 and ACID7 smolts sustained elevated plasma glucose levels post transfer to CW suggesting elevated stress for more than a week following exposure. While gill Na(+), K(+)-ATPase (NKA) activity was only slightly affected in ACID2 and not in ACID7 smolts in FW, acid/Al exposure resulted in a transient decrease in NKA activity following SW exposure in both groups. Acid/Al episodes had limited impact on isoform specific NKA α-subunit mRNA during exposure. However, the transfer of ACID2 and ACID7 smolts to CW showed an increase in NKAα1a mRNA (the FW isoform) and inhibited the up-regulation of NKAα1b (the SW isoform), probably resulting in higher abundance of the enzyme favouring ion uptake. Gill caspase 3B gene transcription did not change in acid/Al treated smolts, indicating no increased

  13. Atlantic salmon (Salmo salar L.) smolts require more than two weeks to recover from acidic water and aluminium exposure.

    PubMed

    Nilsen, Tom O; Ebbesson, Lars O E; Handeland, Sigurd O; Kroglund, Frode; Finstad, Bengt; Angotzi, Anna R; Stefansson, Sigurd O

    2013-10-15

    The detrimental effects of acid rain and aluminium (Al) on salmonids have been extensively studied, yet knowledge about the extent and rate of potential recovery after exposures to acid and Al episodes is limited. Atlantic salmon smolts in freshwater (FW) were exposed for 2 and 7-day episodes (ACID2 and ACID7, respectively) to low pH (5.7±0.2) and inorganic aluminium (Ali; 40±4 μg) and then transferred to good water quality, control water (CW; pH 6.8±0.1; <14±2 μg Ali). Al accumulation on gills after 2 and 7 days of acid/Al exposure was 35.3±14.1 and 26.6±1.8 μg g(-1) dry weight, respectively. These elevated levels decreased 2 days post transfer to CW and remained higher than in control (CON; 5-10 μg Ali) for two weeks. Plasma Na(+) levels in ACID2 and ACID7 smolts decreased to 141±0.8 and 138.6±1.4mM, respectively, and remained significantly lower than CON levels for two weeks post transfer to CW. Similarly, plasma Cl(-) levels in ACID7 smolts (124.3±2.8mM) were significantly lower than in CON, with Cl(-) levels remaining significantly lower in ACID7 (126.2±4.8 mM) and ACID2 (127.6±3.7 mM) than in CON following 9 and 14 days post-transfer to CW, respectively. ACID2 and ACID7 smolts sustained elevated plasma glucose levels post transfer to CW suggesting elevated stress for more than a week following exposure. While gill Na(+), K(+)-ATPase (NKA) activity was only slightly affected in ACID2 and not in ACID7 smolts in FW, acid/Al exposure resulted in a transient decrease in NKA activity following SW exposure in both groups. Acid/Al episodes had limited impact on isoform specific NKA α-subunit mRNA during exposure. However, the transfer of ACID2 and ACID7 smolts to CW showed an increase in NKAα1a mRNA (the FW isoform) and inhibited the up-regulation of NKAα1b (the SW isoform), probably resulting in higher abundance of the enzyme favouring ion uptake. Gill caspase 3B gene transcription did not change in acid/Al treated smolts, indicating no increased

  14. Exposure assessment of food preservatives (sulphites, benzoic and sorbic acid) in Austria.

    PubMed

    Mischek, Daniela; Krapfenbauer-Cermak, Christine

    2012-01-01

    An exposure assessment was performed to estimate the potential intake of preservatives in the Austrian population. Food consumption data of different population groups, such as preschool children aged 3-6 years, female and male adults aged 19-65 years were used for calculation. Levels of the preservatives in food were derived from analyses conducted from January 2007 to August 2010. Dietary intakes of the preservatives were estimated and compared to the respective acceptable daily intakes (ADIs). In the average-intake scenario, assuming that consumers randomly consume food products that do or do not contain food additives, estimated dietary intakes of all studied preservatives are well below the ADI for all population groups. Sulphite exposure accounted for 34%, 84% and 89% of the ADI in preschool children, females and males, respectively. The mean estimated daily intake of benzoic acid was 32% (preschool children), 31% (males) and 36% (females) of the ADI. Sorbic acid intakes correspond to 7% of the ADI in preschool children and 6% of the ADI in adults. In the high-intake scenario assuming that consumers always consume food products that contain additives and considering a kind of brand loyalty of consumers, the ADI is exceeded for sulphites among adults (119 and 124%, respectively). Major contributors to the total intake of sulphites were wine and dried fruits for adults. Mean estimated dietary intakes of benzoic acid exceeded the ADI in all population groups, 135% in preschool children, 124% in females and 118% of the ADI in males, respectively. Dietary intakes of sorbic acid are well below the ADI, accounting for a maximum of 30% of the ADI in preschool children. The highest contributors to benzoic and sorbic acid exposure were fish and fish products mainly caused by high consumption data of this large food group, including also mayonnaise-containing fish salads. Other important sources of sorbic acid were bread, buns and toast bread and fruit and vegetable

  15. Lead exposure assessment from study near a lead-acid battery factory in China.

    PubMed

    Chen, Laiguo; Xu, Zhencheng; Liu, Ming; Huang, Yumei; Fan, Ruifang; Su, Yanhua; Hu, Guocheng; Peng, Xiaowu; Peng, Xiaochun

    2012-07-01

    The production of lead-acid battery in China covered about one-third of the world total output and there are more than 2000 lead-acid battery factories. They may cause the major environment lead pollution. Blood lead levels of several hundreds of residents were over 100 μg/L due to the waste discharges from a lead-acid battery factory in Heyuan, Guangdong province. This study aimed to find out the environmental lead sources, the human lead exposure pathways, and the amplitudes from a lead-acid battery factory. The study results showed that lead levels in soil, dust, tree leaves and human blood declined with the distances increased from the production site. Twenty nine of 32 participants had blood lead levels of over 100 μg/L with an exceptional high value of 639 μg/L for one child. This result suggested that the lead-acid battery production from this factory has caused the elevated lead levels in its neighboring environment and residents. Dust intake was the dominant exposure pathway for humans (over 90%). The lead levels found in adult and toddler (6.19 and 50.1 μg/kg/d, respectively) in the polluted area were far higher than the provisional tolerable weekly intake (PTWI) of 25 μg/kg body weight (translated into 3.5 μg/kg/d), which was established by the joint FAO/WHO Expert Committee. Blood lead levels within the family members were strongly correlated with the house dust lead levels. Our results in this study suggested that further studies in this area should be performed to assess human exposure and relevant human health risks from living close to lead-acid battery factories.

  16. Raman Spectroscopic Analysis Reveals Abnormal Fatty Acid Composition in Tumor Micro- and Macroenvironments in Human Breast and Rat Mammary Cancer

    PubMed Central

    You, Sixian; Tu, Haohua; Zhao, Youbo; Liu, Yuan; Chaney, Eric J.; Marjanovic, Marina; Boppart, Stephen A.

    2016-01-01

    Fatty acids play essential roles in the growth and metastasis of cancer cells. To facilitate their avid growth and proliferation, cancer cells not only alter the fatty acid synthesis and metabolism intracellularly and extracellularly, but also in the macroenvironment via direct or indirect pathways. We report here, using Raman micro-spectroscopy, that an increase in the production of polyunsaturated fatty acids (PUFAs) was identified in both cancerous and normal appearing breast tissue obtained from breast cancer patients and tumor-bearing rats. By minimizing confounding effects from mixed chemicals and optimizing the signal-to-noise ratio of Raman spectra, we observed a large-scale transition from monounsaturated fatty acids to PUFAs in the tumor while only a small subset of fatty acids transitioned to PUFAs in the tumor micro- and macroenvironment. These data have important implications for further clarifying the macroenvironmental effect of cancer progression and provide new potential approaches for characterizing the tumor micro- and macroenvironment of breast cancer in both pre-clinical animal studies and clinical applications. PMID:27596041

  17. Raman Spectroscopic Analysis Reveals Abnormal Fatty Acid Composition in Tumor Micro- and Macroenvironments in Human Breast and Rat Mammary Cancer.

    PubMed

    You, Sixian; Tu, Haohua; Zhao, Youbo; Liu, Yuan; Chaney, Eric J; Marjanovic, Marina; Boppart, Stephen A

    2016-01-01

    Fatty acids play essential roles in the growth and metastasis of cancer cells. To facilitate their avid growth and proliferation, cancer cells not only alter the fatty acid synthesis and metabolism intracellularly and extracellularly, but also in the macroenvironment via direct or indirect pathways. We report here, using Raman micro-spectroscopy, that an increase in the production of polyunsaturated fatty acids (PUFAs) was identified in both cancerous and normal appearing breast tissue obtained from breast cancer patients and tumor-bearing rats. By minimizing confounding effects from mixed chemicals and optimizing the signal-to-noise ratio of Raman spectra, we observed a large-scale transition from monounsaturated fatty acids to PUFAs in the tumor while only a small subset of fatty acids transitioned to PUFAs in the tumor micro- and macroenvironment. These data have important implications for further clarifying the macroenvironmental effect of cancer progression and provide new potential approaches for characterizing the tumor micro- and macroenvironment of breast cancer in both pre-clinical animal studies and clinical applications. PMID:27596041

  18. Alkyl protocatechuates as novel urinary biomarkers of exposure to p-hydroxybenzoic acid esters (parabens).

    PubMed

    Wang, Lei; Kannan, Kurunthachalam

    2013-09-01

    Human exposure to p-hydroxybenzoic acid esters (parabens) is a concern, owing to adverse health effects of these compounds. Parabens are metabolized and eliminated from the human bodies within a few hours of exposure. In this study, for the first time, methyl- and ethyl-protocatechuates (OH-MeP and OH-EtP) and their parent compounds, methyl- (MeP) and ethyl-parabens (EtP), were determined in urine samples collected from U.S. children and adults. Alkyl protocatechuates were found in almost all urine samples, with median concentrations of 11.8 (OH-MeP) and 2.90ng/mL (OH-EtP) in adults, and 5.43 (OH-MeP) and 0.85ng/mL (OH-EtP) in children. In adults, the concentrations of urinary OH-MeP and OH-EtP were higher than the corresponding concentrations of MeP and EtP. Significant correlation between OH-MeP/OH-EtP and MeP/EtP was observed. This is the first report to document hydroxylation of parabens in humans, and to propose hydroxylated metabolites (i.e., alkyl protocatechuates) as alternative biomarkers of exposure to parabens in human biomonitoring studies. The rates of transformation of parabens between children and adults appeared to be different, as evidenced from the slopes of regression between alkyl protocatechuates and parabens. In addition to alkyl protocatechuates, hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were found at considerable levels in the urine samples. The occurrence of a significant proportion of alkyl protocatechuates and 3,4-DHB suggests the need for inclusion of these derivatives in accurate estimation of human exposure to parabens and in epidemiological studies that associate paraben exposure to health outcomes in populations.

  19. Effects of exposure to lead among lead-acid battery factory workers in Sudan.

    PubMed

    Awad el Karim, M A; Hamed, A S; Elhaimi, Y A; Osman, Y; el Karim, M A

    1986-01-01

    Health effects of occupational exposure to lead were investigated among 92 exposed workers in lead-acid battery factory and 40 nonexposed workers serving as a control group from an oil mill in Khartoum North industrial area. The two groups were closely similar in age, stature, body weight, and socioeconomic conditions. A highly significant increase (P less than .01) was recorded in blood lead, urinary coproporphyrin, and basophilic stippled red blood cells of the exposed group in comparison to the control group. Central nervous system symptoms (insomnia, fatigue, weakness, and drowsiness) were reported by 50% and other symptoms such as abdominal colic and constipation were reported by 41% of the exposed group. Blue line on the gum was detected only on 2% of the exposed group. Strong associations between exposure to lead and the prevalence of central nervous system symptoms, abdominal colic, and constipation were recorded. Exposure to exceedingly high levels of lead in the working environment causes adverse health effects.

  20. Omega-3 fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism.

    PubMed

    Ross, Brian M

    2007-01-01

    Omega-3 fatty acids are a type of polyunsaturated fatty acid (PUFA). A growing body of evidence suggests that this form PUFA is a useful and well tolerated treatment for major depressive disorder, a common and serious mental illness. The efficacy of omega-3 PUFA is routinely explained as being due to a deficiency caused by inadequate dietary intake of this class of fatty acid. The hypothesis considered states that low omega-3 PUFA abundance in patients with major depressive and related disorders is due to an underlying genetically determined abnormality. The hypothesis can explain why although a specific and consistent deficit in omega-3, but not omega-6, PUFA occurs in major depressive and related disorders, the literature does not consistently support the notion that this is due to deficient dietary intake. Specifically it is hypothesized that having genetically determined low activity of fatty acid CoA ligase 4 and/or Type IV phospholipase A(2) combined with the low dietary availability of omega-3 PUFA results in reduced cellular uptake of omega-3 PUFA and constitutes a risk factor for depression. The hypothesis also has important consequences for the pharmacological treatment of depression in that it predicts that administering agents which enhance phospholipid synthesis, particularly those containing ethanolamine such as CDP-ethanolamine, should be effective antidepressants especially when co-administered with omega-3 PUFA.

  1. Relation between oesophageal acid exposure and healing of oesophagitis with omeprazole in patients with severe reflux oesophagitis.

    PubMed Central

    Holloway, R H; Dent, J; Narielvala, F; Mackinnon, A M

    1996-01-01

    BACKGROUND/AIMS--Reducing oesophageal acid exposure by suppressing acid secretion with omeprazole is highly effective in healing reflux oesophagitis. Some patients with severe oesophagitis, fail to heal and whether this results from inadequate acid suppression or other factors is unclear. The aim of this study, was to investigate the relation between oesophageal acid exposure and healing in patients with severe reflux oesophagitis treated with omeprazole. METHODS--Sixty one patients with grade 3 or 4 ulcerative oesophagitis were treated for eight weeks with omeprazole 20 mg every morning. Those patients unhealed at eight weeks were treated with 40 mg every morning for a further eight weeks. Endoscopy and 24 hour oesophageal pH monitoring were performed before treatment and at the end of each treatment phase while receiving treatment. RESULTS--Thirty per cent of patients failed to heal with the 20 mg dose. Unhealed patients had greater total 24 hour oesophageal acid exposure before treatment, and while receiving treatment also had greater acid exposure and a smaller reduction in acid exposure than did patients who healed. Forty seven per cent of the unhealed patients also failed to heal with the 40 mg dose. These patients had similar levels of acid exposure before treatment to those who healed, but had greater acid exposure while receiving treatment, particularly at night when supine. CONCLUSIONS--Patients with severe ulcerative oesophagitis who are refractory to omeprazole have greater oesophageal acid exposure while receiving treatment than responding patients. This is due to a reduced responsiveness to acid suppression, and is likely to be an important factor underlying the failure of the oesophagitis to heal. PMID:8707107

  2. Preliminary exposure study to determine the effects of acid deposition on coated steel substrates. Final report

    SciTech Connect

    Moran, P.J.; Simpson, T.C.; Hampel, H.; David, G.D.; Shaw, B.A.

    1990-04-01

    The project involves the evaluation of the effects of acidic pollutants on painted metal substrates. The project examined a commercially available alkyd paint/primer system applied to a low carbon steel substrate exposed under a variety of simulated acidic conditions to determine the micro/macro effects of such exposure. The techniques that were identified as those most sensitive and applicable during the study include tensile adhesion testing, electrochemical impedance spectroscopy, and x-ray photoelectron spectroscopy. A novel electrochemical monitor was developed during this program that allowed the continual monitoring of coating degradation during chamber exposure. It was further found that a good correlation existed between tensile adhesion strength measurements and electrochemical impedance parameters. The program determined that the rate of degradation of the alkyd painted steel coupons was accelerated in the presence of SO2. This effect was most pronounced on samples that contained defects (scribes), that were allowed to form condensed (dew) during the exposure period and that had a horizontal orientation during exposure.

  3. Clinical and histopathological changes of the nasal mucosa induced by occupational exposure to sulphuric acid mists

    PubMed Central

    Grasel, S; Alves, V; da Silva, C S; Cruz, O; Almeida, E; de Oliveira, E

    2003-01-01

    Aims: To assess potential alterations of the nasal mucosa by clinical and histopathological evaluation of workers exposed to sulphuric acid mists at anodising plants, correlating the findings with duration of exposure and sulphuric acid concentrations in the air, and comparing them with a control group. Methods: Fifty two workers from five plants underwent a clinical evaluation (standard questionnaire, clinical, and ear, nose, and throat examination including nasal endoscopy). For the histopathological study, 20 of the 52 subjects (study group) were randomly selected, as well as 11 unexposed subjects (control group), matched by sex, age, and smoking habits. Nasal biopsy specimens were obtained from the anterior septum mucosa and the anterior curvature of the middle turbinate in each individual. A total of 56 nasal mucosa specimens (37 in the study group and 19 in the control group) were evaluated with regard to normal respiratory epithelium or metaplastic epithelium, atypia or dysplasia, and alterations of the lamina propria. Results: The histopathological study revealed squamous metaplasia in 29 (79%) and atypia in 13 (35%) of the 37 study group samples. No association was found between exposure duration and the clinical and histopathological variables, but a significant association was found between sulphuric acid concentrations higher than 200 µg/m3 and pale mucosal patches and ulcerations in the exposed subjects. Logistic regression analysis showed that the exposed subjects had a fivefold risk of developing atypia compared with the unexposed subjects. Conclusions: Workers exposed to sulphuric acid mists presented with a high incidence of nasal symptoms, and macroscopic and microscopic changes of the nasal mucosa, including squamous atypia and dysplasia. The risk for these histopthological lesions increased with higher sulphuric acid concentrations in the air, revealing an exposure-response relation. PMID:12771390

  4. Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: a case-control study.

    PubMed Central

    Hardell, L.; Eriksson, M.; Lenner, P.; Lundgren, E.

    1981-01-01

    A number of men with malignant lymphoma of the histiocytic type and previous exposure to phenoxy acids or chlorophenols were observed and reported in 1979. A matched case-control study has therefore been performed with cases of malignant lymphoma (Hodgkin's disease and non-Hodgkin lymphoma). This study included 169 cases and 338 controls. The results indicate that exposure to phenoxy acids, chlorophenols, and organic solvents may be a causative factor in malignant lymphoma. Combined exposure of these chemicals seemed to increase the risk. Exposure to various other agents was not obviously different in cases and in controls. PMID:7470379

  5. Dermal absorption and skin damage following hydrofluoric acid exposure in an ex vivo human skin model.

    PubMed

    Dennerlein, Kathrin; Kiesewetter, Franklin; Kilo, Sonja; Jäger, Thomas; Göen, Thomas; Korinth, Gintautas; Drexler, Hans

    2016-04-25

    The wide industrial use of hydrofluoric acid (HF) poses a high risk for accidental dermal exposure. Despite local and systemic hazards associated with HF, information on percutaneous penetration and tissue damage is rare. In the present ex vivo study, the dermal absorption of HF (detected in terms of fluoride ions) was quantified and the skin damaging potential as a function of concentration and exposure duration was assessed. Percutaneous penetration of HF (c=5, 30, and 50%) at 3 exposure durations (3, 5, and 10 min) was investigated in a static diffusion cell model using freshly excised human skin. Alterations of skin were histologically evaluated. HF rapidly penetrated through skin under formation of a considerable intradermal reservoir (∼ 13-67% of total absorbed fluoride). Histologically, epidermal alterations were detected already after exposure to 5% HF for 3 min. The degree of skin damage increased with rising concentration and exposure duration leading to coagulation necrosis. For HF concentrations of ≥ 30%, skin damage progressed into deeper skin layers. Topically applied HF concentration was the principal parameter determining HF induced skin effects. The intradermal HF retention capacity associated with progression and prolongation of HF induced skin effects must be considered in the review of skin decontamination procedures.

  6. Respiratory hazards associated with exposure to formaldehyde and solvents in acid-curing paints

    SciTech Connect

    Alexandersson, R.; Hedenstierna, G.

    1988-05-01

    Thirty-eight employees exposed to formaldehyde when working with acid-hardening lacquers and 18 nonexposed control persons employed at the same company were examined to determine lung function (spirometry and nitrogen washout), total immunoglobulin blood concentration, and work-related symptoms. The mean exposure to formaldehyde during an 8-hr workshop was 0.40 mg/m/sup 3/ air, and the mean exposure to peak values was 0.70 mg/m/sup 3/. Mean exposure to solvents was low, i.e., approximately 1/10 of the hygienic effect. Eye, nose, and throat irritation was more common in exposed persons than in controls. Monday morning, after two exposure-free days, forced vital capacity (FVC) values were found to have declined by 0.24 L and forced expiratory volume in 1 sec (FEV/sub 1.0/) by 0.21 L, compared with normal values. There was a weak correlation between the individual concentration of IgG and decrease in FVC and FEV/sub 1.0/. No significant changes were noted in any other lung function variable before a work shift, and no lung function changes were noted over a full work shift. Deviations in FVC and FEV/sub 1.0/ values did not correlate to peaks or mean exposures or employment time.

  7. Human environmental and occupational exposures to boric acid: reconciliation with experimental reproductive toxicity data.

    PubMed

    Bolt, Hermann M; Başaran, Nurşen; Duydu, Yalçın

    2012-01-01

    The reproductive toxicity of boric acid and borates is a matter of current regulatory concern. Based on experimental studies in rats, no-observed-adverse-effect levels (NOAELs) were found to be 17.5 mg boron (B)/kg body weight (b.w.) for male fertility and 9.6 mg B/kg b.w. for developmental toxicity. Recently, occupational human field studies in highly exposed cohorts were reported from China and Turkey, with both studies showing negative results regarding male reproduction. A comparison of the conditions of these studies with the experimental NOAEL conditions are based on reported B blood levels, which is clearly superior to a scaling according to estimated B exposures. A comparison of estimated daily B exposure levels and measured B blood levels confirms the preference of biomonitoring data for a comparison of human field studies. In general, it appears that high environmental exposures to B are lower than possible high occupational exposures. The comparison reveals no contradiction between human and experimental reproductive toxicity data. It clearly appears that human B exposures, even in the highest exposed cohorts, are too low to reach the blood (and target tissue) concentrations that would be required to exert adverse effects on reproductive functions.

  8. Repeated exposure of acidic beverages on esthetic restorative materials: An in-vitro surface microhardness study

    PubMed Central

    Sunny, Steffy M.; Rai, Kavita; Hegde, Amitha M.

    2016-01-01

    Background A manifold increase in the consumption of aerated beverages has witnessed a twin increase in tooth wear and raised demand for esthetic restorative materials. This study aimed to evaluate the surface microhardness changes of esthetic restorative materials following treatment with aerated beverages in an in-vitro situation. Material and Methods The initial surface microhardness of the restorative materials GC Fuji II LC, GC Fuji IX, Nano Glass ionomer, Resin and Nano composite was recorded. These materials were studied under 3 groups that included those exposed to the acidic beverages daily, weekly once in a month and those that had no exposures at all. The final surface microhardness of the materials was recorded following experimentation and was subjected to statistical comparisons. Results The restorative materials were compared for their surface microhardness changes following respective treatments using the T-test and One-way ANOVA analysis. Inter-comparisons between the groups showed statistical significance (p<.05), when treated with both the beverages. The five restorative materials revealed surface microhardness loss; the maximum reduction noticed with the Nano glass ionomer cement tested (p<.0005). Conclusions The surface microhardness of restorative materials markedly reduced upon repeated exposures with acidic beverages; the product with phosphoric acid producing the maximum surface microhardness loss. Key words:Restorative materials, acidic beverages, surface microhardness, resin composites, glass ionomers. PMID:27398183

  9. Ascorbic acid abrogates microparticle generation and vascular injuries associated with high-pressure exposure.

    PubMed

    Yang, Ming; Bhopale, Veena M; Thom, Stephen R

    2015-07-01

    We hypothesized that pathological changes associated with elevations in annexin V-positive microparticles (MPs) following high-pressure exposures can be abrogated by ascorbic acid in a murine model. Mice exposed for 2 h to 790-kPa air and killed at 2 or 13 h postdecompression exhibited over threefold elevations in circulating MPs, as well as subgroups bearing Ly6G, CD41, Ter119, CD31, and CD142 surface proteins. There was evidence of significant neutrophil activation, platelet-neutrophil interactions, and vascular injury to brain, omentum, psoas, and skeletal muscles assessed as leakage of high-molecular-weight dextran. Prophylactic ascorbic acid (500 mg/kg ip) administration prevented all postdecompression neutrophil changes and vascular injuries. Ascorbic acid administration immediately after decompression abrogated most changes, but evidence of vascular leakage in the brain and skeletal muscle at 13 h postdecompression persisted. No significant elevations in these parameters occurred after injection of ascorbic acid alone. The findings support the idea that MP production occurring with exposures to elevated gas pressure is an oxidative stress response and that antioxidants may offer protection from pathological effects associated with decompression. PMID:25977448

  10. Management of a Patient With Faciocervical Burns and Inhalational Injury Due to Hydrofluoric Acid Exposure.

    PubMed

    Yuanhai, Zhang; Xingang, Wang; Liangfang, Ni; Chunmao, Han

    2014-05-01

    Hydrofluoric acid, a highly dangerous substance, can cause tissue damage and systemic toxicity by its unique mechanisms. Many cases of severe faciocervical burns due to hydrofluoric acid exposure are lethal. Herein, we present a case of 37-year-old man who suffered from hydrofluoric acid burns to his face, anterior neck, lips, and nasal cavity. On admission, this patient coughed with much sputum, and the chest auscultation detected rough breath sounds, wheezes, and very weak heart sounds, indicating possible inhalation injury. This case highlights the extreme complexity of managing this kind of injury. Timely and accurate wound treatment and respiratory tract care, as well as active systematic support treatment, played vital roles in the management of this patient.

  11. Arsenate exposure affects amino acids, mineral nutrient status and antioxidants in rice (Oryza sativa L.) genotypes.

    PubMed

    Dwivedi, S; Tripathi, R D; Tripathi, P; Kumar, A; Dave, R; Mishra, S; Singh, R; Sharma, D; Rai, U N; Chakrabarty, D; Trivedi, P K; Adhikari, B; Bag, M K; Dhankher, O P; Tuli, R

    2010-12-15

    Simulated pot experiments were conducted on four rice (Oryza sativa L.) genotypes (Triguna, IR-36, PNR-519, and IET-4786) to examine the effects of As(V) on amino acids and mineral nutrient status in grain along with antioxidant response to arsenic exposure. Rice genotypes responded differentially to As(V) exposure in terms of amino acids and antioxidant profiles. Total amino acid content in grains of all rice genotypes was positively correlated with arsenic accumulation. While, most of the essential amino acids increased in all cultivars except IR-36, glutamic acid and glycine increased in IET-4786 and PNR-519. The level of nonprotein thiols (NPTs) and the activities of superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC 1.6.4.2) and ascorbate peroxidase (APX; EC 1.11.1.11) increased in all rice cultivars except IET-4786. A significant genotypic variation was also observed in specific arsenic uptake (SAU; mg kg(-1)dw), which was in the order of Triguna (134) > IR-36 (71) > PNR-519 (53) > IET-4786 (29). Further, application of As(V) at lower doses (4 and 8 mg L(-1) As) enhanced the accumulation of selenium (Se) and other nutrients (Fe, P, Zn, and S), however, higher dose (12 mg L(-1) As) limits the nutrient uptake in rice. In conclusion, low As accumulating genotype, IET-4786, which also had significantly induced level of essential amino acids, seems suitable for cultivation in moderately As contaminated soil and would be safe for human consumption. PMID:21077666

  12. Comparative responses of freshwater organisms to exposures of a commercial naphthenic acid.

    PubMed

    Kinley, Ciera M; McQueen, Andrew D; Rodgers, John H

    2016-06-01

    Comparative toxicity studies using unconfounded exposures can prioritize the selection of sensitive sentinel test species and refine methods for evaluating ecological risks of complex mixtures like naphthenic acids (NAs), a group of organic acids associated with crude oils and energy-derived waters that have been a source of aquatic toxicity. The objectives of this study were to compare responses of freshwater aquatic organisms (vertebrate, invertebrates, and a macrophyte; in terms of acute toxicity) to Fluka commercial NAs and to compare measured toxicity data with peer-reviewed toxicity data for other commercial NA sources and energy-derived NA sources. Exposures were confirmed using high performance liquid chromatography. Responses (7-d LC50s/EC50) ranged from 1.9 mg L(-1) for Pimephales promelas to 56.2 mg L(-1) for Typha latifolia. Following P. promelas in order of decreasing sensitivity were Ceriodaphnia dubia (7-d LC50 = 2.8 mg L(-1)), Hyalella azteca (7-d LC50 = 4.1 mg L(-1)), Chironomus dilutus (7-d LC50 = 6.5 mg L(-1)), and T. latifolia (7-d EC50 = 56.2 mg L(-1)), indicating that in terms of sensitivities, fish > invertebrates > plant for Fluka NAs in this study. Factors that affect exposures and measurements of exposures differ among commercial and energy-derived NAs and constrain comparisons. Despite differences in exposures, fish and invertebrates were relatively sensitive to both commercial and energy-derived NA sources (based on laboratory measurements and peer-reviewed data) and could be appropriate sentinel species for risk evaluations. PMID:27016812

  13. Firefighters' exposure to perfluoroalkyl acids and 2-butoxyethanol present in firefighting foams.

    PubMed

    Laitinen, Juha Ari; Koponen, Jani; Koikkalainen, Janne; Kiviranta, Hannu

    2014-12-01

    The aim of this study was to assess eight firefighters' exposure to Sthamex 3% AFFF (aqueous film forming foam) in the simulation of aircraft accidents at Oulu airport in Finland. Study was conducted in 2010 before limitation for the use of PFOA and PFOS in AFFFs. Due to prospective limitation also eight commercially available AFFFs were evaluated from occupational and environmental point of view to find substitutive AFFFs for future. The firefighters' exposure to twelve perfluoroalkyl acids (PFAS) was analyzed in order to observe the signs of accumulation during three consecutive training sessions. The firefighters' short-term exposure to 2-butoxyethanol (EGBE) was analyzed by urinalysis of 2-butoxyacetic acid (2-BAA). For the background information also the concentration of PFAS in used AFFF-liquid was analyzed. Fire fighters' serum PFHxS and PFNA concentrations seemed to increase during the three training sessions although they were not the main PFAS in used AFFF. The statistical significance for the elevations was not able to test due to limited size of test group. In two training sessions, the average urinary excretions of 2-BAA exceeded the reference limit of the occupationally unexposed population. In the evaluations of the firefighting foams, non-fluorine based products were favored and the alcohol resistance properties of foams were recommended for consideration due to the increasing use of biofuels.

  14. Firefighters' exposure to perfluoroalkyl acids and 2-butoxyethanol present in firefighting foams.

    PubMed

    Laitinen, Juha Ari; Koponen, Jani; Koikkalainen, Janne; Kiviranta, Hannu

    2014-12-01

    The aim of this study was to assess eight firefighters' exposure to Sthamex 3% AFFF (aqueous film forming foam) in the simulation of aircraft accidents at Oulu airport in Finland. Study was conducted in 2010 before limitation for the use of PFOA and PFOS in AFFFs. Due to prospective limitation also eight commercially available AFFFs were evaluated from occupational and environmental point of view to find substitutive AFFFs for future. The firefighters' exposure to twelve perfluoroalkyl acids (PFAS) was analyzed in order to observe the signs of accumulation during three consecutive training sessions. The firefighters' short-term exposure to 2-butoxyethanol (EGBE) was analyzed by urinalysis of 2-butoxyacetic acid (2-BAA). For the background information also the concentration of PFAS in used AFFF-liquid was analyzed. Fire fighters' serum PFHxS and PFNA concentrations seemed to increase during the three training sessions although they were not the main PFAS in used AFFF. The statistical significance for the elevations was not able to test due to limited size of test group. In two training sessions, the average urinary excretions of 2-BAA exceeded the reference limit of the occupationally unexposed population. In the evaluations of the firefighting foams, non-fluorine based products were favored and the alcohol resistance properties of foams were recommended for consideration due to the increasing use of biofuels. PMID:25447453

  15. Decreased expression of ARV1 results in cholesterol retention in the endoplasmic reticulum and abnormal bile acid metabolism.

    PubMed

    Tong, Fumin; Billheimer, Jeffrey; Shechtman, Caryn F; Liu, Ying; Crooke, Roseann; Graham, Mark; Cohen, David E; Sturley, Stephen L; Rader, Daniel J

    2010-10-29

    Endoplasmic reticulum (ER) membrane cholesterol is maintained at an optimal concentration of ∼5 mol % by the net impact of sterol synthesis, modification, and export. Arv1p was first identified in the yeast Saccharomyces cerevisiae as a key component of this homeostasis due to its probable role in intracellular sterol transport. Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. Repeated dosing of specific antisense oligonucleotides to ARV1 produced a marked reduction of ARV1 transcripts in liver, adipose, and to a lesser extent, intestine. This resulted in marked hypercholesterolemia, elevated serum bile acids, and activation of the hepatic farnesoid X receptor (FXR) regulatory pathway. Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. These studies indicate a critical role of mammalian Arv1p in sterol movement from the ER and in the ensuing regulation of hepatic cholesterol and bile acid metabolism.

  16. Decreased Expression of ARV1 Results in Cholesterol Retention in the Endoplasmic Reticulum and Abnormal Bile Acid Metabolism*

    PubMed Central

    Tong, Fumin; Billheimer, Jeffrey; Shechtman, Caryn F.; Liu, Ying; Crooke, Roseann; Graham, Mark; Cohen, David E.; Sturley, Stephen L.; Rader, Daniel J.

    2010-01-01

    Endoplasmic reticulum (ER) membrane cholesterol is maintained at an optimal concentration of ∼5 mol % by the net impact of sterol synthesis, modification, and export. Arv1p was first identified in the yeast Saccharomyces cerevisiae as a key component of this homeostasis due to its probable role in intracellular sterol transport. Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. Repeated dosing of specific antisense oligonucleotides to ARV1 produced a marked reduction of ARV1 transcripts in liver, adipose, and to a lesser extent, intestine. This resulted in marked hypercholesterolemia, elevated serum bile acids, and activation of the hepatic farnesoid X receptor (FXR) regulatory pathway. Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. These studies indicate a critical role of mammalian Arv1p in sterol movement from the ER and in the ensuing regulation of hepatic cholesterol and bile acid metabolism. PMID:20663892

  17. Abnormal essential fatty acid composition of tissue lipids in genetically diabetic mice is partially corrected by dietary linoleic and gamma-linolenic acids.

    PubMed

    Cunnane, S C; Manku, M S; Horrobin, D F

    1985-05-01

    Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.

  18. Aristolochic acid exposure in Romania and implications for renal cell carcinoma

    PubMed Central

    Turesky, Robert J; Yun, Byeong Hwa; Brennan, Paul; Mates, Dana; Jinga, Viorel; Harnden, Patricia; Banks, Rosamonde E; Blanche, Helene; Bihoreau, Marie-Therese; Chopard, Priscilia; Letourneau, Louis; Lathrop, G Mark; Scelo, Ghislaine

    2016-01-01

    Background: Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas. Methods: We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries. Results: We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 108 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative. Interpretation: Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC. PMID:26657656

  19. Growth response of Pinus ponderosa seedlings and mature tree branches to acid rain and ozone exposure

    SciTech Connect

    Anderson, P.D.; Houpis, J.L.J.; Helms, J.A.

    1994-10-01

    Forests of the central and southern Sierra Nevada in California have been subjected to chronic damage by ozone and other atmospheric pollutants for the past several decades. Until recently, pollutant exposure of northern Sierra Nevada forests has been mild but increasing population and changes in land use throughout the Sacramento Valley and Sierra Nevada foothills may lead to increased pollutant damage in these forests. Although, better documented in other regions of the United States, little is known regarding the potential for acidic precipitation damage to Sierra Nevada forests. Only recently have studies directed towards understanding the potential interactive effects of ozone and acidic precipitation been undertaken. A key issue in resolving potential regional impacts of pollutants on forests is the extent to which research results can be scaled across genotypes and life-stages. Most of the pollution research to date has been performed using seedlings with varying degrees of genetic control. It is important to determine if the results obtained in such studies can be extrapolated to mature trees and to different genetic sources. In this paper, we present results from a one-year study examining the interactive effects of foliar exposure to acidic rain and ozone on the growth of ponderosa pine (Pinus ponderosa), a conifer known to be sensitive to ozone. The response to pollutants is characterized for both seedlings and mature tree branches of three genotypes grown in a common environment.

  20. Estimates of the occupational exposure to tenorm in the phosphoric acid production plant in Iran.

    PubMed

    Fathabadi, N; Vasheghani Farahani, M; Moradi, M; Hadadi, B

    2012-09-01

    Phosphate rock is used world wide for manufacturing phosphoric acid and several chemical fertilisers. It is known that the phosphate rock contains various concentrations of uranium, thorium, radium and their daughters. The subject of this study is the evaluation of the radiation exposure to workers in the phosphoric acid production plant due to technologically enhanced naturally occurring radioactive materials that can result from the presence of naturally occurring radioactive materials in phosphate ores used in the manufacturing of phosphoric acid. Radiation exposure due to direct gamma radiation, dust inhalation and radon gas has been investigated and external and internal doses of exposed workers have been calculated. Natural radioactivity due to (40)K, (226)Ra and (232)Th have been measured in phosphate rock, phosphogypsum, chemical fertilisers and other samples by gamma spectrometry system with a high-purity germanium. The average concentrations of (226)Ra and (40)K observed in the phosphate rock are 760 and 80 Bq kg(-1), respectively. Annual effective dose from external radiation had a mean value of ∼0.673 mSv y(-1). Dust sampling revealed greatest values in the storage area. The annual average effective dose from inhalation of long-lived airborne was 0.113 mSv y(-1). Radon gas concentrations in the processing plant and storage area were found to be of the same value as the background. In this study the estimated annual effective doses to workers were below 1 mSv y(-1). PMID:22361352

  1. Protective effect of oleanolic acid on oxidative injury and cellular abnormalities in doxorubicin induced cardiac toxicity in rats

    PubMed Central

    Goyal, Sameer N; Mahajan, Umesh B; Chandrayan, Govind; Kumawat, Vivek S; Kamble, Sarika; Patil, Pradip; Agrawal, Yogeeta O; Patil, Chandragouda R; Ojha, Shreesh

    2016-01-01

    The prevention of doxorubicin (Dox) induced cardiotoxicity may be co-operative to recover future Dox treatment. The aim of this study was to explore the cardioprotective effects of oleanolic acid (OA), an antioxidant agent, on Dox induced cardiotoxicity. OA is a triterpenoid compound, which exist widely in plant kingdom in free acid form or as a glycosidic triterpenoids saponins. Cardiotoxicity was induced in Wistar rats with single intravenous injection of doxorubicin at dose of 67.75 mg/kg i.v for 48 hrs. At 12 hrs of interval following Dox administration the cardioprotective effect of OA (1.5 mg/kg, i.v.) and Amifostine (AMF) (90 mg/kg i.v., single dose prior 30 min) were evaluated. Induction of cardiotoxicity was confirmed by increase in systolic, diastolic, mean arterial pressures, maximal positive rate of developed left ventricular pressure (+LVdP/dtmax, an indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dtmax, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load). Cardiac markers in such as CK-MB, LDH and alterations in ECG. Dox administration showed alteration in Biochemical parameters and endogenous antioxidants. Administration of OA Showed maximal protection against Dox induced cardiac toxicity as observed by reduction in blood pressure, prevention of left ventricular function and attenuation of biochemical and antioxidant parameters. Based on the findings, its concluded that OA can be used as an adjuvant with Dox therapy in treating cancers. PMID:27069540

  2. Exposure or release of ferulic acid from wheat aleurone: impact on its antioxidant capacity.

    PubMed

    Rosa, Natalia N; Dufour, Claire; Lullien-Pellerin, Valérie; Micard, Valérie

    2013-12-01

    The relationship between the aleurone cell integrity and the exposure or release of bioavailable ferulic acid (FA) with the antioxidant capacity of aleurone in in vitro and under simulated gastric conditions was explored. The antioxidant capacity of aleurone was increased by around 2-fold when its median particle size was reduced to under 50 μm. The opening of aleurone cells increased the physical exposure of FA bound to the insoluble polysaccharides, which seemed to be responsible of the increased antioxidant capacity. Synergistic combination of xylanase and feruloyl esterase was found to be the most efficient enzymatic treatment releasing up to 86% of total FA in bioaccessible forms. This enzymatic treatment significantly enhanced the radical scavenging activity of aleurone by up to 4-fold, which overlapped the overall antioxidant potential estimated from the total content of FA in aleurone. The improvement in the antioxidant capacity of aleurone was also observed in the simulated gastric digestion by inhibition of lipid oxidation.

  3. Acute exposure to realistic acid fog: effects on respiratory function and airway responsiveness in asthmatics.

    PubMed

    Leduc, D; Fally, S; De Vuyst, P; Wollast, R; Yernault, J C

    1995-11-01

    Naturally occurring fogs in industrialized cities are contaminated by acidic air pollutants. In Brussels, Belgium, the pH of polluted fogwater may be as low as 3 with osmolarity as low as 30 mOsm. In order to explore short-term respiratory effects of a realistic acid-polluted fog, we collected samples of acid fog in Brussels, Belgium, which is a densely populated and industrialized city, we defined characteristics of this fog and exposed asthmatic volunteers at rest through a face mask to fogs with physical and chemical characteristics similar to those of natural fogs assessed in this urban area. Fogwater was sampled using a screen collector where droplets are collected by inertial impaction and chemical content of fogwater was assessed by measurement of conductivity, pH, visible colorimetry, high pressure liquid chromatography, and atomic absorption spectrophotometry over a period of one year. The fogwater composition was dominated by NH4+ and SO4- ions. First we evaluated the possible effect of fog acidity alone. For this purpose 14 subjects with asthma were exposed at rest for 1 hr [mass median aerodynamic diameter to a large-particle (MMAD), 9 microns] aerosol with H2SO4 concentration of 500 micrograms/m3 (pH 2.5) and osmolarity of 300 mOsm. We did not observe significant change in pulmonary function or bronchial responsiveness to metacholine. In the second part of the work, 10 asthmatic subjects were exposed to acid fog (MMAD, 7 microns) containing sulfate and ammonium ions (major ions recovered in naturally occurring fogs) with pH 3.5 and osmolarity 30 mOsm. Again, pulmonary function and bronchial reactivity were not modified after inhalation of this fog. It was concluded that short-term exposure to acid fog reproducing acidity and hypoosmolarity of natural polluted fogs does not induce bronchoconstriction and does not change bronchial responsiveness in asthmatics.

  4. Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans.

    PubMed Central

    Kniazeva, Marina; Sieber, Matt; McCauley, Scott; Zhang, Kang; Watts, Jennifer L; Han, Min

    2003-01-01

    While the general steps of fatty acid (FA) biosynthesis are well understood, the individual enzymes involved in the elongation of long chain saturated and polyunsaturated FA (PUFA) are largely unknown. Recent research indicates that these enzymes might be of considerable physiological importance for human health. We use Caenorhabditis elegans to study FA elongation activities and associated abnormal phenotypes. In this article we report that the predicted C. elegans F11E6.5/ELO-2 is a functional enzyme with the FA elongation activity. It is responsible for the elongation of palmitic acid and is involved in PUFA biosynthesis. RNAi-mediated suppression of ELO-2 causes an accumulation of palmitate and an associated decrease in the PUFA fraction in triacylglycerides and phospholipid classes. This imbalance in the FA composition results in multiple phenotypic defects such as slow growth, small body size, reproductive defects, and changes in rhythmic behavior. ELO-2 cooperates with the previously reported ELO-1 in 20-carbon PUFA production, and at least one of the enzymes must function to provide normal growth and development in C. elegans. The presented data indicate that suppression of a single enzyme of the FA elongation machinery is enough to affect various organs and systems in worms. This effect resembles syndromic disorders in humans. PMID:12586704

  5. Acute exposure to acid fog: influence of breathing pattern on effective dose.

    PubMed

    Bowes, S M; Francis, M; Laube, B L; Frank, R

    1995-02-01

    Concern about the possible adverse health effects of acid fog has been fed by two observations: air pollution disasters earlier in this century were typically associated with fog, and current samples of fog water can be strongly acid. To study the acute effects of acid fog on the lung, the authors generated a monodisperse 10 microM MMAD aerosol of H2SO4 with a pH of 2.0 and a nominal concentration of 500 micrograms/m3. They exposed seven healthy young men on alternate days to acid or control equiosmolar NaCl aerosol during 40 min of resting ventilation and 20 min of exercise; the latter was sufficiently intense to induce oronasal breathing. Exposure was by means of a head dome, a head-only exposure device that permitted continuous measurement (unfettered breathing) of Vr, f, VE, and the onset and persistence of oronasal breathing. In this article the authors compare the relative importance of parameters contributing to the between-subject variability in estimated hydrogen ion dose to the lower airways (H+LAW), based on analysis of variance. Physiologic parameters accounted for 70% of the variability, of which 34% was due to differences in duration of oronasal breathing (tON) and 36% to differences in ventilation rate during oronasal breathing (VE(ON)); inhaled hydrogen ion concentration [H+], the environmental parameter, contributed only 30%. Minute ventilation at the time of transition from nasal to oronasal breathing varied significantly among subjects even if normalized to FVC, an index of lung size.

  6. Iodine plus n-3 fatty acid supplementation augments rescue of postnatal neuronal abnormalities in iodine-deficient rat cerebellum.

    PubMed

    Pal, Amit; Mohan, Vishwa; Modi, Dinesh R; Sinha, Rohit A; Rastogi, Leena; Kumar, Praveen; Godbole, Madan M

    2013-08-01

    High prevalence of hypothyroxinaemia in iodine-deficient (ID) mothers has serious implications for mental health of the progeny. Independent supplementation of iodine and n-3 fatty acids (FA) markedly improves growth and cognitive performance of school children. Discerning effects of n-3 FA and iodine on the developing cerebellum have not been ascertained. The present study investigates effects of these two micronutrients separately as well as together in an ID rat model. We studied the effects of these micronutrients on progeny of ID dams by instituting the following supplementation diets: (1) low-iodine diet (LID), (2) LID+potassium iodide (KI), (3) LID+n-3 FA and (4) LID+KI+n-3 FA. Pups were investigated for morphological and biochemical parameters at the peak of cerebellar histogenesis on postnatal day (P) 16 and for neurobehavioural as well as motor coordination parameters at P40. Results indicate that n-3 FA alone, without improvement in circulating thyroid hormone (TH), significantly improves functional, morphological and biochemical indices of the developing cerebellum. Further, results show that co-supplementation with iodine and n-3 FA rescues not only the loss of neurotrophic support, but also salvages motor coordination, memory and learning. This additive effect results in significantly improving neurotrophic support and seems to be mediated by parallel significant increase in TH receptor (TR)α and normalisation of TRβ, retinoic orphan receptor α and p75 neurotrophin receptor, as well as noteworthy prevention of apoptotic cell death and strengthening of anti-oxidative defence. The overall results indicate important mitigating role that n-3 FA may play in enhancing TH nuclear receptor-mediated signalling in the developing cerebellum. PMID:23312094

  7. Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington’s Disease Patients

    PubMed Central

    Naseri, Nima N.; Bonica, Joseph; Xu, Hui; Park, Larry C.; Arjomand, Jamshid; Chen, Zhengming; Gibson, Gary E.

    2016-01-01

    Metabolic dysfunction is well-documented in Huntington’s disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD. The experiments utilize the advantages of lymphoblasts to reveal new insights about HD. The large quantity of homogeneous cell populations permits multiple dynamic measures to be made on exactly comparable tissues. The activities of nine enzymes related to the TCA cycle and the expression of twenty-nine mRNAs encoding for these enzymes and enzyme complexes were measured. Cells were studied under baseline conditions and during metabolic stress. The results support our recent findings that the activities of the pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected depression in MDH activities. Furthermore, message levels for isocitrate dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were responsive to treatments. The use of lymphoblasts allowed us to clarify that the reported decrease in aconitase activity in HD autopsy brains is likely due to secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the TCA cycle are critical therapeutic targets that have been understudied in HD. PMID:27611087

  8. Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.

    PubMed

    Kathirvel, Elango; Morgan, Kengathevy; French, Samuel W; Morgan, Timothy R

    2013-11-01

    Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation. PMID:24176233

  9. Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

    PubMed Central

    Levin, Milton; Leibrecht, Heather; Ryan, James; Van Dolah, Frances; De Guise, Sylvain

    2008-01-01

    The immunotoxic potential of domoic acid (DA), a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 μg/g b.w.) and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 μM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr), a significant decrease in neutrophil phagocytosis (24-hr), a significant decrease in monocyte phagocytosis (48-hr), and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr). In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 μM. B- and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 μM, and significantly decreased at 100 μM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species. PMID:19172200

  10. Accumulation of free amino acids during exposure to drought in three springtail species.

    PubMed

    Holmstrup, Martin; Slotsbo, Stine; Rozsypal, Jan; Henriksen, Per G; Bayley, Mark

    2015-11-01

    Springtails are closely related to insects, but they differ from these with respect to water balance, in particular because springtails are small and have high integumental permeability to water. Here we report a series of experiments addressing the dynamics of osmoregulation, water content and accumulation of free amino acids (FAAs) in three springtail species during exposure to a gradually increasing environmental desiccation simulating conditions in drought exposed soil. Folsomia candida and Protaphorura fimata (both living in the deeper soil layers; euedaphic species) were active throughout the 3week exposure, with the developing drought regime ending at -3.56MPa (the soil water activity at the permanent wilting point of plants is -1.5MPa) and remained hyperosmotic (having an body fluid osmolality higher than the corresponding environment) to their surrounding air. Sinella curviseta (living in upper soil/litter layers; hemiedaphic species) also survived this exposure, but remained hypoosmotic throughout (i.e. with lower osmolality than the environment). The body content of most FAAs increased in response to drought in all three species. Alanine, proline and arginine were the most significantly upregulated FAAs. By combining our results with data in the literature, we could account for 82% of the observed osmolality at -3.56MPa in F. candida and 92% in P. fimata. The osmolality of S. curviseta was only slightly increased under drought, but here FAAs were considerably more important as osmolytes than in the two other species. We propose that FAAs probably have general importance in drought tolerance of springtails.

  11. Use of a quantitative strong ion approach to determine the mechanism for acid-base abnormalities in sick calves with or without diarrhea.

    PubMed

    Constable, Peter D; Stämpfli, Henry R; Navetat, Hérve; Berchtold, Joachim; Schelcher, François

    2005-01-01

    Acid-base abnormalities are frequently present in sick calves. The mechanism for an acid-base disturbance can be characterized using the strong ion approach, which requires accurate values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma weak acids (K(a)). The aims of this study were to experimentally determine A(tot), K(a), and net protein charge values for calf plasma and to apply these values quantitatively to data from sick calves to determine underlying mechanisms for the observed acid-base disturbance. Plasma was harvested from 9 healthy Holstein-Friesian calves and concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-, L-lactate) and nonvolatile buffer ions (total protein, albumin, phosphate) were determined. Plasma was tonometered with CO2 at 37 degrees C, and plasma P(CO2) and pH measured over a range of 15-159 mm Hg and 6.93-7.79, respectively. Strong ion difference (SID) was calculated from the measured strong ion concentrations, and nonlinear regression was used to estimate values for A(tot) and K(a) from the measured pH and P(CO2) and calculated SID. The estimated A(tot) and K(a) values were then validated using data from 2 in vivo studies. Mean (+/- SD) values for calf plasma were A(tot) = 0.343 mmol/g of total protein or 0.622 mmol/g of albumin; K(a) = (0.84 +/- 0.41) x 10(-7); pK(a) = 7.08. The net protein charge of calf plasma was 10.5 mEq/L, equivalent to 0.19 mEq/g of total protein or 0.34 mEq/g of albumin. Application of the strong ion approach to acid-base disturbances in 231 sick calves with or without diarrhea indicated that acidemia was due predominantly to a strong ion acidosis in response to hyponatremia accompanied by normochloremia or hyperchloremia and the presence of unidentified strong anions. These results confirm current recommendations that treatment of acidemia in sick calves with or without diarrhea should focus on intravenous or PO

  12. Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community

    PubMed Central

    Darrow, Lyndsey A.; Groth, Alyx C.; Winquist, Andrea; Shin, Hyeong-Moo; Bartell, Scott M.; Steenland, Kyle

    2016-01-01

    Background: Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers. Objectives: We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease. Methods: Participants completed surveys during 2008–2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005–2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers). Results: Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases). Conclusion: Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically

  13. Maternal exposure to perfluoroalkyl acids measured in whole blood and birth outcomes in offspring.

    PubMed

    Callan, A C; Rotander, A; Thompson, K; Heyworth, J; Mueller, J F; Odland, J Ø; Hinwood, A L

    2016-11-01

    Perfluoralkyl and polyfluoralkyl substances have been measured in plasma and serum of pregnant women as a measure of prenatal exposure. Increased concentrations of individual perfluoroalkyl acids (PFAAs), (typically perfluorooctanoic acid (PFOA) and perfluoroctane sulfonate (PFOS) have been reported to be associated with reductions in birth weight and other birth outcomes. We undertook a study of 14 PFAAs in whole blood (including PFOS, PFHxS, PFHpA, PFOA, PFNA, PFDA and PFUnDA) from 98 pregnant women in Western Australia from 2008 to 2011. Median concentrations (in μg/L) were: PFOS 1.99; PFHxS 0.33; PFOA 0.86; PFNA 0.30; PFDA 0.12 and PFUnDA 0.08. Infants born to women with the highest tertile of PFHxS exposure had an increased odds of being <95% of their optimal birth weight (OR 3.5, 95% CI 1.1-11.5). Conversely, maternal blood concentrations of PFUnDA were associated with non-significant increases in average birth weight (+102g, 95% CI -41, 245) and significant increases in proportion of optimal birth weight (+4.7%, 95% CI 0.7, 8.8) per ln-unit change. This study has reported a range of PFAAs in the whole blood of pregnant women and suggests that PFHxS and PFUnDA may influence foetal growth and warrant further attention. Additional studies are required to identify the sources of PFAA exposure with a view to prevention, in addition to further studies investigating the long term health effects of these ubiquitous chemicals. PMID:27387804

  14. DOCOSAHEXAENOIC ACID PARTIALLY AMELIORATES DEFICITS IN SOCIAL BEHAVIOR AND ULTRASONIC VOCALIZATIONS CAUSED BY PRENATAL ETHANOL EXPOSURE

    PubMed Central

    Wellmann, Kristen A.; George, Finney; Brnouti, Fares; Mooney, Sandra M.

    2015-01-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10 g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol’s damaging effects. PMID:25746516

  15. Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life.

    PubMed

    Keating, Elisa; Correia-Branco, Ana; Araújo, João R; Meireles, Manuela; Fernandes, Rita; Guardão, Luísa; Guimarães, João T; Martel, Fátima; Calhau, Conceição

    2015-03-01

    The aim of this study was to understand whether high folic acid (HFA) exposure during the perigestational period induces metabolic dysfunction in the offspring, later in life. To do this, female Sprague-Dawley rats (G0) were administered a dose of folic acid (FA) recommended for pregnancy (control, C, 2 mg FA/kg of diet, n=5) or a high dose of FA (HFA, 40 mg FA/kg of diet, n=5). Supplementation began at mating and lasted throughout pregnancy and lactation. Body weight and food and fluid intake were monitored in G0 and their offspring (G1) till G1 were 13 months of age. Metabolic blood profiles were assessed in G1 at 3 and 13 months of age (3M and 13M respectively). Both G0 and G1 HFA females had increased body weight gain when compared with controls, particularly 22 (G0) and 10 (G1) weeks after FA supplementation had been stopped. G1 female offspring of HFA mothers had increased glycemia at 3M, and both female and male G1 offspring of HFA mothers had decreased glucose tolerance at 13M, when compared with matched controls. At 13M, G1 female offspring of HFA mothers had increased insulin and decreased adiponectin levels, and G1 male offspring of HFA mothers had increased levels of leptin, when compared with matched controls. In addition, feeding of fructose to adult offspring revealed that perigestational exposure to HFA renders female progeny more susceptible to developing metabolic unbalance upon such a challenge. The results of this work indicate that perigestational HFA exposure the affects long-term metabolic phenotype of the offspring, predisposing them to an insulin-resistant state.

  16. Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure.

    PubMed

    Wellmann, Kristen A; George, Finney; Brnouti, Fares; Mooney, Sandra M

    2015-06-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects.

  17. Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure.

    PubMed

    Wellmann, Kristen A; George, Finney; Brnouti, Fares; Mooney, Sandra M

    2015-06-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects. PMID:25746516

  18. Resistance to freshwater exposure in White Sea Littorina spp. II: Acid-base regulation.

    PubMed

    Sokolova, I M; Bock, C; Pörtner, H O

    2000-03-01

    Parameters of acid-base and energy status were studied by in vivo 31P-nuclear magnetic resonance spectroscopy in three White Sea Littorina spp. (L. littorea, L. saxatilis and L. obtusata) during prolonged anaerobiosis in freshwater. Intracellular pH decreased significantly, especially during the early period of anaerobiosis, but later the decrease in intracellular pH slowed down considerably, suggesting a capacity for intracellular pH regulation in all three species. There was a trend for intracellular pH to fall most rapidly in the least freshwater-resistant species, L. obtusata, as compared to the most resistant, L. littorea. Non-bicarbonate, non-phosphate buffer values estimated by the homogenate technique were similar in the three studied species (28-37 mmol pH(-1) kg(-1) wet weight) and did not change during freshwater exposure. The CaCO3 buffer value of the foot tissues was considerably higher (171-218 mmol pH(-1) kg(-1) wet weight) and decreased significantly during freshwater exposure. The contribution of the multiple tissue buffering systems to intracellular pH regulation in Littorina spp. shifts between different stages of freshwater exposure. Initially, the non-bicarbonate, non-phosphate tissue buffering system seems to be of major importance for metabolic proton buffering at intracellular pH between 7.5 and 7.0. During later stages of anaerobiosis and at lower intracellular pH, the CaCO3 buffer is involved in proton buffering. Decrease in the CaCO3 buffer value during freshwater exposure was in quantitative agreement with the amount of metabolic protons buffered, thus suggesting that CaCO3 tissue stores may serve as a major buffering system during prolonged anaerobiosis in Littorina spp. PMID:10791570

  19. Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets.

    PubMed

    Krahe, Thomas E; Filgueiras, Claudio C; Medina, Alexandre E

    2016-08-01

    Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5g/kg, i.p.), VPA (200mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction. PMID:27208641

  20. Predictors of 2,4-dichlorophenoxyacetic acid exposure among herbicide applicators.

    PubMed

    Bhatti, Parveen; Blair, Aaron; Bell, Erin M; Rothman, Nathaniel; Lan, Qing; Barr, Dana B; Needham, Larry L; Portengen, Lutzen; Figgs, Larry W; Vermeulen, Roel

    2010-03-01

    To determine the major factors affecting the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) among county noxious weed applicators in Kansas, we used a regression technique that accounted for multiple days of exposure. We collected 136 12-h urine samples from 31 applicators during the course of two spraying seasons (April to August of 1994 and 1995). Using mixed-effects models, we constructed exposure models that related urinary 2,4-D measurements to weighted self-reported work activities from daily diaries collected over 5 to 7 days before the collection of the urine sample. Our primary weights were based on an earlier pharmacokinetic analysis of turf applicators; however, we examined a series of alternative weighting schemes to assess the impact of the specific weights and the number of days before urine sample collection that were considered. The derived models accounting for multiple days of exposure related to a single urine measurement seemed robust with regard to the exact weights, but less to the number of days considered; albeit the determinants from the primary model could be fitted with marginal losses of fit to the data from the other weighting schemes that considered a different numbers of days. In the primary model, the total time of all activities (spraying, mixing, other activities), spraying method, month of observation, application concentration, and wet gloves were significant determinants of urinary 2,4-D concentration and explained 16% of the between-worker variance and 23% of the within-worker variance of urinary 2,4-D levels. As a large proportion of the variance remained unexplained, further studies should be conducted to try to systematically assess other exposure determinants.

  1. Selective agonists of retinoic acid receptors: comparative toxicokinetics and embryonic exposure.

    PubMed

    Arafa, H M; Elmazar, M M; Hamada, F M; Reichert, U; Shroot, B; Nau, H

    2000-01-01

    Three biologically active synthetic retinoids were investigated that bind selectively to retinoic acid receptors RARs (alpha, beta and gamma). The retinoids were previously demonstrated to have different teratogenic effects in the mouse in terms of potency and regioselectivity. The teratogenic potency rank order (alpha >beta >gamma) was found to be more or less compatible with the receptor binding affinities and transactivation potencies of the retinoid ligands to their respective receptors. The RARalpha agonist (Am580; CD336) induced a wide spectrum of malformations; CD2019 (RARbeta agonist) and especially CD437 (RARgamma agonist) produced more restricted defects. In the current study we tried to address whether the differences in teratogenic effects are solely related to binding affinity and transactivation differences or also due to differences in embryonic exposure. Therefore, transplacental kinetics of the ligands were assessed following administration of a single oral dose of 15 mg/kg of either retinoid given to NMRI mice on day 11 of gestation. Am580 was rapidly transferred to the embryo resulting in the highest embryonic exposure [embryo to maternal plasma area under the time vs concentration curve (AUC)(0-24 h )ratio (E/M) was 1.7], in accordance with its highest teratogenic potency. The low placental transfer of CD2019 (E/M of 0.3) was compatible with its lower teratogenic potential. Of major interest was the finding that the CD437, though being least teratogenic, exhibited considerable embryonic exposure (E/M of 0.6). These findings suggest that both the embryonic exposure and receptor binding transactivation selectivity are crucial determinants of the teratogenicity of these retinoid ligands.

  2. Effects of sodium arsenate exposure on liver fatty acid profiles and oxidative stress in rats.

    PubMed

    Kharroubi, Wafa; Dhibi, Madiha; Haouas, Zohra; Chreif, Imed; Neffati, Fadoua; Hammami, Mohamed; Sakly, Rachid

    2014-02-01

    The present study aimed to evaluate the effect of arsenic on liver fatty acids (FA) composition, hepatotoxicity and oxidative status markers in rats. Male rats were randomly devised to six groups (n=10 per group) and exposed to sodium arsenate at a dose of 1 and 10 mg/l for 45 and 90 days. Arsenate exposure is associated with significant changes in the FA composition in liver. A significant increase of saturated fatty acids (SFA) in all treated groups (p<0.01) and trans unsaturated fatty acids (trans UFA) in rats exposed both for short term for 10 mg/l (p<0.05) and long term for 1 and 10 mg/l (p<0.001) was observed. However, the cis UFA were significantly decreased in these groups (p<0.05). A markedly increase of indicator in cell membrane viscosity expressed as SFA/UFA was reported in the treated groups (p<0.001). A significant increase in the level of malondialdehyde by 38.3 % after 90 days of exposure at 10 mg/l was observed. Compared to control rats, significant liver damage was observed at 10 mg/l of arsenate by increasing plasma marker enzymes after 90 days. It is through the histological investigations in hepatic tissues of exposed rats that these damage effects of arsenate were confirmed. The antioxidant perturbations were observed to be more important at groups treated by the high dose (p<0.05). An increase in the level of protein carbonyls was observed in all treated groups (p<0.05). The present study provides evidence for a direct effect of arsenite on FA composition disturbance causing an increase of SFA and TFAs isomers, liver dysfunction and oxidative stress. Therefore, arsenate can lead to hepatic damage and propensity towards liver cancer. PMID:23949113

  3. Lead exposure in the lead-acid storage battery manufacturing and PVC compounding industries.

    PubMed

    Ho, S F; Sam, C T; Embi, G B

    1998-09-01

    This study was conducted as part of the Human Exposure Assessment Location (HEAL) Project which comes under the United Nations Environment Programme/World Health Organisation (UNEP/WHO) Global environmental Monitoring System (GEMS). The objective of the study was to evaluate workers' exposure to lead in industries with the highest exposure. All subjects were interviewed about their occupational and smoking histories, the use of personal protective equipment and personal hygiene. The contribution of a dietary source of lead intake from specified foods known to contain lead locally and personal air sampling for lead were assessed. A total of 61 workers from two PVC compounding and 50 workers from two lead acid battery manufacturing plants were studied together with 111 matched controls. In the PVC compounding plants the mean lead-in-air level was 0.0357 mg/m3, with the highest levels occurring during the pouring and mixing operations. This was lower than the mean lead-in-air level of 0.0886 mg/m3 in the lead battery manufacturing plants where the highest exposure was in the loading of lead ingots into milling machines. Workers in lead battery manufacturing had significantly higher mean blood lead than the PVC workers (means, 32.51 and 23.91 mcg/100 ml respectively), but there was poor correlation with lead-in-air levels. Among the lead workers, the Malays had significantly higher blood lead levels than the Chinese (mean blood levels were 33.03 and 25.35 mcg/100 ml respectively) although there was no significant difference between the two ethnic groups in the control group. There were no significant differences between the exposed and control group in terms of dietary intake of specified local foods known to contain lead. However, Malays consumed significantly more fish than the Chinese did. There were no ethnic differences in the hours of overtime work, number of years of exposure, usage of gloves and respirators and smoking habits. Among the Malays, 94.3% eat with

  4. Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

    SciTech Connect

    Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

    2009-12-01

    Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA{sup III}); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA{sup III} [URO-MSC(+)] and after subsequent removal of MMA{sup III} [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA{sup III}, URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA{sup III}. URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA{sup III} exposure, suggesting the presence of MMA{sup III} is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA{sup III} results in: the induction of DNA damage that remains elevated upon removal of MMA{sup III}; increased levels of ROS that play a role in MMA{sup III} induced-DNA damage; and decreased PARP activity in the presence of MMA{sup III}.

  5. Predominant role of the hypothalamic-pituitary axis, not the ovary, in different types of abnormal cycle induction by postnatal exposure to high dose p-tert-octylphenol in rats.

    PubMed

    Yoshida, Midori; Katashima, Sayumi; Tahahashi, Miwa; Ichimura, Ryohei; Inoue, Kaoru; Taya, Kazuyoshi; Watanabe, Gen

    2015-11-01

    To determine whether it is the hypothalamic-pituitary axis or the ovary that plays the predominant role in abnormal estrous cycling induction by postnatal exposure to estrogenic compounds, female rats were subcutaneously injected with 100mg/kg p-tert-octylphenol or vehicle for 5 or 15 days after birth (OP-PND5, OP-PND15 or control). Ovaries were exchanged between control and treated groups on PND28. Controls receiving control or OP-PND5 ovaries showed normal cycles within 4 weeks after the exchange, and corpora lutea were detected in transplanted ovaries. Controls receiving OP-PND15 ovaries consistently increased persistent estrus (PE). OP-PND15 rats receiving control or OP-PND15 ovaries immediately descended into PE, and transplanted ovaries were atrophic with cystic follicles, indicating anovulation. OP-PND5 rats receiving control or OP-PND5 ovaries showed early onset of PE after normal cycling. The hypothalamic-pituitary axis is predominant in abnormal cycling induction by postnatal exposure to OP. OP-PND15 ovaries were impaired compared to other groups.

  6. A methodology for estimating human exposure to perfluorooctanoic acid (PFOA): a retrospective exposure assessment of a community (1951-2003).

    PubMed

    Paustenbach, Dennis J; Panko, Julie M; Scott, Paul K; Unice, Kenneth M

    2007-01-01

    Perfluorooctanoic acid (PFOA) is a persistent chemical that was recently shown to be widely distributed in the ambient environment. Because of concerns about the possible adverse health effects on persons exposed to PFOA, a retrospective exposure assessment was conducted for a population of about 50,000 persons who reside near one of the facilities where this chemical was used. No similar study of any chemical with the properties of PFOA had ever been performed; thus, several novel methods were developed and applied in this analysis. Historical records of the emissions from the facility were the basis for the estimates of the potential intake of (PFOA) by residents over the past 53 yr. Various well-accepted environmental models were dynamically combined in order to estimate the concentrations in all relevant environmental media including ambient air, surface soil, drinking water, and homegrown vegetables. Following considerable analyses, particulate deposition from facility air emissions to soil and the subsequent transfer of the chemical through the soil was determined to be the most likely source of PFOA that was detected in groundwater. The highest off-site environmental concentrations were predicted to occur about 1 mile away. For this approximately square mile area, during the time period 1951-2003, the model-estimated average air concentration was 0.2 microg/m3, the estimated surface soil concentration was 11 microg/kg, and the estimated drinking water concentration was 4 microg/L. Similar data were generated for 20 additional geographical areas around the facility. Comparison of measured PFOA concentrations in groundwater in the various water districts indicated that the models appeared to overpredict recent groundwater concentrations by a factor of 3 to 5. The predicted historical lifetime and average daily estimates of PFOA intake by persons who lived within 5 miles of the plant over the past 50 yr were about 10,000-fold less than the intake of the

  7. Fatty acid composition of spruce needle lipids after exposure to air pollutants

    SciTech Connect

    Wolfenden, J.; Wellburn, A.R. )

    1990-05-01

    Alterations in the fatty acid composition of membrane lipids have been observed in long-term experiments using realistic exposures of air pollutants. Monogalactosyl diglyceride (MGDG), from red spruce, showed a 12% reduction in linolenic acid (18:3) compared with controls, after a 21 week winter fumigation with SO{sub 2} NO{sub 2} (20 ppb each). The composition of phosphatidyl choline from the same trees was unaffected. In Norway spruce exposed to 70 ppb O{sub 3} for 3 consecutive summers there was no treatment effect on 18:3 content of MGDG, which ranged from 70 to 80%, with highest values in November. The percentage of octadecatetranoic acid (18:4) also varied seasonally. Compared with controls, polluted plants had proportionally less 18:4 during autumn, perhaps indicating some effect of O{sub 3} on the winter hardening process. Our observations emphasize the need for long-term experiments to investigate subtle disturbances to seasonal metabolic cycles.

  8. Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS

    PubMed Central

    Hiolski, Emma M; Kendrick, Preston S; Frame, Elizabeth R; Myers, Mark S; Bammler, Theo K; Beyer, Richard P; Farin, Federico M; Wilkerson, Hui-wen; Smith, Donald R; Marcinek, David J; Lefebvre, Kathi A

    2014-01-01

    Domoic acid is an algal-derived seafood toxin that functions as a glutamate agonist and exerts excitotoxicity via overstimulation of glutamate receptors (AMPA, NMDA) in the central nervous system (CNS). At high (symptomatic) doses, domoic acid is well-known to cause seizures, brain lesions and memory loss; however, a significant knowledge gap exists regarding the health impacts of repeated low-level (asymptomatic) exposure. Here, we investigated the impacts of low-level repetitive domoic acid exposure on gene transcription and mitochondrial function in the vertebrate CNS using a zebrafish model in order to: 1) identify transcriptional biomarkers of exposure; and 2) examine potential pathophysiology that may occur in the absence of overt excitotoxic symptoms. We found that transcription of genes related to neurological function and development were significantly altered, and that asymptomatic exposure impaired mitochondrial function. Interestingly, the transcriptome response was highly-variable across the exposure duration (36 weeks), with little to no overlap of specific genes across the six exposure time points (2, 6, 12, 18, 24, and 36 weeks). Moreover, there were no apparent similarities at any time point with the gene transcriptome profile exhibited by the glud1 mouse model of chronic moderate excess glutamate release. These results suggest that although the fundamental mechanisms of toxicity may be similar, gene transcriptome responses to domoic acid exposure do not extrapolate well between different exposure durations. However, the observed impairment of mitochondrial function based on respiration rates and mitochondrial protein content suggests that repetitive low-level exposure does have fundamental cellular level impacts that could contribute to chronic health consequences. PMID:25033243

  9. Abnormal presence of the matrix extracellular phosphoglycoprotein-derived acidic serine- and aspartate-rich motif peptide in human hypophosphatemic dentin.

    PubMed

    Boukpessi, Tchilalo; Gaucher, Celine; Léger, Thibaut; Salmon, Benjamin; Le Faouder, Julie; Willig, Cyril; Rowe, Peter S; Garabédian, Michèle; Meilhac, Olivier; Chaussain, Catherine

    2010-08-01

    Severe dental troubles are associated with X-linked hypophosphatemic rickets and are mainly related to impaired dentin mineralization. In dentin matrix, matrix extracellular phosphoglycoprotein (MEPE) may be protected from proteolysis by a specific interaction with PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome). The objective of our work was to determine whether PHEX impairment induces MEPE cleavage in dentin and the subsequent release of the C-terminal acidic serine- and aspartate-rich motif (ASARM) peptide, which is known to inhibit mineralization. By Western blot analysis, we explored dentin extracts from seven hypophosphatemic patients with mutations of the PHEX gene. A proteomic approach combining immunoprecipitation, surface-enhanced laser desorption/ionization-time of flight-mass spectrometry and matrix-assisted laser desorption ionization-time of flight analysis of the samples completed this exploration. This study shows a 4.1-kDa peptide containing the MEPE-derived ASARM peptide in hypophosphatemic samples. The presence of ASARM was less marked in patients treated with 1-hydroxylated vitamin D and phosphate during growth. Moreover, recombinant ASARM implanted in a rat pulp injury model disturbed the formation of the reparative dentin bridge. These results suggest that abnormal MEPE cleavage occurs when PHEX activity is deficient in humans, the ASARM peptide may be involved in the mineralization defects and the PHEX-MEPE interaction may be indirect, as ensuring a better phosphate and vitamin D environment to the mineralizing dentin prevents MEPE cleavage.

  10. PERSISTENT ABNORMALITIES IN THE RAT MAMMARY GLAND FOLLOWING GESTATIONAL AND LACTATIONAL EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

    EPA Science Inventory

    SUMMARY

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure during gestation has revealed reproductive anomalies in rat offspring, including inconclusive reports of stunted mammary development in females (Brown et al., 1998, Lewis et al., 2001). The current studies wer...

  11. Quantification of naphthoquinone mercapturic acids in urine as biomarkers of naphthalene exposure.

    PubMed

    Klotz, Katrin; Angerer, Jürgen

    2016-02-15

    Naphthalene shows carcinogenic properties in animal experiments. As the substance is ubiquitary present in the environment and has a possibly high exposure at industrial workplaces, the determination of naphthalene metabolites in humans is of environmental-medical as well as occupational-medical importance. Here, biomarkers of 1,2- and 1,4-naphthoquinone, as possibly carcinogenic metabolites in the naphthalene metabolism, are of outstanding significance. We developed and validated a liquid chromatography-tandem mass-spectrometric (LC-MS/MS) method for the simultaneous determination of the naphthoquinone mercapturic acids of 1,2- and 1,4-naphthoquinone in human urine samples as a sum of naphthoquinone- and dihydroxynaphthalene-mercapturic acid. Except for enzymatic hydrolysis and acidification, no further sample preparation is necessary. For sample clean-up, a column switching procedure is applied. The mercapturic acids are extracted from the urinary matrix on a restricted access material (RAM RP 18) and separated on a reversed phase column (Synergi Polar RP C18). The metabolites were quantified by tandem mass spectrometry using labelled D5-1,4-NQMA as internal standard. The limits of detection are 3μg/l for 1,2-NQMA and 1μg/l for 1,4-NQMA. Intraday- and interday precision for pooled urine (spiked with 10μg/l and 30μg/l of the analytes) ranges from 5.9 to 15.1% for 1,2-NQMA and from 2.0 to 10.8% for 1,4-NQMA. The developed method is suited for the sensitive and specific determination of the mercapturic acids of naphthoquinones in human urine. A good precision and low limits of detection were achieved. Application of those new biomarkers in biomonitoring studies may give deeper insights into the mechanisms of the human naphthalene metabolism. PMID:26812176

  12. Effects of in utero retinoic acid exposure on mouse pelage hair follicle development.

    PubMed

    García-Fernández, Rosa A; Pérez-Martínez, Claudia; Escudero-Diez, Alfredo; García-Iglesias, Maria J

    2002-06-01

    We investigated in vivo the histological and immunohistochemical responses of mouse hair pelage follicle morphogenesis to prenatal exposure to a potentially nonteratogenic dose of all-trans-retinoic acid (RA), as a basis studying the preventive effect of RA on adult mouse skin carcinogenesis. In pregnant mice, a single oral dose of RA at 30 mg kg-1 body weight given on day 11.5 of gestation caused no RA-induced changes in the morphology or temporal expression patterns of keratins during pelage hair follicle morphogenesis. The only differential effect of RA was a statistically significant increase in the number of BrdU-positive nuclei in hair bulbs from RA exposed fetuses compared with nonexposed mice. The absence of adverse RA effects suggests that this experimental design may represent a valuable protocol for use in studies on the in vivo effects of this retinoid on different skin diseases.

  13. The ameliorative effect of ascorbic acid and Ginkgo biloba on learning and memory deficits associated with fluoride exposure

    PubMed Central

    Raghuveer, Vasudeva C.; Rao, Mallikarjuna C.; Somayaji, Nagabhooshana S.; Babu, Prakash B.

    2013-01-01

    Chronic exposure to fluoride causes dental and skeletal fluorosis. Fluoride exposure is also detrimental to soft tissues and organs. The present study aimed at evaluation of the effect of Ginkgo biloba and ascorbic acid on learning and memory deficits caused by fluoride exposure. Male Wistar rats were divided into five groups (n=6). Group 1 control. Groups 2 to 5 received 100 ppm of sodium fluoride over 30 days. Groups 3, 4 and 5 were further treated for 15 days receiving respectively 1% gum acacia solution, 100 mg/kg body weight ascorbic acid, and 100mg/kg body weight Ginkgo biloba extract. After 45 days, all animals were subjected to behavioural tests. The results showed that fluoride affected learning and memory. Fluoride causes oxidative stress and neurodegeneration, thereby affecting learning and memory. Ascorbic acid and Ginkgo biloba were found to augment the reversal of learning and memory deficits caused by fluoride ingestion. PMID:24678261

  14. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. )

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  15. Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality.

    PubMed

    Koren, Netta; Simsa-Maziel, Stav; Shahar, Ron; Schwartz, Betty; Monsonego-Ornan, Efrat

    2014-06-01

    Omega-3 fatty acids (FAs) are essential nutritional components that must be obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial for bone health, and several mechanisms have been suggested to mediate their effects on bone, including alterations in calcium absorption and urinary calcium loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and inhibition of osteoclastogenesis. However, to date, there is scant information regarding the effect of omega-3 FAs on the developing skeleton during the rapid growth phase. In this study we aim to evaluate the effect of exposure to high levels of omega-3 FAs on bone development and quality during prenatal and early postnatal period. For this purpose, we used the fat-1 transgenic mice that have the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic cell line as models. We show that exposure to high concentrations of omega-3 FAs at a young age accelerates bone growth through alterations of the growth plate, associated with increased chondrocyte proliferation and differentiation. We further propose that those effects are mediated by the receptors G-protein coupled receptor 120 (GPR120) and hepatic nuclear factor 4α, which are expressed by chondrocytes in culture. Additionally, using a combined study on the structural and mechanical bone parameters, we show that high omega-3 levels contribute to superior trabecular and cortical structure, as well as to stiffer bones and improved bone quality. Most interestingly, the fat-1 model allowed us to demonstrate the role of maternal high omega-3 concentration on bone growth during the gestation and postnatal period.

  16. Heat exposure increases circulating fatty acids but not lipid oxidation at rest and during exercise.

    PubMed

    O'Hearn, Katharine; Tingelstad, Hans Christian; Blondin, Denis; Tang, Vera; Filion, Lionel G; Haman, François

    2016-01-01

    Alterations in lipid oxidation during exercise have been well studied, but limited data exists on the effects of passive heat exposure and exercise in the heat on changes in lipid oxidation. This study was designed to examine: (1) the effects of heat exposure on lipid metabolism during passive heating and subsequent exercise in the heat by focusing on changes in whole-body lipid oxidation and plasma lipid concentrations, and (2) the effects of extended passive pre-heating on exercise performance in the heat. Male participants (n=8) were passively heated for 120 min at 42 °C, then exercised on a treadmill in the same temperature at 50% V̇O2 max for 30 min (HEAT). This same procedure was followed on a separate occasion at 23 °C (CON). Results showed that lipid oxidation rates were not different between HEAT and CON during passive heating or exercise. However, non-esterified fatty acid (NEFA) concentrations were significantly higher following passive heating (618 µM, 95% CI: 479-757) compared to CON (391 µM, 95% CI: 270-511). The same trend was observed following exercise (2036 µM, 95% CI: 1604-2469 for HEAT and 1351 µM, 95% CI: 1002-1699). Triacylglycerol, phospholipid and cholesterol levels were not different between HEAT and CON at any point. Four of 8 participants could not complete 30 min of exercise in HEAT, resulting in a 14% decline in total external work. Rate of perceived exertion over the final 5 min of exercise was higher in HEAT (9.5) than CON (5). We conclude that: (1) heat exposure results in increased circulating NEFA at rest and during exercise without changes in whole-body lipid utilization, and (2) passive pre-heating reduces work capacity during exercise in the heat and increases the perceived intensity of a given workload.

  17. Vulnerability to dietary n-3 polyunsaturated fatty acid deficiency after exposure to early stress in rats.

    PubMed

    Ferreira, Charles Francisco; Bernardi, Juliana Rombaldi; Krolow, Rachel; Arcego, Danusa Mar; Fries, Gabriel Rodrigo; de Aguiar, Bianca Wollenhaupt; Senter, Gabrielle; Kapczinski, Flávio Pereira; Silveira, Patrícia Pelufo; Dalmaz, Carla

    2013-06-01

    The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the second hour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.

  18. Lynch syndrome and exposure to aristolochic acid in upper-tract urothelial carcinoma: its clinical impact?

    PubMed Central

    Colin, Pierre; Seisen, Thomas; Mathieu, Romain; Shariat, Sharohkh F.

    2016-01-01

    The purpose of the current review was to describe the clinical risk for Lynch syndrome (LS) after exposure to aristolochic acid (AA) in cases of upper urinary-tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed using the Medline database (National Library of Medicine, PubMed) using the following keywords: epidemiology, risk factor, AA, Balkan nephropathy (BNe), LS, hereditary cancer, hereditary non-polyposis colorectal cancer (HNPCC), mismatch repair genes, urothelial carcinomas, upper urinary tract, renal pelvis, ureter, Amsterdam criteria, genetic counselling, mismatch repair genes, genetic instability, microsatellite, and Bethesda guidelines. LS is a specific risk for UTUC, which is the third most frequent cancer (in its tumor spectrum) after colon and uterine lesions. Mutation of the MSH2 gene is the most commonly described cause of UTUC in LS. Diagnosis is based on clinical suspicion and is guided by Bethesda and Amsterdam criteria. It is secondarily confirmed by immunohistochemical analyses of the tumor and a search for gene mutations. The presence of LS in patients with UTUC is a favorable prognosis factor for survival during follow-ups. AA is a specific environmental risk factor for UTUC and tubulo-interstitial nephropathy. It has been involved in the development of nephropathies in link with the Balkan disease and intake of Chinese herbal medicine. More broadly, the use of traditional plant medicines from the genus Aristolochia has created worldwide public-health concerns. UTUCs share common risk factors with other urothelial carcinomas such as tobacco or occupational exposure. However, these tumors have also specific risk factors such as AA exposure and LS that clinicians should be aware of because of their clinical implication in further management and follow-up. PMID:27785421

  19. Evaluation of the toxicity data for peracetic acid in deriving occupational exposure limits: a minireview.

    PubMed

    Pechacek, Nathan; Osorio, Magdalena; Caudill, Jeff; Peterson, Bridget

    2015-02-17

    Peracetic acid (PAA) is a peroxide-based chemistry that is highly reactive and can produce strong local effects upon direct contact with the eyes, skin and respiratory tract. Given its increasing prominence in industry, attention has focused on health hazards and associated risks for PAA in the workplace. Occupational exposure limits (OEL) are one means to mitigate risks associated with chemical hazards in the workplace. A mini-review of the toxicity data for PAA was conducted in order to determine if the data were sufficient to derive health-based OELs. The available data for PAA frequently come from unpublished studies that lack sufficient study details, suffer from gaps in available information and often follow unconventional testing methodology. Despite these limitations, animal and human data suggest sensory irritation as the most sensitive endpoint associated with inhalation of PAA. Rodent RD50 data (the concentration estimated to cause a 50% depression in respiratory rate) were selected as the critical studies in deriving OELs. Based on these data, a range of 0.36-0.51mg/m(3) (0.1-0.2ppm) was calculated for a time-weighted average (TWA), and 1.2-1.7mg/m(3) (0.4-0.5ppm) as a range for a short-term exposure limit (STEL). These ranges compare favorably to other published OELs for PAA. Considering the applicable health hazards for this chemistry, a joint TWA/STEL OEL approach for PAA is deemed the most appropriate in assessing workplace exposures to PAA, and the selection of specific values within these proposed ranges represents a risk management decision. PMID:25542141

  20. Accumulation of free amino acids during exposure to drought in three springtail species.

    PubMed

    Holmstrup, Martin; Slotsbo, Stine; Rozsypal, Jan; Henriksen, Per G; Bayley, Mark

    2015-11-01

    Springtails are closely related to insects, but they differ from these with respect to water balance, in particular because springtails are small and have high integumental permeability to water. Here we report a series of experiments addressing the dynamics of osmoregulation, water content and accumulation of free amino acids (FAAs) in three springtail species during exposure to a gradually increasing environmental desiccation simulating conditions in drought exposed soil. Folsomia candida and Protaphorura fimata (both living in the deeper soil layers; euedaphic species) were active throughout the 3week exposure, with the developing drought regime ending at -3.56MPa (the soil water activity at the permanent wilting point of plants is -1.5MPa) and remained hyperosmotic (having an body fluid osmolality higher than the corresponding environment) to their surrounding air. Sinella curviseta (living in upper soil/litter layers; hemiedaphic species) also survived this exposure, but remained hypoosmotic throughout (i.e. with lower osmolality than the environment). The body content of most FAAs increased in response to drought in all three species. Alanine, proline and arginine were the most significantly upregulated FAAs. By combining our results with data in the literature, we could account for 82% of the observed osmolality at -3.56MPa in F. candida and 92% in P. fimata. The osmolality of S. curviseta was only slightly increased under drought, but here FAAs were considerably more important as osmolytes than in the two other species. We propose that FAAs probably have general importance in drought tolerance of springtails. PMID:26428866

  1. Hematological effect of benzene exposure with emphasis of muconic acid as a biomarker.

    PubMed

    Ibrahim, Khadiga S; Amer, Nagat M; El-dossuky, Elsaid A; Emara, Ahmed M; El-Fattah, Abd El-Samei M Abd; Shahy, Eman Mohamed

    2014-06-01

    Human exposure to benzene in work environment is a global occupational health problem. It is established that benzene requires to be metabolized to induce its effects. Benzene has been associated with various hematotoxins and carcinogens. The aim of this study was to investigate the effect of benzene on complete blood picture, with emphasis of trans, trans-muconic acid (t,t-MA) as a biomarker of benzene in urine, considering the influence of cigarette smoke. A total of 81 workers (61 males and 20 females) have been occupationally exposed to benzene. In addition, 83 workers (55males and 28 females) were also recruited as a control group. Complete blood picture was analyzed and urinary t,t-MA was determined by liquid chromatography. In addition, creatinine in the urine samples was determined. Levels of blood elements (white blood cells, red blood cells and platelets) were decreased among exposed workers compared with the controls. The urinary level of t,t-MA/creatinine of the exposed workers was elevated especially in the smoking group compared to the controls. This study recommends that complete blood picture and t,t-MA are helpful biomarker tests that should be done to detect the early effects of benzene exposure.

  2. Investigation of the formation of physical damage on automotive finishes due to acidic reagent exposure

    SciTech Connect

    White, D.F.; Fornes, R.E.; Gilbert, R.D.; Speer, J.A. )

    1993-10-15

    Automotive paints with clear-coat surfaces can be physically damaged by exposure to acidic reagents produced in a smog chamber designed to reproduce real environmental conditions. Visual and reflectance microscopy observations show that deposition of material formed from the reaction of the clear coat and the reagent drop occurs on the paint surface after the drop evaporates to a critical size, with the greatest deposition occurring at the edge of the drop. This type of deposition suggests a free-energy minimization process favoring the formation of stable nuclei at the reagent drop edge. With heating after the drop evaporation to stimulate exposure to the sun, a damaged area containing sulfur that is in the shape of a circular ring is observed at the location of the deposits. The majority of the visual damage appears to result from an interaction between the deposit and the paint at elevated temperatures. Results from profilometry, scanning electron microscopy, and reflectance microscopy show that the damaged areas are ring-shaped cracked blisters on the surface resulting from the clear coat separating into layers.

  3. Butoxyethoxyacetic acid, a biomarker of exposure to water-based cleaning agents.

    PubMed

    Göen, Thomas; Korinth, Gintautas; Drexler, Hans

    2002-08-01

    The aim of the study was to investigate the suitability of butoxyethoxyacetic acid (BEAA) as a biomarker of exposure to water-based cleaning agents containing diethylene glycol mono butyl ether (DEGBE). The study was performed in two printing plants where water-based products containing 10-15% DEGBE were used for rubber and blanket washes. Thirty nine newspaper pressroom workers (exposed) and 19 employees of newspaper despatch departments (controls) were investigated. By questionnaire, the workers were asked about the use of personal protective measures. BEAA was determined in post-shift urine using GC-MS. The BEAA concentration in the urine of exposed workers ranged up to 75.1 mg/l (median 6.3 mg/l), whereas in urine samples of the controls the BEAA level was below or around the determination limit of 0.5 mg/l. A protective effect on DEGBE uptake was observed with the use of protective gloves. This observation implies that dermal penetration of DEGBE may be important in exposure monitoring. PMID:12191891

  4. Metabolomics analysis reveals the association between lipid abnormalities and oxidative stress, inflammation, fibrosis, and Nrf2 dysfunction in aristolochic acid-induced nephropathy

    PubMed Central

    Zhao, Ying-Yong; Wang, Hui-Ling; Cheng, Xian-Long; Wei, Feng; Bai, Xu; Lin, Rui-Chao; Vaziri, Nosratola D.

    2015-01-01

    Alternative medicines are commonly used for the disease prevention and treatment worldwide. Aristolochic acid (AAI) nephropathy (AAN) is a common and rapidly progressive interstitial nephropathy caused by ingestion of Aristolochia herbal medications. Available data on pathophysiology and molecular mechanisms of AAN are limited and were explored here. SD rats were randomized to AAN and control groups. AAN group was treated with AAI by oral gavage for 12 weeks and observed for additional 12 weeks. Kidneys were processed for histological evaluation, Western blotting, and metabolomics analyses using UPLC-QTOF/HDMS. The concentrations of two phosphatidylcholines, two diglycerides and two acyl-carnitines were significantly altered in AAI treated rats at week 4 when renal function and histology were unchanged. Data obtained on weeks 8 to 24 revealed progressive tubulointerstitial fibrosis, inflammation, renal dysfunction, activation of NF-κB, TGF-β, and oxidative pathways, impaired Nrf2 system, and profound changes in lipid metabolites including numerous PC, lysoPC, PE, lysoPE, ceramides and triglycerides. In conclusion, exposure to AAI results in dynamic changes in kidney tissue fatty acid, phospholipid, and glycerolipid metabolisms prior to and after the onset of detectable changes in renal function or histology. These findings point to participation of altered tissue lipid metabolism in the pathogenesis of AAN. PMID:26251179

  5. Exposure to domoic acid affects larval development of king scallop Pecten maximus (Linnaeus, 1758).

    PubMed

    Liu, Hui; Kelly, Maeve S; Campbell, Dirk A; Dong, Shuang Lin; Zhu, Jian Xin; Wang, Su Feng

    2007-02-28

    Domoic acid (DA) is a highly toxic phycotoxin produced by bloom forming marine diatoms Pseudo-nitzschia spp. Bivalves can accumulate this toxin to a high level through their feeding activities, and thus illness or death in can occur in consumers of bivalves. In this study, king scallop, Pecten maximus, larvae were exposed to dissolved domoic acid (DA) for 25d, and the toxin accumulation and effects of harbouring this toxin were investigated. Scallop larvae incorporated DA continuously during the larval culture period and accumulated a maximum DA level of 5.21pgind(-1) when exposed to a solution of 50ngml(-1) dissolved DA. As a result of the DA treatment, larval growth, measured in terms of shell length and the appearance of the eye-spot, and larval survival were significantly compromised. This is the first study on DA incorporation dynamics in P. maximus larvae, signifying the potential of using shellfish larvae for the study on mechanisms of phycotoxin accumulation. The negative effect of DA exposure suggests that this toxin could possibly influence natural recruitment in P. maximus, and it may be necessary to protect hatchery-cultured scallop larvae from DA during toxic Pseudo-nitzschia blooms.

  6. Effects of acid exposure on the conformation, stability, and aggregation of monoclonal antibodies.

    PubMed

    Ejima, Daisuke; Tsumoto, Kouhei; Fukada, Harumi; Yumioka, Ryosuke; Nagase, Kazuo; Arakawa, Tsutomu; Philo, John S

    2007-03-01

    Exposure of antibodies to low pH is often unavoidable for purification and viral clearance. The conformation and stability of two humanized monoclonal antibodies (hIgG4-A and -B) directed against different antigens and a mouse monoclonal antibody (mIgG1) in 0.1M citrate at acidic pH were studied using circular dichroism (CD), differential scanning calorimetry (DSC), and sedimentation velocity. Near- and far-UV CD spectra showed that exposure of these antibodies to pH 2.7-3.9 induced only limited conformational changes, although the changes were greater at the lower pH. However, the acid conformation is far from unfolded or so-called molten globule structure. Incubation of hIgG4-A at pH 2.7 and 3.5 at 4 degrees C over the course of 24 h caused little change in the near-UV CD spectra, indicating that the acid conformation is stable. Sedimentation velocity showed that the hIgG4-A is largely monomeric at pH 2.7 and 3.5 as well as at pH 6.0. No time-dependent changes in sedimentation profile occurred upon incubation at these low pHs, consistent with the conformational stability observed by CD. The sedimentation coefficient of the monomer at pH 2.7 or 3.5 again suggested that no gross conformational changes occur at these pHs. DSC analysis of the antibodies showed thermal unfolding at pH 2.7-3.9 as well as at pH 6.0, but with decreased melting temperatures at the lower pH. These results are consistent with the view that the antibodies undergo limited conformational change, and that incubation at 4 degrees C at low pH results in no time-dependent conformational changes. Titration of hIgG4-A from pH 3.5 to 6.0 resulted in recovery of native monomeric proteins whose CD and DSC profiles resembled those of the original sample. However, titration from pH 2.7 resulted in lower recovery of monomeric antibody, indicating that the greater conformational changes observed at this pH cannot be fully reversed to the native structure by a simple pH titration.

  7. Influence of the degree of exposure to lead on relations between alcohol consumption and the biological indices of lead exposure: epidemiological study in a lead acid battery factory.

    PubMed Central

    Cezard, C; Demarquilly, C; Boniface, M; Haguenoer, J M

    1992-01-01

    Alcohol has been shown to interact with lead to influence haem biosynthesis. The aim of this study was to define the dependence of this interaction on the degree of exposure to lead. Exposure to alcohol was estimated by measurement of alcohol concentrations in a sample of urine collected during the morning (AlcUM) (0.82 (SD 4.36) mmol/l) and in a sample collected during the afternoon (AlcUA) (1.15 (SD 3.49) mmol/l). The biological monitoring of exposure to lead included measurements of blood lead (Pb-B) (1.82 (SD 0.72) mumol/l), urinary delta-aminolaevulinic acid (ALAU) (35.33 (SD 28.00) mumol/l; d = 1.015), and erythrocyte zinc-protoporphyrin (ZPP) (112.90 (SD 83.71) nmol/mmol Hb) concentrations. The study of the influence of the degree of occupational exposure to lead on relations between alcohol consumption and effects of the exposure to lead led to the consideration of two different groups--namely, mildly and strongly exposed subjects. In the first group, individual biological susceptibility seemed to play a preponderant part. In the second, the pool of lead present in the body seemed to be sufficiently important to mask the effects of individual susceptibility. PMID:1390270

  8. Influence of the degree of exposure to lead on relations between alcohol consumption and the biological indices of lead exposure: epidemiological study in a lead acid battery factory.

    PubMed

    Cezard, C; Demarquilly, C; Boniface, M; Haguenoer, J M

    1992-09-01

    Alcohol has been shown to interact with lead to influence haem biosynthesis. The aim of this study was to define the dependence of this interaction on the degree of exposure to lead. Exposure to alcohol was estimated by measurement of alcohol concentrations in a sample of urine collected during the morning (AlcUM) (0.82 (SD 4.36) mmol/l) and in a sample collected during the afternoon (AlcUA) (1.15 (SD 3.49) mmol/l). The biological monitoring of exposure to lead included measurements of blood lead (Pb-B) (1.82 (SD 0.72) mumol/l), urinary delta-aminolaevulinic acid (ALAU) (35.33 (SD 28.00) mumol/l; d = 1.015), and erythrocyte zinc-protoporphyrin (ZPP) (112.90 (SD 83.71) nmol/mmol Hb) concentrations. The study of the influence of the degree of occupational exposure to lead on relations between alcohol consumption and effects of the exposure to lead led to the consideration of two different groups--namely, mildly and strongly exposed subjects. In the first group, individual biological susceptibility seemed to play a preponderant part. In the second, the pool of lead present in the body seemed to be sufficiently important to mask the effects of individual susceptibility.

  9. The protective role of ascorbic acid on hippocampal CA1 pyramidal neurons in a rat model of maternal lead exposure.

    PubMed

    Sepehri, Hamid; Ganji, Farzaneh

    2016-07-01

    Oxidative stress is a major pathogenic mechanism of lead neurotoxicity. The antioxidant ascorbic acid protects hippocampal pyramidal neurons against cell death during congenital lead exposure; however, critical functions like synaptic transmission, integration, and plasticity depend on preservation of dendritic and somal morphology. This study was designed to examine if ascorbic acid also protects neuronal morphology during developmental lead exposure. Timed pregnant rats were divided into four treatment groups: (1) control, (2) 100mg/kg ascorbic acid once a day via gavage, (3) 0.05% lead acetate in drinking water, and (4) 0.05% lead+100mg/kg oral ascorbic acid. Brains of eight male pups (P25) per treatment group were processed for Golgi staining. Changes in hippocampal CA1 pyramidal neurons' somal size were estimated by cross-sectional area and changes in dendritic arborization by Sholl's analysis. One-way ANOVA was used to compare results among treatment groups. Lead-exposed pups exhibited a significant decrease in somal size compared to controls (P<0.01) that was reversed by cotreatment with ascorbic acid. Sholl's analysis revealed a significant increase in apical dendritic branch points near cell body (P<0.05) and a decreased total dendritic length in both apical and basal dendritic trees of CA1 neurons (P<0.05). Ascorbic acid significantly but only partially reversed the somal and dendritic damage caused by developmental lead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved.

  10. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

    EPA Science Inventory

    Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the bi...

  11. Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

    PubMed

    de Bortoli, N; Martinucci, I; Savarino, E; Franchi, R; Bertani, L; Russo, S; Ceccarelli, L; Costa, F; Bellini, M; Blandizzi, C; Savarino, V; Marchi, S

    2016-01-01

    Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

  12. Exposure to Kynurenic Acid During Adolescence Produces Memory Deficits in Adulthood

    PubMed Central

    Akagbosu, Cynthia O.; Evans, Gretchen C.; Gulick, Danielle; Suckow, Raymond F.; Bucci, David J.

    2012-01-01

    The glia-derived molecule kynurenic acid (KYNA) is an antagonist of α7 nicotinic acetylcholine receptors and the glycineB binding site on n-methyl-d-aspartateglutamate receptors, both of which have critical roles in neural plasticity as well as learning and memory. KYNA levels are increased in the brains and cerebral spinal fluid of persons with schizophrenia, leading to the notion that changes in KYNA concentration might contribute to cognitive dysfunction associated with this disorder. Indeed, recent studies indicate that increasing endogenous KYNA concentration by administering l-kynurenine (L-KYN, the precursor of KYNA) impairs spatial as well as contextual learning and memory in adult rats. In the present study, rats were treated with L-KYN (100 mg/kg) throughout adolescence to increase endogenous KYNA concentration during this critical time in brain development. Rats were then tested drug-free as adults to test the hypothesis that exposure to elevated levels of KYNA during development may contribute to cognitive dysfunction later in life. Consistent with prior studies in which adult rats were treated acutely with L-KYN, juvenile rats exposed to increased KYNA concentration during adolescence exhibited deficits in contextual fear memory, but cue-specific fear memory was not impaired. In addition, rats treated with L-KYN as adolescents were impaired on a novel object recognition memory task when tested as adults. The memory deficits could not be explained by drug-induced changes in locomotor activity or shock sensitivity. Together, these findings add to the growing literature supporting the notion that exposure to increased concentration of KYNA may contribute to cognitive deficits typically observed in schizophrenia. PMID:21172906

  13. Color Stability of Enamel following Different Acid Etching and Color Exposure Times

    PubMed Central

    Jahanbin, Arezoo; Basafa, Mohammad; Moazzami, Mostafa; Basafa, Behnoush; Eslami, Neda

    2014-01-01

    Background and aims. The aim of this study was to evaluate the effect of different etching times on enamel color stability after immediate versus delayed exposure to colored artificial saliva (CAS). Materials and methods. Human first premolars were divided into five groups of twenty. A colorimeter was used according to the CIE system on the mid-buccal and mid-lingual surfaces to evaluate initial tooth color. Samples in group A remained unetched. In groups B to E, buccal and lingual surfaces were initially etched with phosphoric acid for 15 and 60 seconds, respectively. Then, the samples in groups A and C were immersed in colored artificial saliva (cola+saliva). In group B, the teeth were immersed in simple artificial saliva (AS). Samples in groups D and E were immersed in AS for 24 and 72 hours, respectively before being immersed in colored AS. The teeth were immersed for one month in each solution before color measurement. During the test period, the teeth were retrieved from the staining solution and stored in AS for five minutes. This was repeated 60 times. Color changes of buccal and lingual surfaces were calculated. Kruskal-Wallis and Wilcoxon tests were used for statistical analysis (α ≤0.05). Results. There were no significant differences between the groups in term of ΔE of buccal (P = 0.148) and lingual surfaces (P = 0.73). Conclusion. Extended time of etching did not result in significant enamel color change. Immediate and delayed exposure of etched enamel to staining solutions did not result in clinically detectable tooth color changes. PMID:25093048

  14. Impact of boric acid exposure at different concentrations on testicular DNA and male rats fertility.

    PubMed

    El-Dakdoky, Mai H; Abd El-Wahab, Hanan M F

    2013-06-01

    The aim of this study was to investigate the consequences of exposure to three levels of boric acid (BA) on male rats reproduction, fertility and progeny outcome, with emphasis on testicular DNA level and quality. Adult male rats (12 weeks old) were treated orally with 125, 250 and 500 mg/kg bwt/d of BA for 60 d. The results indicated that BA administration at 125 mg/kg bwt had no adverse effects on fertility, sperm characteristics or prenatal development of the impregnated females. However, at dose 250 mg, BA treatment significantly increased serum nitric oxide, testosterone, estradiol levels and testicular boron and calcium levels and also significantly reduced serum arginase activity, sperm quality and testicular DNA content with minor DNA fragmentation. The impact of BA exposure at dose 250 mg on male rats fertility was translated into increases in pre-implantation loss with a resulting decrease in the number of live fetuses/litter. In addition to the significant alteration of biochemical measurements, observed at dose 250 mg, administration of BA at 500 mg caused testicular atrophy, severe damage of spermatogenesis, spermiation failure and significant reduction of Mg and Zn testicular levels. None of the male rats, treated with 500 mg/kg bwt, could impregnate untreated females, suggesting the occurrence of definitive loss of fertility. In conclusion, BA impaired fertility, in a dose-dependant manner, by targeting the highly proliferative cells, the germ cells, through decreasing DNA synthetic rate rather than the induction of DNA damage. PMID:23301826

  15. Impact of boric acid exposure at different concentrations on testicular DNA and male rats fertility.

    PubMed

    El-Dakdoky, Mai H; Abd El-Wahab, Hanan M F

    2013-06-01

    The aim of this study was to investigate the consequences of exposure to three levels of boric acid (BA) on male rats reproduction, fertility and progeny outcome, with emphasis on testicular DNA level and quality. Adult male rats (12 weeks old) were treated orally with 125, 250 and 500 mg/kg bwt/d of BA for 60 d. The results indicated that BA administration at 125 mg/kg bwt had no adverse effects on fertility, sperm characteristics or prenatal development of the impregnated females. However, at dose 250 mg, BA treatment significantly increased serum nitric oxide, testosterone, estradiol levels and testicular boron and calcium levels and also significantly reduced serum arginase activity, sperm quality and testicular DNA content with minor DNA fragmentation. The impact of BA exposure at dose 250 mg on male rats fertility was translated into increases in pre-implantation loss with a resulting decrease in the number of live fetuses/litter. In addition to the significant alteration of biochemical measurements, observed at dose 250 mg, administration of BA at 500 mg caused testicular atrophy, severe damage of spermatogenesis, spermiation failure and significant reduction of Mg and Zn testicular levels. None of the male rats, treated with 500 mg/kg bwt, could impregnate untreated females, suggesting the occurrence of definitive loss of fertility. In conclusion, BA impaired fertility, in a dose-dependant manner, by targeting the highly proliferative cells, the germ cells, through decreasing DNA synthetic rate rather than the induction of DNA damage.

  16. Trichloroacetic acid cycling in Sitka spruce saplings and effects on sapling health following long term exposure.

    PubMed

    Dickey, C A; Heal, K V; Stidson, R T; Koren, R; Schröder, P; Cape, J N; Heal, M R

    2004-07-01

    Trichloroacetic acid (TCA, CCl(3)COOH) has been associated with forest damage but the source of TCA to trees is poorly characterised. To investigate the routes and effects of TCA uptake in conifers, 120 Sitka spruce (Picea sitchensis (Bong.) Carr) saplings were exposed to control, 10 or 100 microg l(-1) solutions of TCA applied twice weekly to foliage only or soil only over two consecutive 5-month growing seasons. At the end of each growing season similar elevated TCA concentrations (approximate range 200-300 ng g(-1) dwt) were detected in both foliage and soil-dosed saplings exposed to 100 microg l(-1) TCA solutions showing that TCA uptake can occur from both exposure routes. Higher TCA concentrations in branchwood of foliage-dosed saplings suggest that atmospheric TCA in solution is taken up indirectly into conifer needles via branch and stemwood. TCA concentrations in needles declined slowly by only 25-30% over 6 months of winter without dosing. No effect of TCA exposure on sapling growth was measured during the experiment. However at the end of the first growing season needles of saplings exposed to 10 or 100 microg l(-1) foliage-applied TCA showed significantly more visible damage, higher activities of some detoxifying enzymes, lower protein contents and poorer water control than needles of saplings dosed with the same TCA concentrations to the soil. At the end of each growing season the combined TCA storage in needles, stemwood, branchwood and soil of each sapling was <6% of TCA applied. Even with an estimated half-life of tens of days for within-sapling elimination of TCA during the growing season, this indicates that TCA is eliminated rapidly before uptake or accumulates in another compartment. Although TCA stored in sapling needles accounted for only a small proportion of TCA stored in the sapling/soil system it appears to significantly affect some measures of sapling health.

  17. Effects of acid aerosol exposure on the surface properties of airway mucus

    SciTech Connect

    Lee, M.M.; Schuerch, S.; Roth, S.H.

    1995-12-31

    It was hypothesized that the mucous layer lining the tracheas of rats and guinea pigs contains surfactant material capable of lowering the air/mucus surface tension, {gamma}, and that exposure to an irritant aerosol would raise the {gamma}. The {gamma} of the surface film was measured directly by a spreading droplet technique and indirectly by displacement of polymethyl methacrylate particles into the aqueous layer. The morphology of the mucous film was examined by electron microscopy after nonaqueous fixation. {gamma} was 33.3 {plus_minus} 0.70 (SE) mN/m and 32.3 {plus_minus} 0.68 (SE) mN/m for the normal rat and guinea pig trachea, respectively. Exposure for 4 h to aerosols of sulfuric acid (94.1 {plus_minus} 18.68 (SD) and 43.3 {plus_minus} 4.57 (SD) mg/m{sup 3}) caused a several-fold increase in thickness of the mucous layer with exudation of protein-like material. The osmiophilic surfactant film at the air/mucus interface became irregularly thickened and multilayered. Despite these morphological changes {gamma} remained low, 33.2 {plus_minus} 0.43 (SE) mN/m and 32.6 {plus_minus} 0.60 (SE) mN/m for rats and guinea pigs, respectively, and displacement of particles into the subphase was not compromised. The results indicate that rodent tracheas are able to maintain a low surface tension in the presence of injury. 24 refs., 9 figs.

  18. Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats.

    PubMed

    Zhao, Wei-Man; Jiang, Shu-Wen; Chen, Yang; Zhong, Ze-Yu; Wang, Zhong-Jian; Zhang, Mian; Li, Ying; Xu, Ping; Liu, Li; Liu, Xiao-Dong

    2015-07-01

    The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

  19. Folic acid and its photoproducts, 6-formylpterin and pterin-6-carboxylic acid, as generators of reactive oxygen species in skin cells during UVA exposure.

    PubMed

    Juzeniene, Asta; Grigalavicius, Mantas; Ma, Li Wei; Juraleviciute, Marina

    2016-02-01

    Folic acid (FA) is the synthetic form of folate (vitamin B9), present in supplements and fortified foods. During ultraviolet (UV) radiation FA is degraded to 6-formylpterin (FPT) and pterin-6-carboxylic acid (PCA) which generate reactive oxygen species (ROS) and may be phototoxic. The aim of the present study was to investigate the production of ROS and phototoxicity of FA, FPT and PCA in skin cells during UVA exposure. The production of ROS and phototoxicity of FA, FPT and PCA were studied in the immortal human keratinocytes (HaCaT) and malignant skin cells (A431 and WM115) during UVA exposure. Increased ROS production and the photoinactivation of cells in vitro were observed during UVA exposure in the presence of FA, FPT and PCA. HPLC analysis revealed that 10 μM FA photodegradation was around 2.1 and 5.8-fold faster than that of 5 μM and 1 μM FA. Photodegradation of FA is concentration dependent, and even non-phototoxic doses of FA and its photoproducts, FPT and PCA, generate high levels of ROS in vitro. FA, FPT and PCA are phototoxic in vitro. The photodegradation of topical or unmetabolized FA during UV exposure via sunlight, sunbeds or phototherapy may lead to ROS production, to the cutaneous folate deficiency, skin photocarcinogenesis and other deleterious skin effects. Further studies are needed to confirm whether UV exposure can decrease cutaneous and serum folate levels in humans taking FA supplements or using cosmetic creams with FA.

  20. PERFLUOROOCTANOIC ACID AND PERFLUORONONANOIC ACID IN FETAL AND NEONATAL MICE FOLLOWING IN UTERO EXPOSURE TO 8-2 FLUOROTELOMER ALCOHOL

    EPA Science Inventory

    8-2 fluorotelomer alcohol (FTOH) and its metabolites, perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), are developmental toxicants, but metabolism and distribution during pregnancy is not known. To examine this, timed-pregnant mice received a single gavage dose (...

  1. Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behavior, and Decreased Cerebellar Glutathione Concentration in Rats

    PubMed Central

    Negishi, Takayuki; Matsunaga, Yuki

    2013-01-01

    In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0–6 weeks of age] and/or late period [7–12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA. PMID:24008832

  2. Immune response of the bay scallop, Argopecten irradians, after exposure to the algicide palmitoleic acid.

    PubMed

    Chi, Cheng; Giri, Sib Sankar; Jun, Jin Woo; Yun, Saekil; Kim, Hyoun Joong; Kim, Sang Guen; Park, Se Chang

    2016-10-01

    Palmitoleic acid (PA) is an effective algicide against the toxin-producing dinoflagellate Alexandrium tamarense; however, its effects on the immune system of the edible bay scallop Argopecten irradians are unclear. Therefore, we investigated the effects of PA on the immune response in A. irradians by assessing total haemocyte counts (THC), alkaline phosphatase activity (ALP), nitrite oxide (NO), glutathione (GSH), and lactate dehydrogenase (LDH) levels, as well as the expression of immune-related genes (FREP, PGRP, HSP90, MnSOD, and Cu/ZnSOD) at various hours post-exposure (hpe) to the compound. THC decreased in PA-treated groups, whereas ALP increased significantly in all of the PA treatment groups at 3 hpe, after which it significantly decreased. The LDH and NO levels were significantly enhanced in the high and medium concentration group. Notably, the GSH level increased in all PA treatment groups at each time interval. Our study revealed that after treatment with different concentrations of PA, variable effects on the expression of genes involved in the immune system response were observed. The results of our study demonstrate that immersing scallops in PA at effective concentrations could result in differential effects on immune system responses and expression of immune-related genes. Specifically, PA may disrupt the endocrine system or affect signal transduction pathways in the scallops. Therefore, the present study highlights the potential risk of using the PA as an algicide to control algal bloom outbreaks in the marine environment.

  3. Human Exposure and Elimination Kinetics of Chlorinated Polyfluoroalkyl Ether Sulfonic Acids (Cl-PFESAs).

    PubMed

    Shi, Yali; Vestergren, Robin; Xu, Lin; Zhou, Zhen; Li, Chuangxiu; Liang, Yong; Cai, Yaqi

    2016-03-01

    The incomplete mass-balance of organic fluorine in human serum indicates the existence of unknown per- and polyfluoroalkyl substances (PFASs) with persistent and bioaccumulative properties. Here we characterized human exposure and elimination kinetics of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) in metal plating workers (n = 19), high fish consumers (n = 45), and background controls (n = 8). Cl-PFESAs were detected in >98% of the sampled individuals with serum concentrations ranging <0.019-5040 ng/mL. Statistically higher median serum levels were observed in high fish consumers (93.7 ng/mL) and metal plating workers (51.5 ng/mL) compared to the background control group (4.78 ng/mL) (Kruskal-Wallis rank sum test, p < 0.01). Cl-PFESAs could account for 0.269 to 93.3% of ∑PFASs in human serum indicating that this compound class may explain a substantial fraction of previously unidentified organic fluorine in the Chinese population. Estimated half-lives for renal clearance (median 280 years; range 7.1-4230 years) and total elimination (median 15.3 years; range 10.1-56.4 years) for the eight carbon Cl-PFESA suggest that this is the most biopersistent PFAS in humans reported to date. The apparent ubiquitous distribution and slow elimination kinetics in humans underscore the need for more research and regulatory actions on Cl-PFESAs and PFAS alternatives with similar chemical structures.

  4. Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats

    PubMed Central

    Mony, Tamanna Jahan; Lee, Jae Won; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel; Lee, Hee Jae

    2016-01-01

    Objective We reported that postnatal exposure of rats to valproic acid (VPA) stimulated proliferation of glial precursors during cortical gliogenesis. However, there are no reports whether enhanced postnatal gliogenesis affects behaviors related to neuropsychiatric disorders. Methods After VPA treatment during the postnatal day (PND) 2 to PND 4, four behavioral test, such as open field locomotor test, elevated plus maze test, three-chamber social interaction test, and passive avoidance test, were performed at PND 21 or 22. Results VPA treated rats showed significant hyperactive behavior in the open field locomotor test (p<0.05). Moreover, the velocity of movement in the VPA group was increased by 69.5% (p<0.01). In the elevated plus maze test, VPA exposed rats expressed significantly lower percentage of time spent on and of entries into open arms more than the control group (p<0.05). Also, both sociability and social preference indices with strangers in the three-chamber social interaction test were significantly lower in the VPA exposed rats (p<0.05). Conclusion Our results suggest that altered glial cell development is another locus at which pathogenetic factors can operate to contribute to the neurodevelopmental disorder. PMID:27776385

  5. Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.

    PubMed

    Mills, Brian D; Pearce, Hadley L; Khan, Omar; Jarrett, Ben R; Fair, Damien A; Lahvis, Garet P

    2016-07-15

    Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rs-fcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability.

  6. Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.

    PubMed

    Mills, Brian D; Pearce, Hadley L; Khan, Omar; Jarrett, Ben R; Fair, Damien A; Lahvis, Garet P

    2016-07-15

    Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rs-fcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability. PMID:27050322

  7. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    SciTech Connect

    Noble, E.P.; Ritchie, T. )

    1989-01-01

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with (3H)inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of (3H)inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers.

  8. Acid sulphate soil disturbance and metals in groundwater: implications for human exposure through home grown produce.

    PubMed

    Hinwood, Andrea Lee; Horwitz, Pierre; Appleyard, Steve; Barton, Caroline; Wajrak, Magda

    2006-09-01

    A significant emerging environmental problem is the disturbance and oxidation of soils with high levels of iron sulphide minerals resulting in acidification and causing the mobilization of metals into groundwater. This process is occurring in many parts of the world. In Western Australia, impacted groundwater is extracted by residents for domestic use. We sought to establish domestic use patterns of bore water and the concentration of metals. Sixty-seven domestic bore water samples clearly indicated oxidation of sulphidic materials with heavy metal concentrations ranging for aluminium (exposure to heavy metals via the consumption of home grown produce. This warrants further investigation in light of increasing acid sulphate soil disturbance in many locations.

  9. Loblolly pine and slash pine responses to acute aluminum and acid exposures.

    PubMed

    Nowak, Jaroslaw; Friend, Alexander L

    2006-09-01

    In response to concerns about aluminum and HCl exposure associated with rocket motor testing and launches, survival and growth of full-sib families of loblolly pine (Pinus taeda L.) and slash pine (Pinus elliottii Engelm.) were evaluated in a nursery bed experiment. Each species was exposed to a single soil application of aluminum chloride (0.33 M AlCl(3), pH 2.5), hydrochloric acid (0.39 M HCl, pH 0.6) or water, with or without mycorrhizal inoculation with Pisolithus tinctorius (Coker and Couch). After 20 weeks without inoculation, survival in AlCl(3) and HCl treatments averaged 52% for loblolly pine and 72% for slash pine. Inoculation improved survival of loblolly pine, receiving HCl from 49 to 73%, and of those receiving AlCl3, from 55 to 90%. Inoculation also resulted in improved survival and growth of individual families in AlCl(3), but not in HCl treatments. Results illustrate the relative resistance of both pine species to the acute treatments supplied, the improvement in resistance associated with mycorrhizal inoculation and the importance of field testing, following hydroponic screening, to verify the resistance to soil-supplied stresses.

  10. The effects of sequential exposure to acidic fog and ozone on pulmonary function in exercising subjects

    SciTech Connect

    Aris, R.; Christian, D.; Sheppard, D.; Balmes, J.R. )

    1991-01-01

    In Southern California coastal regions, morning fog is often acidified by the presence of nitric acid (HNO{sub 3}). Peak exposure to ozone (O{sub 3}) usually occurs in the afternoon and evening, after the fog has dissipated. To determine whether fog containing HNO{sub 3} might enhance pulmonary responses to O{sub 3}, we studied a group of healthy, athletic subjects selected for lung function sensitivity to O{sub 3}. On 3 separate days, the subjects exercised for 2 h in atmospheres containing HNO{sub 3} fog (0.5 mg/ml), H{sub 2}O fog, or clean, filtered air. After a 1-h break, they exercised for an additional 3 h in an atmosphere containing 0.20 ppm O{sub 3}. Surprisingly, the mean O{sub 3}-induced decrements in FEV1 and FVC were smaller after exercise in each fog-containing atmosphere than they were after exercise in clean, filtered air. The mean (+/- SEM) O{sub 3}-induced decrements in FEV1 were 26.4 +/- 5.3% after air, 17.1 +/- 3.7% after H{sub 2}O fog, and 18.0 +/- 4.3% after HNO{sub 3} fog, and in FVC they were 19.9 +/- 4.7% after air, 13.6 +/- 2.8% after H{sub 2}O fog, and 13.6 +/- 4.2% after HNO{sub 3} fog.

  11. Immune response of the bay scallop, Argopecten irradians, after exposure to the algicide palmitoleic acid.

    PubMed

    Chi, Cheng; Giri, Sib Sankar; Jun, Jin Woo; Yun, Saekil; Kim, Hyoun Joong; Kim, Sang Guen; Park, Se Chang

    2016-10-01

    Palmitoleic acid (PA) is an effective algicide against the toxin-producing dinoflagellate Alexandrium tamarense; however, its effects on the immune system of the edible bay scallop Argopecten irradians are unclear. Therefore, we investigated the effects of PA on the immune response in A. irradians by assessing total haemocyte counts (THC), alkaline phosphatase activity (ALP), nitrite oxide (NO), glutathione (GSH), and lactate dehydrogenase (LDH) levels, as well as the expression of immune-related genes (FREP, PGRP, HSP90, MnSOD, and Cu/ZnSOD) at various hours post-exposure (hpe) to the compound. THC decreased in PA-treated groups, whereas ALP increased significantly in all of the PA treatment groups at 3 hpe, after which it significantly decreased. The LDH and NO levels were significantly enhanced in the high and medium concentration group. Notably, the GSH level increased in all PA treatment groups at each time interval. Our study revealed that after treatment with different concentrations of PA, variable effects on the expression of genes involved in the immune system response were observed. The results of our study demonstrate that immersing scallops in PA at effective concentrations could result in differential effects on immune system responses and expression of immune-related genes. Specifically, PA may disrupt the endocrine system or affect signal transduction pathways in the scallops. Therefore, the present study highlights the potential risk of using the PA as an algicide to control algal bloom outbreaks in the marine environment. PMID:27542615

  12. Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring.

    PubMed

    Church, M W; Jen, K-L C; Anumba, J I; Jackson, D A; Adams, B R; Hotra, J W

    2010-01-01

    Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation is beneficial to fetal and infant development and might reduce the incidence and severity of preterm births by prolonging pregnancy. Consequently, supplementing maternal diets with large amounts of omega-3 FA is gaining acceptance. However, both over- and under-supplementation with omega-3 FA can harm offspring development. Adverse fetal and neonatal conditions in general can enhance age-related neural degeneration, shorten life span and cause other adult-onset disorders. We hypothesized that maternal over- and under-nutrition with omega-3 FA would shorten the offspring's life span and enhance neural degeneration in old adulthood. To test these hypotheses, female Wistar rats were randomly assigned to one of the three diet conditions starting from day 1 of pregnancy through the entire period of pregnancy and lactation. The three diets were Control omega-3 FA (omega-3/omega-6 ratio approximately 0.14), Excess omega-3 FA (omega-3/omega-6 ratio approximately 14.5) and Deficient omega-3 FA (omega-3/omega-6 ratio approximately 0% ratio). When possible, one male and female offspring from each litter were assessed for life span and sensory/neural degeneration (n=15 litters/group). The Excess offspring had shorter life spans compared to their Control and Deficient cohorts (mean+/-SEM=506+/-24, 601+/-14 and 585+/-21 days, pabnormalities and lower body weights in old adulthood. In conclusion, omega-3 FA over-nutrition or imbalance during pregnancy and lactation had adverse effects on life span and sensory/neurological function in old adulthood. The adverse outcomes in the Excess offspring were likely due to a "nutritional toxicity" during fetal and/or neonatal development

  13. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

    PubMed Central

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F.; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  14. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice.

    PubMed

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  15. Continuous exposure to a novel stressor based on water aversion induces abnormal circadian locomotor rhythms and sleep-wake cycles in mice.

    PubMed

    Miyazaki, Koyomi; Itoh, Nanako; Ohyama, Sumika; Kadota, Koji; Oishi, Katsutaka

    2013-01-01

    Psychological stressors prominently affect diurnal rhythms, including locomotor activity, sleep, blood pressure, and body temperature, in humans. Here, we found that a novel continuous stress imposed by the perpetual avoidance of water on a wheel (PAWW) affected several physiological diurnal rhythms in mice. One week of PAWW stress decayed robust circadian locomotor rhythmicity, while locomotor activity was evident even during the light period when the mice are normally asleep. Daytime activity was significantly upregulated, whereas nighttime activity was downregulated, resulting in a low amplitude of activity. Total daily activity gradually decreased with increasing exposure to PAWW stress. The mice could be exposed to PAWW stress for over 3 weeks without adaptation. Furthermore, continuous PAWW stress enhanced food intake, but decreased body weight and plasma leptin levels, indicating that sleep loss and PAWW stress altered the energy balance in these mice. The diurnal rhythm of corticosterone levels was not severely affected. The body temperature rhythm was diurnal in the stressed mice, but significantly dysregulated during the dark period. Plasma catecholamines were elevated in the stressed mice. Continuous PAWW stress reduced the duration of daytime sleep, especially during the first half of the light period, and increased nighttime sleepiness. Continuous PAWW stress also simultaneously obscured sleep/wake and locomotor activity rhythms compared with control mice. These sleep architecture phenotypes under stress are similar to those of patients with insomnia. The stressed mice could be entrained to the light/dark cycle, and when they were transferred to constant darkness, they exhibited a free-running circadian rhythm with a timing of activity onset predicted by the phase of their entrained rhythms. Circadian gene expression in the liver and muscle was unaltered, indicating that the peripheral clocks in these tissues remained intact. PMID:23383193

  16. Acute acidic exposure induces p53-mediated oxidative stress and DNA damage in tilapia (Oreochromis niloticus) blood cells.

    PubMed

    Mai, Wei-jun; Yan, Jun-lun; Wang, Lei; Zheng, Ying; Xin, Yu; Wang, Wei-na

    2010-11-01

    Acid rain and inputs of acidic effluent can result in increased acidity in aquatic ecosystems, where it is known to have a significant impact and possibly, to cause the decline of some populations of aquatic organisms. In previous studies, intracellular acid-induced oxidative stress has been shown to cause DNA damage, and cooperatively activate the expression of the p53 gene. The acute effects of acidic environments on shrimp and fish have been widely studied. However, the molecular mechanism of acid-induced injury remains largely unknown. In this study, we examined the cellular responses of tilapia to acidic exposure-induced oxidative stress and antioxidant enzyme gene expression. Furthermore, we determined how acute acid stress activates the ATM-p53 signal pathway. We measured the upregulation of reactive oxygen species (ROS) production, the intracellular Ca(2)(+) concentration ([Ca(2)(+)](i)), the tail DNA values, the malondialdehyde (MDA) level in the blood cells and the percentage of dead and damaged blood cells. Our results suggest that oxidative stress and DNA damage occurred in tilapia in conditions where the pH was 5.3. Apoptosis was detected by Hoechst staining, which was mainly associated with changes in cell viability. The parameters that we measured were related to acid-induced DNA damage, and all parameters changed in the blood cells through time. The effects of acute acid exposure (pH 5.3) on the expression of ATM, p53, p21, Bax, manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) were investigated in tilapia blood cells. The results showed that acute acid stress induced upregulation of ATM, p53 and p21, associated with increasing of DNA damage and apoptosis in blood cells. Additionally, the expression of Bax was slightly increased. Moreover, consensus p53-binding sequences were identified in tilapia MnSOD and GPx gene promoter regions and increased levels of ROS in the blood cells coincided with increased mRNA expression of p53, Mn

  17. Making fate and exposure models for freshwater ecotoxicity in life cycle assessment suitable for organic acids and bases.

    PubMed

    van Zelm, Rosalie; Stam, Gea; Huijbregts, Mark A J; van de Meent, Dik

    2013-01-01

    Freshwater fate and exposure factors were determined for organic acids and bases, making use of the knowledge on electrical interaction of ionizing chemicals and their sorption to particles. The fate factor represents the residence time in the environment whereas exposure factors equal the dissolved fraction of a chemical. Multimedia fate, exposure, and effect model USES-LCA was updated to take into account the influence of ionization, based upon the acid dissociation constant (pK(a)) of a chemical, and the environmental pH. Freshwater fate (FF) and exposure (XF) factors were determined for 415 acids and 496 bases emitted to freshwater, air, and soil. The relevance of taking account of the degree of ionization of chemicals was tested by determining the ratio (R) of the new vs. fate and exposure factors determined with USES-LCA suitable for neutral chemicals only. Our results show that the majority of freshwater fate and exposure factors of chemicals that are largely ionized in the environment are larger with the ionics model compared to the factors determined with the neutrals model version. R(FF) ranged from 2.4×10(-1) to 1.6×10(1) for freshwater emissions, from 1.2×10(-2) to 2.0×10(4) for soil emissions and from 5.8×10(-2) to 6.0×10(3) for air emissions, and R(XF) from 5.3×10(-1) to 2.2×10(1). Prediction of changed solid-water partitioning, implying a change in runoff and in removal via sedimentation, and prediction of negligible air-water partition coefficient, leading to negligible volatilization were the main contributors to the changes in freshwater fate factors.

  18. Potential citric acid exposure and toxicity to Hawaiian hoary bats (Lasiurus cinereus semotus) associated with Eleutherodactylus frog control.

    PubMed

    Pitt, William C; Witmer, Gary W; Jojola, Susan M; Sin, Hans

    2014-04-01

    We examined potential exposure of Hawaiian hoary bats (Lasiurus cinereus semotus) to citric acid, a minimum risk pesticide registered for control of invasive Eleutherodactylus frog populations. Hoary bats are nocturnal insectivores that roost solitarily in foliage, federally listed as endangered, and are endemic to Hawaii. Oral ingestion during grooming of contaminated fur appears to be the principal route by which these bats might be exposed to citric acid. We made assessments of oral toxicity, citric acid consumption, retention of material on fur, and grooming using big brown bats (Eptesicus fuscus) as a surrogate species. We evaluated both ground application and aerial application of 16 % solutions of citric acid during frog control operations. Absorbent bat effigies exposed to ground and aerial operational spray applications retained means of 1.54 and 0.02 g, respectively, of dry citric acid, although retention by the effigies was much higher than bat carcasses drenched in citric acid solutions. A high dose delivered orally (2,811 mg/kg) was toxic to the big brown bats and emesis occurred in 1 bat dosed as low as the 759 mg/kg level. No effect was observed with the lower doses examined (≤ 542 mg/kg). Bats sprayed with 5 ml of 16 % (w/w) citric acid solution showed no evidence of intoxication. In field situations, it is unlikely that bats would be sprayed directly or ingest much citric acid retained by fur. Based on our observations, we believe Hawaiian hoary bats to be at very low risk from harmful exposure to a toxic dose of citric acid during frog control operations.

  19. Fatty acid profiles as a potential lipidomic biomarker of exposure to brevetoxin for endangered Florida manatees (Trichechus manatus latirostris).

    PubMed

    Wetzel, Dana L; Reynolds, John E; Sprinkel, Jay M; Schwacke, Lori; Mercurio, Philip; Rommel, Sentiel A

    2010-11-15

    Fatty acid signature analysis (FASA) is an important tool by which marine mammal scientists gain insight into foraging ecology. Fatty acid profiles (resulting from FASA) represent a potential biomarker to assess exposure to natural and anthropogenic stressors. Florida manatees are well studied, and an excellent necropsy program provides a basis against which to assess this budding tool. Results using samples from 54 manatees assigned to four cause-of-death categories indicated that those animals exposed to or that died due to brevetoxin exposure (red tide, or RT samples) demonstrate a distinctive hepatic fatty acid profile. Discriminant function analysis indicated that hepatic fatty acids could be used to classify RT versus non-RT liver samples with reasonable certainty. A discriminant function was derived based on 8 fatty acids which correctly classified 100% of samples from a training dataset (10 RT and 25 non-RT) and 85% of samples in a cross-validation dataset (5 RT and 13 non-RT). Of the latter dataset, all RT samples were correctly classified, but two of thirteen non-RT samples were incorrectly classified. However, the "incorrect" samples came from manatees that died due to other causes during documented red tide outbreaks; thus although the proximal cause of death was due to watercraft collisions, exposure to brevetoxin may have affected these individuals in ways that increased their vulnerability. This use of FASA could: a) provide an additional forensic tool to help scientists and managers to understand cause of death or debilitation due to exposure to red tide in manatees; b) serve as a model that could be applied to studies to improve assessments of cause of death in other marine mammals; and c) be used, as in humans, to help diagnose metabolic disorders or disease states in manatees and other species.

  20. Fatty acid profiles as a potential lipidomic biomarker of exposure to brevetoxin for endangered Florida manatees (Trichechus manatus latirostris).

    PubMed

    Wetzel, Dana L; Reynolds, John E; Sprinkel, Jay M; Schwacke, Lori; Mercurio, Philip; Rommel, Sentiel A

    2010-11-15

    Fatty acid signature analysis (FASA) is an important tool by which marine mammal scientists gain insight into foraging ecology. Fatty acid profiles (resulting from FASA) represent a potential biomarker to assess exposure to natural and anthropogenic stressors. Florida manatees are well studied, and an excellent necropsy program provides a basis against which to assess this budding tool. Results using samples from 54 manatees assigned to four cause-of-death categories indicated that those animals exposed to or that died due to brevetoxin exposure (red tide, or RT samples) demonstrate a distinctive hepatic fatty acid profile. Discriminant function analysis indicated that hepatic fatty acids could be used to classify RT versus non-RT liver samples with reasonable certainty. A discriminant function was derived based on 8 fatty acids which correctly classified 100% of samples from a training dataset (10 RT and 25 non-RT) and 85% of samples in a cross-validation dataset (5 RT and 13 non-RT). Of the latter dataset, all RT samples were correctly classified, but two of thirteen non-RT samples were incorrectly classified. However, the "incorrect" samples came from manatees that died due to other causes during documented red tide outbreaks; thus although the proximal cause of death was due to watercraft collisions, exposure to brevetoxin may have affected these individuals in ways that increased their vulnerability. This use of FASA could: a) provide an additional forensic tool to help scientists and managers to understand cause of death or debilitation due to exposure to red tide in manatees; b) serve as a model that could be applied to studies to improve assessments of cause of death in other marine mammals; and c) be used, as in humans, to help diagnose metabolic disorders or disease states in manatees and other species. PMID:20880571

  1. Endocrine disruption effects of long-term exposure to perfluorodecanoic acid (PFDA) and perfluorotridecanoic acid (PFTrDA) in zebrafish (Danio rerio) and related mechanisms.

    PubMed

    Jo, Areum; Ji, Kyunghee; Choi, Kyungho

    2014-08-01

    Perfluoroalkyl acids (PFAAs) have been frequently detected in both the environment and biota, however the endocrine disruption potentials and underlying mechanism of long-chain PFAAs have not yet been fully understood in fish. In the present study, the effects of perfluorodecanoic acid (PFDA) and perfluorotridecanoic acid (PFTrDA) on sex steroid hormones and expression of mRNA of selected genes in hypothalamic-pituitary-gonad (HPG) axis were evaluated after 120 d exposure of zebrafish. In addition, production of sex hormones and transcription of steroidogenic genes were measured after in vitro exposure of H295R cells for 48 h. Exposure to PFTrDA resulted in reduced production of testosterone (T) along with lesser expression of CYP17A mRNA in H295R cells. In zebrafish, significant up-regulation of vtg1 was observed in males exposed to PFDA, whereas down-regulation was observed in females exposed to PFTrDA. In male zebrafish, concentrations of 17β-estradiol (E2) were significantly increased at 0.01 mg L(-1) PFTrDA. Significant increases in ratios of E2/T and E2/11-ketotestosterone (11-KT) were observed in male zebrafish after exposure to PFDA or PFTrDA, indicating estrogenic potentials of these compounds. The results of this study showed that long-term exposure to PFDA or PFTrDA could modulate sex steroid hormone production and related gene transcription of the HPG axis in a sex-dependent manner. Consequences of endocrine disruptions in reproduction performances of the fish warrant further investigation.

  2. Does developmental exposure to perflurooctanoic acid (PFOA) induce immunopathologies commonly observed in neurodevelopmental disorders?

    PubMed

    Hu, Qing; Franklin, Jason N; Bryan, Ian; Morris, Erin; Wood, Andrew; DeWitt, Jamie C

    2012-12-01

    Immune comorbidities often are reported in subsets of patients with neurodevelopmental disorders, including autism spectrum disorders and attention-deficit hyperactivity disorder. A common immunopathology is an increase in serum autoantibodies against myelin basic protein (MBP) relative to control patients. Increases in autoantibodies suggest possible deficits in self-tolerance that may contribute to the formation of brain-specific autoantibodies and subsequent effects on the central nervous system (CNS). Oppositely, the formation of neuronal autoantibodies may be a reaction to neuronal injury or damage. Perfluorooctanoic acid (PFOA) is an environmental pollutant that induces multisystem toxicity in rodent models, including immunotoxicity and neurotoxicity. We hypothesized that developmental exposure to PFOA may induce immunotoxicity similar to that observed in subsets of patients with neurodevelopmental disorders. To test this hypothesis, we evaluated subsets of T cells from spleens, serum markers of autoreactivity, and levels of MBP and T cell infiltration in the cerebella of adult offspring exposed to 0.02, 0.2, or 2mg/kg of PFOA given to dams from gestation through lactation. Litter weights of offspring from dams exposed to 2mg/kg of PFOA were reduced by 32.6%, on average, from postnatal day one (PND1) through weaning (PND21). The percentage of splenic CD4+CD25+Foxp3+ T cells in male and female offspring from dams exposed to 2mg/kg of PFOA was reduced by 22% relative to the control percentage. Ex vivo co-cultures of splenic CD4+CD25+ T cells and CD4+CD25- T cells from dosed male offspring produced less IL-10 relative to control cells. Anti-ssDNA, a serum marker of autoreactivity, was decreased by 26%, on average, in female offspring from dams exposed to 0.02 and 2mg/kg PFOA. No other endpoints were statistically different by dose. These data suggest that developmental PFOA exposure may impact T cell responses and may be a possible route to downstream effects on

  3. A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome.

    PubMed

    Lee, Bao Hui; Indran, Inthrani Raja; Tan, Huey Min; Li, Yu; Zhang, Zhiwei; Li, Jun; Yong, Eu-Leong

    2016-01-01

    Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.

  4. Evaluation of biomarkers of environmental exposures: urinary haloacetic acids associated with ingestion of chlorinated drinking water.

    PubMed

    Kim, H; Haltmeier, P; Klotz, J B; Weisel, C P

    1999-02-01

    A study was conducted to determine if DCAA and TCAA urinary excretion rates are valid biomarkers of chronic ingestion exposure to these disinfection by-products of chlorination of drinking water. Entire first morning urine voids, time-of-visit urine samples, and tap water samples were collected from 47 female subjects. In addition, a 48-h recall questionnaire was administered to determine the amounts and types of liquids ingested by each subject as well as other exposures that could lead to DCAA and TCAA urinary excretion. The TCAA excretion rate for the first morning urine samples was significantly correlated with the estimated 48-h TCAA ingestion exposure for 25 subjects whose ingestion exposures primarily occurred at home, while the DCAA excretion rate was not correlated with the DCAA ingestion exposure. Thus, urinary TCAA appears to be a valid biomarker of chronic ingestion exposure to TCAA from chlorinated water, while urinary DCAA is not. It is proposed that the difference in the biological half-lives between these two compounds is the rationale for this finding. The biological half-life of TCAA is longer than successive exposure intervals; thus TCAA accumulates until it reaches a steady state. The half-life of DCAA is shorter than successive exposure intervals; thus DCAA is almost completely metabolized following an exposure and is eliminated from the body. This study suggests that biological half-life, exposure interval, and sample collection interval should be considered in selecting biomarkers and designing studies to validate them.

  5. Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity.

    PubMed

    Kaliannan, K; Wang, B; Li, X-Y; Bhan, A K; Kang, J X

    2016-06-01

    Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics.

  6. Design considerations for ozone and acid aerosol exposure and health investigations: the Fairview Lake summer camp - photochemical smog case study

    SciTech Connect

    Lioy, P.J.; Spektor, D.; Thurston, G.; Citak, K.; Lippmann, M.; Bock, N.; Speizer, F.E.; Hayes, C.

    1987-01-01

    The health effects associated with ozone and acidic particulate sulfate exposures to active children have been and are being addressed in field epidemiological studies at summer camps in rural areas of the Northeastern US. The rationale and study design for studies, which have been conducted in Pennsylvania and New Jersey, are developed and reviewed. As background, results are summarized for human clinical and epidemiological studies and animal studies. These provided the basis for selection of health outcomes measured results from chemical characterization and transport studies are reviewed to define the criteria used for selection of a site which is effected by high ozone and acid species during photochemical smog episodes. The integration of the study design is discussed in detail by reviewing its application to the 1984 - Fairview Lake Camp Study (July 8 to August 4). The features of the camp study are reviewed, including the study population, pulmonary function procedures and analyses, air pollution monitoring instrumentation, and the site characteristics. The pollution exposure data are presented, for ozone and acidic sulfates and examined for the range and distribution concentration. Further information is provided on the intensity and duration of episodes encountered over the course of the study. Episodes occurred which had ozone and acid sulfates, ozone alone, and acid sulfates alone. 56 references, 9 figures.

  7. Perfluoroalkyl acids and their precursors in Swedish food: The relative importance of direct and indirect dietary exposure.

    PubMed

    Gebbink, Wouter A; Glynn, Anders; Darnerud, Per Ola; Berger, Urs

    2015-03-01

    We analyzed food market basket samples obtained in Sweden from 1999, 2005, and 2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds. Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2) were detected in the year pools with the highest ∑diPAP concentrations in 1999 and 2005. All precursors were predominantly found in meat, fish, and/or eggs based on analysis of individual food groups from 1999. Based on year pools, PFOS precursors contributed between 4 and 1% as an indirect source to total dietary PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total exposure. The lowest precursor contributions were generally seen in food samples from 2010.

  8. The effect of nitric acid exposure on Galileo spacecraft titanium alloy Ti-6Al-4V propellant tanks

    NASA Technical Reports Server (NTRS)

    Hsieh, Cheng; O'Donnell, Tim; Yavrouian, Andre

    1990-01-01

    The Ti-6Al-4V-constructed retropropulsion-module tanks of the Galileo spacecraft were purged with nitrogen tetroxide in order to wait out a major launch rescheduling; nitric acid is among the residual products of such an operation. A test program was conducted on representative samples to ascertain the fracture toughness and stress corrosion threshold of the tanks' material, in view of Space Shuttle safety and mission-reliability requirements. It was found that the tanks' structural integrity was not degraded by nitric acid exposure.

  9. Effect of concentration and cumulative exposure of inhaled sulfuric acid on tracheobronchial particle clearance in healthy humans.

    PubMed

    Spektor, D M; Yen, B M; Lippmann, M

    1989-02-01

    We have previously shown that 1-hr exposures to 0.5 microns sulfuric acid (H2SO4) mist at 100 and 1000 micrograms/m3 produced transient alterations of bronchial mucociliary clearance of monodispersed 7.6 and 4.2 microns mass median aerodynamic diameter gamma-tagged ferric oxide (Fe2O3) in healthy nonsmoking humans in a dose-dependent manner. To determine the role, if any, of the length of exposure, 10 healthy volunteers were exposed to 100 micrograms/m3 H2SO4 for 1 hr and 2 hr on separate occasions, 1 week apart, with measurements of their mucociliary clearance of 5.2 microns Fe2O3 particles inhaled both before and after the inhalation of the H2SO4. Their rate of bronchial mucociliary clearance was markedly reduced for both Fe2O3 aerosols, with slower clearance of the aerosol inhaled after the H2SO4 exposure. For the tagged Fe2O3 aerosol inhaled after exposure for 2 hr at 100 micrograms/m3 H2SO4, the tracheobronchial clearance halftime, (T50), tripled from control, and the reduced rate of clearance was still evident 3 hr after the end of exposure. The 1-hr 100 micrograms/m3 H2SO4 exposure doubled T50 from control, and the reduced rate of clearance lasted for about 2 hr after the end of exposure. These results indicate that the effect of doubling the length of exposure was as great or greater than an order of magnitude increase in the concentration of H2SO4.

  10. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures.

    PubMed

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang; Xiao, Jinglei; Yu, Buwei

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures. PMID:27597963

  11. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

    PubMed Central

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures. PMID:27597963

  12. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

    PubMed Central

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures.

  13. Gestational exposure to methylmercury and n-3 fatty acids: effects on high- and low-rate operant behavior in adulthood.

    PubMed

    Paletz, Elliott M; Craig-Schmidt, Margaret C; Newland, M Christopher

    2006-01-01

    Fish in the diet is the major source of methylmercury (MeHg) exposure, but eating fish also provides important nutrients. Many fish species contain essential long chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), an omega-3 (or n-3) fatty acid, that is important for neural development and function. To examine interactions between MeHg and n-3 fatty acids, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm MeHg via drinking water, approximating exposures of 0, 40, and 400 mug/kg/day. They also received pre- and postnatal exposure to a diet containing either fish oil or coconut oil, creating a 2 (Diet)x3 (MeHg) full factorial design, with 6-8 rats per cell. The diets were high or marginal, respectively, in n-3 fatty acids but approximately equal in n-6 fatty acids. No exposure-related effects on developmental milestones or growth were noted. Behavior was evaluated using a series of rapidly increasing fixed ratio (FR) schedules of sucrose reinforcement; 1, 5, 25 and 75 lever presses were required for sucrose delivery, with three sessions provided at each requirement. This phase was followed by four sessions of a differential-reinforcement-of-low-rate-behavior (DRL) schedule, in which presses preceded by 10 s (or more) without a press were reinforced. Subsequently, several progressive ratio (PR) schedules that increased response requirements throughout a single session by a rate of 5%, 10%, or 20% were imposed. Rats exposed during gestation to MeHg had significantly higher response rates than controls under the large FR schedules, during the first session of DRL, and the PR 5% schedule, but neither fish oil nor coconut oil modified MeHg's effects. This finding is consistent with hypotheses that developmental MeHg exposure produced perseverative responding or altered the sensitivity of behavior to its reinforcing consequences and that certain reinforcement contingencies can unmask MeHg's effects.

  14. Exposure to Perfluorononanoic acid during pregnancy: Evaluations of rat and mice model

    EPA Science Inventory

    Perfluorononanoic acid (PFNA) is a persistent environmental contaminant. Although its levels in the environment are lower than those of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA), its presence in humans is rising and is of concern. Previous studies have in...

  15. Effects of Perfluorinated Phosphonic Acid Exposure during pregnancy in the mouse

    EPA Science Inventory

    Perfluorinated phosphonic acids (PFPAs) are a member of the perfluoroalkyl acid (PFAA) family, and are structurally similar to the perfluoroalkyl sulfonates and perfluoroalkyl carboxylates. These chemicals have recently been detected in the environment, particularly in surface wa...

  16. An Evaluation of Gestational Exposure to Perfluorooctanoic Acid (PFOA): Effects on Body Composition and Physiological Factors

    EPA Science Inventory

    Exposure to environmental pollutants can be a factor for induction of metabolic disorders. This study examined if exposure to PFOA during development could alter body composition and other physiological outcomes. Study 1: Pregnant CD-1 mice were gavaged with PFOA at 0,0.001,0.01,...

  17. Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.

    PubMed

    Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Leite, Carlos Eduardo; De Paula Cognato, Giana; Bonan, Carla Denise

    2015-01-01

    Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48μM) exposure during the first 48hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24hpf, 48hpf, and 72hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods.

  18. Acute exposure to realistic acid fog: Effects on respiratory function and airway responsiveness in asthmatics

    SciTech Connect

    Leduc, D.; De Vuyst, P.; Yernault, J.C.

    1995-11-01

    The biological effects of acid fog composed primarily of ammonium ions and sulfate are described. Subjects with asthma were exposed for one hour to sulfuric acid aerosol. Significant changes were not observed. Other asthma subjects were exposed to acid fog containing sulfate and ammonium ions. Again, pulmonary and bronchial function were not modified after inhalation.

  19. Neurobehavioral effects of exposure to propionic acid revisited-Does psychosocial stress interfere with distractive effects in volunteers?

    PubMed

    Pacharra, Marlene; Schäper, Michael; Kleinbeck, Stefan; Blaszkewicz, Meinolf; Golka, Klaus; van Thriel, Christoph

    2016-07-01

    Local irritants stimulate the nervous system via chemosensory pathways that trigger cognitive distraction, subjective complaints about impaired health, and physiological defense reflexes (e.g. eye-blinks). At workplaces and in the environment chemical exposures often co-occur with psychosocial stress. This study investigated if stress modulates adverse effects of exposure to the local irritant and malodorant propionic acid (PA). Forty-eight participants were randomly assigned to an experimental (false negative feedback+salient surveillance) or control group. In a cross-over design, both groups were exposed for 4h to PA in concentrations of 0.3 and 0-20ppm (time-weighted average=10ppm). In the experimental group, the stress protocol induced moderate psychosocial stress as indicated by salivary cortisol and subjective responses. Despite concentration-dependent increases in chemosensory perceptions and symptoms, the level of exposure to PA had no impact upon the results of four out of six neurobehavioral tests. In the sustained attention test, there was a significant increase in error rates that corresponded to the exposure levels. However, a concentration-dependent impairment of spatial working memory and an adverse increase in eye-blink frequency were restricted to the control group. Stressed participants had shorter simple reaction times and high eye-blink frequency irrespective of exposure suggesting enhanced alertness. Psychosocial stress increased complaints, ocular irritation and unspecific symptoms at the end of the 0.3ppm exposure to a level that was comparable with that in the control group during exposure to 0-20ppm. Results indicate that the adverse effects of a local irritant and psychosocial stress are non-additive.

  20. Dietary exposure of Hong Kong adults to fatty acid esters of 3-monochloropropane-1,2-diol.

    PubMed

    Chung, H Y; Chung, Stephen W C; Chan, B T P; Ho, Yuk Yin; Xiao, Ying

    2013-01-01

    A total of 290 individual food samples were collected in Hong Kong, China, for 3-monochloropropane-1,2-diol (3-MCPD) fatty acid esters analysis. Most samples were processed food and in ready-to-eat form. The results show that the levels of 3-MCPD fatty acid esters were high in biscuits, fats and oils, snacks and Chinese pastry with mean bound 3-MCPD levels of 440, 390, 270 and 270 μg kg⁻¹, respectively. The dietary exposures to bound 3-MCPD of average and high adult consumers were estimated to be 0.20 and 0.53 μg kg bw⁻¹ day⁻¹, respectively. The primary toxicological concern of 3-MCPD fatty acid esters is its potential to release 3-MCPD in vivo during digestion in the gastrointestinal tract. 3-MCPD would affect the kidney, the central nervous system and the male reproductive system of rats. Assuming that 100% of the 3-MCPD was released from 3-MCPD fatty acid esters by hydrolysis in the digestive system, the dietary exposures to 3-MCPD for average and high adult consumers were only 10% and 26% of the provisional maximum tolerable daily intake (PMTDI) of 3-MCPD established by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) (2 μg kg bw⁻¹ day⁻¹), respectively. The results suggest that both average and high adult consumers are unlikely to experience major toxicological effects of 3-MCPD.

  1. Abnormalities in the Metabolism of Fatty Acids and Triacylglycerols in the Liver of the Goto-Kakizaki Rat: A Model for Non-Obese Type 2 Diabetes.

    PubMed

    Karahashi, Minako; Hirata-Hanta, Yuko; Kawabata, Kohei; Tsutsumi, Daisuke; Kametani, Misaki; Takamatsu, Nanako; Sakamoto, Takeshi; Yamazaki, Tohru; Asano, Satoshi; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

    2016-08-01

    The Goto-Kakizaki (GK) rat is widely used as an animal model for spontaneous-onset type 2 diabetes without obesity; nevertheless, little information is available on the metabolism of fatty acids and triacylglycerols (TAG) in their livers. We investigated the mechanisms underlying the alterations in the metabolism of fatty acids and TAG in their livers, in comparison with Zucker (fa/fa) rats, which are obese and insulin resistant. Lipid profiles, the expression of genes for enzymes and proteins related to the metabolism of fatty acid and TAG, de novo synthesis of fatty acids and TAG in vivo, fatty acid synthase activity in vitro, fatty acid oxidation in liver slices, and very-low-density-lipoprotein (VLDL)-TAG secretion in vivo were estimated. Our results revealed that (1) the TAG accumulation was moderate, (2) the de novo fatty acid synthesis was increased by upregulation of fatty acid synthase in a post-transcriptional manner, (3) fatty acid oxidation was also augmented through the induction of carnitine palmitoyltransferase 1a, and (4) the secretion rate of VLDL-TAG remained unchanged in the livers of GK rats. These results suggest that, despite the fact that GK rats exhibit non-obese type 2 diabetes, the upregulation of de novo lipogenesis is largely compensated by the upregulation of fatty acid oxidation, resulting in only moderate increase in TAG accumulation in the liver. PMID:27372943

  2. Determination of Exposure to the Alternaria Mycotoxin Tenuazonic Acid and Its Isomer allo-Tenuazonic Acid in a German Population by Stable Isotope Dilution HPLC-MS(3).

    PubMed

    Hövelmann, Yannick; Hickert, Sebastian; Cramer, Benedikt; Humpf, Hans-Ulrich

    2016-08-31

    The content of the Alternaria toxin tenuazonic acid and its isomer allo-tenuazonic acid was quantitated in urine of a German cohort (n = 48) using a newly developed and successfully validated solid phase extraction based stable isotope dilution HPLC-MS(3) method. Tenuazonic acid was detected in all of the samples and quantifiable in 97.9% of these samples in a range of 0.16-44.4 ng/mL (average = 6.58 ng/mL) or 0.07-63.8 ng/mg creatinine (average = 8.13 ng/mg creatinine). allo-Tenuazonic acid was for the first time detected in human urine (95.8% of the samples positive) and quantitated in 68.8% of the samples in a range of 0.11-5.72 ng/mL (average = 1.25 ng/mL) or 0.08-10.1 ng/mg creatinine (average = 1.52 ng/mg creatinine), representing 3.40-25.0% of the sum of both isomers (average = 12.4%). Food-frequency questionnaires were used to document food consumption of study participants to correlate mycotoxin exposure to nutritional habits. Although no statistically significant correlation between consumption of a specific food and urinary excretion of tenuazonic acid could be determined, a trend regarding elevated intake of cereal products and higher excretion of tenuazonic acid was evident. On the basis of these results, a provisional mean daily intake (PDI) for both tenuazonic acid and allo-tenuazonic acid was calculated, being 0.183 and 0.025 μg/kg body weight, respectively. A combined mean PDI for both isomers amounts to 0.208 μg/kg body weight with the highest individual PDI for one of the participants (1.582 μg/kg body weight) slightly exceeding the threshold of toxicological concern assumed for tenuazonic acid by the European Food Safety Authority of 1.500 μg/kg body weight. This is the first study to investigate the tenuazonic acid content in human urine of a larger sample cohort enabling the calculation of PDIs for tenuazonic acid and allo-tenuazonic acid. PMID:27452834

  3. Vitamin C, uric acid, and glutathione gradients in murine stratum corneum and their susceptibility to ozone exposure.

    PubMed

    Weber, S U; Thiele, J J; Cross, C E; Packer, L

    1999-12-01

    The stratum corneum has been recognized as the main cutaneous oxidation target of atmospheric ozone (O3), a major part of photochemical smog. This study reports the presence and distribution of vitamin C, glutathione, and uric acid in murine stratum corneum, and evaluates their susceptibility to acute environmental exposure to O3. Based on tape stripping and a modified extraction method with high performance liquid chromatography electrochemical analysis, we detected vitamin C (208.0 +/- 82.5 pmol per 10 consecutive pooled tapes), glutathione (283.7 +/-96.3), and uric acid (286.4 +/-47.1) in murine stratum corneum as compared with only 16.5 +/- 1.4 pmol alpha-tocopherol. Vitamin C, glutathione (both p < 00.001), and urate (p < 0.01) were found to exhibit a gradient with the lowest concentrations in the outer layers and a steep increase in the deeper layers. To investigate the effect of O3 exposure on hydrophilic antioxidants, we exposed SKH-1 hairless mice to O3 concentrations of 0, 0.8, 1, and 10 p.p.m., and stratum corneum was analyzed before and after exposure. Whereas mock exposure with 0 p.p. m. for 2 h had no significant effect, O3 doses of 1 p.p.m. for 2 h and above showed depletion of all three antioxidants. Vitamin C was decreased to 80% +/- 15% of its pretreatment content (p < 0.05), GSH to 41% +/- 24% (p < 0.01), and uric acid to 44% +/- 28% (p < 0.01). This report demonstrates the previously unrecognized role of hydrophilic antioxidants in the stratum corneum and provides further evidence that O3 induces oxidative stress in this outer skin layer.

  4. Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

    PubMed Central

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Torres, Larissa Helena Lobo; Durão, Ana Carolina Cardoso Santos; Shimada, Ana Lucia Borges; Almeida, Francine Maria; Hebeda, Cristina Bichels; Lopes, Fernanda Degobbi Tenorio Quirino Santos; Dolhnikoff, Marisa; Martins, Milton Arruda; Silva, Luiz Fernando Ferraz; Farsky, Sandra Helena Poliselli; Saldiva, Paulo Hilário Nascimento; Ulrich, Cornelia M.; Owen, Robert W.; Marcourakis, Tania; Trevisan, Maria Teresa Salles; Mauad, Thais

    2013-01-01

    Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50 μg of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100 μL of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs. PMID:23533495

  5. Anacardic acids from cashew nuts ameliorate lung damage induced by exposure to diesel exhaust particles in mice.

    PubMed

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Torres, Larissa Helena Lobo; Durão, Ana Carolina Cardoso Santos; Shimada, Ana Lucia Borges; Almeida, Francine Maria; Hebeda, Cristina Bichels; Lopes, Fernanda Degobbi Tenorio Quirino Santos; Dolhnikoff, Marisa; Martins, Milton Arruda; Silva, Luiz Fernando Ferraz; Farsky, Sandra Helena Poliselli; Saldiva, Paulo Hilário Nascimento; Ulrich, Cornelia M; Owen, Robert W; Marcourakis, Tania; Trevisan, Maria Teresa Salles; Mauad, Thais

    2013-01-01

    Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50  μ g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100  μ L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.

  6. Free fatty acid receptor 1 (FFAR1/GPR40) signaling affects insulin secretion by enhancing mitochondrial respiration during palmitate exposure.

    PubMed

    Kristinsson, Hjalti; Bergsten, Peter; Sargsyan, Ernest

    2015-12-01

    Fatty acids affect insulin secretion via metabolism and FFAR1-mediated signaling. Recent reports indicate that these two pathways act synergistically. Still it remains unclear how they interrelate. Taking into account the key role of mitochondria in insulin secretion, we attempted to dissect the metabolic and FFAR1-mediated effects of fatty acids on mitochondrial function. One-hour culture of MIN6 cells with palmitate significantly enhanced mitochondrial respiration. Antagonism or silencing of FFAR1 prevented the palmitate-induced rise in respiration. On the other hand, in the absence of extracellular palmitate FFAR1 agonists caused a modest increase in respiration. Using an agonist of the M3 muscarinic acetylcholine receptor and PKC inhibitor we found that in the presence of the fatty acid mitochondrial respiration is regulated via Gαq protein-coupled receptor signaling. The increase in respiration in palmitate-treated cells was largely due to increased glucose utilization and oxidation. However, glucose utilization was not dependent on FFAR1 signaling. Collectively, these results indicate that mitochondrial respiration in palmitate-treated cells is enhanced via combined action of intracellular metabolism of the fatty acid and the Gαq-coupled FFAR1 signaling. Long-term palmitate exposure reduced ATP-coupling efficiency of mitochondria and deteriorated insulin secretion. The presence of the FFAR1 antagonist during culture did not improve ATP-coupling efficiency, however, it resulted in enhanced mitochondrial respiration and improved insulin secretion after culture. Taken together, our study demonstrates that during palmitate exposure, integrated actions of fatty acid metabolism and fatty acid-induced FFAR1 signaling on mitochondrial respiration underlie the synergistic action of the two pathways on insulin secretion.

  7. Gene Expression Profiles in Zebrafish Brain after Acute Exposure to Domoic Acid at Symptomatic and Asymptomatic Doses

    PubMed Central

    Lefebvre, Kathi A.; Tilton, Susan C.; Bammler, Theo K.; Beyer, Richard P.; Srinouanprachan, Sengkeo; Stapleton, Patricia L.; Farin, Federico M.; Gallagher, Evan P.

    2009-01-01

    Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of ionotropic glutamate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) injection of DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 μg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 μg DA/g) within 5–20 min of IC injection. All zebrafish receiving low-dose DA (0.47 μg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p ≤ 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including the zebrafish homolog of human NDRG4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. In general, DA-modulated gene expression was consistent with other model species thereby validating zebrafish as an appropriate vertebrate model to study mechanisms of DA neurotoxicity. These data provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. PMID:18936300

  8. Immunomodulatory effects upon in vitro exposure of California sea lion and southern sea otter peripheral blood leukocytes to domoic acid.

    PubMed

    Levin, Milton; Joshi, Dhanashree; Draghi, Andrew; Gulland, Frances M; Jessup, David; De Guise, Sylvain

    2010-04-01

    During red tide bloom events, the marine diatom Pseudo-nitzschia produces the toxin domoic acid (DA), which has been associated with stranding and mortality events involving California sea lions (Zalophus californianus) and southern sea otters (Enhydra lutris). In addition to these well-documented DA-induced neurotoxic events, there is increasing concern that DA may exert chronic effects, such as immunomodulation, which may potentially increase an individual's susceptibility to a number of opportunistic infections following nonlethal exposure. We investigated the effects of DA on innate (phagocytosis and respiratory burst) and adaptive (mitogen-induced lymphocyte proliferation) immune functions with the use of peripheral blood leukocytes collected from healthy California sea lions and southern sea otters upon in vitro exposure to 0 (unexposed control), 0.0001, 0.001, 0.01, 0.1, 1.0, 10, and 100 microM DA. Domoic acid did not significantly modulate phagocytosis or respiratory burst in either species. For California sea lions, DA significantly increased ConA-induced T-lymphocyte proliferation upon exposure to DA concentrations ranging from 0.0001 to 10 microM, resulting in a nonlinear dose-response curve. There was no effect on lymphocyte proliferation at the highest concentration of DA tested. No effects on lymphocyte proliferation were observed in southern sea otters. Importantly, the in vitro DA concentrations affecting T-cell proliferation were within or below the range of DA in serum measured in free-ranging California sea lions following natural exposure, suggesting a risk for immunomodulation in free-ranging animals. Understanding the risk for immunomodulation upon DA exposure will contribute in the health assessment and management of California sea lions and southern sea otters, as well as guide veterinarians and wildlife rehabilitators in caring for and treating afflicted animals. PMID:20688647

  9. Use of urinary trichloroacetic acid as an exposure biomarker of disinfection by-products in cancer studies.

    PubMed

    Salas, Lucas A; Gracia-Lavedan, Esther; Goñi, Fernando; Moreno, Victor; Villanueva, Cristina M

    2014-11-01

    Urinary trichloroacetic acid (TCAA) has been proposed as a valid exposure biomarker for ingested disinfection by-products (DBP) for reproductive studies. However, it has never been used in epidemiologic studies on cancer. We investigate the performance of urinary TCAA as a biomarker of DBP exposure in the framework of an epidemiologic study on cancer. We conducted home visits to collect tap water, first morning void urine, and a 48h fluid intake diary among 120 controls from a case-control study of colorectal cancer in Barcelona, Spain. We measured urine TCAA and creatinine, and 9 haloacetic acids and 4 trihalomethanes (THM) in tap water. Lifetime THM exposure was estimated based on residential history since age 18 plus routine monitoring data. Robust linear regressions were used to estimate mean change in urinary TCAA adjusted by covariates. Among the studied group, mean age was 74 years (range 63-85) and 41 (34%) were females. Mean total tap water consumption was 2.2l/48h (standard error, 0.1l/48h). Geometric mean urine TCAA excretion rate was 17.3pmol/min [95%CI: 14.0-21.3], which increased 2% for a 10% increase in TCAA ingestion and decreased with total tap water consumption (-17%/l), water intake outside home (-32%), plasmatic volume (-64%/l), in smokers (-79%), and in users of non-steroidal anti-inflammatory drugs (-50%). Urinary TCAA levels were not associated with lifetime THM exposure. In conclusion, our findings support that urine TCAA is not a valid biomarker in case-control studies of adult cancer given that advanced age, comorbidites and medication use are prevalent and are determinants of urine TCAA levels, apart from ingested TCAA levels. In addition, low TCAA concentrations in drinking water limit the validity of urine TCAA as an exposure biomarker. PMID:25462676

  10. Prevalence and risk factors of non-carious cervical lesions related to occupational exposure to acid mists.

    PubMed

    Bomfim, Rafael Aiello; Crosato, Edgard; Mazzilli, Luiz Eugênio Nigro; Frias, Antonio Carlos

    2015-01-01

    This study evaluates the prevalence and risk factors of non-carious cervical lesions (NCCLs) in a Brazilian population of workers exposed and non-exposed to acid mists and chemical products. One hundred workers (46 exposed and 54 non-exposed) were evaluated in a Centro de Referência em Saúde do Trabalhador - CEREST (Worker's Health Reference Center). The workers responded to questionnaires regarding their personal information and about alcohol consumption and tobacco use. A clinical examination was conducted to evaluate the presence of NCCLs, according to WHO parameters. Statistical analyses were performed by unconditional logistic regression and multiple linear regression, with the critical level of p < 0.05. NCCLs were significantly associated with age groups (18-34, 35-44, 45-68 years). The unconditional logistic regression showed that the presence of NCCLs was better explained by age group (OR = 4.04; CI 95% 1.77-9.22) and occupational exposure to acid mists and chemical products (OR = 3.84; CI 95% 1.10-13.49), whereas the linear multiple regression revealed that NCCLs were better explained by years of smoking (p = 0.01) and age group (p = 0.04). The prevalence of NCCLs in the study population was particularly high (76.84%), and the risk factors for NCCLs were age, exposure to acid mists and smoking habit. Controlling risk factors through preventive and educative measures, allied to the use of personal protective equipment to prevent the occupational exposure to acid mists, may contribute to minimizing the prevalence of NCCLs. PMID:26154372

  11. Prevalence and risk factors of non-carious cervical lesions related to occupational exposure to acid mists.

    PubMed

    Bomfim, Rafael Aiello; Crosato, Edgard; Mazzilli, Luiz Eugênio Nigro; Frias, Antonio Carlos

    2015-01-01

    This study evaluates the prevalence and risk factors of non-carious cervical lesions (NCCLs) in a Brazilian population of workers exposed and non-exposed to acid mists and chemical products. One hundred workers (46 exposed and 54 non-exposed) were evaluated in a Centro de Referência em Saúde do Trabalhador - CEREST (Worker's Health Reference Center). The workers responded to questionnaires regarding their personal information and about alcohol consumption and tobacco use. A clinical examination was conducted to evaluate the presence of NCCLs, according to WHO parameters. Statistical analyses were performed by unconditional logistic regression and multiple linear regression, with the critical level of p < 0.05. NCCLs were significantly associated with age groups (18-34, 35-44, 45-68 years). The unconditional logistic regression showed that the presence of NCCLs was better explained by age group (OR = 4.04; CI 95% 1.77-9.22) and occupational exposure to acid mists and chemical products (OR = 3.84; CI 95% 1.10-13.49), whereas the linear multiple regression revealed that NCCLs were better explained by years of smoking (p = 0.01) and age group (p = 0.04). The prevalence of NCCLs in the study population was particularly high (76.84%), and the risk factors for NCCLs were age, exposure to acid mists and smoking habit. Controlling risk factors through preventive and educative measures, allied to the use of personal protective equipment to prevent the occupational exposure to acid mists, may contribute to minimizing the prevalence of NCCLs.

  12. Problems in the estimation of human exposure to components of acid precipitation precursors.

    PubMed

    Ferris, B G; Spengler, J D

    1985-11-01

    Problems associated with estimation of human exposure to ambient air pollutants are discussed. Ideally, we would prefer to have some indication of actual dose. For most pollutants this is not presently feasible. Specific problems discussed are adequacy of outdoor monitors; the need to correct for exposures and time spent indoors; the need to have particle size distributions described and the chemistry of the particles presented. These indicate the need to develop lightweight accurate and reliable personal monitors.

  13. Prenatal Exposure to Perfluorocarboxylic Acids (PFCAs) and Fetal and Postnatal Growth in the Taiwan Maternal and Infant Cohort Study

    PubMed Central

    Wang, Yan; Adgent, Margaret; Su, Pen-Hua; Chen, Hsiao-Yen; Chen, Pau-Chung; Hsiung, Chao A.; Wang, Shu-Li

    2016-01-01

    Background: Perfluorocarboxylic acids (PFCAs) are environmentally and biologically persistent synthetic chemicals. PFCAs include perfluorooctanoic acid (PFOA; C8) and long-chain PFCAs (C9–C20). Studies examining long-chain PFCAs and fetal and postnatal growth are limited. Objectives: We investigated the associations of prenatal exposure to long-chain PFCAs with fetal and postnatal growth. Methods: For 223 Taiwanese mothers and their term infants, we measured PFOA and four long-chain PFCAs (ng/mL) in third-trimester maternal serum; infant weight (kg), length and head circumference (cm) at birth; and childhood weight and height at approximately 2, 5, 8, and 11 years of age. For each sex, we used multivariable linear regression to examine associations between ln-transformed prenatal PFCAs and continuous infant measures, and logistic regression to examine small for gestational age (SGA). Linear mixed models were applied to prenatal PFCAs and childhood weight and height z-scores. Results: In girls, prenatal perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) concentrations were inversely associated with birth weight [e.g., βbirth weight (kg) = –0.06, 95% CI: –0.11, –0.01 per 1 ln-unit PFUnDA increase]; prenatal PFDeA and PFUnDA were associated with elevated odds of SGA; and PFDeA, PFUnDA, and PFDoDA were associated with lower average childhood height z-score. In boys, prenatal PFNA, and PFDoDA were associated with reductions in height at certain ages in childhood, but not with size at birth. Conclusions: Prenatal exposure to long-chain PFCAs may interfere with fetal and childhood growth in girls, and childhood growth in boys. Citation: Wang Y, Adgent M, Su PH, Chen HY, Chen PC, Hsiung CA, Wang SL. 2016. Prenatal exposure to perfluorocarboxylic acids (PFCAs) and fetal and postnatal growth in the Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 124:1794–1800;

  14. Evaluation of exposure to organophosphate, carbamate, phenoxy acid, and chlorophenol pesticides in pregnant women from 10 Caribbean countries.

    PubMed

    Forde, Martin S; Robertson, Lyndon; Laouan Sidi, Elhadji A; Côté, Suzanne; Gaudreau, Eric; Drescher, Olivia; Ayotte, Pierre

    2015-09-01

    Pesticides are commonly used in tropical regions such as the Caribbean for both household and agricultural purposes. Of particular concern is exposure during pregnancy, as these compounds can cross the placental barrier and interfere with fetal development. The objective of this study was to evaluate exposure of pregnant women residing in 10 Caribbean countries to the following commonly used classes of pesticides in the Caribbean: organophosphates (OPs), carbamates, phenoxy acids, and chlorophenols. Out of 438 urine samples collected, 15 samples were randomly selected from each Caribbean country giving a total of 150 samples. Samples were analyzed for the following metabolites: six OP dialkylphosphate metabolites [dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP)]; two carbamate metabolites [2-isopropoxyphenol (2-IPP) and carbofuranphenol]; one phenoxy acid 2,4-dichlorophenoxyacetic acid (2,4-D); and five chlorophenols [2,4-dichlorophenol (DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (TCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP)]. OP metabolites were consistently detected in ≥60% of the samples from Antigua and Barbuda, Bermuda, and Jamaica. Of the carbamate metabolites, 2-IPP was detected in seven of the 10 Caribbean countries with a detection frequency around 30%, whereas carbofuranphenol was detected in only one sample. The detection frequency for the phenoxy acid 2,4-D ranged from 20% in Grenada to a maximum of 67% in Belize. Evidence of exposure to chlorophenol pesticides was also established with 2,4-DCP by geometric means ranging from 0.52 μg L(-1) in St Lucia to a maximum of 1.68 μg L(-1) in Bermuda. Several extreme concentrations of 2,5-DCP were detected in four Caribbean countries-Belize (1100 μg L(-1)), Bermuda (870 μg L(-1)), Jamaica (1300 μg L(-1)), and St Kitts and Nevis (1400 μg L(-1

  15. Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila.

    PubMed

    Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L

    2014-11-11

    Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD.

  16. Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

    PubMed Central

    Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

    2014-01-01

    Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

  17. Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila.

    PubMed

    Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L

    2014-01-01

    Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

  18. Fatty Acids Composition and Biofilm Production of Attenuated Salmonella typhimurium dam and seqA Mutants After Exposure to UV-C.

    PubMed

    Abdelwaheb, Chatti; Lobna, Maalej; Bouchra, BelHadj Abdallah; Selma, Kloula; Ahmed, Landoulsi

    2015-10-01

    The goal of this work was the investigation of correlation between some peculiarities of membrane fatty acids composition, biofilm formation, and motility of dam and/or seqA mutants in Salmonella typhimurium bacterial cells and UV-C radiations. The exposure changed the fatty acids composition of dam and seqA/dam strains. Significant increase of unsaturated fatty acids was observed. Swarming and swimming were enhanced only in dam mutant and biofilm formation increased significantly in all tested strains after UV-C exposure. These results suggest that increased sensitivity toward UV-C rays in dam strains might be due to fatty acid alteration.

  19. Omega-3 Fatty Acid Consumption and Prostate Cancer: A Review of Exposure Measures and Results of Epidemiological Studies.

    PubMed

    Dinwiddie, Michael T; Terry, Paul D; Whelan, Jay; Patzer, Rachel E

    2016-07-01

    Animal studies have shown that dietary omega-3 polyunsaturated fatty acids (n-3) may play a role in the development of prostate cancer, but the results of epidemiologic studies have been equivocal. Associations in humans may vary depending on study design, measurement methodology of fatty acid intake, intake ranges, and stage of cancer development. To address this, we identified 36 published studies through PubMed (Medline) from 1993 through 2013 on long-chain n-3s and prostate cancer. Exposure measurements included dietary assessment and biomarker levels. Associations for total, early, and late stage prostate cancer were examined by subgroup of study design and exposure measure type and by using forest plots to illustrate the relative strength of associations within each subgroup. We also tested for potential threshold effects by considering studies that included measurement cut-points that met intake levels recommended by the American Heart Association. We found no consistent evidence supporting a role of n-3s in either the causation or prevention of prostate cancer at any stage or grade. Results did not vary appreciably by study design, exposure measurement, intake level, or stage of cancer development.

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

    PubMed

    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

  1. Experimental model of lead nephropathy. II. Effect of removal from lead exposure and chelation treatment with dimercaptosuccinic acid (DMSA).

    PubMed

    Khalil-Manesh, F; Gonick, H C; Cohen, A; Bergamaschi, E; Mutti, A

    1992-06-01

    Male Sprague-Dawley rats were exposed to high-dose (0.5%) lead acetate for periods ranging from 1 to 9 months; then lead exposure was discontinued, and animals were sacrificed after 12 months. Controls were pair-fed. Two additional groups of low-dose (0.01%) and high-dose (0.5%) rats were exposed to lead for 6 months, then lead was discontinued and the rats were treated with three 5-day courses of 0.5% DMSA (dimercaptosuccinic acid) over the next 6 months. Controls were rats exposed to lead for 6 months, then removed from exposure for 6 months without receiving DMSA. Low-dose lead-treated rats showed no significant pathological changes with or without DMSA treatment, but exhibited a significant increase in GFR after DMSA. High-dose lead-treated animals showed no functional or pathological changes when lead exposure was discontinued after 1 month. However, when duration of exposure was 6 or 9 months, GFR was decreased and serum creatinine and urea nitrogen were increased as compared to controls. Tubulointerstitial disease was severe. Administration of DMSA resulted in an improvement in GFR and a decrease in albuminuria, together with a reduction in size and number of nuclear inclusion bodies in proximal tubules. However, tubulointerstitial scarring was only minimally reduced. It may be concluded that, except for brief initial exposure, discontinuation of high-dose lead exposure fails to reverse lead-induced renal damage. Treatment with the chelator, DMSA, improves renal function but has less effect on pathological alterations. As GFR improved after DMSA treatment in both low-dose and high-dose lead-treated rats, irrespective of the degree of pathological alterations, it may be concluded that the DMSA effect is most likely mediated by hemodynamic changes.

  2. Benzene exposure, assessed by urinary trans,trans-muconic acid, in urban children with elevated blood lead levels.

    PubMed Central

    Weaver, V M; Davoli, C T; Heller, P J; Fitzwilliam, A; Peters, H L; Sunyer, J; Murphy, S E; Goldstein, G W; Groopman, J D

    1996-01-01

    A pilot study was performed to evaluate the feasibility of using trans,trans-muconic acid (MA) as a biomarker of environmental benzene exposure. A secondary aim was to provide data on the extent of exposure to selected toxicants in a unique population consisting of inner-city children who were already overexposed to one urban hazard, lead. Potential sources of benzene were assessed by a questionnaire. Exposure biomarkers included urinary MA and cotinine and blood lead. Mean MA was 176.6 +/- 341.7 ng/mg creatinine in the 79 children who participated. A wide range of values was found with as many as 10.1%, depending on the comparison study, above the highest levels reported in adults not exposed by occupation. Mean MA was increased in children evaluated in the afternoon compared to morning, those at or above the median for time spent playing near the street, and those studied in the first half of the investigation. MA levels were not associated with blood lead or, consistently, with either questionnaire environmental tobacco smoke (ETS) data or cotinine. As expected, the mean blood lead level was elevated (23.6 micrograms/dl). Mean cotinine was also increased at 79.2 ng/mg creatinine. We conclude that the use of MA as a biomarker for environmental benzene exposure is feasible since it was detectable in 72% of subjects with a wide range of values present. In future studies, correlation of MA with personal air sampling in environmental exposure will be essential to fully interpret the significance of these findings. In addition, these inner-city children comprise a high risk group for exposure to environmental toxicants including ETS, lead, and probably benzene, based on questionnaire sources and its presence in ETS. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 4. Figure 5. PMID:8919771

  3. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    SciTech Connect

    Strecker, Ruben; Weigt, Stefan; Braunbeck, Thomas

    2013-04-15

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head.

  4. The Effects of Lead Exposure on Serum Uric Acid and Hyperuricemia in Chinese Adults: A Cross-Sectional Study.

    PubMed

    Dai, Haijiang; Huang, Zhijun; Deng, Qihong; Li, Ying; Xiao, Ting; Ning, Xingping; Lu, Yao; Yuan, Hong

    2015-08-18

    The aim of this study was to assess the correlation between blood lead levels and both serum uric acid and hyperuricemia in adult residents living within an area of China with lead pollution. We conducted a cross-sectional analysis of 2120 subjects (1180 of whom were male) between the ages of 20 and 75 years who had undergone health examinations at the Centers for Disease Control and Prevention (CDC) in a lead-polluted area of China between January 2013 and August 2014. Blood lead was positively correlated with serum uric acid in both males (r = 0.095, p = 0.001) and females (r = 0.134, p < 0.001). Multivariate linear regression analysis demonstrated that for males, blood lead (p = 0.006), age (p = 0.001), current smoking (p = 0.012), education (p = 0.001), triglycerides (TG) (p < 0.001), and serum creatinine (p < 0.001) were independently associated with serum uric acid. For females, blood lead (p < 0.001), body mass index (BMI) (p = 0.009), and TG (p < 0.001) were independently associated with serum uric acid. After multiple adjustments, blood lead was significantly associated with a higher prevalence of hyperuricemia when female subjects were categorized into quartiles (for the highest quartile vs. the lowest quartile, odds ratio (OR) = 2.190; 95% confidence interval (CI): 1.106-4.338; p = 0.025); however, no such association was observed for male subjects. Continuous lead exposure has an independent impact on serum uric acid for both males and females, although this impact is more pronounced for females than for males. Lead exposure is significantly associated with hyperuricemia for females but not for males.

  5. Effects of short-term acid and aluminum exposure on the parr-smolt transformation in Atlantic salmon (Salmo salar): Disruption of seawater tolerance and endocrine status

    USGS Publications Warehouse

    Monette, M.Y.; Bjornsson, Bjorn Thrandur; McCormick, S.D.

    2008-01-01

    Episodic acidification resulting in increased acidity and inorganic aluminum (Ali) is known to interfere with the parr-smolt transformation of Atlantic salmon (Salmo salar), and has been implicated as a possible cause of population decline. To determine the extent and mechanism(s) by which short-term acid/Al exposure compromises smolt development, Atlantic salmon smolts were exposed to either control (pH 6.7-6.9) or acid/Al (pH 5.4-6.3, 28-64 ??g l-1 Ali) conditions for 2 and 5 days, and impacts on freshwater (FW) ion regulation, seawater (SW) tolerance, plasma hormone levels and stress response were examined. Gill Al concentrations were elevated in all smolts exposed to acid/Al relative to controls confirming exposure to increased Ali. There was no effect of acid/Al on plasma ion concentrations in FW however, smolts exposed to acid/Al followed by a 24 h SW challenge exhibited greater plasma Cl- levels than controls, indicating reduced SW tolerance. Loss of SW tolerance was accompanied by reductions in gill Na+,K+-ATPase (NKA) activity and Na+,K+,2Cl- (NKCC) cotransporter protein abundance. Acid/Al exposure resulted in decreased plasma insulin-like growth factor (IGF-I) and 3,3???,5???-triiodo-l-thyronine (T3) levels, whereas no effect of treatment was seen on plasma cortisol, growth hormone (GH), or thyroxine (T4) levels. Acid/Al exposure resulted in increased hematocrit and plasma glucose levels in FW, but both returned to control levels after 24 h in SW. The results indicate that smolt development and SW tolerance are compromised by short-term exposure to acid/Al in the absence of detectable impacts on FW ion regulation. Loss of SW tolerance during short-term acid/Al exposure likely results from reductions in gill NKA and NKCC, possibly mediated by decreases in plasma IGF-I and T3. ?? 2008 Elsevier Inc.

  6. Perfluoroalkyl acids (PFAAs) in indoor and outdoor dusts around a mega fluorochemical industrial park in China: Implications for human exposure.

    PubMed

    Su, Hongqiao; Lu, Yonglong; Wang, Pei; Shi, Yajuan; Li, Qifeng; Zhou, Yunqiao; Johnson, Andrew C

    2016-09-01

    The manufacture of fluorochemicals can lead to high levels of perfluoroalkyl acids (PFAAs) contaminating the surrounding environment and consequently elevated exposure to the local residents. In this study, measurements of PFAAs associated with indoor and outdoor dusts around a mega fluorochemical industrial park (FIP) were made. Perfluorooctanoic acid (PFOA) and short-chain perfluoroalkyl carboxylic acids (C4-C7 PFCAs) were the predominant forms in all samples. The signature of the PFAAs in dusts in the local area matched that found within the FIP complex. The contamination plume in the local area could be linked to the prevailing wind direction starting from the FIP. The dust concentrations decreased exponentially with distance from the FIP (noticeably in the first 5km). PFAAs contamination could be detected at the furthest location, 20km away from the FIP. The concentrations of PFAAs were higher in indoor dust (73-13,500ng/g, median: 979ng/g) than those in outdoor dust (5-9495ng/g, median: 62ng/g) at every location. The highest estimated daily intake of PFOA via dust ingestion (26.0ng/kg·bw/day) was for toddlers (2-5years) living 2km away from the FIP, which is posing human health risk, though exposure remains within the provisional tolerable daily intake values. PMID:27393120

  7. Positive Adaptive State: Microarray Evaluation of Gene Expression in Salmonella Enterica Typhimurium Upon Exposure to Sub-Therapeutic Levels of Nalidixic Acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to evaluate changes in gene expression that occur upon exposure to sub-therapeutic levels of a quinolones antibioitic, Salmonella enterica Typhimurium ATCC# 14028 was exposed to 1.6 ug/L of nalidixic acid (NA). Microarray analysis of the expression profile during exposure to NA was compared...

  8. GENE EXPRESSION PROFILING OF MOUSE SKIN AND PAPILLOMAS FOLLOWING CHRONIC EXPOSURE TO MONOMETHYLARSONOUS ACID IN K6/ODC TRANSGENIC MICE

    EPA Science Inventory

    Methylarsonous acid [MMA(III)], a common metabolite of inorganic arsenic metabolism, increases tumor frequency in the skin of K6/ODC transgenic mice following a chronic exposure. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcin...

  9. Free amino acid pool of a sea anemone: exposure and recovery after an oil spill. [Sea Anemones

    SciTech Connect

    Kasschau, M.R.; Howard, C.L.

    1984-07-01

    A number of laboratory studies on marine invertebrates have shown changes in free amino acid (FAA) pools in response to various pollutants. During a nineteen-month field study to determine the effects of natural environmental parameters on the FAA pools to the Gulf Coast sea anemone, Bunodosoma cavernata, an oil tanker collision occurred about 8 miles off Galveston Island. The initial spill from the tanker Burma Agate occurred on November 1, 1979 with large leakages continuing for several weeks. There was no visible sign of oil on the first collection date 13 days after the spill, but 11 days later the anemones were covered with an oil sheen. As a result of this natural exposure to the oil, the authors decided to monitor the sea anemones for changes in the FAA pool during the oil exposure and recovery period.

  10. Acid-based balance and blood gas changes in the fresh water field crab, Barytelphusa guerini, on exposure to organic and inorganic lead

    SciTech Connect

    Tulasi, S.J.; Rao, J.V.R.

    1988-02-01

    The acid-base status of crustacean haemolymph depends on various environmental and physiological factors. Acid base status of the haemolymph is known to be influenced by temperature, salinity, strenuous activity and moulting. The studies on the acid-base regulation of the fresh water crabs are meager. The acid-base changes in fishes during environmental stress conditions like acid stress and zinc toxicity had been reported. But the effect of environmental pollutants like the heavy metals on the acid-base regulation of the fresh water crabs have not been previously reported. The haemolymph of the fresh water crab was found to accumulate high amounts of lead on exposure to organic and inorganic lead. Hence the present investigation has been undertaken to study the haemolymph acid-base status on exposure to subtoxic levels of organic and inorganic lead.

  11. Validation of trichloroacetic acid exposure via drinking water during pregnancy using a urinary TCAA biomarker.

    PubMed

    Smith, Rachel B; Nieuwenhuijsen, Mark J; Wright, John; Raynor, Pauline; Cocker, John; Jones, Kate; Kappaostopoulou-Karadanelli, Maria; Toledano, Mireille B

    2013-10-01

    Disinfection by-product (DBP) exposure during pregnancy may be related to reduced fetal growth, but the evidence is inconclusive and improved DBP exposure assessment is required. The authors conducted a nested exposure study on a subset (n=39) of pregnant women in the Born in Bradford cohort to assess validity of TCAA exposure assessment based on tap water sampling and self-reported water-use; water-use questionnaire validity; and use of a one-time urinary TCAA biomarker. TCAA levels in urine and home tap water supply were quantified, and water use was measured via a questionnaire and 7-day diary, at 28 weeks gestation. Diary and urine measures were repeated later in pregnancy (n=14). TCAA level in home tap water supply was not correlated with urinary TCAA (0.18, P=0.29). Cold unfiltered tap water intake at home measured by questionnaire was correlated with urinary TCAA (0.44, P=0.007), but correlation was stronger still for cold unfiltered tap water intake reported over the 3 days prior to urine sampling (0.60, P<0.001). For unemployed women TCAA ingestion at home, derived from tap water sampling and self-reported water-use, correlated strongly with urinary TCAA (0.78, P<0.001), but for employed women the correlation was weak (0.31, P=0.20). Results suggest individual tap water intake is most influential in determining TCAA exposure variability in this cohort, and that TCAA ingestion at home is a valid proxy for TCAA exposure for unemployed women but less satisfactory for employed women.

  12. Laser confers less embryo exposure than acid tyrode for embryo biopsy in preimplantation genetic diagnosis cycles: a randomized study

    PubMed Central

    2011-01-01

    We compared two methods of zona pellucida drilling. 213 embryos were biopsied with acid Tyrode. Each biopsy took 3 minutes and the entire procedure ~29 minutes. 5% of blastomeres lysed, 49% of embryos became blastocyst and 36% of patients became pregnant. 229 embryos were biopsied with laser. Each biopsy took 30 seconds and the entire procedure ~7 minutes. 2.5% of blastomeres lysed, 50.6% of embryos became blastocyst and 47% of patients became pregnant. We can conclude that laser can be used for embryo biopsy. Reduction of embryo exposure and of removed blastomeres is associated with increased blastocysts available for transfer and a better clinical outcome. PMID:21527004

  13. The interaction between humic acid and naphthalene after exposure to visible and UV light

    NASA Astrophysics Data System (ADS)

    Nechaev, L. V.; Tchaikovskaya, O. N.

    2015-12-01

    Dissolved organic matter plays an important role in pollution migration from human waste to aquatic environments. In this study, the effect of humic acid (HA) on the photo-chemical transformation of naphthalene by irradiation model solar and UV light was reported using fluorescence quenching titrations. It was calculated the interactions between naphthalene and humic acids. It is found that the molecular complex of humic acid and naphthalene is more stable to UV irradiation, compared with the model solar radiation. The application of molecular fluorescence spectrometry is a useful sensitive tool evaluate intermolecular HA and naphthalene interactions.

  14. Urinary Tetrabromobenzoic Acid (TBBA) as a Biomarker of Exposure to the Flame Retardant Mixture Firemaster® 550

    PubMed Central

    Hoffman, Kate; Fang, Mingliang; Horman, Brian; Patisaul, Heather B.; Garantziotis, Stavros; Birnbaum, Linda S.

    2014-01-01

    Background: Firemaster® 550 (FM550) is commonly added to residential furniture to reduce its flammability. Recent toxicological evidence suggests that FM550 may be endocrine disrupting and obesogenic. Objectives: Our objectives were to develop methods to assess exposure to FM550 in human populations and to identify potential routes of exposure. Methods: Using mass spectrometry methods, we developed a method to measure 2,3,4,5-tetrabromobenzoic acid (TBBA), a urinary metabolite of the major brominated FM550 component 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB). The method was applied to a cohort of adult volunteers (n = 64). Participants completed questionnaires, provided urine and handwipe samples, and collected dust samples from their homes. We measured TBB and the other major brominated FM550 component, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), in paired dust and handwipe samples. Results: TBBA was detected in 72.4% of urine samples. Although TBBA is a rapidly formed metabolite, analyses indicated moderate temporal reliability (interclass correlation coefficient = 0.56; 95% confidence interval: 0.46, 0.66). TBB and TBPH were detected frequently in dust samples [geometric mean (GM) = 315.1 and 364.7 ng/g, respectively] and in handwipes (GM = 31.4 and 23.4 ng, respectively). Levels of TBB and TBPH in dust were positively correlated with levels in handwipes. In addition, levels of TBB in handwipes were positively correlated with urinary TBBA. Results suggest frequent hand washing may reduce the mass of TBB on participants’ hands and reduce urinary TBBA levels. Conclusions: Cumulatively, our data indicate that exposures to FM550 are widespread and that the home environment may be an important source of exposure. Urinary TBBA provides a potentially useful biomarker of FM550 exposure for epidemiologic studies. Citation: Hoffman K, Fang M, Horman B, Patisaul HB, Garantziotis S, Birnbaum LS, Stapleton HM. 2014. Urinary tetrabromobenzoic acid (TBBA) as a

  15. Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption

    PubMed Central

    Mahaffey, Kathryn R; Sunderland, Elsie M; Chan, Hing Man; Choi, Anna L; Grandjean, Philippe; Mariën, Koenraad; Oken, Emily; Sakamoto, Mineshi; Schoeny, Rita; Weihe, Pál; Yan, Chong-Huai; Yasutake, Akira

    2011-01-01

    Fish and shellfish are widely available foods that provide important nutrients, particularly n-3 polyunsaturated fatty acids (n-3 PUFAs), to many populations globally. These nutrients, especially docosahexaenoic acid, confer benefits to brain and visual system development in infants and reduce risks of certain forms of heart disease in adults. However, fish and shellfish can also be a major source of methylmercury (MeHg), a known neurotoxicant that is particularly harmful to fetal brain development. This review documents the latest knowledge on the risks and benefits of seafood consumption for perinatal development of infants. It is possible to choose fish species that are both high in n-3 PUFAs and low in MeHg. A framework for providing dietary advice for women of childbearing age on how to maximize the dietary intake of n-3 PUFAs while minimizing MeHg exposures is suggested. PMID:21884130

  16. Retrospective Exposure Estimation and Predicted versus Observed Serum Perfluorooctanoic Acid Concentrations for Participants in the C8 Health Project

    PubMed Central

    Vieira, Verónica M.; Ryan, P. Barry; Steenland, Kyle; Bartell, Scott M.

    2011-01-01

    Background: People living or working in eastern Ohio and western West Virginia have been exposed to perfluorooctanoic acid (PFOA) released by DuPont Washington Works facilities. Objectives: Our objective was to estimate historical PFOA exposures and serum concentrations experienced by 45,276 non-occupationally exposed participants in the C8 Health Project who consented to share their residential histories and a 2005–2006 serum PFOA measurement. Methods: We estimated annual PFOA exposure rates for each individual based on predicted calibrated water concentrations and predicted air concentrations using an environmental fate and transport model, individual residential histories, and maps of public water supply networks. We coupled individual exposure estimates with a one-compartment absorption, distribution, metabolism, and excretion (ADME) model to estimate time-dependent serum concentrations. Results: For all participants (n = 45,276), predicted and observed median serum concentrations in 2005–2006 are 14.2 and 24.3 ppb, respectively [Spearman’s rank correlation coefficient (rs) = 0.67]. For participants who provided daily public well water consumption rate and who had the same residence and workplace in one of six municipal water districts for 5 years before the serum sample (n = 1,074), predicted and observed median serum concentrations in 2005–2006 are 32.2 and 40.0 ppb, respectively (rs = 0.82). Conclusions: Serum PFOA concentrations predicted by linked exposure and ADME models correlated well with observed 2005–2006 human serum concentrations for C8 Health Project participants. These individualized retrospective exposure and serum estimates are being used in a variety of epidemiologic studies being conducted in this region. PMID:21813367

  17. Calculation of chemical elimination half-life from blood with an ongoing exposure source: the example of perfluorooctanoic acid (PFOA).

    PubMed

    Russell, Mark H; Waterland, Robert L; Wong, Fiona

    2015-06-01

    Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008. PMID:25149361

  18. Oleic acid exposure of cultured endothelial cells alters lipid mediator production

    EPA Science Inventory

    Diesel, biodiesel, and other combustion sources contain free fatty acid (FFA) components capable of entering the body through particulate inhalation. FFA can also be endogenously released into circulation in response to stress. When in circulation, bioactive FFA may interact with...

  19. DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANOIC ACID (PFOA) AFTER CROSS FOSTER AND RESTRICTED GESTATIONAL EXPOSURES.

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is a compound which persists and is found ubiquitously in the environment, wildlife and humans. PFOA affects growth, development and viability of offspring of mice exposed during pregnancy. This study segregates the contributions of gestational and...

  20. Perturbations in polar lipids, starvation survival and reproduction following exposure to unsaturated fatty acids or environmental toxicants in Daphnia magna.

    PubMed

    Sengupta, Namrata; Gerard, Patrick D; Baldwin, William S

    2016-02-01

    Acclimating to toxicant stress is energy expensive. In laboratory toxicology tests dietary conditions are ideal, but not in natural environments where nutrient resources vary in quality and quantity. We compared the effects of additional lipid resources, docosahexaenoic acid (n-3; DHA) or linoleic acid (n-6; LA), or the effects of the toxicants, atrazine or triclosan on post-treatment starvation survival, reproduction, and lipid profiles. Chemical exposure prior to starvation had chemical-specific effects as DHA showed moderately beneficial effects on starvation survival and all of the other chemicals showed adverse effects on either survival or reproduction. Surprisingly, pre-exposure to triclosan inhibits adult maturation and in turn completely blocks reproduction during the starvation phase. The two HR96 activators tested, atrazine and LA adversely reduce post-reproduction survival 70% during starvation and in turn show poor fecundity. DHA and LA show distinctly different lipid profiles as DHA primarily increases the percentage of large (>37 carbon) phosphatidylcholine (PC) species and LA primarily increases the percentage of smaller (<37 carbon) PC species. The toxicants atrazine and triclosan moderately perturb a large number of different phospholipids including several phosphatidylethanolamine species. Some of these polar lipid species may be biomarkers for diets rich in specific fatty acids or toxicant classes. Overall our data demonstrates that toxicants can perturb lipid utilization and storage in daphnids in a chemical specific manner, and different chemicals can produce distinct polar lipid profiles. In summary, biological effects caused by fatty acids and toxicants are associated with changes in the production and use of lipids. PMID:26606184

  1. Perturbations in polar lipids, starvation survival and reproduction following exposure to unsaturated fatty acids or environmental toxicants in Daphnia magna.

    PubMed

    Sengupta, Namrata; Gerard, Patrick D; Baldwin, William S

    2016-02-01

    Acclimating to toxicant stress is energy expensive. In laboratory toxicology tests dietary conditions are ideal, but not in natural environments where nutrient resources vary in quality and quantity. We compared the effects of additional lipid resources, docosahexaenoic acid (n-3; DHA) or linoleic acid (n-6; LA), or the effects of the toxicants, atrazine or triclosan on post-treatment starvation survival, reproduction, and lipid profiles. Chemical exposure prior to starvation had chemical-specific effects as DHA showed moderately beneficial effects on starvation survival and all of the other chemicals showed adverse effects on either survival or reproduction. Surprisingly, pre-exposure to triclosan inhibits adult maturation and in turn completely blocks reproduction during the starvation phase. The two HR96 activators tested, atrazine and LA adversely reduce post-reproduction survival 70% during starvation and in turn show poor fecundity. DHA and LA show distinctly different lipid profiles as DHA primarily increases the percentage of large (>37 carbon) phosphatidylcholine (PC) species and LA primarily increases the percentage of smaller (<37 carbon) PC species. The toxicants atrazine and triclosan moderately perturb a large number of different phospholipids including several phosphatidylethanolamine species. Some of these polar lipid species may be biomarkers for diets rich in specific fatty acids or toxicant classes. Overall our data demonstrates that toxicants can perturb lipid utilization and storage in daphnids in a chemical specific manner, and different chemicals can produce distinct polar lipid profiles. In summary, biological effects caused by fatty acids and toxicants are associated with changes in the production and use of lipids.

  2. Influence of long-term exposure to simulated acid rain on development, reproduction and acaricide susceptibility of the carmine spider mite, Tetranychus cinnabarinus.

    PubMed

    Wang, Jin-Jun; Zhang, Jian-Ping; He, Lin; Zhao, Zhi-Mo

    2006-01-01

    Development, reproduction and acaricide susceptibility of Tetranychus cinnabarinus (Boisduvals) (Acari: Tetranychidae) were investigated after long-term (about 40 generations) exposure to various levels of acid rain; pH 2.5, 3.0, 4.0, and 5.6. Deionized water (pH 6.8) served as a control. The mites were reared on eggplant leaves at 28 degrees C, 80%RH and a photoperiod of 14:10 (L:D) in the laboratory. The results showed that the duration of the immature stage was significantly affected by acid rain exposure. The shortest duration (8.90 days) was recorded for populations exposed to pH 5.6 acid rain, while the longest duration (9.37 days) occurred after exposure to pH 2.5 acid rain. Compared with the control population, adult longevity was shortened with an increase in acidity. Similarly, the oviposition duration was also shortened by an increase in acidity. Statistically, female fecundity did not differ significantly between pH 5.6, pH 4.0 and control populations, but did differ significantly between the control population and those exposed to pH 2.5 and pH 3.0 acid rain. This suggested that the mite suffered reproductive defects after long-term exposure to acid rain with higher acidity (pH 2.5 and 3.0). The intrinsic rate of increase among different populations was not significantly affected, but the net reproductive rate of populations exposed to pH 2.5 and 3.0 acid rain was significantly less than pH 4.0, 5.6, and control populations. Bioassay results showed that after long-term exposure to acid rain, susceptibility of the mites to two acaricides, dichlorvos and fenpropathrin, did not change significantly.

  3. The effect of duration of exposure on sulfuric acid-induced pulmonary function changes in asthmatic adolescent subjects: A dose-response study

    SciTech Connect

    Koenig, J.Q.; Covert, D.S.; Larson, T.V.; Pierson, W.E. )

    1992-09-01

    To evaluate the pulmonary effects of varying doses of sulfuric acid, adolescent subjects with asthma were exposed to 35 or 70 micrograms/m3 sulfuric acid for 45 or 90 min. Exposure was carried out during intermittent moderate exercise. The pulmonary functions measured before and after exposure were FEV1, FVC, and total respiratory resistance. The 45 min exposures were associated with larger decreases in FEV1 (-6% or -3%) than the 90 min exposures (-1% or +2%). Analysis of variance of the change in FEV1 among the exposures revealed that the 45 min exposure to 35 micrograms/m3 was significant (p = 0.03). The p value for 45 min exposure to 70 micrograms/m3 was not significant (p = 0.08). Using analysis of variance, neither of the 90 min exposures was associated with a significant decrease in FEV1 compared to air exposure. Also, none of the changes in FVC or RT was significant. When baseline to post-exposure changes were compared for each of the five test atmospheres using paired t tests, both of the 45 min exposures were associated with statistical significance (p < 0.001 for 35 micrograms/m3 and p < 0.005 for 70 micrograms/m3). This baseline to post exposure change was not statistically significant for the 90 min exposures. The reason for the lesser effect on pulmonary function at increased exposure duration is not known; it may be due to changes in either varying deposition patterns or changes in buffering capacity of the cells lining the airways. With respect to individual sensitivities to H2SO4, the data showed a significant consistency across test atmospheres.

  4. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  5. Biochemical and morphological changes in carp (Cyprinus carpio L.) liver following exposure to copper sulfate and tannic acid.

    PubMed

    Varanka, Z; Rojik, I; Varanka, I; Nemcsók, J; Abrahám, M

    2001-03-01

    As a consequence of human activity various toxicants reach the aquatic ecosystems; humics may interact with them and may change their toxicity. Many fish are exposed to a considerable concentration of humics and pollutants. Because of paucity of data on the biochemical action of tannins in the presence of the fungicide CuSO4 a comparative study was undertaken. The alterations of redox-parameters in carp liver were monitored and tissue necrosis was followed by measuring the plasma transaminase activities and by electron microscopy. Tannic acid, a representative phenolic/humic compound, exerted prooxidant effects in carp, which may be partially due to formation of prooxidant intermediates/end-products via its biotransformation. Alternatively, tannic acid may partially inhibit the antioxidant enzymes of fish. The response to CuSO4 was more severe. Although tannic acid alone acted as a prooxidant in fish, electron micrographs demonstrated that it reduced the necrotizing effect of copper, which may be due to the complexing activity of tannic acid with the biomolecules of the hepatocytes and to the H2O2-degrading activity of tannin-CuSO4 combination. Our results indicate that the heavy metal-detoxifying capacity of tannin may be significant; however, tannin-exposure alone or combined with metals may be toxic for fish due to enzyme inhibition and oxidative stress induction. PMID:11255117

  6. The effect of ultrasonic irrigation before and after citric acid treatment on collagen fibril exposure: an in vitro SEM study.

    PubMed

    Higashi, T; Okamoto, H

    1995-10-01

    The surface characteristics of periodontally diseased human teeth after two treatments were compared both before and after partial demineralization with citric acid. Thirteen teeth were obtained from patients with advanced periodontal disease. Three teeth were selected for control groups and 10 were used for experimental groups. All diseased root surfaces were identified and outlined. The roots were cut longitudinally into two sections. They were then scaled and root planed and the paired sections were separately classified into two control or two experimental groups. Three sections in control group 1 were rinsed by syringe with saline solution. The three sections in control group 2 were treated with ultrasonic irrigation. The 10 sections in experimental group 1 were rinsed by syringe with saline solution before and after citric acid application; the 10 sections in experimental group 2 were irrigated ultrasonically before and after citric acid application. The concentration of the citric acid was 25% (pH 1.62) and the immersion time was 3 minutes. The root samples were examined by scanning electron microscope. A significant amount of grinding debris covered on all the root surfaces in control group 1, whereas smear was removed in control group 2. The features of root surfaces of the two experimental groups differed considerably. All specimens in experimental group 2 exhibited collagen fibrils exposed as a consequence of citric acid etching. On the other hand, the smear layer was not thoroughly removed from the root surface in experimental group 1, which meant that few collagen fibrils were exposed after partial demineralization. From these results, ultrasonic irrigation before and after citric acid application improves exposure of collagen fibrils, which may be desirable for clinical success in periodontal regenerative therapy.

  7. Deterioration of concrete structures by acid deposition — an assessment of the role of rainwater on deterioration by laboratory and field exposure experiments using mortar specimens

    NASA Astrophysics Data System (ADS)

    Okochi, Hiroshi; Kameda, Hideki; Hasegawa, Shin-ichi; Saito, Nobuhiko; Kubota, Ken; Igawa, Manabu

    Deterioration of concrete structures caused by acid deposition was investigated by laboratory and field exposure of portland cement mortar specimens to acid deposition. Laboratory exposure experiment showed that the dissolved amount of calcium hydrates, which were the major components in mortar, increased with the increase in the acidity of simulated acid rain solution and the decrease in the flow rate. There was little difference in their amount among different temperature treatments after each exposure to the solution with the same acidity, namely left at room temperature, heated at 70°C, and cooled at -2°C. The neutralization progressed more deeply under the heated and cooled condition and was accelerated by even acid rain with pH 4.7 during a long period (90 exposure cycles, which correspond to the rainfall amount of 15 years in Japan). A field exposure experiment for two years indicated that the carbonation of calcium hydrates and the formation of other corrosion products such as chloride, nitrate, and sulfate were limited to the surface of mortar specimens. The neutralization progressed more deeply in mortar specimens sheltered from rainwater than in those washed by rainwater.

  8. Fatty acid composition and extreme temperature tolerance following exposure to fluctuating temperatures in a soil arthropod.

    PubMed

    van Dooremalen, Coby; Suring, Wouter; Ellers, Jacintha

    2011-09-01

    Ectotherms commonly adjust their lipid composition to ambient temperature to counteract detrimental thermal effects on lipid fluidity. However, the extent of lipid remodeling and the associated fitness consequences under continuous temperature fluctuations are not well-described. The objective of this study was to investigate the effect of repeated temperature fluctuations on fatty acid composition and thermal tolerance. We exposed the springtail Orchesella cincta to two constant temperatures of 5 and 20°C, and a continuously fluctuating treatment between 5 and 20°C every 2 days. Fatty acid composition differed significantly between constant low and high temperatures. As expected, animals were most cold tolerant in the low temperature treatment, while heat tolerance was highest under high temperature. Under fluctuating temperatures, fatty acid composition changed with temperature initially, but later in the experiment fatty acid composition stabilized and closely resembled that found under constant warm temperatures. Consistent with this, heat tolerance in the fluctuating temperature treatment was comparable to the constant warm treatment. Cold tolerance in the fluctuating temperature treatment was intermediate compared to animals acclimated to constant cold or warmth, despite the fact that fatty acid composition was adjusted to warm conditions. This unexpected finding suggests that in animals acclimated to fluctuating temperatures an additional underlying mechanism is involved in the cold shock response. Other aspects of homeoviscous adaptation may protect animals during extreme cold. This paper forms a next step to fully understand the functioning of ectotherms in more thermally variable environments. PMID:21704631

  9. Nephroprotective effect of date fruit extract against dichloroacetic acid exposure in adult rats.

    PubMed

    El Arem, Amira; Thouri, Amira; Zekri, Mouna; Saafi, Emna Behija; Ghrairi, Fatma; Zakhama, Abdelfattah; Achour, Lotfi

    2014-03-01

    The aim of this study was to investigate the protective effects of aqueous date extract (ADE) on dichloroacetic acid (DCA)-induced nephrotoxicity. In vitro, total phenolic content estimated in the ADE were 417.71mg gallic acid equivalents/100g fresh weights (FW), while total flavonoid and tannins contents were 285.23 and 73.65mg catechin equivalents/100g FW, respectively. The ADE has strong scavenging activity. Ferulic, caffeic and p-coumaric acids are the major's compounds. Nephrotoxicity was induced in male Wistar rats by the administration of 0.5 and 2g/L DCA as drinking water. Some of these rats received also by gavage ADE (4mL/kg) before the administration of DCA. After two months of experiment, DCA administration caused elevated levels of renal MDA, significant depletion of GSH levels, altered the antioxidant enzyme activities and deteriorated the renal functions as assessed by the increased plasma urea, uric acid and creatinine levels compared to control rats. The treatment with the ADE significantly normalized the increased plasma levels of creatinine, urea and uric acid, reduced the elevated MDA levels, significantly normalized the antioxidant enzyme activities and GSH level and restored the altered kidney histology in rats treated with DCA. Therefore, it was speculated that ADE protects rats from kidney damage through its antioxidant capacity.

  10. An ecological risk assessment of the exposure and effects of 2,4-D acid to rainbow trout (Onchorhyncus mykiss)

    USGS Publications Warehouse

    Fairchild, J.F.; Feltz, K.P.; Allert, A.L.; Sappington, L.C.; Nelson, K.J.; Valle, J.A.

    2009-01-01

    Numerous state and federal agencies are increasingly concerned with the rapid expansion of invasive, noxious weeds across the United States. Herbicides are frequently applied as weed control measures in forest and rangeland ecosystems that frequently overlap with critical habitats of threatened and endangered fish species. However, there is little published chronic toxicity data for herbicides and fish that can be used to assess ecological risk of herbicides in aquatic environments. We conducted 96-h flowthrough acute and 30-day chronic toxicity studies with swim-up larvae and juvenile rainbow trout (Onchorhyncus mykiss) exposed to the free acid form of 2,4-D. Juvenile rainbow trout were acutely sensitive to 2,4-D acid equivalent at 494 mg/L (95% confidence interval [CI] 334-668 mg/L; 96-h ALC50). Accelerated life-testing procedures, used to estimate chronic mortality from acute data, predicted that a 30-day exposure of juvenile rainbow trout to 2,4-D would result in 1% and 10% mortality at 260 and 343 mg/L, respectively. Swim-up larvae were chronically more sensitive than juveniles using growth as the measurement end point. The 30-day lowest observable effect concentration (LOEC) of 2,4-D on growth of swim-up larvae was 108 mg/L, whereas the 30-day no observable effect concentration (NOEC) was 54 mg/L. The 30-day maximum acceptable toxicant concentration (MATC) of 2,4-D for rainbow trout, determined as the geometric mean of the NOEC and the LOEC, was 76 mg/L. The acute:chronic ratio was 6.5 (i.e., 494/76). We observed no chronic effects on growth of juvenile rainbow trout at the highest concentration tested (108 mg/L). Worst-case aquatic exposures to 2,4-D (4 mg/L) occur when the herbicide is directly applied to aquatic ecosystems for aquatic weed control and resulted in a 30-day safety factor of 19 based on the MATC for growth (i.e., 76/4). Highest nontarget aquatic exposures to 2,4-D applied following terrestrial use is calculated at 0.136 mg/L and resulted in a

  11. Perfluorooctanoic acid (PFOA)-induced liver lesions in two strains of mice following developmental exposures: PPARα is not required

    PubMed Central

    Filgo, Adam J.; Quist, Erin M.; Hoenerhoff, Mark J.; Brix, Amy E.; Kissling, Grace E.; Fenton, Suzanne E.

    2014-01-01

    Perfluorooctanoate acid (PFOA) is a ubiquitous pollutant that causes liver toxicity in rodents, a process believed to be dependent on peroxisome proliferation activated receptor alpha (PPARα) activation. Differences between humans and rodents have made the human relevance of some health effects caused by PFOA controversial. We analyzed liver toxicity at 18 months following gestational PFOA exposure in CD-1 and 129/Sv strains of mice and compared PFOA-induced effects between strains and in wild type (WT) and PPARα-knockout (KO) 129/Sv mice. Pregnant mice were exposed daily to doses (0.01–5mg/kg/BW) of PFOA from gestation days 1–17. The female offspring were necropsied at 18 months and liver sections underwent a full pathology review. Hepatocellular adenomas formed in PFOA-exposed PPARα-KO 129/Sv and CD-1 mice, and were absent in untreated controls from those groups and WT 129/Sv. Hepatocellular hypertrophy was significantly increased by PFOA exposure in CD-1 and an increased severity was found in WT 129/Sv mice. PFOA significantly increased non-neoplastic liver lesions in PPARα-KO mice (hepatocyte hypertrophy, bile duct hyperplasia and hematopoietic cell proliferation). Low dose gestational exposures to PFOA induced latent PPARα independent liver toxicity that was observed in aged mice. Evidence of liver toxicity in PPARα-KO mice warrants further investigation into PPARα independent pathways. PMID:25398757

  12. Human exposure assessment of silver and copper migrating from an antimicrobial nanocoated packaging material into an acidic food simulant.

    PubMed

    Hannon, Joseph Christopher; Kerry, Joseph P; Cruz-Romero, Malco; Azlin-Hasim, Shafrina; Morris, Michael; Cummins, Enda

    2016-09-01

    To examine the human exposure to a novel silver and copper nanoparticle (AgNP and CuNP)/polystyrene-polyethylene oxide block copolymer (PS-b-PEO) food packaging coating, the migration of Ag and Cu into 3% acetic acid (3% HAc) food simulant was assessed at 60 °C for 10 days. Significantly lower migration was observed for Ag (0.46 mg/kg food) compared to Cu (0.82 mg/kg food) measured by inductively coupled plasma - atomic emission spectrometry (ICP-AES). In addition, no distinct population of AgNPs or CuNPs were observed in 3% HAc by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The predicted human exposure to Ag and Cu was used to calculate a margin of exposure (MOE) for ionic species of Ag and Cu, which indicated the safe use of the food packaging in a hypothetical scenario (e.g. as fruit juice packaging). While migration exceeded regulatory limits, the calculated MOE suggests current migration limits may be conservative for specific nano-packaging applications.

  13. Human exposure assessment of silver and copper migrating from an antimicrobial nanocoated packaging material into an acidic food simulant.

    PubMed

    Hannon, Joseph Christopher; Kerry, Joseph P; Cruz-Romero, Malco; Azlin-Hasim, Shafrina; Morris, Michael; Cummins, Enda

    2016-09-01

    To examine the human exposure to a novel silver and copper nanoparticle (AgNP and CuNP)/polystyrene-polyethylene oxide block copolymer (PS-b-PEO) food packaging coating, the migration of Ag and Cu into 3% acetic acid (3% HAc) food simulant was assessed at 60 °C for 10 days. Significantly lower migration was observed for Ag (0.46 mg/kg food) compared to Cu (0.82 mg/kg food) measured by inductively coupled plasma - atomic emission spectrometry (ICP-AES). In addition, no distinct population of AgNPs or CuNPs were observed in 3% HAc by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The predicted human exposure to Ag and Cu was used to calculate a margin of exposure (MOE) for ionic species of Ag and Cu, which indicated the safe use of the food packaging in a hypothetical scenario (e.g. as fruit juice packaging). While migration exceeded regulatory limits, the calculated MOE suggests current migration limits may be conservative for specific nano-packaging applications. PMID:27402098

  14. Acid deposition effects on materials: Evaluation of nickel after four years of exposure

    SciTech Connect

    Tidblad, J.; Leygraf, C. . Dept. of Applied Electrochemistry and Corrosion Science); Kucera, V. )

    1993-07-01

    The atmospheric corrosion of nickel after 4 years of exposure inside a sheltered box has been investigated. Quantitative evaluation of corrosion attack resulted in a linear relation between the weight increase of nickel and the sulfur dioxide concentration. Analysis of corrosion products by X-ray photoelectron spectroscopy combined with diffuse reflectance infrared Fourier transform spectroscopy and X-ray powder diffraction agreed with previous conclusions and suggested the initial formation of an amorphous basic nickel sulfate with less protective ability and subsequent formation of a crystalline basic nickel sulfate with higher protective ability. A carbonate was also detected, more abundant at lower weight increases. Conductivity of precipitation correlated with the weight increase of nickel but not so much as SO[sub 2]. High levels of this parameter are related to high concentrations of the different ions in precipitation. A complementary exposure program was performed to compare actual exposure conditions inside and outside the sample box. It was concluded that the SO[sub 2] deposition outside and inside the sample box differ approximately by a factor of 10. This difference could be separated into air flow conditions (a factor of 2) and concentrations (a factor of 5).

  15. Exposure to 2,4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.

    PubMed

    Alves, M G; Neuhaus-Oliveira, A; Moreira, P I; Socorro, S; Oliveira, P F

    2013-07-01

    The purpose of this study was to determine the effects of 2,4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism. Immature rat SCs were maintained 50h under basal conditions or exposed to 2,4-D (100nM, 10μM and 1mM). SCs exposed to 10μM and 1mM of 2,4-D presented lower intracellular glucose and lactate content. Exposure to 10μM of 2,4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10μM of 2,4-D. Exposure to 100nM and 10μM also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2,4-D. Exposure to 2,4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis.

  16. Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

    SciTech Connect

    Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech; Turski, Waldemar A.; Dekundy, Andrzej

    2009-10-15

    Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks {alpha}7 subtype of nicotinic acetylcholine receptors (nAChRs). The present studies were aimed at assessing effects of acute and chronic nicotine exposure on KYNA production in rat brain slices in vitro and ex vivo. In brain slices, nicotine significantly increased KYNA formation at 10 mM but not at 1 or 5 mM. Different nAChR antagonists (dihydro-{beta}-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 {mu}g/ml) on KYNA brain content were evaluated ex vivo. Acute treatment with nicotine (1 mg/kg i.p.) did not affect KYNA level in rat brain. The subchronic exposure to nicotine in drinking water significantly increased KYNA by 43%, while chronic exposure to nicotine resulted in a reduction in KYNA by 47%. Co-administration of mecamylamine with nicotine in drinking water for 30 days reversed the effect exerted by nicotine on KYNA concentration in the cerebral cortex. The present results provide evidence for the hypothesis of reciprocal interaction between the nicotinic cholinergic system and the kynurenine pathway in the brain.

  17. Membrane lipid composition of pancreatic AR42J cells: modification by exposure to different fatty acids.

    PubMed

    Audi, Nama'a; Mesa, María D; Martínez, María A; Martínez-Victoria, Emilio; Mañas, Mariano; Yago, María D

    2007-04-01

    Dietary fat type influences fatty acids in rat pancreatic membranes, in association with modulation of secretory activity and cell signalling in viable acini. We aimed to confirm whether AR42J cells are a valid model to study the interactions between lipids and pancreatic acinar cell function. For this purpose we have (i) compared the baseline fatty acid composition of AR42J cells with that of pancreatic membranes from rats fed a standard chow; (ii) investigated if fatty acids in AR42J membranes can be modified in culture; and (iii) studied if similar compositional variations that can be evoked in rats when dietary fat type is altered occur in AR42J cells. Weaning Wistar rats were fed for 8 weeks either a commercial chow (C) or semi-purified diets containing virgin olive oil (VOO) or sunflower oil (SO) as fat source. AR42J cells were incubated for 72 hrs in medium containing unmodified fetal calf serum (FCS, AR42J-C cells), FCS enriched with 18:1 n-9 (AR42J-O cells), or FCS enriched with 18:2 n-6 (AR42J-L cells). Fatty acids in crude membranes from rat pancreas and AR42J cells were determined by gas-liquid chromatography. Differences in membrane fatty acids between C rats and AR42J-C cells can be explained in part by variations in the amount of fatty acids in the extracellular environment. Supplementation of FCS with 18:1 n-9 or 18:2 n-6 changed the fatty acid spectrum of AR42J cells in a manner that resembles the pattern found, respectively, in VOO and SO rats, although AR42J-L cells were unable to accumulate 20:4 n-6. The AR42J cell line can be a useful tool to assess the effect of membrane compositional changes on acinar cell function. However, differences in baseline characteristics, and perhaps fatty acid metabolism, indicate that results obtained in AR42J cells should be confirmed with experiments in the whole animal.

  18. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  19. PRENATAL AND POSTNATAL EFFECTS IN RATS OF PERFLUORONONANOIC ACID EXPOSURE IN UTERO

    EPA Science Inventory

    In recent years, our understanding of the developmental toxicity of perfluoroalkyl acids (PFAAs) has focused on the C8 compounds. Ubiquitous environmental contaminants, PFAA’s are utilized as surfactants in a variety of industrial applications. Although several PFAAs have been ex...

  20. Resistance of biofilm-covered mortars to microbiologically influenced deterioration simulated by sulfuric acid exposure

    SciTech Connect

    Soleimani, Sahar Isgor, O. Burkan Ormeci, Banu

    2013-11-15

    Following the reported success of biofilm applications on metal surfaces to inhibit microbiologically influenced corrosion, effectiveness and sustainability of E. coli DH5α biofilm on mortar surface to prevent microbiologically influenced concrete deterioration (MICD) are investigated. Experiments simulating microbial attack were carried out by exposing incrementally biofilm-covered mortar specimens to sulfuric acid solutions with pH ranging from 3 to 6. Results showed that calcium concentration in control reactors without biofilm was 23–47% higher than the reactors with biofilm-covered mortar. Formation of amorphous silica gel as an indication of early stages of acid attack was observed only on the control mortar specimens without biofilm. During acidification, the biofilm continued to grow and its thickness almost doubled from ∼ 30 μm before acidification to ∼ 60 μm after acidification. These results demonstrated that E. coli DH5α biofilm was able to provide a protective and sustainable barrier on mortar surfaces against medium to strong sulfuric acid attack. -- Highlights: •Effectiveness of E.coli DH5α biofilm to prevent MICD was studied. •Conditions that lead to MICD were simulated by chemical acidification. •Biofilm-covered mortar specimens were exposed to sulfuric acid solutions. •The presence of biofilm helped reduce the chemically-induced mortar deterioration. •Biofilm remained alive and continued to grow during the acidification process.

  1. {Delta}-Aminolevulinic acid dehydratase: A sensitive indicator of lead exposure in broiler chicks: (Gallus domesticus)

    SciTech Connect

    Bakalli, R.I.; Pesti, G.M.; Konjufca, V.

    1995-12-01

    Delta-aminolevulinic acid dehydratase, EC 4.2.1.24 (ALAD) is one of the enzymes participating in heme synthesis. The study reported in this paper was designed to determine the activity of erythrocyte ALAD anbd the relationship between this enzyme and tissue lead levels in chickens, during Pb intake and after withdrawing Bv from the feed. 20 refs., 3 tabs.

  2. Sequestering CO(2) by mineral carbonation: stability against acid rain exposure.

    PubMed

    Allen, Daniel J; Brent, Geoff F

    2010-04-01

    Mineral carbonation is a potentially attractive alternative to storage of compressed CO(2) in underground repositories, known as geosequestration. Processes for the conversion of basic ores, such as magnesium silicates, to carbonates have been proposed by various researchers, with storage of the carbonate as backfill in the original mine representing a solid carbon sink. The stability of such carbon sinks against acid rain and other sources of strong acids is examined here. It is acknowledged that in the presence of strong acid, carbonates will dissolve and release carbon dioxide. A sensitivity analysis covering annual average rainfall and pH that may be encountered in industrialized areas of the United States, China, Europe, and Australia was conducted to determine maximum CO(2) rerelease rates from mineral carbonation carbon sinks. This analysis is based on a worst-case premise that is equivalent to assuming infinitely rapid kinetics of dissolution of the carbonate. The analysis shows that under any likely conditions of pH and rainfall, leakage rates of stored CO(2) are negligible. This is illustrated in a hypothetical case study under Australian conditions. It is thus proposed that sequestration by mineral carbonation can be considered to be permanent on practical human time scales. Other possible sources of acid have also been considered.

  3. Transcriptome Profiling of Shewanella oneidensis Gene Expressionfollowing Exposure to Acidic and Alkaline pH

    SciTech Connect

    Leaphart, Adam B.; Thompson, Dorothea K.; Huang, Katherine; Alm,Eric; Wan, Xiu-Feng; Arkin, Adam P.; Brown, Steven D.; Wu, Liyou; Yan,Tingfen; Liu, Xueduan; Wickham, Gene S.; Zhou, Jizhong

    2007-04-02

    The molecular response of Shewanella oneidensis MR-1 tovariations in extracellular pH was investigated based on genomewide geneexpression profiling. Microarray analysis revealed that cells elicitedboth general and specific transcriptome responses when challenged withenvironmental acid (pH 4) or base (pH 10) conditions over a 60-minperiod. Global responses included the differential expression of genesfunctionally linked to amino acid metabolism, transcriptional regulationand signal transduction, transport, cell membrane structure, andoxidative stress protection. Response to acid stress included theelevated expression of genes encoding glycogen biosynthetic enzymes,phosphate transporters, and the RNA polymerase sigma-38 factor (rpoS),whereas the molecular response to alkaline pH was characterized byupregulation of nhaA and nhaR, which are predicted to encode an Na+/H+antiporter and transcriptional activator, respectively, as well assulfate transport and sulfur metabolism genes. Collectively, theseresults suggest that S. oneidensis modulates multiple transporters, cellenvelope components, and pathways of amino acid consumption and centralintermediary metabolism as part of its transcriptome response to changingexternal pH conditions.

  4. Evaluation of continuous 4 day exposure to peracetic acid as a treatment for Ichthyophthirius multifiliis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The parasitic ciliate Ichthyophthirius multifiliis infests all species of freshwater fish and can cause severe economic losses in fish breeding. The most effective treatment, malachite green, has been banned in Europe and North America for use in food-fish production. Peracetic acid (PAA) was foun...

  5. Sequestering CO(2) by mineral carbonation: stability against acid rain exposure.

    PubMed

    Allen, Daniel J; Brent, Geoff F

    2010-04-01

    Mineral carbonation is a potentially attractive alternative to storage of compressed CO(2) in underground repositories, known as geosequestration. Processes for the conversion of basic ores, such as magnesium silicates, to carbonates have been proposed by various researchers, with storage of the carbonate as backfill in the original mine representing a solid carbon sink. The stability of such carbon sinks against acid rain and other sources of strong acids is examined here. It is acknowledged that in the presence of strong acid, carbonates will dissolve and release carbon dioxide. A sensitivity analysis covering annual average rainfall and pH that may be encountered in industrialized areas of the United States, China, Europe, and Australia was conducted to determine maximum CO(2) rerelease rates from mineral carbonation carbon sinks. This analysis is based on a worst-case premise that is equivalent to assuming infinitely rapid kinetics of dissolution of the carbonate. The analysis shows that under any likely conditions of pH and rainfall, leakage rates of stored CO(2) are negligible. This is illustrated in a hypothetical case study under Australian conditions. It is thus proposed that sequestration by mineral carbonation can be considered to be permanent on practical human time scales. Other possible sources of acid have also been considered. PMID:20199068

  6. Evaluation of preventive and control measures for lead exposure in a South African lead-acid battery recycling smelter.

    PubMed

    Dyosi, Sindiswa

    2007-10-01

    In South Africa, new lead regulations released in February 2002 served as motivation for a cross-sectional study investigating the effectiveness of preventive and control measures implemented in a lead smelter that recycles lead-acid batteries. Twenty-two workers were observed and interviewed. Structured questionnaires were used to gather workers' personal information, perception about their work environment, health risks, and work practices. Retrospective data from air monitoring and medical surveillance programs were obtained from the plant's records. The smelter implemented a number of control measures for lead exposure, including engineering controls, administrative controls, and, as a last resort, personal protective equipment. Engineering controls were rated the best control measure and included local exhaust ventilation systems and wet methods. Positive pressure systems were used in the offices and laboratory. The local exhaust ventilation system was rated the best engineering control measure. Although control measures were used, areas such as smelting and refinery had average lead in air levels above 0.15 mg/m(3), the occupational exposure limit for lead. This was a concern especially with regard to the smelting area because those workers had the second highest mean blood lead levels; workers in the battery breaking area had the highest. Regular use of personal protective equipment by some workers in the "lead exposure zones" was not observed. Although the mean blood lead levels had been below 40 micro g/dL for more than 90% of the workers since 2001, more than 70% of workers reported concerns about their health while working in the smelter. Even though control measures were implemented, they were not adequate because in some areas lead in air exceeded the occupational exposure limit. Therefore, improvement of existing measures and regular monitoring of personal protective equipment use were included in the recommendations given to the smelter.

  7. Lack of sensitivity of urinary trans,trans-muconic acid in determining low-level (ppb) benzene exposure in children.

    PubMed

    Barbieri, Anna; Accorsi, Antonio; Raffi, Giovanni Battista; Nicoli, Luciana; Violante, Francesco Saverio

    2002-01-01

    Benzene is a widespread pollutant of which the main source in the outside environment is automotive traffic. Benzene is also present in cigarette smoke, and small quantities exist in drinking water and food; all of these sources contribute to pollution of indoor environments. Benzene exposure may be studied with biologic indicators. In the present study, the authors evaluated whether differences in urinary concentrations of trans,transmuconic acid (t,t-MA) were detectable in a sample of 150 children and if the chemical was correlated with environmental exposures to low levels of benzene. The children attended primary schools that had significantly different-but low-environmental benzene levels. Analysis of urinary t,t-MA was achieved with high-performance liquid chromatography (photodiode array detector), and analysis of passive air samplers for benzene was performed with gas chromatography-mass spectrometry. Statistical analysis (Kruskal-Wallis test) indicated that differences in urinary levels of t,t-MA in children from urban and rural areas were not statistically significant (p = .07), nor were there significant differences between children with and without relatives who smoked (p = .69). As has been shown in other studies of children and adults, results of our study evidenced (1) the difficulty of correlating concentrations of urinary biomarkers with environmental exposure to benzene at a parts-per-billion level (i.e., traffic and environmental tobacco smoke) and, consequently, (2) the lack of specificity of t,t-MA as a biological indicator for the study of a population's exposure. PMID:12507175

  8. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation.

    PubMed

    Goudarzi, Maryam; Chauthe, Siddheshwar; Strawn, Steven J; Weber, Waylon M; Brenner, David J; Fornace, Albert J

    2016-01-01

    With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; external γ irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 ((137)Cs) and Strontium-90 ((90)Sr). The multiple reaction monitoring analysis showed that, while exposure to (137)Cs and (90)Sr induced a statistically significant and persistent decrease, similar doses of external γ beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to (90)Sr and (137)Cs and to external γ beam radiation. PMID:27213362

  9. Influence of in ovo mercury exposure, lake acidity, and other factors on common loon egg and chick quality in Wisconsin.

    PubMed

    Kenow, Kevin P; Meyer, Michael W; Rossmann, Ronald; Gray, Brian R; Arts, Michael T

    2015-08-01

    A field study was conducted in Wisconsin (USA) to characterize in ovo mercury (Hg) exposure in common loons (Gavia immer). Total Hg mass fractions ranged from 0.17 µg/g to 1.23 µg/g wet weight in eggs collected from nests on lakes representing a wide range of pH (5.0-8.1) and were modeled as a function of maternal loon Hg exposure and egg laying order. Blood total Hg mass fractions in a sample of loon chicks ranged from 0.84 µg/g to 3.86 µg/g wet weight at hatch. Factors other than mercury exposure that may have persistent consequences on development of chicks from eggs collected on low-pH lakes (i.e., egg selenium, calcium, and fatty acid mass fractions) do not seem to be contributing to reported differences in loon chick quality as a function of lake pH. However, it was observed that adult male loons holding territories on neutral-pH lakes were larger on average than those occupying territories on low-pH lakes. Differences in adult body size of common loons holding territories on neutral-versus low-pH lakes may have genetic implications for differences in lake-source-related quality (i.e., size) in chicks. The tendency for high in ovo Hg exposure and smaller adult male size to co-occur in low-pH lakes complicates the interpretation of the relative contributions of each to resulting chick quality.

  10. Influence of in ovo mercury exposure, lake acidity, and other factors on common loon egg and chick quality in Wisconsin

    USGS Publications Warehouse

    Kenow, Kevin P.; Meyer, Michael W.; Rossmann, Ronald; Gray, Brian R.; Arts, Michael T.

    2015-01-01

    A field study was conducted in Wisconsin (USA) to characterize in ovo mercury (Hg) exposure in common loons (Gavia immer). Total Hg mass fractions ranged from 0.17 mg/g to 1.23mg/g wet weight in eggs collected from nests on lakes representing a wide range of pH (5.0–8.1) and were modeled as a function of maternal loon Hg exposure and egg laying order. Blood total Hg mass fractions in a sample of loon chicks ranged from 0.84ug/g to 3.86 ug/g wet weight at hatch. Factors other than mercury exposure that may have persistent consequences on development of chicks from eggs collected on low-pH lakes (i.e., egg selenium, calcium, and fatty acid mass fractions) do not seem to be contributing to reported differences in loon chick quality as a function of lake pH. However, it was observed that adult male loons holding territories on neutral-pH lakes were larger on average than those occupying territories on low-pH lakes. Differences in adult body size of common loons holding territories on neutral-versus low-pH lakes may have genetic implications for differences in lake-source-related quality (i.e., size) in chicks. The tendency for high in ovo Hg exposure and smaller adult male size to co-occur in low-pH lakes complicates the interpretation of the relative contributions of each to resulting chick quality.

  11. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

    PubMed Central

    Goudarzi, Maryam; Chauthe, Siddheshwar; Strawn, Steven J.; Weber, Waylon M.; Brenner, David J.; Fornace, Albert J.

    2016-01-01

    With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs) and Strontium-90 (90Sr). The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation. PMID:27213362

  12. Green chemistry in urinalysis for trichloroethanol and trichloroacetic acid as markers of exposure to chlorinated hydrocarbon solvents.

    PubMed

    Inoue, Osamu; Ukai, Hirohiko; Ikeda, Masayuki

    2006-01-01

    The aim of the present study was to develop a method of urinalysis for trichloroacetic acid (TCA) and trichloroethanol (TCE), and therefore total trichloro-compounds (TTC) as the sum, with least use of hazardous chemicals, being green in that sense. After acid hydrolysis followed by dilution with an ethanol (EtOH)-methanol (MeOH)-water mixture, capillary gas-choromatography with an electron-capture detector can quantify TCA and TCE in the diluted hydrolyzate. Comparison studies showed that the results were identical among three methods, i.e., 1. the method developed in the present study, 2. a head-space GC with acid hydrolysis of conjugated TCE and methyl-esterification of TCA, and 3. traditional colorimetry with Fujiwara reaction. When applied to exposure-excretion analysis, the three methods gave results reproducible to each other. Over-all evaluation therefore was such that the method developed in the present study is as equally reliable as previously developed methods. It should be further noted that the procedures are very simple, with minimum use of occupationally or environmentally hazardous chemicals. In case the determination of only TCA is requested, it is possible to skip the hydrolysis step so that the treatment prior to the GC analysis is even simpler, i.e., just a 60-fold dilution of the urine sample with the EtOH-MeOH-water mixture. It was also demonstrated that correction of urinary analyte levels for urine density in terms of creatinine or specific gravity did not improve the correlation with the intensity of TRI exposure. PMID:16610561

  13. Morphological abnormalities among lampreys

    USGS Publications Warehouse

    Manion, Patrick J.

    1967-01-01

    The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.

  14. Sequence-specific formation of d-amino acids in a monoclonal antibody during light exposure.

    PubMed

    Mozziconacci, Olivier; Schöneich, Christian

    2014-11-01

    The photoirradiation of a monoclonal antibody 1 (mAb1) at λ = 254 nm and λmax = 305 nm resulted in the sequence-specific generation of d-Val, d-Tyr, and potentially d-Ala and d-Arg, in the heavy chain sequence [95-101] YCARVVY. d-Amino acid formation is most likely the product of reversible intermediary carbon-centered radical formation at the (α)C-positions of the respective amino acids ((α)C(•) radicals) through the action of Cys thiyl radicals (CysS(•)). The latter can be generated photochemically either through direct homolysis of cystine or through photoinduced electron transfer from Trp and/or Tyr residues. The potential of mAb1 sequences to undergo epimerization was first evaluated through covalent H/D exchange during photoirradiation in D2O, and proteolytic peptides exhibiting deuterium incorporation were monitored by HPLC-MS/MS analysis. Subsequently, mAb1 was photoirradiated in H2O, and peptides, for which deuterium incorporation in D2O had been documented, were purified by HPLC and subjected to hydrolysis and amino acid analysis. Importantly, not all peptide sequences which incorporated deuterium during photoirradiation in D2O also exhibited photoinduced d-amino acid formation. For example, the heavy chain sequence [12-18] VQPGGSL showed significant deuterium incorporation during photoirradiation in D2O, but no photoinduced formation of d-amino acids was detected. Instead this sequence contained ca. 22% d-Val in both a photoirradiated and a control sample. This observation could indicate that d-Val may have been generated either during production and/or storage or during sample preparation. While sample preparation did not lead to the formation of d-Val or other d-amino acids in the control sample for the heavy chain sequence [95-101] YCARVVY, we may have to consider that during hydrolysis N-terminal residues (such as in VQPGGSL) may be more prone to epimerization. We conclude that the photoinduced, radical-dependent formation of d-amino acids

  15. Oxidant and acid aerosol exposure in healthy subjects and subjects with asthma. Part I: Effects of oxidants, combined with sulfuric or nitric acid, on the pulmonary function of adolescents with asthma.

    PubMed

    Koenig, J Q; Covert, D S; Pierson, W E; Hanley, Q S; Rebolledo, V; Dumler, K; McKinney, S E

    1994-11-01

    Both peak flow decrements in children at summer camps and increased hospital admissions for asthma have been associated with summer "acid haze," which is composed of ozone and various acidic species. The objective of this study was to investigate the pulmonary effects of acid summer haze in a controlled laboratory setting. Twenty-eight adolescent subjects with allergic asthma, exercise-induced bronchospasm, and a positive response to a standardized methacholine challenge enrolled in the study; 22 completed the study. Each subject inhaled one of four test atmospheres by mouthpiece on two consecutive days. The order of exposure to the four test atmospheres was assigned via a random protocol: air, oxidants (0.12 parts per million [ppm]* ozone plus 0.30 ppm nitrogen dioxide), oxidants plus sulfuric acid at 70 micrograms/m3 of air, or oxidants plus 0.05 ppm nitric acid. Exposure to each of the different atmospheres was separated by at least one week. The exposures were carried out during alternating 15-minute periods of rest and moderate exercise for a total exposure period of 90 minutes per day. Pulmonary function was measured before and after exposure on both test days and again on the third day as a follow-up measurement. A postexposure methacholine challenge was performed on Day 3. Low methacholine concentrations were chosen for the postexposure challenge to avoid provoking a response. The protocol was designed to detect subtle changes in airway reactivity. The statistical significance of the pulmonary function values was tested using paired t tests. First, we compared the difference between baseline and postexposure measurements after air exposure on Day 1 with the differences between baseline and postexposure measurements after Day 1 exposure to each of the other three atmospheres. Second, we compared the difference between baseline and postexposure measurements after the Day 2 air exposure with the differences between baseline and postexposure measurements after

  16. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    USGS Publications Warehouse

    Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

    2010-01-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

  17. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum.

    PubMed

    Monette, Michelle Y; Yada, Takashi; Matey, Victoria; McCormick, Stephen D

    2010-08-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 micrpg l(-1) Al), acid and low Al (LAl: pH 5.4, 11 microg l(-1) Al), acid and moderate Al (MAl: pH 5.3, 42 microg l(-1) Al), and acid and high Al (HAl: pH 5.4, 56 microg l(-1) Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na(+)/K(+)-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl(-) channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al

  18. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease.

    PubMed

    Simopoulos, Artemis P

    2013-08-01

    Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health. PMID:23896654

  19. Sustained exposure to abscisic acid enhances the colonization potential of the mutualist fungus Piriformospora indica on Arabidopsis thaliana roots.

    PubMed

    Peskan-Berghöfer, Tatjana; Vilches-Barro, Amaya; Müller, Teresa M; Glawischnig, Erich; Reichelt, Michael; Gershenzon, Jonathan; Rausch, Thomas

    2015-11-01

    Root colonization by the beneficial fungus Piriformospora indica is controlled by plant innate immunity, but factors that channel this interaction into a mutualistic relationship are not known. We have explored the impact of abscisic acid (ABA) and osmotic stress on the P. indica interaction with Arabidopsis thaliana. The activation of plant innate immunity in roots was determined by measuring the concentration of the phytoalexin camalexin and expression of transcription factors regulating the biosynthesis of tryptophan-related defence metabolites. Furthermore, the impact of the fungus on the content of ABA, salicylic acid, jasmonic acid (JA) and JA-related metabolites was examined. We demonstrated that treatment with exogenous ABA or the ABA analogue pyrabactin increased fungal colonization efficiency without impairment of plant fitness. Concomitantly, ABA-deficient mutants of A. thaliana (aba1-6 and aba2-1) were less colonized, while plants exposed to moderate stress were more colonized than corresponding controls. Sustained exposure to ABA attenuated expression of transcription factors MYB51, MYB122 and WRKY33 in roots upon P. indica challenge or chitin treatment, and prevented an increase in camalexin content. The results indicate that ABA can strengthen the interaction with P. indica as a consequence of its impact on plant innate immunity. Consequently, ABA will be relevant for the establishment and outcome of the symbiosis under stress conditions.

  20. Steering the efficiency of carbon nanotube-silicon photovoltaic cells by acid vapor exposure: a real-time spectroscopic tracking.

    PubMed

    Pintossi, C; Pagliara, S; Drera, G; De Nicola, F; Castrucci, P; De Crescenzi, M; Crivellari, M; Boscardin, M; Sangaletti, L

    2015-05-13

    Hybrid carbon nanotube-silicon (CNT-Si) junctions have been investigated by angle resolved photoemission spectroscopy (AR-XPS) with the aim to clarify the effects of a nonstoichiometric silicon oxide buried interface on the overall cell efficiency. A complex silicon oxide interface has been clearly identified and its origin and role in the heterojunction have been probed by exposing the cells to hydrofluoric (HF) and nitric (HNO3) acid. Real-time monitoring of the cell efficiencies during the steps following acid exposure (up to 1 week after etching) revealed a correlation between the thickness and chemical state of the oxide layer and the cell efficiencies. By matching the AR-XPS and Raman spectroscopy with the electrical response data it has been possible to discriminate the effects on the cell efficiency of the buried SiO(x) interface from those related to CNT acid doping. The overall cell behavior recorded for different thicknesses of the SiO(x) interface indicates that the buried oxide layer is likely acting as a passivating/inversion layer in a metal-insulator-semiconductor junction.

  1. Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells.

    PubMed

    Howell, George; Mangum, Lauren

    2011-02-01

    Exposure to the organochlorine compounds p,p'-dichlorodiphenyldichloroethylene (DDE) and oxychlordane have been associated with an increased prevalence of diabetes. Although the exact etiology of diabetes, especially type 2 diabetes, is not known, it is thought that adipose dysfunction plays a vital role in the progression of this disease. Thus, the present study examined whether exposure to these bioaccumulative compounds promotes adipocyte dysfunction including alterations in adipogenesis, fatty acid storage, and adipokine production within the adipocyte. We employed the NIH3T3-L1 cell line as a model for adipogenesis and mature adipocyte function. Exposure to DDE or oxychlordane prior to and throughout differentiation did not affect adipogenesis. In mature NIH3T3-L1 adipocytes, exposure to oxychlordane, DDE, or dieldrin had no effect on insulin-stimulated fatty acid uptake but did increase basal fatty acid uptake over a 24 h period. There was no observed effect of exposure to these compounds on lipolysis. Exposure to DDE significantly increased the release of leptin, resistin, and adiponectin from mature adipocytes with corresponding increases in expression of resistin and adiponectin. Taken together, the current data suggest that exposure to these compounds, especially DDE, may promote some aspects of adipocyte dysfunction that are commonly associated with obesity and type 2 diabetes.

  2. Copper corrosion mechanism in the presence of formic acid vapor for short exposure times

    SciTech Connect

    Bastidas, J.M.; Lopez-Delgado, A.; Cano, E.; Polo, J.L.; Lopez, F.A.

    2000-03-01

    The rate of copper corrosion originated by the action of formic acid vapors at 100% relative humidity was studied. Five formic vapor concentration levels (10, 50, 100, 200, and 300 ppm) were used. A copper corrosion rate of up to 1,300 mg/m{sup 2} d was measured for a period of 21 days using a gravimetric method. The patina layers were characterized using cathodic reduction, X-ray powder diffraction. Fourier transform infrared spectrometry, and scanning electron microscopy techniques. Some of the components identified in the corrosion-product layers were cuprite (Cu{sub 2}O), cupric hydroxide hydrate [Cu(OH){sub 2}{sm_bullet}H{sub 2}O], and copper formate hydrate [Cu(HCOO){sub 2}{sm_bullet}4H{sub 2}O]. The latter was formed by both cupric hydroxide and formic acid-cuprous ion complex mechanisms.

  3. Acute lung function responses to ambient acid aerosol exposures in children

    SciTech Connect

    Raizenne, M.E.; Burnett, R.T.; Stern, B.; Franklin, C.A.; Spengler, J.D.

    1989-02-01

    We examined the relationship between lung function changes and ambient acid aerosol episodes in children attending a residential summer camp. Young females (112) performed daily spirometry, and 96 were assessed on one occasion for airway hyperresponsiveness using a methacholine bronchoprovocation test. Air quality measurements were performed on site and four distinct acid aerosol episodes were observed during the 41-day study. The maximum values observed during the 41-day study were: O/sub 3/ at 143 ppb; H/sub 2/SO/sub 4/ at 47.7 micrograms/m/sup 3/; and (H+) at 550 nmole/m/sup 3/. Maximum decrements of 3.5 and 7% for FEV1 and PEF, respectively, were observed to be associated with the air pollution episodes. There was some evidence of a differential lung function response to the episodes where children with a positive response to a methacholine challenge had larger decrements compared to their nonresponsive counterparts.

  4. Acute lung function responses to ambient acid aerosol exposures in children.

    PubMed

    Raizenne, M E; Burnett, R T; Stern, B; Franklin, C A; Spengler, J D

    1989-02-01

    We examined the relationship between lung function changes and ambient acid aerosol episodes in children attending a residential summer camp. Young females (112) performed daily spirometry, and 96 were assessed on one occasion for airway hyperresponsiveness using a methacholine bronchoprovocation test. Air quality measurements were performed on site and four distinct acid aerosol episodes were observed during the 41-day study. The maximum values observed during the 41-day study were: O3 at 143 ppb; H2SO4 at 47.7 micrograms/m3; and [H+] at 550 nmole/m3. Maximum decrements of 3.5 and 7% for FEV1 and PEF, respectively, were observed to be associated with the air pollution episodes. There was some evidence of a differential lung function response to the episodes where children with a positive response to a methacholine challenge had larger decrements compared to their nonresponsive counterparts.

  5. Potential effects of tooth-brushing on human dentin wear following exposure to acidic soft drinks.

    PubMed

    Choi, S; Park, K-H; Cheong, Y; Moon, S W; Park, Y-G; Park, H-K

    2012-08-01

    This study used scanning electron microscopy and atomic force microscopy to examine the short-term potential effects of brushing time and the start-time of tooth-brushing after demineralization on primary dentin wear in vitro. Thirty-six noncarious primary central incisors were assigned to 12 experimental groups. Exposure to cola drinks was used to initiate the demineralization process. Three brushing times (5, 15 and 30 s) and four start-times of brushing (0, 30, 60 and 120 min) after an erosive attack were used for the abrasion process. Tooth-brushing the softened dentin surface led to increases in the open tubular fraction and microstructural changes on the dentin surface. Brushing immediately after exposure to cola resulted in the greatest irreversible dentin loss, whereas brushing 60 or 120 min after pretreatment resulted in the least irreversible dentin loss. However, brushing time had no effect on the irreversible loss of dentin wear. Based on these experimental results, tooth-brushing should be performed at least 60 min after consuming a cola drink to achieve the desired tooth cleaning and avoid the introduction of surface lesions on dentin.

  6. Ameloglyphics: A possible forensic tool for person identification following high temperature and acid exposure

    PubMed Central

    Juneja, Manjushree; Juneja, Saurabh; Rakesh, Nagaraju; Bhoomareddy Kantharaj, Yashoda Devi

    2016-01-01

    Introduction: Forensic odontology is a branch that is evolving over time and has opened newer avenues that may help in the identification of individuals. Tooth prints are the enamel rod end patterns on tooth surface and they are considered as a hard tissue analog to fingerprints. Teeth have the highest resistance to most environmental effects like fire, desiccation, and decomposition, and may be used as a forensic evidence. Aims and Objectives: The aim of the study was to evaluate if the tooth prints could be used for an individual's identification and reproducibility and permanency of these tooth prints after exposing the teeth to acid and various degrees of temperature. Materials and Methods: 90 tooth prints from 20 freshly extracted maxillary premolar teeth were obtained. Cellophane tape technique was used to record enamel rod end patterns on tooth surface. Ten teeth (one from each patient) were immersed in 36.46% hydrochloric acid and the tooth prints were obtained at various intervals (5 min, 10 min, and 20 min). The other 10 teeth (one from each patient) were incinerated and impression was made at various intervals (80° C, 400° C, 600° C, and 750° C). Tooth prints obtained from different teeth (total of 90 tooth prints) were analyzed using Verifinger® standard SDK version 5.0 software. Results: All the 20 original tooth prints were distinct from each other and no inter-individual or intra-individual similarity was found. The tooth prints from the same tooth after it was exposed to acid or heat were reproducible and showed high to very high similarity with the original tooth print of that particular tooth stored in the database. Conclusion: Tooth prints may be used as an effective aid in person identification even in adverse conditions such as burn and acid attack injuries. PMID:27051220

  7. Effectiveness of a positive pressure respirator for controlling lead exposure in acid storage battery manufacturing

    SciTech Connect

    Grauvogel, L.W.

    1986-02-01

    Effective protection factors for lead-acid storage battery manufacturing workers using powered air-purifying respirators and their corresponding blood lead histories are reported and compared with results for half-mask, negative pressure respirators. Airborne lead protection factors for the powered, air-purifying respirator ranged from 2 to 74, while lead levels in the blood remained stable or decreased for 8 of the 13 workers monitored when compared to negative pressure respirator use levels.

  8. Effectiveness of a positive pressure respirator for controlling lead exposure in acid storage battery manufacturing.

    PubMed

    Grauvogel, L W

    1986-02-01

    Effective protection factors for lead-acid storage battery manufacturing workers using powered air-purifying respirators and their corresponding blood lead histories are reported and compared with results for half-mask, negative pressure respirators. Airborne lead protection factors for the powered, air-purifying respirator ranged from 2 to 74, while lead levels in the blood remained stable or decreased for 8 of the 13 workers monitored when compared to negative pressure respirator use levels. PMID:3456697

  9. Effectiveness of a positive pressure respirator for controlling lead exposure in acid storage battery manufacturing.

    PubMed

    Grauvogel, L W

    1986-02-01

    Effective protection factors for lead-acid storage battery manufacturing workers using powered air-purifying respirators and their corresponding blood lead histories are reported and compared with results for half-mask, negative pressure respirators. Airborne lead protection factors for the powered, air-purifying respirator ranged from 2 to 74, while lead levels in the blood remained stable or decreased for 8 of the 13 workers monitored when compared to negative pressure respirator use levels.

  10. Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets.

    PubMed

    Ruenz, Meike; Bakuradze, Tamara; Eisenbrand, Gerhard; Richling, Elke

    2016-04-01

    The present human intervention study investigated the relation between the intake of acrylamide (AA) in diets with minimized, low, and high AA contents and the levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14 healthy male volunteers over a period of 9 days, under controlled conditions excluding any inadvertent AA exposure. Dietary exposure to AA was measured by determining AA contents in duplicates of all meals consumed by the volunteers. The study design included an initial washout period of 3 days on AA-minimized diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical washout periods of 2 days each followed the AA exposure days (day 4, low exposure, and day 7, high exposure). At the respective AA intake days, volunteers ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) μg AA/kg bw/d with their food. Both low and high AA intakes resulted in an AAMA output within 72 h corresponding to 58 % of the respective AA intake. At the end of the initial 3-day washout period, an AAMA baseline level of 93 ± 31 nmol/d was recorded, suggestive for an assumed net AA baseline exposure level of 0.2-0.3 μg AA/kg bw/d.

  11. Abnormal uterine bleeding.

    PubMed

    Jennings, J C

    1995-11-01

    Physicians who care for female patients cannot avoid the frequent complaint of abnormal uterine bleeding. Knowledge of the disorders that cause this problem can prevent serious consequences in many patients and improve the quality of life for many others. The availability of noninvasive and minimally invasive diagnostic studies and minimally invasive surgical treatment has revolutionized management of abnormal uterine bleeding. Similar to any other disorder, the extent to which a physician manages abnormal uterine bleeding depends on his or her own level of comfort. When limitations of either diagnostic or therapeutic capability are encountered, consultation and referral should be used to the best interest of patients.

  12. Reexamination of London, England, mortality in relation to exposure to acidic aerosols during 1963-1972 winters

    SciTech Connect

    Thurston, G.D.; Ito, K.; Lippmann, M.; Hayes, C.

    1989-02-01

    Air pollution epidemiology since the 1950s has been able to demonstrate that increases in daily mortality in London, England, were associated with elevated concentrations of index air pollutants, i.e., British Smoke (BS) and sulfur dioxide (SO/sub 2/). In this work, we reanalyze that portion of the 1958-1972 winter mortality-pollution record for which daily direct acid aerosol measurements were made at a central site in London (St. Bartholomew's Medical College). The purposes of these exploratory analyses are to examine the dataset for indications of a relationship between acid aerosol pollution and human mortality and to compare any noted associations with those for other pollution variables. It is found that the log of acid aerosol concentrations is more strongly associated with raw total mortality in bivariate analyses than is BS or SO2, despite the fact that acid data are available from only one central site (versus seven disperse sites for BS and SO/sub 2/). The logarithmic nature of the exposure side of the H/sub 2/SO/sub 4/-mortality relationship implies a saturation model of pollution effects, possibly due to multiday pollution harvesting influences on a susceptible subpopulation. Moreover, mortality-pollution cross-correlation analyses indicate that mortality effects usually follow pollution in time, supporting a causal relationship between the two. The apparent advantage of H/sub 2/SO/sub 4/ over BS in predicting total raw mortality is consistent with the hypothesis that it is the portion of particulate mass of greater health significance and may also allow the development of London mortality results which are more easily transferable to other environments than is the case for existing BS results.

  13. Reexamination of London, England, mortality in relation to exposure to acidic aerosols during 1963-1972 winters.

    PubMed

    Thurston, G D; Ito, K; Lippmann, M; Hayes, C

    1989-02-01

    Air pollution epidemiology since the 1950s has been able to demonstrate that increases in daily mortality in London, England, were associated with elevated concentrations of index air pollutants, i.e., British Smoke (BS) and sulfur dioxide (SO2). In this work, we reanalyze that portion of the 1958-1972 winter mortality-pollution record for which daily direct acid aerosol measurements were made at a central site in London (St. Bartholomew's Medical College). The purposes of these exploratory analyses are to examine the dataset for indications of a relationship between acid aerosol pollution and human mortality and to compare any noted associations with those for other pollution variables. It is found that the log of acid aerosol concentrations is more strongly associated with raw total mortality in bivariate analyses than is BS or SO2, despite the fact that acid data are available from only one central site (versus seven disperse sites for BS and SO2). The logarithmic nature of the exposure side of the H2SO4-mortality relationship implies a saturation model of pollution effects, possibly due to multiday pollution harvesting influences on a susceptible subpopulation. Moreover, mortality-pollution cross-correlation analyses indicate that mortality effects usually follow pollution in time, supporting a causal relationship between the two. The apparent advantage of H2SO4 over BS in predicting total raw mortality is consistent with the hypothesis that it is the portion of particulate mass of greater health significance and may also allow the development of London mortality results which are more easily transferable to other environments than is the case for existing BS results.

  14. Reexamination of London, England, mortality in relation to exposure to acidic aerosols during 1963-1972 winters.

    PubMed Central

    Thurston, G D; Ito, K; Lippmann, M; Hayes, C

    1989-01-01

    Air pollution epidemiology since the 1950s has been able to demonstrate that increases in daily mortality in London, England, were associated with elevated concentrations of index air pollutants, i.e., British Smoke (BS) and sulfur dioxide (SO2). In this work, we reanalyze that portion of the 1958-1972 winter mortality-pollution record for which daily direct acid aerosol measurements were made at a central site in London (St. Bartholomew's Medical College). The purposes of these exploratory analyses are to examine the dataset for indications of a relationship between acid aerosol pollution and human mortality and to compare any noted associations with those for other pollution variables. It is found that the log of acid aerosol concentrations is more strongly associated with raw total mortality in bivariate analyses than is BS or SO2, despite the fact that acid data are available from only one central site (versus seven disperse sites for BS and SO2). The logarithmic nature of the exposure side of the H2SO4-mortality relationship implies a saturation model of pollution effects, possibly due to multiday pollution harvesting influences on a susceptible subpopulation. Moreover, mortality-pollution cross-correlation analyses indicate that mortality effects usually follow pollution in time, supporting a causal relationship between the two. The apparent advantage of H2SO4 over BS in predicting total raw mortality is consistent with the hypothesis that it is the portion of particulate mass of greater health significance and may also allow the development of London mortality results which are more easily transferable to other environments than is the case for existing BS results. PMID:2785034

  15. Effect of dexamethasone and oxygen exposure on neonatal rat lung retinoic acid receptor proteins.

    PubMed

    McMenamy, K R; Anderson, M J; Zachman, R D

    1994-10-01

    Retinol deficiency in animal models results in histopathologic airway changes that appear similar to those found in human premature infants with bronchopulmonary dysplasia (BPD). Dexamethasone (DEX), a steroid now often used in the treatment of BPD, might potentially affect lung vitamin A homeostasis since it alters serum and liver retinoid stores in certain models. Our objective was to determine the effect of DEX on neonatal rat lung retinoid status and the binding of retinoic acid (RA) to cytosolic and nuclear receptor proteins. We examined this effect both in room air and when the animals breathed 95% oxygen (O2). Twenty-four 1-day-old rat pups received either 1 microgram/g DEX subcutaneously, an equal volume of normal saline (NS) subcutaneously at 0 (start experiment time), 24, and 48 hours, or no injection at all, and were sacrificed at 72 hours. Twelve rats in each treatment group were housed in room air and 12 in each group were exposed to > 95% O2 for the 3 day period. Lung and liver were analyzed for retinyl palmitate (RP). Nuclear retinoic acid receptor (RAR) and cellular retinoic acid binding protein (CRABP) were measured by specific binding assays. DEX decreased liver RP by 33-55% and rat pup lung RP by over 60%; it also decreased lung RAR binding (mean dpm/microgram protein +/- SEM) in both room air and oxygen groups: Air (11.2 +/- 1.0) vs. Air/DEX (4.6 +/- 1.3, n = 6; P < 0.01), and O2 (18.2 +/- 0.6) vs. O2/DEX (3.2 +/- 0.6, n = 6; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7838622

  16. Bacillus cereus cell response upon exposure to acid environment: toward the identification of potential biomarkers

    PubMed Central

    Desriac, Noémie; Broussolle, Véronique; Postollec, Florence; Mathot, Anne-Gabrielle; Sohier, Danièle; Coroller, Louis; Leguerinel, Ivan

    2013-01-01

    Microorganisms are able to adapt to different environments and evolve rapidly, allowing them to cope with their new environments. Such adaptive response and associated protections toward other lethal stresses, is a crucial survival strategy for a wide spectrum of microorganisms, including food spoilage bacteria, pathogens, and organisms used in functional food applications. The growing demand for minimal processed food yields to an increasing use of combination of hurdles or mild preservation factors in the food industry. A commonly used hurdle is low pH which allows the decrease in bacterial growth rate but also the inactivation of pathogens or spoilage microorganisms. Bacillus cereus is a well-known food-borne pathogen leading to economical and safety issues in food industry. Because survival mechanisms implemented will allow bacteria to cope with environmental changes, it is important to provide understanding of B. cereus stress response. Thus this review deals with the adaptive traits of B. cereus cells facing to acid stress conditions. The acid stress response of B. cereus could be divided into four groups (i) general stress response (ii) pH homeostasis, (iii) metabolic modifications and alkali production and (iv) secondary oxidative stress response. This current knowledge may be useful to understand how B. cereus cells may cope to acid environment such as encountered in food products and thus to find some molecular biomarkers of the bacterial behavior. These biomarkers could be furthermore used to develop new microbial behavior prediction tools which can provide insights into underlying molecular physiological states which govern the behavior of microorganisms and thus opening the avenue toward the detection of stress adaptive behavior at an early stage and the control of stress-induced resistance throughout the food chain. PMID:24106490

  17. Influence of high past lead-in-air exposures on the lead-in-blood levels of lead-acid battery workers with continuing exposure.

    PubMed

    Hodgkins, D G; Hinkamp, D L; Robins, T G; Schork, M A; Krebs, W H

    1991-07-01

    We investigated the relationship between air lead levels and blood lead levels in 132 lead-acid battery workers in two plants who were followed for 30 months between 1983 and 1985 with frequent air lead and blood lead determinations. Both plants converted to more modern, expanded-metal battery manufacturing technologies around 1978 with associated reductions in mean air lead exposures from greater than 100 to less than 30 micrograms/m3. In multiple regression analyses including consideration of job category, seniority, age, ethnicity, gender, and smoking habit as covariates, there was a highly significant association of blood lead in micrograms/dL with air lead in micrograms/m3 (partial R2 = .20, P less than .0001) among the 68 workers in plant B but no association (P = .91) in plant A. Restriction of the regression analysis to those 44 workers in plant B with less than or equal to 22 years of seniority yielded the most significant air lead-blood lead association (partial R2 = .36, P less than .0001). Among the remaining 24 plant B workers, seniority, but not air lead, had a significant positive association with blood lead. Despite very stable air lead levels over the 30-month study, the 51 workers in plant A with more than 20 years' seniority had a mean decline of 0.04 microgram/dL in mean blood lead over the study period, whereas the 13 workers in plant A with less than or equal to 20 years' seniority had a mean increase of 7.6 microgram/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  19. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  20. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  1. Exposures of 129 preschool children to organochlorines, organophosphates, pyrethroids, and acid herbicides at their homes and daycares in North Carolina.

    PubMed

    Morgan, Marsha K; Wilson, Nancy K; Chuang, Jane C

    2014-04-03

    Few data exist on the concurrent exposures of young children to past-use and current-use pesticides in their everyday environments. In this further analysis of study data, we quantified the potential exposures and intake doses of 129 preschool children, ages 20 to 66 months, to 16 pesticides (eight organochlorines, two organophosphates, three pyrethroids, and three acid herbicides). Environmental samples (soil, dust, outdoor air, and indoor air) and personal samples (hand wipes, solid food, and liquid food) were collected at 129 homes and 13 daycare centers in six counties in North Carolina between 2000 and 2001. α-Chlordane, γ-chlordane, heptachlor, chlorpyrifos, diazinon, cis-permethrin, trans-permethrin, and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected ≥50% in two or more media in both settings. Of these pesticides, the children's estimated median potential intake doses through dietary ingestion, nondietary ingestion, and inhalation routes were the highest for 2,4-D and cis/trans-permethrin (both 4.84 ng/kg/day), cis/trans-permethrin (2.39 ng/kg/day), and heptachlor (1.71 ng/kg/day), respectively. The children's estimated median potential aggregate intake doses by all three routes were quantifiable for chlorpyrifos (4.6 ng/kg/day), cis/trans-permethrin (12.5 ng/kg/day), and 2,4-D (4.9 ng/kg/day). In conclusion, these children were likely exposed daily to several pesticides from several sources and routes at their homes and daycares.

  2. Exposures of 129 Preschool Children to Organochlorines, Organophosphates, Pyrethroids, and Acid Herbicides at Their Homes and Daycares in North Carolina

    PubMed Central

    Morgan, Marsha K.; Wilson, Nancy K.; Chuang, Jane C.

    2014-01-01

    Few data exist on the concurrent exposures of young children to past-use and current-use pesticides in their everyday environments. In this further analysis of study data, we quantified the potential exposures and intake doses of 129 preschool children, ages 20 to 66 months, to 16 pesticides (eight organochlorines, two organophosphates, three pyrethroids, and three acid herbicides). Environmental samples (soil, dust, outdoor air, and indoor air) and personal samples (hand wipes, solid food, and liquid food) were collected at 129 homes and 13 daycare centers in six counties in North Carolina between 2000 and 2001. α-Chlordane, γ-chlordane, heptachlor, chlorpyrifos, diazinon, cis-permethrin, trans-permethrin, and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected ≥50% in two or more media in both settings. Of these pesticides, the children’s estimated median potential intake doses through dietary ingestion, nondietary ingestion, and inhalation routes were the highest for 2,4-D and cis/trans-permethrin (both 4.84 ng/kg/day), cis/trans-permethrin (2.39 ng/kg/day), and heptachlor (1.71 ng/kg/day), respectively. The children’s estimated median potential aggregate intake doses by all three routes were quantifiable for chlorpyrifos (4.6 ng/kg/day), cis/trans-permethrin (12.5 ng/kg/day), and 2,4-D (4.9 ng/kg/day). In conclusion, these children were likely exposed daily to several pesticides from several sources and routes at their homes and daycares. PMID:24705361

  3. Molecular-biological analysis of acute lung injury (ALI) induced by heat exposure and/or intravenous administration of oleic acid.

    PubMed

    Inoue, Hiromasa; Nakagawa, Yasuhisa; Ikemura, Mayumi; Usugi, Eri; Nata, Masayuki

    2012-11-01

    The aim of this study was to molecular-biologically investigate the interaction between heat exposure and pulmonary fat embolization in regards to the development of acute lung injury (ALI). Ten-week-old Wistar male rats were divided into four groups: (1) oleic acid injected into caudal vein after heat exposure, (2) oleic acid injected without heat exposure, (3) soybean oil injected after heat exposure, and (4) soybean oil injected without heat exposure, and then mRNA expression of eight inflammatory mediators related to ALI/acute respiratory distress syndrome (ARDS) and heat shock protein 70 (Hsp70) in lung was determined 1h after the injection. mRNA expression of interleukin 1 beta (Il1b), tumor necrosis factor alpha (Tnfa), vascular endothelial growth factor A (Vegfa), transforming growth factor beta 1 (Tgfb1) and Hsp70 was significantly increased by heat exposure, while that of Il1b, interleukin 6 (Il6), Tnfa, macrophage inflammatory protein 2 (Mip2) and granulocyte macrophage-colony stimulating factor (Gm-csf) was significantly elevated by the injection of oleic acid. Moreover, the expressions of inflammatory cytokines and chemokines in lung almost paralleled their mRNA expressions. In particular, IL-1β expression was synergistically elevated by heat exposure followed by injection of oleic acid. Additionally, IL-6 expression tended to increase under the same conditions as well. It is likely that heat exposure itself injures lung tissue within a short time, and that more than two conditions which induce ALI/ARDS interact with each other synergistically, exacerbating the development of ALI/ARDS.

  4. Changes in the viscosity of hyaluronic acid after exposure to a myeloperoxidase-derived oxidant

    SciTech Connect

    Baker, M.S.; Green, S.P.; Lowther, D.A.

    1989-04-01

    Both purified hyaluronic acid (HA) and bovine synovial fluid react with OCI-, the major oxidant produced by the myeloperoxidase (MPO)/H/sub 2/O/sub 2//CI- system, resulting in a decrease in their specific viscosity. This reaction is inhibited in the presence of excess methionine. H/sub 2/O/sub 2/ alone decreases the viscosity of HA, presumably by the Fenton reaction, in the absence (but not in the presence) of the iron chelator, diethyltriaminepentacetic acid (DETAPAC). In the presence of DETAPAC, incubation of HA with the complete MPO/H/sub 2/O/sub 2//CI- system lowered the viscosity of HA. Analysis of 3H-HA exposed to OCI- by gel filtration chromatography indicated that cleavage of HA occurred only at higher OCI- concentrations. We suggest that the reduction in viscosity of HA by the MPO/H/sub 2/O/sub 2//CI- system may be due to a combination of oxidative cleavage and changes in the conformation of the molecule. We speculate that the changes in the molecular size of rheumatoid synovial fluid HA may be due to the action of the neutrophil MPO/H/sub 2/O/sub 2//CI- system.

  5. Preliminary investigation of effects of sublethal acid exposure on maternal behavior in the Crayfish Orconectes virilis

    SciTech Connect

    France, R.L.

    1985-11-01

    The occurrence of crayfish inhabiting the littoral regions of many oligotrophic acid sensitive lakes makes these organisms vulnerable to spring pH decreases. Egg extrusion in Orconectes spp. found in south-central Ontario is generally synchronous and occurs during or slightly after ice melting in late April, a time at which these lakes receive between 36-77% of the year's export of H from their watersheds. To understand how a toxicant affects crayfish reproduction it is necessary that the maternal and embryonic responses to experimental perturbation be separated. In an acidified lake in the Experimental Lakes Area, northwestern Ontario, 6.9-16.9% of the egg-bearing females experienced partial mortality of their broods at pH 5.4-5.6. An ancillary experiment was undertaken here to determine if this egg mortality could be a result of low pH-induced behavioral modification of the maternal female, rather than direct acid toxicity to the developing eggs.

  6. Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic reticulum stress during hepatocarcinogen exposure

    PubMed Central

    Vandewynckel, Yves-Paul; Laukens, Debby; Devisscher, Lindsey; Paridaens, Annelies; Bogaerts, Eliene; Verhelst, Xavier; Van den Bussche, Anja; Raevens, Sarah; Van Steenkiste, Christophe; Van Troys, Marleen; Ampe, Christophe; Descamps, Benedicte; Vanhove, Chris; Govaere, Olivier; Geerts, Anja; Van Vlierberghe, Hans

    2015-01-01

    Hepatocellular carcinoma (HCC) is characterized by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which activates the unfolded protein response (UPR). However, the role of ER stress in tumor initiation and progression is controversial. To determine the impact of ER stress, we applied tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties. The effects of TUDCA were assessed using a diethylnitrosamine-induced mouse HCC model in preventive and therapeutic settings. Cell metabolic activity, proliferation and invasion were investigated in vitro. Tumor progression was assessed in the HepG2 xenograft model. Administration of TUDCA in the preventive setting reduced carcinogen-induced elevation of alanine and aspartate aminotransferase levels, apoptosis of hepatocytes and tumor burden. TUDCA also reduced eukaryotic initiation factor 2α (eIf2α) phosphorylation, C/EBP homologous protein expression and caspase-12 processing. Thus, TUDCA suppresses carcinogen-induced pro-apoptotic UPR. TUDCA alleviated hepatic inflammation by increasing NF-κB inhibitor IκBα. Furthermore, TUDCA altered the invasive phenotype and enhanced metabolic activity but not proliferation in HCC cells. TUDCA administration after tumor development did not alter orthotopic tumor or xenograft growth. Taken together, TUDCA attenuates hepatocarcinogenesis by suppressing carcinogen-induced ER stress-mediated cell death and inflammation without stimulating tumor progression. Therefore, this chemical chaperone could represent a novel chemopreventive agent. PMID:26293671

  7. Formation of fatty acid esterified vitamin D3 in rat skin by exposure to ultraviolet radiation

    SciTech Connect

    Takada, K.

    1983-04-01

    The formation of fatty acid esters of vitamin D3 was demonstrated in rat skin exposed to artificial ultraviolet rays by using multi-dimensional high-performance liquid chromatography, ultraviolet spectrophotometry, and gas-liquid chromatography-mass spectrometry. This result indicated that the fatty acid esters of 7-dehydrocholesterol in rat skin (at least 80% of 7-dehydrocholesterol in rat skin is esterified) is also isomerized into vitamin D3 ester in vivo. The initial percentage of the esterified form was 84.3% and this did not significantly change up to the time when about half of the skin total vitamin D3 disappeared (2 days). Consequently, it was speculated that the vitamin D3 ester was delivered into the blood circulation from skin without having been hydrolyzed. This was supported by the presence of vitamin D3 ester in rat plasma exposed to ultraviolet radiation. In addition, in connection with the study of the restriction of vitamin D3 synthesis, distribution of total vitamin D3 in rat skin exposed to ultraviolet irradiation in vivo was compared with that in isolated skin exposed to ultraviolet radiation. The dermal layer of the isolated skin contained about 4 times more total vitamin D3 than that of in vivo skin. This finding suggests not only that ultraviolet rays could not penetrate deeply into the in vivo skin, but that the restriction of cutaneous synthesis of vitamin D3 observed in vivo may arise from this reduced penetration of ultraviolet rays.

  8. Assessment of the deoxyribonucleic acid damage caused by occupational exposure to chemical compounds in Isfahan Polyacryl Company

    PubMed Central

    Etebari, Mahmoud; Jafarian-Dehkordi, Abbas; Kahookar, Ahmad; Moradi, Shahla

    2014-01-01

    Background: Chemical pollutants found in industrial environments can cause chronic genotoxicity in vulnerable individuals during the long-term exposure. The primary purpose of the present study was to assess the deoxyribonucleic acid (DNA) damage caused by occupational exposure to industrial chemicals and secondary purpose is to investigate the effect of possible risk factors of genotoxicity. Materials and Methods: The blood samples of the workers of Isfahan Polyacryl Company were evaluated in terms of genotoxicity using the comet assay method. The percentage of DNA in the tail and tail moment were measured and DNA damage was evaluated. Furthermore, the effect of age, smoking, duration of working in the company and working in two parts of the company on the degree of vulnerability to genotoxicity was assessed. Results: The amount of DNA damage in the target group (the production line workers) was significantly higher than the control group (the staffs), 3.87 versus 1.52 as tail moment, (P < 0.0001). DNA damage was significantly higher in smoker groups compared with non-smoker target group and control group, 4.18 versus 3.07 and 1.52 respectively as tail moment, (P < 0.0001). Furthermore, it was higher in person working in two different parts of the company compared to those work in one part and control group, 4.63 versus 3.74 and 1.52 respectively as tail moment, (P < 0.0001). Conclusion: Occupational exposure to Polyacryl caused DNA damage. Smoking and working in two parts of the company may have a significant role in DNA damage. PMID:25197297

  9. Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

    PubMed Central

    DeAngeli, Nicole E.; Todd, Travis P.; Chang, Stephen E.; Yeh, Hermes H.; Yeh, Pamela W.; Bucci, David J.

    2015-01-01

    Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

  10. Exposure to monomethylarsonous acid (MMA{sup III}) leads to altered selenoprotein synthesis in a primary human lung cell model

    SciTech Connect

    Meno, Sarah R.; Nelson, Rebecca; Hintze, Korry J.; Self, William T.

    2009-09-01

    Monomethylarsonous acid (MMA{sup III}), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMA{sup III} is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMA{sup III} on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMA{sup III} resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMA{sup III} treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMA{sup III}, as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMA{sup III} induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMA{sup III} alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element.

  11. Histological changes and antioxidant enzyme activity in signal crayfish (Pacifastacus leniusculus) associated with sub-acute peracetic acid exposure.

    PubMed

    Chupani, Latifeh; Zuskova, Eliska; Stara, Alzbeta; Velisek, Josef; Kouba, Antonin

    2016-01-01

    Peracetic acid (PAA) is a powerful disinfectant recently adopted as a therapeutic agent in aquaculture. A concentration of 10 mg L(-1) PAA effectively suppresses zoospores of Aphanomyces astaci, the agent of crayfish plague. To aid in establishing safe therapeutic guideline, the effects of PAA on treated crayfish were investigated through assessment of histological changes and oxidative damage. Adult female signal crayfish Pacifastacus leniusculus (n = 135) were exposed to 2 mg L(-1) and 10 mg L(-1) of PAA for 7 days followed by a 7 day recovery period in clean water. Superoxide dismutase activity was significantly lower in gill and hepatopancreas after three days exposure to 10 mg L(1) PAA than in the group treated with 2 mg L(-1) PAA and a control in only clean water. Catalase activity in gill and hepatopancreas remained unaffected by both exposures. Glutathione reductase was significantly decreased in gill of 10 mg L(-1) PAA treated crayfish and increased in group exposed to 2 mg L(-1) compared to control after 7 days exposure. Antioxidant enzyme activity in exposed groups returned to control values after recovery period. Gill, hepatopancreas, and antennal gland showed slight damage in crayfish treated with 2 mg L(-1) of PAA compared to the control group. The extent and frequency of histological alterations were more pronounced in animals exposed to 10 mg L(-1). The gill was the most affected organ, infiltrated by granular hemocytes and displaying malformations of lamella tips and disorganization of epithelial cells. After a 7 day recovery period, the infiltrating cells in affected tissues of the exposed crayfish began to return to normal levels. Results suggested that the given concentrations could be applied to signal crayfish against crayfish plague agent in aquaculture; however, further studies are required for safe use. PMID:26611721

  12. Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts.

    PubMed

    Honda, Hiroshi; Fujii, Kenkichi; Yamaguchi, Tohru; Ikeda, Naohiro; Nishiyama, Naohiro; Kasamatsu, Toshio

    2012-11-01

    Glycidol fatty acid esters (GEs) have been found as impurities in refined edible oils including diacylglycerol (DAG) oil, and concerns of possible exposure to glycidol (G), a known animal carcinogen, during digestion have been raised. We previously measured N-(2,3-dihydroxy-propyl)valine (diHOPrVal), a G hemoglobin adduct, for DAG oil exposed and non-exposed groups and showed there was no significant difference between them. In the present study, we conducted an additional analysis to verify the outcome of the previous report. The first experiment was designed as a matched case-control study to adjust variables with an increased sample size. The average levels of diHOPrVal were 6.9 pmol/g-globin (95%CI: 4.9-9.0) for 14 DAG oil exposed subjects and 7.3 pmol/g-globin (95%CI: 6.1-8.5) for 42 non-exposed volunteers, and no significant difference in levels was found between the two groups. In a second experiment, we compared the adduct levels of 12 DAG oil exposed subjects before and after discontinuing use of DAG oil, and found there was no significant change in diHOPrVal levels (from 7.1±1.1 to 7.5±1.4 pmol/g-globin). These results suggest that there was no increased exposure to G for humans who ingested DAG oil daily, although the evaluated population was limited.

  13. A SURVEY OF LIQUID CHROMATOGRAPHIC-MASS SPECTROMETRIC ANALYSIS OF MERCAPTURIC ACID BIOMARKERS IN OCCUPATIONAL AND ENVIRONMENTAL EXPOSURE MONITORING

    PubMed Central

    Mathias, Patricia I.; B’Hymer, Clayton

    2015-01-01

    High-performance liquid chromatography/mass spectrometry (HPLC/MS) is sensitive and specific for targeted quantitative analysis and is readily utilized for small molecules from biological matricies. This brief review describes recent selected HPLC/MS methods for the determination of urinary mercapturic acids (mercapturates) which are useful as biomarkers in characterizing human exposure to electrophilic industrial chemicals in occupational and environmental studies. Electrophilic compounds owing to their reactivity are used in chemical and industrial processes. They are present in industrial emissions, are combustion products of fossil fuels, and are components in tobacco smoke. Their presence in both the industrial and general environment are of concern for human and environmental health. Urinary mercapturates which are the products of metabolic detoxification of reactive chemicals provide a non-invasive tool to investigate human exposure to electrophilic toxicants. Selected recent mercapturate quantification methods are summarized and specific cases are presented. The biological formation of mercapturates is introduced and their use as biomarkers of metabolic processing of electrophilic compounds is discussed. Also, the use of liquid chromatography/tandem mass spectrometry in simultaneous determinations of the mercapturates of multiple parent compounds in a single determination is considered, as well as future trends and limitations in this area of research. PMID:24746702

  14. Effect of chronic exposure to ozone and nitric acid on cytochrome P450 monooxygenase system of rat lung and liver

    SciTech Connect

    Sindhu, R.K.; Mautz, W.J.; Ichiro Fujita, Nai-San Wang; Yutaka, Kikkawa

    1996-03-08

    Male F344/N rats were exposed to 0.15ppm ozone (O{sub 3}) and 50{mu}g/m{sup 3} nitric acid (HNO{sub 3}) vapor alone and in combination for 4h/day 3days/week for a total of 40 weeks. Exposure to HNO{sub 3} vapor alone caused a significant increase of 7-ethoxyresorufin O-deethylase (EROD) activity in the hepatic microsomes (p{le}0.05). Monoclonal cytochrome P450 aA1/1A2 antibody-precipitable EROD activity in the hepatic microsomes was increased by 59% (p{le}0.01) and 40T (p{le}0.05), respectively, in the HNO{sub 3} vapor and {sub 3}+HNO{sub 3} vapor groups. In the pulmonary microsomes, benzphetamine N-demethylase (BPND) activity was increased by 72% (p{le}0.01), 85% (p{le}0.01) and decreased by 15% (p{le}0.01), respectively, by exposure to O{sub 3}, O{sub 3}+HNO{sub 3} and HNO{sub 3} vapor, but was unaffected in the hepatic microsomes.

  15. A survey of liquid chromatographic-mass spectrometric analysis of mercapturic acid biomarkers in occupational and environmental exposure monitoring.

    PubMed

    Mathias, Patricia I; B'Hymer, Clayton

    2014-08-01

    High-performance liquid chromatography/mass spectrometry (HPLC/MS) is sensitive and specific for targeted quantitative analysis and is readily utilized for small molecules from biological matrices. This brief review describes recent selected HPLC/MS methods for the determination of urinary mercapturic acids (mercapturates) which are useful as biomarkers in characterizing human exposure to electrophilic industrial chemicals in occupational and environmental studies. Electrophilic compounds owing to their reactivity are used in chemical and industrial processes. They are present in industrial emissions, are combustion products of fossil fuels, and are components in tobacco smoke. Their presence in both the industrial and general environments are of concern for human and environmental health. Urinary mercapturates which are the products of metabolic detoxification of reactive chemicals provide a non-invasive tool to investigate human exposure to electrophilic toxicants. Selected recent mercapturate quantification methods are summarized and specific cases are presented. The biological formation of mercapturates is introduced and their use as biomarkers of metabolic processing of electrophilic compounds is discussed. Also, the use of liquid chromatography/tandem mass spectrometry in simultaneous determinations of the mercapturates of multiple parent compounds in a single determination is considered, as well as future trends and limitations in this area of research.

  16. Kinetics of Antibody Aggregation at Neutral pH and Ambient Temperatures Triggered by Temporal Exposure to Acid.

    PubMed

    Imamura, Hiroshi; Honda, Shinya

    2016-09-15

    The purification process of an antibody in manufacturing involves temporal exposure of the molecules to low pH followed by neutralization-pH-shift stress-which causes aggregation. It remains unclear how aggregation triggered by pH-shift stress grows at neutral pH and how it depends on the temperature in an ambient range. We used static and dynamic light scattering to monitor the time-dependent evolution of the aggregate size of the pH-shift stressed antibody between 4.0 and 40.0 °C. A power-law relationship between the effective molecular weight and the effective hydrodynamic radius was found, indicating that the aggregates were fractal with a dimension of 1.98. We found that the aggregation kinetics in the lower-temperature range, 4.0-25.0 °C, were well described by the Smoluchowski aggregation equation. The temperature dependence of the effective aggregation rate constant gave 13 ± 1 kcal/mol of endothermic activation energy. Temporal acid exposure creates an enriched population of unfolded protein molecules that are competent of aggregating. Therefore, the energetically unfavorable unfolding step is not required and the aggregation proceeds faster. These findings provide a basis for predicting the growth of aggregates during storage under practical, ambient conditions. PMID:27537343

  17. High-resolution differentiation of transmissible spongiform encephalopathy strains by quantitative N-terminal amino acid profiling (N-TAAP) of PK-digested abnormal prion protein.

    PubMed

    Gielbert, Adriana; Davis, Linda A; Sayers, A Robin; Hope, James; Gill, Andrew C; Sauer, Maurice J

    2009-03-01

    New forms of transmissible spongiform encephalopathy (TSE) continue to be identified, and consequently sensitive differential diagnosis is increasingly important both for the management of disease in humans and livestock and in providing confidence in the safety of the food chain. TSE diseases are associated with accumulation of protease-resistant prion protein (PrP(Sc)) and detection of this marker protein is central to diagnosis. Proteolysis by proteinase K (PK) generates protease-resistant products (PrP(res)) with partially variable N-termini. The conformation(s) of PrP(Sc) and thus the points of PK cleavage are thought to be dependent on the strain of prion disease. Western blot (WB) analysis of PrP(res) gives characteristic migration patterns that can be used to diagnose TSEs, but the relatively low resolution of this technique limits its ability to differentiate certain disease strains. Mass spectrometry (MS) has the capability to resolve these various PK cleavage sites to the level of individual amino acid residues. In the present study multiple selected reaction monitoring (mSRM) was used to detect and quantify PrP(res) N-terminal tryptic peptides by MS and thus to define the N-terminal amino acid profiles (N-TAAPs) of PrP(res) characteristic for various TSEs in sheep. The fragmentation behaviour of the N-terminal tryptic peptides was studied to allow selection of the transitions specific for each peptide. Different PrP(res) preparation methods were evaluated and the most effective approach applied to differentiate the N-TAAPs corresponding to various sheep TSE isolates. Marked differences were identified between the N-TAAPs of bovine spongiform encephalopathy (BSE) and classical scrapie, and between classical scrapie and the experimental strains SSBP/1 and CH1641, thereby validating this approach as a means of TSE-strain specific diagnosis.

  18. Oxidant and acid aerosol exposure in healthy subjects and subjects with asthma. Part 1. Effects of oxidants, combined with sulfuric or nitric acid, on the pulmonary function of adolescents with asthma. Part 2. Effects of sequential sulfuric acid and ozone exposures on the pulmonary function of healthy subjects and subjects with asthma. Research report, February 1989-April 1994

    SciTech Connect

    Koenig, J.Q.; Covert, D.S.; Pierson, W.E.; Hanley, Q.S.; Rebolledo, V.

    1994-11-01

    The study investigated the pulmonary effects of acid summer haze in a controlled laboratory setting. Of 28 adolescent subjects with allergic asthma, exercise-induced bronchospasm, and a positive response to a standardized methacholine challenge enrolled in the study, 22 completed the study. For two consecutive days each subject inhaled each of four test atmospheres by mouthpiece. The order of exposure to the four test atmospheres was assigned via a random protocol; air, oxidants (0.12 parts per million (ppm) ozone plus 0.30 ppm nitrogen dioxide), oxidants plus sulfuric acid at 70 micro/m3 of air, or oxidants plus 0.05 ppm nitric acid. Exposure to each of the different atmospheres was separated by at least one week. A postexposure methacholine challenge was performed on Day 3.

  19. Effects of prolonged, sequential exposure to acid fog and ozone on pulmonary function in exercising, normal subjects. Final report, 28 Feb 89-28 Dec 90

    SciTech Connect

    Balmes, J.

    1990-05-01

    Thirty-nine apparently healthy and asymptomatic subjects were selected for a study that screened for sensitivity to ozone. After three hours of ozone exposure (at 0.20 ppm), eighteen of the subjects (46 percent) experienced a 10 percent reduction in forced expiratory volume, an indicator of exhaling ability. After four hours of exposure, 62 percent of the subjects experienced a similar reduction in expiratory volume. Further, narrowing of airways among the sensitive subjects was suggested by results of the methacholine challenge test, a standard test for measuring airway resistance. The lung capacity of all subjects decreased progressively during ozone exposures. Capacity was unchanged during acidic fog and pollutant-free air exposures. No statistically significant differences in airway resistance, airway responsiveness and symptoms that could be attributed to acid fog exposure were observed. The study indicates that exposue to fog containing nitric acid followed by exposure to ozone does not have additive or synergistic acute effects. However, the study confirms earlier indications that many apparently healthy and asymptomatic individuals are susceptible to and adversely affected by ozone at relatively low concentrations.

  20. The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.

    PubMed

    Pennimpede, Tracie; Cameron, Don A; MacLean, Glenn A; Li, Hui; Abu-Abed, Suzan; Petkovich, Martin

    2010-10-01

    Retinoic acid (RA) is a pleiotropic derivative of vitamin A, or retinol, which is responsible for all of the bioactivity associated with this vitamin. The teratogenic influences of vitamin A deficiency and excess RA in rodents were first observed more than 50 years ago. Efforts over the last 15-20 years have refined these observations by defining the molecular mechanisms that control RA availability and signaling during murine embryonic development. This review will discuss our current understanding of the role of RA in teratogenesis, with specific emphasis on the essential function of the RA catabolic CYP26 enzymes in preventing teratogenic consequences caused by uncontrolled distribution of RA. Particular focus will be paid to the RA-sensitive tissues of the caudal and cranial regions, the limb, and the testis, and how genetic mutation of factors controlling RA distribution have revealed important roles for RA during embryogenesis.

  1. DISTRIBUTION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN DIFFERENT PARTS OF THE RAT BRAIN UNDER CADMIUM EXPOSURE.

    PubMed

    Kovalchuk, Yu P; Prischepa, I V; Si, U; Nedzvetsky, V S; Kot, Y G; Persky, E E; Ushakova, G A

    2015-01-01

    The chronic effects of low doses of cadmium on the distribution of soluble and filament forms of glial fibrillary acidic protein (GFAP) and their polypeptide fragments in different parts of the rat brain were investigated. Obtained results showed dose-dependent effect of cadmium on the soluble form of GFAP and more pronounced effect on the filament form and composition of the polypeptide fragments of the protein in the rat brain. Prolonged intoxication by cadmium ions in a dose of 1.0 μg/kg of body weight induced a significant decrease in soluble GFAP and an increase in the filament form in the rat brain, pointing to the development of reactive astrogliosis and the risk of neurodegeneration.

  2. Modulation of multiple sclerosis by sunlight exposure: role of cis-urocanic acid.

    PubMed

    Correale, Jorge; Farez, Mauricio F

    2013-08-15

    The role of cis-urocanic acid (UCA) as a UV-mediated immunomodulator in MS patients was investigated. Plasma levels of cis-UCA were significantly lower in MS patients compared to controls. Stimulation of MBP- and MOG-specific T cells in the presence of cis-UCA, significantly increased IL-10, and inhibited IFN-γ production. PBMCs cultured in the presence of cis-UCA increased CD4(+)CD25(+)FoxP3(+) regulatory T cell percentages. Dendritic cells cultured in the presence of cis-UCA significantly reduced Ag presentation capacity. Finally, cis-UCA activated the 5-HT2A receptor, inducing the increase in phosphorylated forms of ERK 1/2 and JNK2. Thus, in addition to vitamin D, cis-UCA also appears to be an additional UV-mediated immunomodulator. PMID:23800457

  3. Analysis of health effects resulting from population exposures to acid precipitation precursors.

    PubMed Central

    Ozkaynak, H; Spengler, J D

    1985-01-01

    Types of available studies relevant to the quantification of air pollution health effects and their principal limitations are discussed. Assessments are provided based on review and re-analysis of previously reported data bases, synthesis of published findings, and original analysis of health data sets using new methods or recent size-specific particle mass measurements. Interim results from ongoing research activities on airborne particle health effects are presented. It is shown that preliminary results obtained from cross-sectional and time-series mortality studies appear to be consistent, indicating that particulate air pollution, even at current levels, could be of concern for public health. Throughout the paper, methodological deficiencies and remaining gaps in knowledge are identified. In particular, uncertainties associated with the reported exposure-response coefficients are assessed. Finally, by characterizing the limitations of analysis we propose various recommendations for future studies and research that will serve to further define the nature, magnitude, and uncertainties of air pollution health risks. PMID:4076093

  4. Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure.

    PubMed

    Abali, Remzi; Yuksel, Mehmet Aytac; Aktas, Cevat; Celik, Cem; Guzel, Savas; Erfan, Gamze; Sahin, Onder

    2013-08-01

    Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0 mg/kg/day (group 1), 7.5 mg/kg/day (group 2) or 15 mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.

  5. Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure.

    PubMed

    Piermartiri, Tetsade C B; Pan, Hongna; Chen, Jun; McDonough, John; Grunberg, Neil; Apland, James P; Marini, Ann M

    2015-09-01

    Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism. PMID:25920465

  6. The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy.

    PubMed

    Davis, Michael; Myers, Karyn M

    2002-11-15

    Although much is now known about the neural basis of fear acquisition, the mechanisms of fear inhibition or suppression remain largely obscure. Fear inhibition is studied in the laboratory through the use of an extinction procedure, in which an animal (typically a rat) is exposed to nonreinforced presentations of a conditioned stimulus (CS; e.g., a light or tone) that had previously been paired with a fear-inducing unconditioned stimulus (US; e.g., a mild footshock). Over the course of such training, the conditioned fear response exhibited by the rat in the presence of the CS is reduced in amplitude and frequency. This procedure is analogous to those employed in the treatment of fear dysregulation in humans, which typically involve exposure to the feared object in the absence of any overt danger. Recent work on the neural basis of extinction indicates that the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are critically involved. Gamma-aminobutyric acid may act to inhibit brain areas involved in fear learning (e.g., the amygdala), and glutamate, acting at N-methyl-D-aspartate receptors, may play a role in the neural plasticity that permits this GABA-mediated inhibition to be exerted appropriately. These insights have significant implications for the conduct of extinction-based clinical interventions for fear disorders.

  7. Does the model for end-stage liver disease score predict transfusion amount, acid-base imbalance, haemodynamic and oxidative abnormalities during living donor liver transplantation?

    PubMed

    Lee, J; Chung, M Y

    2011-01-01

    The model for end-stage liver disease (MELD) score is associated with the severity of liver failure in transplant patients. This study examined whether life-threatening stress factors during liver transplantation differed according to the patients' preoperative MELD scores. Forty-four patients who underwent living donor liver transplantation were divided into a high MELD group (MELD score ≥ 20) (n = 25) and a low MELD group (MELD score < 20) (n = 19). The volume of blood components transfused, acid-base homeostasis variables, and haemodynamic and oxidative variables were measured at each stage of the surgery. The systemic vascular resistance index was significantly lower in the high MELD group than in the low MELD group at all time points. The oxygen utility index and the oxygen extraction ratio were all significantly lower in the high MELD group than in the low MELD group only at the preanhepatic stage and not at later stages of surgery. Intraoperative transfusion volume and the severity of metabolic acidosis were not associated with the preoperative MELD score.

  8. The laminin binding protein p40 is involved in inducing limb abnormality of mouse fetuses as the effects of methoxyacetic acid treatment.

    PubMed

    Ruyani, Aceng; Sudarwati, Sri; Sutasurya, Lien A; Sumarsono, Sony H; Gloe, Torsten

    2003-09-01

    This study is intended to characterize a protein that is linked with mouse limb teratogenicity as the effects of methoxyacetic acid (MAA) treatment. A single dose of MAA (10 mmol/kg body weight) was given by gavage on gestation day (GD) 11, whereas the control group were administered vehicle only. The pregnant mice were killed at 4 h after MAA treatment, and forelimb buds were isolated from both the control and treated group embryos. Proteins from forelimb buds GD 11 + 4 h, which were precipitated out using 40-60% ammonium sulfate, then were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-D SDS-PAGE) technique. The 2-D gels reveal one protein with 41.6 kDa and pI 6.4, which expression was downregulated after MAA treatment. Tentative protein identification via peptide mass database search and definitive protein identification via a primary sequence database search indicate that the protein matches exactly to 34/67 kDa laminin binding protein (LBP; P14206, SwissProt), which is encoded by p40 gene (MGI:105381). The identity was further verified by Western blotting with an antibody against the 67 kDa LBP. The results suggest that MAA treatment to pregnant mice downregulates the LBP-p40 in the forelimb buds.

  9. Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

    PubMed

    Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; McNamara, Robert K

    2014-03-01

    Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats.

  10. Fetal alcohol exposure: consequences, diagnosis, and treatment.

    PubMed

    Pruett, Dawn; Waterman, Emily Hubbard; Caughey, Aaron B

    2013-01-01

    Maternal alcohol use during pregnancy is prevalent, with as many as 12% of pregnant women consuming alcohol. Alcohol intake may vary from an occasional drink, to weekly binge drinking, to chronic alcohol use throughout pregnancy. Whereas there are certain known consequences from fetal alcohol exposure, such as fetal alcohol syndrome, other effects are less well defined. Craniofacial dysmorphologies, abnormalities of organ systems, behavioral and intellectual deficits, and fetal death have all been attributed to maternal alcohol consumption. This review article considers the theoretical mechanisms of how alcohol affects the fetus, including the variable susceptibility to fetal alcohol exposure and the implications of ethanol dose and timing of exposure. Criteria for diagnosis of fetal alcohol syndrome are discussed, as well as new methods for early detection of maternal alcohol use and fetal alcohol exposure, such as the use of fatty acid ethyl esters. Finally, current and novel treatment strategies, both in utero and post utero, are reviewed.

  11. Intracerebroventricular injection of propionic acid, an enteric metabolite implicated in autism, induces social abnormalities that do not differ between seizure-prone (FAST) and seizure-resistant (SLOW) rats.

    PubMed

    Shultz, Sandy R; Aziz, Noor A B; Yang, Li; Sun, Mujun; MacFabe, Derrick F; O'Brien, Terence J

    2015-02-01

    Autism is a complex neurodevelopmental disorder that is characterized by social abnormalities. Genetic, dietary and gut-related factors are implicated in autism, however the causal properties of these factors and how they may interact are unclear. Propionic acid (PPA) is a product of gut microbiota and a food preservative. PPA has been linked to autism, and PPA administration to rats is an animal model of the condition. Seizure-prone (FAST) and seizure-resistant (SLOW) rats were initially developed to investigate differential vulnerability to developing epilepsy. However, FAST rats also display autistic-like features, and have been proposed as a genetic model of autism. Here we examined the effects of PPA on social behavior in FAST and SLOW rats. A single intracerebroventricular injection of PPA, or phosphate-buffered saline (PBS), was administered to young-adult male FAST and SLOW rats. Immediately after treatment, rats were placed in same-treatment and same-strain pairs, and underwent social behavior testing. PPA induced social abnormalities in both FAST and SLOW rat strains. While there was no evidence of social impairment in FAST rats that were not treated with PPA, these rats were hyperactive relative to SLOW rats. Post-mortem immunofluorescence analysis of brain tissue indicated that PPA treatment resulted in increased astrogliosis in the corpus callosum and cortex compared to PBS treatment. FAST rats had increased astrogliosis in the cortex compared to SLOW rats. Together these findings support the use of PPA as a rat model of autism, but indicate there are no interactive effects between the PPA and FAST models.

  12. Urinary t,t-muconic acid as an indicator of exposure to benzene.

    PubMed Central

    Inoue, O; Seiji, K; Nakatsuka, H; Watanabe, T; Yin, S N; Li, G L; Cai, S X; Jin, C; Ikeda, M

    1989-01-01

    A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene. PMID:2923822

  13. Non-relapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation

    PubMed Central

    McDermott, Cara L.; Sandmaier, Brenda M.; Storer, Barry; Li, Hong; Mager, Donald E.; Boeckh, Michael J.; Bemer, Meagan J.; Knutson, Jennifer; McCune, Jeannine S.

    2013-01-01

    We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplant. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (N=132) or unrelated (N=176) donors, and received post-grafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in nine patients, eight of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades 3–4 acute graft versus host disease (aGVHD) and increased non-relapse mortality, but not with day 28 T-cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades 3–4 aGVHD and non-relapse mortality in patients receiving an unrelated donor graft. PMID:23660171

  14. Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation.

    PubMed

    McDermott, Cara L; Sandmaier, Brenda M; Storer, Barry; Li, Hong; Mager, Donald E; Boeckh, Michael J; Bemer, Meagan J; Knutson, Jennifer; McCune, Jeannine S

    2013-08-01

    We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplantation. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (n = 132) or unrelated (n = 176) donors, and received postgrafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in 9 patients, 8 of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades III to IV acute graft-versus-host disease and increased nonrelapse mortality but not with day 28 T cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades III to IV acute graft-versus-host disease and nonrelapse mortality in patients receiving an unrelated donor graft.

  15. Fibroblasts behavior after N-acetylcysteine and amino acids exposure: extracellular matrix gene expression.

    PubMed

    Avantaggiato, Anna; Palmieri, Annalisa; Bertuzzi, Gianluigi; Carinci, Francesco

    2014-06-01

    Reactive oxygen species (ROS) are chemically reactive molecules with impaired electrons that make them unstable and able to react easily with a great variety of molecules. The main targets of ROS are DNA, proteins, and membrane phospholipids. In the skin, ROS are able to affect the production of collagen and elastin, the main components of the extracellular matrix (ECM). This action contributes to the skin's aging. N-Acetylcysteine (NAC) is an acetylated cysteine residue with excellent anti-oxidant activity that boosts glutathione (GSH) levels. This study evaluates the effect of a solution of NAC and amino acids, which is used in aesthetic medicine as an intra-dermal injective treatment, on fibroblast behavior. To this aim, the expression levels of some ECM-related genes (HAS1, HYAL1 ELN, ELANE, MMP2, MMP3, MMP13, COL1A1, COL3A1) were analyzed on cultured dermal fibroblasts using real-time reverse transcription polymerase chain reaction (RT-PCR). All but two collagen genes were up-regulated after 24 hr of treatment. PMID:24438160

  16. Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation.

    PubMed

    McDermott, Cara L; Sandmaier, Brenda M; Storer, Barry; Li, Hong; Mager, Donald E; Boeckh, Michael J; Bemer, Meagan J; Knutson, Jennifer; McCune, Jeannine S

    2013-08-01

    We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplantation. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (n = 132) or unrelated (n = 176) donors, and received postgrafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in 9 patients, 8 of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades III to IV acute graft-versus-host disease and increased nonrelapse mortality but not with day 28 T cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades III to IV acute graft-versus-host disease and nonrelapse mortality in patients receiving an unrelated donor graft. PMID:23660171

  17. Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

    PubMed

    Maeda, Yoshiteru; Suzuki, Atsushi; Ishii, Junnichi; Sekiguchi-Ueda, Sahoko; Shibata, Megumi; Yoshino, Yasumasa; Asano, Shogo; Hayakawa, Nobuki; Nakamura, Kazuhiro; Akiyama, Yasukazu; Kitagawa, Fumihiko; Sakuishi, Toshiaki; Fujita, Takashi; Hashimoto, Shuji; Ozaki, Yukio; Itoh, Mitsuyasu

    2015-05-01

    Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

  18. Common carp Cyprinus carpio responses to sub-chronic exposure to perfluorooctanoic acid.

    PubMed

    Giari, Luisa; Vincenzi, Fabio; Badini, Simone; Guerranti, Cristiana; Dezfuli, Bahram S; Fano, Elisa A; Castaldelli, Giuseppe

    2016-08-01

    Perfluorooctanoic acid (PFOA) is an important and diffuse perfluorinated alkylated substance, but knowledge of the toxicological effects of this endocrine disrupter in fish is limited. Adult common carp Cyprinus carpio, L. were exposed to 200 ng/l (a concentration reported in impacted aquatic ecosystems) and 2 mg/l PFOA solutions in a flow-through system for 56 days to determine tissue accumulation and histological alterations of the primary target organs. PFOA was extracted from blood, gill, liver, muscle, kidney, gonad, and brain by an ion-pairing liquid extraction procedure and quantified using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. The limit of detection (LOD) was 0.4 ng/g wet weight (ww). PFOA was not detectable in unexposed fish or in fish exposed to 200 ng/l, but was >LOD in most samples of carp exposed to 2 mg/l. Mean PFOA concentration ranged from 0.5 to 65 ng/g ww, depending on the tissue, with highest levels in the blood and liver. There were no significant differences in condition factor, hepato-somatic index, or gonado-somatic index among the fish of the three groups. Histological, histochemical, and immunohistochemical staining was performed on sections of liver and gonad. Occurrence of atretic oocytes and a paucity of spermatozoa were documented in carp treated with 2 mg/l PFOA. Exposed fish did not show gross hepatic anomalies, but there was enhancement of hepatocytes in proliferation (positive to anti-PCNA antibody) compared to controls. PMID:27107988

  19. Long-term exposure of Sitka spruce seedlings to trichloroacetic acid.

    PubMed

    Cape, J Neil; Reeves, Nicholas M; Schröder, Peter; Heal, Mathew R

    2003-07-01

    Trichloroacetic acid (TCA) has been implicated as an airborne pollutant responsible for adverse effects on forest health. There is considerable debate as to whether TCA observed in trees and forest soils is derived from atmospheric deposition or from in situ production. This experiment reports the results from treating 4-year-old Sitka spruce (Picea sitchensis (Bong.) Carr) plants in a greenhouse over a growing season with TCA supplied either to the soil or to the foliage at concentrations of 10 and 100 ng mL(-1). Similar uptake of TCA by needles was observed for both modes of treatment, with significant accumulation of TCA (300 ng g(-1) dry wt) at the higher concentration. Larger concentrations in stem tissue were seen for the foliar-applied TCA (280 ng g(-1)) than for the soil-applied TCA (70 ng g(-1)), suggesting that direct stem uptake may be important. Six months after treatments stopped, TCA concentrations in the needles of plants exposed to 100 ng mL(-1) TCA were still enhanced, showing that biological degradation of TCA in needles was slow over the winter. By contrast, no significant enhancement of TCA in soil could be detected in the directly treated soils even during the experiment. The protein content of needles treated with the higher concentration of TCA by either route was significantly smaller than for the controls, but there was no effect of TCA on the conjugation of 1-chloro-2,4-dinitrobenzene in roots nor on the conjugation of 1,2-dichloro-4-nitrobenzene in needles.

  20. EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE

    EPA Science Inventory

    EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE. D.K. Tarka1,2 , G.R. Klinefelter2, J.C. Rockett2, J.D. Suarez2, N.L. Roberts2 and J.M. Rogers1,2. 1 University of North Carol...

  1. EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID

    EPA Science Inventory

    Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

    The drinking water disinfect...

  2. EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO DIBROMOACETIC ACID, A DRINKING WATER DISINFECTANT BY-PRODUCT

    EPA Science Inventory

    Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

    The drinking water disinfect...

  3. [Hair shaft abnormalities].

    PubMed

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  4. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

    SciTech Connect

    Gamboa da Costa, Gonçalo; Jacob, Cristina C.; Von Tungeln, Linda S.; Hasbrouck, Nicholas R.; Olson, Greg R.; Hattan, David G.; Reimschuessel, Renate; Beland, Frederick A.

    2012-07-15

    The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

  5. Effect of Exposure to Atmospheric Ultrafine Particles on Production of Free Fatty Acids and Lipid Metabolites in the Mouse Small Intestine

    PubMed Central

    Li, Rongsong; Navab, Kaveh; Hough, Greg; Daher, Nancy; Zhang, Min; Mittelstein, David; Lee, Katherine; Pakbin, Payam; Saffari, Arian; Bhetraratana, May; Sulaiman, Dawoud; Beebe, Tyler; Wu, Lan; Jen, Nelson; Wine, Eytan; Tseng, Chi-Hong; Araujo, Jesus A.; Fogelman, Alan; Sioutas, Constantinos; Navab, Mohamed

    2014-01-01

    Background: Exposure to ambient ultrafine particulate matter (UFP) is a well-recognized risk factor for cardiovascular and respiratory diseases. However, little is known about the effects of air pollution on gastrointestinal disorders. Objective: We sought to assess whether exposure to ambient UFP (diameter < 180 nm) increased free fatty acids and lipid metabolites in the mouse small intestine. Methods: Ldlr-null mice were exposed to filtered air (FA) or UFP collected at an urban Los Angeles, California, site that was heavily affected by vehicular emissions; the exposure was carried out for 10 weeks in the presence or absence of D-4F, an apolipoprotein A-I mimetic peptide with antioxidant and anti-inflammation properties on a high-fat or normal chow diet. Results: Compared with FA, exposure to UFP significantly increased intestinal hydroxyeicosatetraenoic acids (HETEs), including 15-HETE, 12-HETE, 5-HETE, as well as hydroxyoctadecadienoic acids (HODEs), including 13-HODE and 9-HODE. Arachidonic acid (AA) and prostaglandin D2 (PGD2) as well as some of the lysophosphatidic acids (LPA) in the small intestine were also increased in response to UFP exposure. Administration of D-4F significantly reduced UFP-mediated increase in HETEs, HODEs, AA, PGD2, and LPA. Although exposure to UFP further led to shortened villus length accompanied by prominent macrophage and neutrophil infiltration into the intestinal villi, administration of D-4F mitigated macrophage infiltration. Conclusions: Exposure to UFP promotes lipid metabolism, villus shortening, and inflammatory responses in mouse small intestine, whereas administration of D-4F attenuated these effects. Our findings provide a basis to further assess the mechanisms underlying UFP-mediated lipid metabolism in the digestive system with clinical relevance to gut homeostasis and diseases. Citation: Li R, Navab K, Hough G, Daher N, Zhang M, Mittelstein D, Lee K, Pakbin P, Saffari A, Bhetraratana M, Sulaiman D, Beebe T, Wu L, Jen

  6. Effects of α-lipoic acid supplementation on sexual difference of growth performance, heat exposure-induced metabolic response and lipid peroxidation of raw meat in broiler chickens.

    PubMed

    Hamano, Y

    2014-01-01

    1. The effects of α-lipoic acid administration on sexual differences in growth performance, heat exposure-induced metabolic response and lipid peroxidation of raw meat in broiler chickens were studied. 2. Two-week-old male and female broiler chicks were divided into two groups each, as a 2 × 2 factorial arrangement. Half the birds were fed on a diet supplemented with α-lipoic acid (100 mg/kg) and half on a control diet. All groups were reared to 6 weeks of age at 25°C and, thereafter, exposed to 33°C for 8 h per day for 3 d. 3. Under thermo-neutral conditions, α-lipoic acid decreased feed consumption and body weight gain of male chickens. However, the feed conversion rate and tissue mass of breast muscle and abdominal fat were unchanged. 4. In plasma metabolites, α-lipoic acid increased the molar ratio of non-esterified fatty acids to free glycerol, regardless of sex and heat exposure. A decrease in β-hydroxybutyrate was observed in the α-lipoic acid-fed male chickens. In the heat-exposed chickens, α-lipoic acid lowered the molar ratio of plasma lactate to pyruvate in relation to the enhanced concentrations of plasma pyruvate. However, no sexual difference was observed. 5. The value of thiobarbituric acid reactive substances in breast meat of heat-stressed chickens that was refrigerated for 3 or 7 d was higher in males than in females. An antioxidative effect of α-lipoic acid was observed in the meat of male chickens. 6. The present study suggests that the α-lipoic acid-inducing fatty acid metabolism and antioxidative effect persisted during the heat stress, even though a sexual difference in the responsiveness was seen in broiler chickens.

  7. Experimental evaluation of the contribution of acidic pH and Fe concentration to the structure, function and tolerance to metals (Cu and Zn) exposure in fluvial biofilms.

    PubMed

    Luís, Ana Teresa; Bonet, Berta; Corcoll, Natàlia; Almeida, Salomé F P; da Silva, Eduardo Ferreira; Figueira, Etelvina; Guasch, Helena

    2014-09-01

    An indoor channel system was colonised with fluvial biofilms to study the chronic effects of high Fe and SO4(2-) concentrations and acidic pH, the water chemistry in the surrounding streams of Aljustrel mining area (Alentejo, Portugal), and their contribution to community (in)tolerance to metal toxicity by short-term experiments with Cu and Zn. Biofilms were subjected to four different treatments during 8 weeks: high Fe and SO4(2-) concentrations (1 mg Fe l(-1)+ 700 mg SO4(2-) l(-1)) and acidic pH, high Fe and SO4(2-) at alkaline pH; lower Fe and SO4(2-) at acidic pH: and lower Fe and SO4(2-) concentrations at alkaline pH as negative control. During chronic exposure, acidic pH affected growth negatively, based on low values of algal biomass and the autotrophic index, high values of the antioxidant enzyme activities and low diversity diatom communities, dominated by acidophilic species (Pinnularia aljustrelica) in acidic treatments, being the effects more marked with high Fe and SO4(2-). Co-tolerance to metals (Cu and Zn) was also shown in biofilms from the acidic treatments, contrasting with the higher sensitivity observed in the alkaline treatments. We can conclude that the Aljustrel mining area acidic environment limits algal growth and exerts a strong selection pressure on the community composition which is in turn, more tolerant to metal exposure. PMID:25011920

  8. Interactive effects of acidity and aluminum exposure on the life cycle of the midge Chironomus riparius (Diptera)

    SciTech Connect

    Palawski, D.U.; Hunn, J.B.; Chester, D.N.; Wiedneyer, R.H. )

    1989-12-01

    The chronic toxicity of acidic pH and the toxicity of aluminum at pH 5.6 and pH 5.0 to the midge Chironomus riparius were determined in 30-day flow-through exposures. Larvae were exposed to water pHs of 7.2, 6.2, 5.8, 5.3, and 4.5; total aluminum concentrations were 14.6, 34.8, 61.4, 128.7, and 259.2 microgram/L at a water pH of 5.6 and to aluminum concentrations of 15.6, 32.5, 56.9, 111.4, and 235.2 microgram/L at a water pH of 5.0. The survival of midges was only 11% at pH 4.5 and 52.3% at pH 5.8. In soft water (12 mg/L as CaCO3) at pH 5.6, survival declined significantly at aluminum concentrations of 61 to 259 microgram/L, but significantly increased at 14.6 microgram/L. In soft water at pH 5.0, survival increased at concentrations of 14.6 to 111.4 microgram/L but decreased significantly at 235.2 microgram/L. At both pH 5.6 and pH 5.0, the toxicological response of midges to aluminum was thus bimodal, in that acid stress was slightly ameliorated by relatively low aluminum concentrations, but exacerbated by higher concentrations. 25 refs., 55 tabs.

  9. Synthesis of fatty acid ethyl esters in mammalian tissues after ethanol exposure: a systematic review of the literature.

    PubMed

    Zelner, Irene; Matlow, Jeremy N; Natekar, Aniket; Koren, Gideon

    2013-08-01

    The ability to undergo non-oxidative metabolism from ethanol to fatty acid ethyl esters (FAEEs) varies greatly among tissues and organs. To gain a greater understanding of non-oxidative ethanol metabolism to FAEE, we aimed to collect all published data on FAEE synthesis in mammalian organs and tissues to identify all tissues, organs, and enzymes that are known to, or likely possess FAEE-synthetic activity. A systematic search for relevant papers was performed and two independent reviewers examined potentially relevant abstracts (articles on FAEEs that pertain to ethanol exposure) to determine whether they met the inclusion criteria. Information on FAEE synthesis was retrieved from papers meeting the inclusion/exclusion criteria and summarized by organ/tissue/matrix examined. The systematic search through four databases yielded 78 articles that investigated FAEE synthesis by tissues, tissue fractions and cell lines, and 29 articles that attempted to purify and/or characterize the enzymes involved in FAEE synthesis. Two enzyme activities have been studied: FAEE synthase (FAEES, which conjugates ethanol and free fatty acid) and acyl-CoA: ethanol O-acyltransferase (AEAT, which conjugates ethanol and fatty acyl-CoA). Both activities are expressed by a variety of different enzymes. FAEES activity is the most widely studied and has been purified from several tissues and shown to be associated with several well-known enzymes, while the identity of enzymes possessing AEAT activity remains unknown. The organs and tissues that have been shown to synthesize FAEEs are discussed, with special emphasis on the studies that attempted to elucidate the enzymology of FAEE synthesis in those tissues.

  10. Synthesis of fatty acid ethyl esters in mammalian tissues after ethanol exposure: a systematic review of the literature.

    PubMed

    Zelner, Irene; Matlow, Jeremy N; Natekar, Aniket; Koren, Gideon

    2013-08-01

    The ability to undergo non-oxidative metabolism from ethanol to fatty acid ethyl esters (FAEEs) varies greatly among tissues and organs. To gain a greater understanding of non-oxidative ethanol metabolism to FAEE, we aimed to collect all published data on FAEE synthesis in mammalian organs and tissues to identify all tissues, organs, and enzymes that are known to, or likely possess FAEE-synthetic activity. A systematic search for relevant papers was performed and two independent reviewers examined potentially relevant abstracts (articles on FAEEs that pertain to ethanol exposure) to determine whether they met the inclusion criteria. Information on FAEE synthesis was retrieved from papers meeting the inclusion/exclusion criteria and summarized by organ/tissue/matrix examined. The systematic search through four databases yielded 78 articles that investigated FAEE synthesis by tissues, tissue fractions and cell lines, and 29 articles that attempted to purify and/or characterize the enzymes involved in FAEE synthesis. Two enzyme activities have been studied: FAEE synthase (FAEES, which conjugates ethanol and free fatty acid) and acyl-CoA: ethanol O-acyltransferase (AEAT, which conjugates ethanol and fatty acyl-CoA). Both activities are expressed by a variety of different enzymes. FAEES activity is the most widely studied and has been purified from several tissues and shown to be associated with several well-known enzymes, while the identity of enzymes possessing AEAT activity remains unknown. The organs and tissues that have been shown to synthesize FAEEs are discussed, with special emphasis on the studies that attempted to elucidate the enzymology of FAEE synthesis in those tissues. PMID:23713893

  11. Controlling surface roughness in vapor-deposited poly(amic acid) films by solvent-vapor exposure.

    PubMed

    Anthamatten, Mitchell; Letts, Stephan A; Cook, Robert C

    2004-07-20

    A series of vapor-deposited poly(amic acid) (PAA) films were exposed to dimethyl sulfoxide (DMSO) vapors to investigate sorption kinetics and surface smoothing phenomena. Gravimetric sorption and secondary-ion mass spectrometry (SIMS) results are both consistent with frontal (case II) diffusion. These experiments suggest that the solvent front is defined by a sharp interface that delineates the swollen material from the unswollen material. Solvent-vapor smoothing was studied by first depositing PAA onto rough aluminum surfaces, and then, during solvent-vapor exposure, the surface topology was continuously monitored using a light interference microscope. The resulting time-dependent power spectra indicate that high-frequency defects smooth faster than low-frequency defects. This frequency dependence was further investigated by depositing PAA onto a series of sinusoidal surfaces and exposing them to solvent vapor inside a flow channel. The sinusoidal amplitudes decay exponentially with time, with decay constants that are proportional to the surface frequency. To explain the physics of surface smoothing, a two-parameter model is presented and agrees qualitatively with experimental data.

  12. A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)

    PubMed Central

    Forman, J; Moline, J; Cernichiari, E; Sayegh, S; Torres, J C; Landrigan, M M; Hudson, J; Adel, H N; Landrigan, P J

    2000-01-01

    Nine children and their mother were exposed to vapors of metallic mercury. The source of the exposure appears to have been a 6-oz vial of mercury taken from a neighbor's home. The neighbor reportedly operated a business preparing mercury-filled amulets for practitioners of the Afro-Caribbean religion Santeria. At diagnosis, urinary mercury levels in the children ranged from 61 to 1,213 microg/g creatinine, with a geometric mean of 214.3 microg/m creatinine. All of the children were asymptomatic. To prevent development of neurotoxicity, we treated the children with oral meso-2,3-dimercaptosuccinic acid (DMSA). During chelation, the geometric mean urine level rose initially by 268% to 573.2 microg mercury/g creatinine (p<0.0005). At the 6-week follow-up examination after treatment, the geometric mean urine mercury level had fallen to 102.1 microg/g creatinine, which was 17.8% of the geometric mean level observed during treatment (p<0.0005) and 47.6% of the original baseline level (p<0.001). Thus, oral chelation with DMSA produced a significant mercury diuresis in these children. We observed no adverse side effects of treatment. DMSA appears to be an effective and safe chelating agent for treatment of pediatric overexposure to metallic mercury. Images Figure 1 PMID:10856034

  13. Effects of prenatal exposure to valproic acid on the development of juvenile-typical social play in rats.

    PubMed

    Raza, Sarah; Himmler, Brett T; Himmler, Stephanie M; Harker, Allonna; Kolb, Bryan; Pellis, Sergio M; Gibb, Robbin

    2015-12-01

    Autism is a severe neurodevelopmental disorder characterized by qualitative impairments in social behavior, communication, and aberrant repetitive behaviors. A major focus of animal models of autism has been to mimic the social deficits of the disorder. The present study assessed whether rats exposed prenatally to valproic acid (VPA) show deficits in social play as juveniles that are consistent with the social deficits observed in autism. Dams were exposed to an acute dose of VPA on gestational day 12.5. Later, the playful interactions and associated ultrasonic vocalizations of the juveniles were examined. It was predicted that VPA-treated rats should play less than the controls. Characteristic of neurobehavioral insult at this early age, the VPA-treated juveniles showed significant increases in the frequency of body shakes and sexual mounting, but played at the same frequency as the controls. However, when playing, they were less likely to use tactics that facilitated bodily contact and vocalized less. These data suggest that prenatal VPA exposure disrupts some aspects of being able to communicate effectively and engage partners in dynamic interactions - deficits that are consistent with those observed in autism. PMID:26230723

  14. Effects of chronic exposure to soft, acidic water on gill development and chloride cell numbers in embryo-larval brook trout, Salvelinus fontinalis

    USGS Publications Warehouse

    Conklin, D.J.; Mowbray, R.C.; Gingerich, W.H.

    1992-01-01

    Recruitment failure is considered to be a major factor contributing to the decline of fish populations in soft, acidic waters; direct mortality of embryo-larval fishes has been postulated as a major cause of the decline. Little is understood of the physiological consequences to embryo-larval fishes of prolonged exposure to soft, acidic waters; however, dysfunction of respiratory and ionoregulatory processes is suspected. In order to evaluate the effects of acid exposure on the respiratory and ionoregulatory systems of developing brook trout, Salvelinus fontinalis, differences in gill morphology and numbers of chloride cells were compared between groups cf developing embryo-larval fish continuously exposed to moderately hard well water (130.0 mg.l-1 as CaCO3, pH 7.94) or to reconstituted soft, acidic water (4.4 mg.l-1 as CaCO3, pH 5.25) designed to mimic acidic waters of northern Wisconsin acidified lakes. Exposures were maintained for up to 48 days (82 days after fertilization) during critical periods of growth and differentiation of branchial structures. The second right gill arch of each fish was examined for changes in the development of filaments and lamellae and for differences in numbers of chloride cells. Gills of fish that developed in soft, acidic water contained greater numbers of normal and degenerating chloride cells, exhibited hyperplasia of primary epithelium and multiple fusions of adjacent filaments and lamellar epithelium than the gills of control fish. Filament and lamellar lengths and numbers of lamellae per filament were significantly less (P< 0.05) in fish that developed in soft, acidic water than in fish exposed to well water.

  15. Immunotoxic effects of cis-urocanic acid exposure in C57BL/6N and C3H/HeN mice.

    PubMed

    Prater, M Renee; Gogal, Robert M; De Fabo, Edward C; Longstreth, Janice; Holladay, Steven D

    2003-04-01

    Exposure to ultraviolet radiation results in increased levels of intradermal cis-urocanic acid (cUCA) and alters cutaneous immunity by interfering with processing and presentation of antigen by Langerhans cells. Reports on effects of systemic immunotoxicity with 30 day cUCA exposure in laboratory rodents include thymic atrophy, thymic hypocellularity and decreased T-cell-mediated immunity; however, immune effects of single exposure or 5 day cUCA administration, which may better mimic human exposures, are poorly defined. The present study initially evaluated immune effects of single, 5 day, and 4 week cUCA exposure in C57BL/6N mice. Single administration of intradermal cUCA resulted in decreased splenocyte phagocytosis that persisted for 30 days after cUCA exposure. Five day consecutive cUCA exposure decreased numbers of phenotypically mature CD4(+)CD8(-) and CD4(-)CD8(+) (single positive) thymocytes, increased CD4(+)CD8(+) (double positive) immature thymocytes and increased splenocyte proliferation. Prolonged cUCA exposure (4 weeks) caused profound thymic hypocellularity and splenic hypercellularity and increased splenic macrophage chemiluminescence. Because of this apparent sensitivity of C57BL/6N mice to cUCA, thymic hypocellularity was compared between C57BL/6N and C3H/HeN mice dosed with cUCA, and was found to be more pronounced in the C57BL/6N strain. These results are an extension of previous conclusions on immune modulation caused by cUCA in the spleen and thymus. Further, the observed variation in sensitivity between the mouse strains is consistent with known genetic susceptibility of these strains to the immunomodulatory effects of exposure to sunlight. PMID:12733650

  16. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed.

  17. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  18. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  19. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  20. Survival of Salmonella strains differing in their biofilm-formation capability upon exposure to hydrochloric and acetic acid and to high salt.

    PubMed

    Hasegawa, Akio; Hara-Kudo, Yukiko; Kumagai, Susumu

    2011-09-01

    Acidic and osmotic treatments are part of hurdle systems to control pathogens such as Salmonella in food. In the current study, Salmonella enterica isolates previously shown to differ in their ability to form biofilms were grown in diluted tryptic soy broth (TSB) (1:5 dilution in distilled water) and subsequently exposed to phosphate-buffered saline (PBS) adjusted to pH 3.0 with HCl, PBS adjusted to pH 3.9 with acetic acid or rice vinegar diluted 1:15 with distilled water (pH 3.9). Cells grown in diluted TSB were also exposed to distilled water, pH 7.6, containing 5 M NaCl. No differences in survival upon exposure to PBS adjusted to pH 3.0 with HCl or distilled water containing high salt were observed between the isolates; however, exposure to acetic acid and rice vinegar resulted in lower survival levels of isolates previously shown to be poor biofilm formers. The numbers (log(10) cfu/ml) of surviving cells after exposure for 36 hr to acetic acid and rice vinegar were 4.43 ± 0.24 vs. 2.27 ± 0.87 (P<0.05) and 5.19 ± 0.12 vs. 2.33 ± 0.93 (P<0.05) for isolates with a high vs. low biofilm-forming ability. The survival data could be fitted with the Weibull model. The data suggest that the ability of Salmonella strains to survive in the presence of acetic acid and rice vinegar parallels their ability to form biofilms. Thus, Salmonella with a high biofilm-formation capability might be more difficult to kill with acetic acid found in foods or cleaning solutions.