Sample records for abnormal acid exposure

  1. Distal esophageal hypercontractility is related to abnormal acid exposure.

    PubMed

    Soto-Pérez, Julio César; Sobrino-Cossío, Sergio; Higgins, Paul B; Comuzzie, Anthony G; Vargas Romero, Jose Antonio; Reding-Bernal, Arturo; López-Alvarenga, Juan Carlos

    2011-02-01

    Nutcracker esophagus (NE) is a frequent primary motility disorder of the distal esophagus, and the relationship with acid exposure remains controversial. We studied simultaneous distal esophageal hypercontractility (EH) using two sensors at 8 and 3 cm above the lower sphincter (LES) and abnormal exposure to acid (pH DeMeester score). From 400 screened patients with chest pain and heartburn, 54 (age 44.5 ± 8.8 years and 74% females) had abnormal manometry and underwent acid exposure measurement. Frequencies of the EH disorder were classic NE (EH(3 cm)) found in 29 (40.8%) patients, diffuse (EH(3,8 cm)) in 30 patients (42.3%), and upper segmental (EH(8 cm)) in 12 patients (16.9%). We found a positive correlation among age with high amplitude in EH(3 cm) and EH(3,8 cm). DeMeester's score (DMS) had the lowest value for EH(3,8 cm) (2.58 ± 0.23) compared with EH(8 cm) (3.78 ± 0.3, p <0.003) and EH(3 cm) (3.12 ± 0.2, p <0.06). Surface response for joint effect of age and DMS on amplitude at EH(3 cm) confirmed the highest amplitude was for older age and lower DMS. EH(3 cm) and EH(3,8 cm) were common for esophageal motility and were inversely associated with DMS. Meanwhile, acid exposure was higher in younger patients and hypercontractility was more frequent in older subjects. The former group may benefit more from proton pump inhibitors and the latter from visceral analgesics or possibly both. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.

  2. Pathological bolus exposure may define gastro-esophageal reflux better than pathological acid exposure in patients with globus.

    PubMed

    Sinn, Dong Hyun; Kim, Beom Jin; Son, Hee Jung; Kim, Jae J; Rhee, Jong Chul; Rhee, Poong-Lyul

    2012-01-01

    Conventionally, pathological acid exposure (PAE), defined by acid reflux only, is used to identify gastro-esophageal reflux disease (GERD). However, weak acid reflux or non-acid reflux also induces reflux symptoms. Defining abnormal reflux based on all reflux episodes may better identify GERD and would be more useful among patients with atypical GERD symptoms, such as globus. Impedance-pHmetry results of 31 globus patients, off acid suppressants, were analysed. A median of 24 episodes of reflux were observed. Of the reflux episodes, 54% were non-acid reflux and 50% reached the proximal extent. PAE was observed in 6 patients (19%). For 5 patients (16%) without PAE, there was evidence of increased bolus exposure compared to normal controls (an intraesophageal bolus exposure for more than 1.4% of the recording time, defined as pathological bolus exposure, PBE). When GERD was defined by PAE or esophagitis, the prevalence of GERD was 29%. When GERD was defined by PBE, PAE or esophagitis, the prevalence was 42%. PBE identified 13% of the patients who otherwise would have been missed. A significant proportion of patients without PAE had evidence of PBE. PBE may be a more useful definition for identifying patients with abnormal increase in reflux in patients with globus. Further studies are warranted.

  3. Neurological abnormalities associated with CDMA exposure.

    PubMed

    Hocking, B; Westerman, R

    2001-09-01

    Dysaesthesiae of the scalp and neurological abnormality after mobile phone use have been reported previously, but the roles of the phone per se or the radiations in causing these findings have been questioned. We report finding a neurological abnormality in a patient after accidental exposure of the left side of the face to mobile phone radiation [code division multiple access (CDMA)] from a down-powered mobile phone base station antenna. He had headaches, unilateral left blurred vision and pupil constriction, unilateral altered sensation on the forehead, and abnormalities of current perception thresholds on testing the left trigeminal ophthalmic nerve. His nerve function recovered during 6 months follow-up. His exposure was 0.015-0.06 mW/cm(2) over 1-2 h. The implications regarding health effects of radiofrequency radiation are discussed.

  4. Discounting the duration of bolus exposure in impedance testing underestimates acid reflux.

    PubMed

    Vikneswaran, Namasivayam; Murray, Joseph A

    2016-06-08

    Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH < 4) than impedance criteria (total reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH < 4) identified more studies as abnormal than MII-detected acid reflux episodes [42 vs 34 % (p < 0.01)]. Mean acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p < 0.01)], upright [58.6 s vs 13.1 s (p < 0.01)], and recumbent positions [136.7 s vs 14.2 s (p < 0.01)] with the greatest difference seen in the recumbent position. The mean ratio of mean acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position.

  5. Abnormal fatty acids in Canadian children with autism.

    PubMed

    Jory, Joan

    2016-04-01

    Fatty acids are critical for pediatric neurodevelopment and are abnormal in autism, although prior studies have demonstrated conflicting results and methodological differences. To our knowledge, there are no published data on fatty acid in Canadian children with autism. The aim of this study was to investigate red blood cell and serum fatty acid status to identify whether abnormalities exist in Canadian children with autism, and to enhance future cross-study comparison. Eleven Canadian children with autism (3 girls, 8 boys; age 3.05 ± 0.79 y) and 15 controls (9 girls, 6 boys; age 3.87 ± 1.06 y) met inclusion criteria, which included prior Diagnostic and Statistical Manual diagnosis of autism spectrum disorder, no recent medication or supplements, no specialty diets, and no recent illness. The children with autism demonstrated lower red blood cell docosahexaenoic acid (P < 0.0003), eicosapentaenoic acid (P < 0.03), arachidonic acid (P < 0.002), and ω-3/ω-6 ratios (P < 0.001). They also demonstrated lower serum docosahexaenoic acid (P < 0.02), arachidonic acid (P < 0.05), and linoleic acid (P < 0.02) levels. Fatty acids in both serum and red blood cells were abnormal in this small group of Canadian children with autism than in controls, underlining a need for larger age- and sex-matched investigations in this community. A potential role for fatty acid abnormalities within the complex epigenetic etiology of autism is proposed in relation to emerging understanding of relationships between cobalamin metabolism, gut microbiota, and propionic acid production. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. Persistent behavioral effects following early life exposure to retinoic acid or valproic acid in zebrafish

    PubMed Central

    Bailey, Jordan M.; Oliveri, Anthony N.; Karbhari, Nishika; Brooks, Roy A.J.; De La Rocha, Amberlene J.; Janardhan, Sheila; Levin, Edward D.

    2015-01-01

    BACKGROUND Moderate to severe dysregulation in retinoid signaling during early development is associated with a constellation of physical malformations and/or neural tube defects, including spina bifida. It is thought that more subtle dysregulation of this system, which might be achievable via dietary (i.e. hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans, will manifest on behavioral domains including sociability, without overt physical abnormalities. METHODS During early life, zebrafish were exposed to low doses of two chemicals that disrupt retinoid signaling. From 0-5 dpf, larvae were reared in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2 nM) or valproic acid (0, 0.5, 5.0 or 50 uM). One cohort of zebrafish was assessed using a locomotor activity screen at 6-dpf; another was reared to adulthood and assessed using a neurobehavioral test battery (startle habituation, novel tank exploration, shoaling, and predator escape/avoidance). RESULTS There was no significant increase in the incidence of physical malformation among exposed fish compared to controls. Both retinoic acid and valproic acid exposures during development disrupted larval activity with persisting behavioral alterations later in life, primarily manifesting as decreased social affiliation. CONCLUSIONS Social behavior and some aspects of motor function were altered in exposed fish; the importance of examining emotional or psychological consequences of early life exposure to retinoid acting chemicals is discussed. PMID:26439099

  8. Environmentally toxicant exposures induced intragenerational transmission of liver abnormalities in mice

    PubMed Central

    Al-Griw, Mohamed A.; Treesh, Soad A.; Alghazeer, Rabia O.; Regeai, Sassia O.

    2017-01-01

    Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE) on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day). The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide) in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring generations. Hence

  9. Is exposure to cocaine or cigarette smoke during pregnancy associated with infant visual abnormalities?

    PubMed

    Hajnal, Beatrice Latal; Ferriero, Donna M; Partridge, J Colin; Dempsey, Delia A; Good, William V

    2004-08-01

    The aim of this study was to assess the association between cocaine or cigarette smoke exposure in utero and visual outcome. A total of 153 healthy infants (89 males, 64 females; gestational age range 34 to 42 weeks) were prospectively enrolled in a masked, race-matched study. Quantitative analyses of urine and meconium were used to document exposure to cigarette smoke and cocaine. Infants with exposure to other illicit drugs, excepting marijuana, were excluded. At 6 weeks of age, grating acuity and visual system abnormalities (VSA; eyelid oedema, gaze abnormalities, and visual inattention) of 96 infants from the original study sample were assessed with the Teller acuity card procedure and a detailed neurological examination. Neither cocaine nor cigarette smoke exposure was associated with acuity or VSA. However, VSAs were associated with abnormal neurological examination, independent of drug exposure and other risk factors (odds ratio 7.9; 95% confidence interval 2.0 to 31.5;p=0.004). This unexpected finding could prove a helpful clinical marker for the infant at risk for neurological abnormalities.

  10. Pleural abnormalities and exposure to elongate mineral particles in Minnesota iron ore (taconite) workers.

    PubMed

    Perlman, David; Mandel, Jeffrey H; Odo, Nnaemeka; Ryan, Andy; Lambert, Christine; MacLehose, Richard F; Ramachandran, Gurumurthy; Alexander, Bruce H

    2018-05-01

    Iron ore (taconite) mining and processing are an important industry in northern Minnesota and western Michigan. Concerns around exposures have centered largely on exposure to non-asbestiform amphibole elongate mineral particles (EMPs) found in the eastern portion of the Minnesota iron range. A cross sectional survey was undertaken of current and former taconite workers and spouses along with a detailed exposure assessment. Participants provided an occupational history and had a chest radiograph performed. A total of 1188 workers participated. Potential exposures to non-amphibole EMPs were evident across multiple jobs in all active mines. Pleural abnormalities were found in 16.8% of workers. There was an association of pleural abnormalities with cumulative EMP exposure that was not specific to the eastern portion of the range. There was evidence of a mild to moderate increase in pleural abnormalities in this population of miners, associated with geographically non-specific cumulative EMP exposure. © 2018 Wiley Periodicals, Inc.

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

    PubMed

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

    2003-11-01

    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.

  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. Esophageal manometry findings and degree of acid exposure in short and long Barrett's esophagus.

    PubMed

    Helman, Laura; Biccas, Beatriz Nunes; Lemme, Eponina M O; Novais, Paula; Fittipaldi, Viviane

    2012-01-01

    Barrett's esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus and is classified as short-segment (<3 cm - SSBE) or long-segment (>3 cm - LSSBE). It is suggested that LSSBE is associated with more severe esophageal motor abnormalities and increased acid exposure time than SSBE. To evaluate the prevalence of esophageal manometriy abnormalities and acid exposure times in patients with SSBE and LSSBE. Barrett's esophagus patients identified by upper endoscopy and confirmed by histopathology were, retrospectively, reviewed and divided into two groups: SSBE and LSBE. Demographic data, symptom duration, prevalence of hiatal hernia, lower esophagus sphincter basal pressure, prevalence of esophageal body abnormalities and acid exposure times were evaluated. Forty-six patients with SSBE (24 males - 52.2%, mean age of 55.2 years) and 28 patients with LSBE (18 males - 64.3%, mean age of 50.5 years). Mean symptom duration was 9.9 years for SSBE and 12.9 years for LSSBE. Hiatal hernia was present in 84.2% of SSBE, 96.3% of LSBE; average lower esophagus sphincter pressure in SSBE 9.15 mm Hg, in LSBE 6.99 mm Hg; lower esophagus sphincter hypotension in SSBE was 65.9%, in LSSBE 82.1%; aperistalsis in SSBE 6.5%, LSSBE 3.6%; mild/moderate ineffective esophageal motility in SSBE 34.8%, LSBE 46.4%; severe moderate ineffective esophageal motility in SSBE 10.9%, LSBE 7,1%; nutcracker esophagus/segmental nutcracker esophagus in SSBE 8.6%, LSBE 0%; normal body in SSBE 39.1%, in LSBE 42.9%, no statistical difference for any of these values (P<0.05). Average % total time pH<4 in SSBE 9.12, LSBE 17.27 (P<0.000); % time pH<4 upright in SSBE 11.91; LSBE 24.29 (P=0.003); % time pH<4 supine in SSBE 10.86, LSBE 33.26 (P = 0.000). There was no difference between the prevalence of motor disorders in patients with SSBE and LSSBE. Acid reflux in upright and supine positions was more intense in LSBE.

  14. Obesity increases oesophageal acid exposure

    PubMed Central

    El‐Serag, Hashem B; Ergun, Gulchin A; Pandolfino, John; Fitzgerald, Stephanie; Tran, Thomas; Kramer, Jennifer R

    2007-01-01

    Background Obesity has been associated with gastro‐oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear. Aim To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures. Methods A cross‐sectional study of consecutive patients undergoing 24 h pH‐metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses. Results 206 patients (63% women) with a mean age of 51.4 years who were not on acid‐suppressing drugs were enrolled. A body mass index (BMI) of >30 kg/m2 (compared with BMI<25 kg/m2) was associated with a significant increase in acid reflux episodes, long reflux episodes (>5 min), time with pH<4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI>30 kg/m2 and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure. Conclusions Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure. PMID:17127706

  15. 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. © 2014 Wiley Periodicals, Inc.

  16. Human Brain Abnormalities Associated With Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder

    PubMed Central

    Jarmasz, Jessica S.; Basalah, Duaa A.; Chudley, Albert E.; Del Bigio, Marc R.

    2017-01-01

    Abstract Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980–2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings were categorized into 5 age groups. Alcohol exposure was difficult to quantify. When documented, almost all mothers smoked tobacco, many abused other substances, and prenatal care was poor or nonexistent. Placental abnormalities were common (68%) in fetal cases. We identified micrencephaly (brain weight <5th percentile) in 31, neural tube defects in 5, isolated hydrocephalus in 6, corpus callosum defects in 6 (including some with complex anomalies), probable prenatal ischemic lesions in 5 (excluding complications of prematurity), minor subarachnoid heterotopias in 4, holoprosencephaly in 1, lissencephaly in 1, and cardiac anomalies in 26 cases. The brain abnormalities associated with prenatal alcohol exposure are varied; cause–effect relationships cannot be determined. FASD is likely not a monotoxic disorder. The animal experimental literature, which emphasizes controlled exposure to ethanol alone, is therefore inadequate. Prevention must be the main societal goal, however, a clear understanding of the neuropathology is necessary for provision of care to individuals already affected. PMID:28859338

  17. Dietary exposure to brominated flame retardants and abnormal Pap test results.

    PubMed

    Jamieson, Denise J; Terrell, Metrecia L; Aguocha, Nnenna N; Small, Chanley M; Cameron, Lorraine L; Marcus, Michele

    2011-09-01

    This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests.

  18. Dietary Exposure to Brominated Flame Retardants and Abnormal Pap Test Results

    PubMed Central

    Jamieson, Denise J.; Terrell, Metrecia L.; Aguocha, Nnenna N.; Small, Chanley M.; Cameron, Lorraine L.

    2011-01-01

    Abstract Objective This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. Methods Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. Results Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). Conclusions It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests. PMID:21797757

  19. Electrolyte and acid-base abnormalities associated with purging behaviors.

    PubMed

    Mehler, Philip S; Walsh, Kristine

    2016-03-01

    Eating disorders that are associated with purging behaviors are complicated by frequent blood electrolyte and acid-base abnormalities. Herein, we review the major electrolyte and acid-base abnormalities and their treatment methods. The body of rigorous, eating disorder-specific literature on this topical area is not robust enough to perform a systematic review as defined by PRISMA guidelines. Therefore, a qualitative review of mostly medical literature was conducted. Hypokalemia, hyponatremia, and sodium chloride-responsive metabolic alkalosis are the most common serum changes that occur as a result of purging behaviors. They vary depending on the mode and frequency of purging behaviors. They can all potentially cause dangerous medical complications and are in need of definitive medical treatment. Eating disorders that are associated with purging behaviors are associated with a number of electrolyte and acid-base changes which are complex in their origin, documented to be medically dangerous and this definitive treatment is necessary to help achieve a successful treatment outcome, and in need of definitive treatment as described herein. © 2016 Wiley Periodicals, Inc.

  20. Childhood physical abnormalities following paternal exposure to sulfur mustard gas in Iran: a case-control study

    PubMed Central

    2010-01-01

    Background Mustard gas, a known chemical weapon, was used during the Iran-Iraq war of 1980-1988. We aimed to determine if exposure to mustard gas among men was significantly associated with abnormalities and disorders among progenies. Methods Using a case-control design, we identified all progenies of Sardasht men (exposed group, n = 498), who were born at least nine months after the exposure, compared to age-matched controls in Rabat, a nearby city (non-exposed group, n = 689). We conducted a thorough medical history, physical examination, and appropriate paraclinical studies to detect any physical abnormality and/or disorder. Given the presence of correlated data, we applied Generalized Estimating Equation (GEE) multivariable models to determine associations. Results The overall frequency of detected physical abnormalities and disorders was significantly higher in the exposed group (19% vs. 11%, Odds Ratio [OR] 1.93, 95% Confidence Interval [CI], 1.37-2.72, P = 0.0002). This was consistent across sexes. Congenital anomalies (OR 3.54, 95% CI, 1.58-7.93, P = 0.002) and asthma (OR, 3.12, 95% CI, 1.43-6.80, P = 0.004) were most commonly associated with exposure. No single abnormality was associated with paternal exposure to mustard gas. Conclusion Our study demonstrates a generational effect of exposure to mustard gas. The lasting effects of mustard gas exposure in parents effects fertility and may impact child health and development in the long-term. PMID:20630096

  1. Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

    PubMed

    Woodley, Frederick W; Moore-Clingenpeel, Melissa; Machado, Rodrigo Strehl; Nemastil, Christopher J; Jadcherla, Sudarshan R; Hayes, Don; Kopp, Benjamin T; Kaul, Ajay; Di Lorenzo, Carlo; Mousa, Hayat

    2017-09-01

    Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis ( p =0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

  2. Abnormal environmental light exposure in the intensive care environment.

    PubMed

    Fan, Emily P; Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C; Maas, Matthew B

    2017-08-01

    We sought to characterize ambient light exposure in the intensive care unit (ICU) environment to identify patterns of light exposure relevant to circadian regulation. A light monitor was affixed to subjects' bed at eye level in a modern intensive care unit and continuously recorded illuminescence for at least 24h per subject. Blood was sampled hourly and measured for plasma melatonin. Subjects underwent hourly vital sign and bedside neurologic assessments. Care protocols and the ICU environment were not modified for the study. A total of 67,324 30-second epochs of light data were collected from 17 subjects. Light intensity peaked in the late morning, median 64.1 (interquartile range 19.7-138.7) lux. The 75th percentile of light intensity exceeded 100lx only between 9AM and noon, and never exceeded 150lx. There was no correlation between melatonin amplitude and daytime, nighttime or total light exposure (Spearman's correlation coefficients all <0.2 and p>0.5). Patients' environmental light exposure in the intensive care unit is consistently low and follows a diurnal pattern. No effect of nighttime light exposure was observed on melatonin secretion. Inadequate daytime light exposure in the ICU may contribute to abnormal circadian rhythms. Copyright © 2017 Elsevier Inc. All rights reserved.

  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. Pulmonary function abnormalities and airway irritation symptoms of metal fumes exposure on automobile spot welders.

    PubMed

    Luo, Jiin-Chyuan John; Hsu, Kuang-Hung; Shen, Wu-Shiun

    2006-06-01

    Spot or resistance welding has been considered less hazardous than other types of welding. Automobile manufacturing is a major industry in Taiwan. Spot and arc welding are common processes in this industry. The respiratory effects on automobile spot welders exposed to metal fumes are investigated. The cohort consisted of 41 male auto-body spot welders, 76 male arc welders, 71 male office workers, and 59 assemblers without welding exposure. Inductivity Coupled Plasma Mass Spectrophotometer (ICP-MS) was applied to detect metals' (zinc, copper, nickel) levels in the post-shift urine samples. Demographic data, work history, smoking status, and respiratory tract irritation symptoms were gathered by a standard self-administered questionnaire. Pulmonary function tests were also performed. There were significantly higher values for average urine metals' (zinc, copper, nickel) levels in spot welders and arc welders than in the non-welding controls. There were 4 out of 23 (17.4%) abnormal forced vital capacity (FVC) among the high-exposed spot welders, 2 out of 18 (11.1%) among the low-exposed spot welders, and 6 out of 130 (4.6%) non-welding-exposed workers. There was a significant linear trend between spot welding exposure and the prevalence of restrictive airway abnormalities (P = 0.036) after adjusting for other factors. There were 9 out of 23 (39.1%) abnormal peak expiratory flow rate (PEFR) among high-exposed spot welders, 5 out of 18 (27.8%) among the low-exposed spot welders, and 28 out of 130 (21.5%) non-welding-exposed workers. There was a borderline significant linear trend between spot welding exposure and the prevalence of obstructive lung function abnormalities (P = 0.084) after adjusting for other factors. There was also a significant dose-response relationship of airway irritation symptoms (cough, phlegm, chronic bronchitis) among the spot welders. Arc welders with high exposure status also had a significant risk of obstructive lung abnormalities (PEFR

  5. Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.

    PubMed

    Mousa, Alyaa M; Al-Fadhli, Ameera S; Rao, Muddanna S; Kilarkaje, Narayana

    2015-01-01

    Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion, gestational lead exposure in rats induces fetal toxicity and developmental abnormalities. The lead exposure also impairs development of cerebellar layers, induces structural changes, and apoptosis in the fetal cerebellar cortex. These results suggest that lead exposure during gestation is extremely toxic to developing cerebellum in rats.

  6. Bile Acids and Tryptophan Metabolism Are Novel Pathways Involved in Metabolic Abnormalities in BPA-Exposed Pregnant Mice and Male Offspring.

    PubMed

    Susiarjo, Martha; Xin, Frances; Stefaniak, Martha; Mesaros, Clementina; Simmons, Rebecca A; Bartolomei, Marisa S

    2017-08-01

    Increasing evidence has demonstrated that exposure to endocrine-disrupting chemicals impacts maternal and fetal health, but the underlying mechanisms are still unclear. We previously showed that dietary exposure to 10 µg/kg body weight (bw)/d and 10 mg/kg bw/d of bisphenol A (BPA) during pregnancy induced metabolic abnormalities in F1 male offspring and gestational glucose intolerance in F0 pregnant mice. The aim of this study was to elucidate the underlying etiologies of BPA exposure-induced metabolic disease by analyzing the male fetal liver metabolome. Using the Metabolon Discover HD4 Platform, our laboratory identified metabolic pathways that were altered by BPA exposure, including biochemicals in lipid and amino acid metabolism. Specifically, primary and secondary bile acids were increased in liver from BPA-exposed embryonic day 18.5 male fetuses. We subsequently showed that increased bile acid was associated with a defective farnesoid X receptor-dependent negative feedback mechanism in BPA-exposed fetuses. In addition, through metabolomics, we observed that BPA-exposed fetuses had elevated tryptophan levels. Independent liquid chromatography and mass spectrometry measurement revealed that BPA-exposed dams also had increased tryptophan levels relative to those of controls. Because several key enzymes in tryptophan catabolism are vitamin B6 dependent and vitamin B6 deficiencies have been linked to gestational diabetes, we tested the impact of vitamin B6 supplementation and showed that it rescued gestational glucose intolerance in BPA-exposed pregnant mice. Our study has therefore identified two pathways (bile acid and tryptophan metabolism) that potentially underlie BPA-induced maternal and fetal metabolic disease. Copyright © 2017 Endocrine Society.

  7. Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice.

    PubMed

    Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Hasebe, Shigeru; Kawase, Haruki; Tanabe, Wataru; Tsukada, Shinji; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-11-01

    Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities. We recently found that prenatal VPA exposure causes hypofunction of the prefrontal dopaminergic system in mice. This suggests that the dopaminergic system may be a potential pharmacological target for treatment of behavioral abnormalities in ASD patients. In the present study, we examined the effects of antipsychotic drugs, which affect the dopaminergic system, on the social interaction deficits, recognition memory impairment, and reduction in dendritic spine density in the VPA mouse model of ASD. Both acute and chronic administrations of the atypical antipsychotic drugs risperidone and aripiprazole increased prefrontal dopamine (DA) release, while the typical antipsychotic drug haloperidol did not. Chronic risperidone and aripiprazole, but not haloperidol, increased the expression of c-Fos in the prefrontal cortex, although they all increased c-Fos expression in the striatum. Chronic, but not acute, administrations of risperidone and aripiprazole improved the VPA-induced social interaction deficits and recognition memory impairment, as well as the reduction in dendritic spine density in the prefrontal cortex and hippocampus. In contrast, chronic administration of haloperidol did not ameliorate VPA-induced abnormalities in behaviors and dendritic spine density. These findings indicate that chronic risperidone and aripiprazole treatments improve VPA-induced abnormalities in behaviors and prefrontal dendritic spine density, which may be mediated by repeated elevation of extracellular DA in the prefrontal cortex. Our results also imply that loss of prefrontal dendritic spines may be involved in the abnormal behaviors in the VPA mouse model of ASD.

  8. 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

  9. Role of the lower esophageal sphincter on esophageal acid exposure - a review of over 2000 patients.

    PubMed

    Tsuboi, Kazuto; Hoshino, Masato; Sundaram, Abhishek; Yano, Fumiaki; Mittal, Sumeet K

    2012-01-01

    Three lower esophageal sphincter (LES) characteristics associated with gastro-esophageal reflux disease (GERD) are, LES pressure = 6 mmHg, abdominal length (AL) <1 cm and overall length (OL) <2 cm. The objective of this study was to validate this relationship and evaluate the extent of impact various LES characteristics have on the degree of distal esophageal acid exposure. A retrospective review of a prospectively maintained database identified patients who underwent esophageal manometry and pH studies at Creighton University Medical Center between 1984 and 2008. Patients with esophageal body dysmotility, prior foregut surgery, missing data, no documented symptoms or no pH study, were excluded. Study subjects were categorized as follows: (1) normal LES (N-LES): patients with LES pressure of 6-26 mmHg, AL = 1.0 cm and OL = 2 cm; (2) incompetent LES (Inc-LES): patients with LES pressure <6.0 mmHg orAL <1 cm or OL <2 cm; and (3) hypertensive LES (HTN-LES): patients with LES pressure >26.0 mmHg with AL = 1 cm and OL = 2 cm. The DeMeester score was used to compare differences in acid exposure between different groups. Two thousand and twenty patients satisfied study criteria. Distal esophageal acid exposure as reflected by the DeMeester score in patients with Inc-LES (median=20.05) was significantly higher than in patients with an N-LES (median=9.5), which in turn was significantly higher than in patients with an HTN-LES. Increasing LES pressure and AL provided protection against acid exposure in a graded fashion. Increasing number of inadequate LES characteristics were associated with an increase both in the percentage of patients with abnormal DeMeester score and the degree of acid exposure. LES pressure (=6 mmHg) and AL (<1 cm) are associated with increased lower esophageal acid exposure, and need to be addressed for definitive management of GERD.

  10. DDT exposure of zebrafish embryos enhances seizure susceptibility: relationship to fetal p,p'-DDE burden and domoic acid exposure of California sea lions.

    PubMed

    Tiedeken, Jessica A; Ramsdell, John S

    2009-01-01

    California sea lions have a large body burden of organochlorine pesticides, and over the last decade they have also been subject to domoic acid poisoning. Domoic acid poisoning, previously recognized in adult animals, is now viewed as a major cause of prenatal mortality. The appearance of a chronic juvenile domoic acid disease in the sea lions, characterized by behavioral abnormalities and epilepsy, is consistent with early life poisoning and may be potentiated by organochlorine burden. We investigated the interactive effect of DDT (dichlorodiphenyltrichloroethane) on neurodevelopment using a zebrafish (Danio rerio) model for seizure behavior to examine the susceptibility to domoic acid-induced seizures after completion of neurodevelopment. Embryos were exposed (6-30 hr postfertilization) to either o,p'-DDT or p,p'-DDE (dichlorodiphenyldichloroethylene) during neurodevelopment via a 0.1% dimethyl sulfoxide solution. These larval (7 days postfertilization) fish were then exposed to either the seizure-inducing drug pentylenetetrazol (PTZ) or domoic acid; resulting seizure behavior was monitored and analyzed for changes using cameras and behavioral tracking software. Embryonic exposure to DDTs enhanced PTZ seizures and caused distinct and increased seizure behaviors to domoic acid, most notably a type of head-shaking behavior. These studies demonstrate that embryonic exposure to DDTs leads to asymptomatic animals at completion of neurodevelopment with greater sensitivity to domoic acid-induced seizures. The body burden levels of p,p'-DDE are close to the range recently found in fetal California sea lions and suggest a potential interactive effect of p,p'-DDE embryonic poisoning and domoic acid toxicity.

  11. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

    PubMed

    Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-08-30

    We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

    PubMed

    Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

    2011-07-07

    Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

  13. Attenuation of abnormalities in the lipid metabolism during experimental myocardial infarction induced by isoproterenol in rats: beneficial effect of ferulic acid and ascorbic acid.

    PubMed

    Yogeeta, Surinder Kumar; Hanumantra, Rao Balaji Raghavendran; Gnanapragasam, Arunachalam; Senthilkumar, Subramanian; Subhashini, Rajakannu; Devaki, Thiruvengadam

    2006-05-01

    The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.

  14. Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort

    PubMed Central

    Gold, Diane R.; Rifas-Shiman, Sheryl L.; Koutrakis, Petros; Schwartz, Joel D.; Kloog, Itai; Melly, Steven; Coull, Brent A.; Zanobetti, Antonella; Gillman, Matthew W.; Oken, Emily

    2014-01-01

    Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied. Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data. Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m3 for PM2.5 and from 0.1 to 1.7 μg/m3 for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM. Conclusions: Greater exposure to PM2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy. Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose

  15. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    PubMed Central

    2011-01-01

    Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

  16. Oropharyngeal acid reflux and motility abnormalities of the proximal esophagus.

    PubMed

    Passaretti, Sandro; Mazzoleni, Giorgia; Vailati, Cristian; Testoni, Pier Alberto

    2016-10-28

    To investigate the relationship between pathological oropharyngeal (OP) acid exposure and esophageal motility in patients with extra-esophageal syndromes. In this prospective study we enrolled consecutive outpatients with extra-esophageal symptoms suspected to be related to gastroesophageal reflux disease (GERD). We enrolled only patients with a reflux symptom index (RSI) score-higher than 13 and with previous lung, allergy and ear, nose and throat evaluations excluding other specific diagnoses. All patients underwent 24-h OP pH-metry with the Dx probe and esophageal high-resolution manometry (HRM). Patients were divided into two groups on the basis of a normal or pathological pH-metric finding (Ryan Score) and all manometric characteristics of the two groups were compared. We examined 135 patients with chronic extra-esophageal syndromes. Fifty-one were considered eligible for the study. Of these, 42 decided to participate in the protocol. Patients were divided into two groups on the basis of normal or pathological OP acid exposure. All the HRM parameters were compared for the two groups. Significant differences were found in the median upper esophageal sphincter resting pressure (median 71 mmHg vs 126 mmHg, P = 0.004) and the median proximal contractile integral (median 215.5 cm•mmHg•s vs 313.5 cm•mmHg•s, P = 0.039), both being lower in the group with pathological OP acid exposure, and the number of contractions with small or large breaks, which were more frequent in the same group. This group also had a larger number of peristaltic contractions with breaks in the 20 mmHg isobaric contour (38.7% vs 15.38%, P < 0.0001). In patients with suspected GERD-related extra-esophageal syndromes pathological OP acid exposure was associated with weaker proximal esophageal motility.

  17. Arsenic Exposure, Dermatological Lesions, Hypertension, and Chromosomal Abnormalities among People in a Rural Community of Northwest Iran

    PubMed Central

    Dastgiri, Saeed; Fizi, Mohammad A.H.; Olfati, Nahid; Zolali, Shahin; Pouladi, Nasser; Azarfam, Parvin

    2010-01-01

    Chronic exposure to arsenic compounds is one of the major public-health problems in many developing and some developed countries. The aim of this study was to investigate the effects of chronic exposure to arsenic on dermatological lesions, hypertension, and chromosomal abnormalities among people in a community in the northwest of Iran. The occurrence of dermatological lesions, hypertension, and chromosomal abnormalities was investigated in two groups: Ghopuz village, including 101 subjects with chronic exposure to arsenic in drinking-water and Mayan village, including 107 subjects with no exposure. Daily/yearly absorbed amounts of arsenic were calculated for all subjects. Cumulative arsenic index for each individual was then estimated on the basis of age, water consumption, and location of residence. Arsenic concentration in drinking-water sources in Ghopuz and Mayan villages was 1031±1103 μg/L and non-detectable respectively. The mean systolic blood pressure in the exposure group [n=137, 95% confidence interval (CI 132–142)] was significantly higher than that in the control group (n=107, 95% CI 99.9–114). A similar significant difference was observed for diastolic blood pressure (exposed: n=82, 95% CI 79–85 vs non-exposed: n=71, 95% CI 66–75). The incidence of hyperkeratosis was 34 times higher among the exposure group compared to the control subjects [odds ratio (OR)=34, p<0.001)]. A significant difference was also observed in the occurrence of skin-pigmentation between the two groups (OR=2.4, p<0.007). Location and severity of the pigmentations were statistically different between the two groups. Twenty-five percent of the subjects in the exposure group showed chromosomal abnormalities (p=0.05). Arsenic exposure was a serious health problem in the region. More studies are needed to investigate the long-term effects and dose-response relationship of arsenic in the region and similar areas. Wide-ranging monitoring programmes for drinking-water sources

  18. 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

  19. 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. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease.

    PubMed

    Zhong, Chanjuan; Duan, Liping; Wang, Kun; Xu, Zhijie; Ge, Ying; Yang, Changqing; Han, Yajing

    2013-05-01

    The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance. A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII-pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques. Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = -0.41, p < 0.001), and a weak but significant correlation (r = -0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = -0.637, p < 0.001) and claudin-1 and the baseline impedance (r = -0.648, p < 0.001). Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.

  1. Effect of 2 ppm ozone exposure on rat lung lipid fatty acids

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

    Rabinowitz, J.L.; Bassett, D.J.

    Based on in vitro studies, the initial damage to lung cells by ozone exposure is believed to result in part from the breakdown of lipid polyunsaturated fatty acids to aldehydes, ozonides, and peroxides. The present study measured lipid breakdown products in lungs isolated from rats pretreated with (1-/sup 14/C)acetate 12 h before exposure for 4 h to either air or 2 ppm ozone. Lipid fatty acid breakdown was indicated by a 112% increase in thiobarbituric acid-reactive substances on ozone exposure and by changes in chemical and radioactive measurements of mono- and dicarboxylic acids formed by treatment of lipid fractions withmore » hydrogen peroxide. Ozone exposure resulted in a 63% increase in recovery of short-chain fatty acids accounted for by increased recoveries of malonic acid by 37%, hexanoic acid by 47%, nonanoic acid by 118%, and azelaic acid by 107%. Recovery of glutaric acid was enhanced 15-fold by ozone exposure. Although decreases in tissue arachidonic acid could not be detected, oleic acid was significantly decreased by 36%. Recovery of radiolabel as short-chain fatty acids was increased by 65% on ozone exposure and was mainly accounted for by enhanced labeling of nonanoic and glutaric acid fractions. The failure to observe significant increases in /sup 14/C recovery in the other fractions suggested ozone-induced breakdown of unlabeled fatty acids. These results demonstrate the cleavage of unsaturated fatty acid double bonds following in vivo exposure of lungs to ozone. Breakdown of arachidonic and oleic acids was specifically identified by increased recoveries of glutaric and nonanoic acids, respectively.« less

  2. 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

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

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

    Huang, Hegui; He, Zheng; Zhu, Chunyan

    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 (4 g/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 observedmore » 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. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.« less

  4. Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.

    PubMed

    Freeman, G L; Colston, J T; Miller, D D

    1994-01-01

    The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.

  5. Cortical gyrification is abnormal in children with prenatal alcohol exposure.

    PubMed

    Hendrickson, Timothy J; Mueller, Bryon A; Sowell, Elizabeth R; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Wozniak, Jeffrey R

    2017-01-01

    Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined. Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure. Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ). Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.

  6. Radiographic abnormalities in relation to total dust exposure at a bauxite refinery and alumina-based chemical products plant.

    PubMed

    Townsend, M C; Sussman, N B; Enterline, P E; Morgan, W K; Belk, H D; Dinman, B D

    1988-07-01

    A cross-sectional study of 788 male employees of an aluminum production company examined the relationship of radiographic abnormalities to smoking and dust exposure from the mining and refining of bauxite to alumina. Among the aluminas produced were low temperature range transitional forms. The present analyses were limited to nonsmokers and current smokers. Two National Institute of Occupational Safety and Health (NIOSH)-certified "B" readers interpreted the radiographs. The predominant radiographic abnormalities noted were scanty, small, irregular opacities in the lower zones of profusion 0/1 to 1/1. Rounded opacities were rare. Among nonsmokers with low dust exposures, the prevalence of opacities greater than or equal to 1/0 showed no trend with increasing age and duration of exposure, suggesting no relationship between age and prevalence of opacities of Category 1 or more in this cohort (p greater than 0.10). Nonsmokers who had accumulated higher dust exposures showed a trend of increasing prevalence of opacities with increasing duration, suggesting an effect of occupational exposure at higher cumulative exposure levels (p less than 0.05). In most exposure categories, smokers exceeded nonsmokers in their prevalence of opacities greater than or equal to 1/0; the overall prevalence among smokers being 12 and 11% according to Readers A and B, respectively, compared with 4% in nonsmokers (p less than 0.01). In conclusion, 7 to 8% of aluminum workers in this cohort had radiographic findings of scanty, small, irregular opacities, the prevalence of which was increased among smokers (p less than 0.01). There was a moderate increase in the prevalence of opacities with increasing tenure in nonsmokers with high cumulative exposures (p less than 0.05).

  7. Abnormalities of High Density Lipoproteins in Abetalipoproteinemia*

    PubMed Central

    Jones, John W.; Ways, Peter

    1967-01-01

    Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts. 2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states. The available evidence suggests that the abnormally low levels of HDL3 and the deranged phospholipid distribution are more specific for abetalipoproteinemia than the fatty acid abnormalities. However, the absence of these abnormalities in obligate heterozygous subjects makes their relationship to the primary defect of abetalipoproteinemia difficult to assess. Images PMID:6027078

  8. 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...

  9. Platelet Arachidonic Acid Deficiency May Contribute to Abnormal Platelet Function During Parenteral Fish Oil Monotherapy in a Piglet Model.

    PubMed

    Turner, Justine M; Field, Catherine J; Goruk, Sue; Wizzard, Pamela; Dicken, Bryan J; Bruce, Aisha; Wales, Paul W

    2016-05-01

    Fish oil monotherapy has been an advance for treating intestinal failure-associated liver disease (IFALD). However, such patients are at risk of bleeding complications from liver disease and because fish oil can inhibit thrombosis. We have previously reported abnormal platelet function in neonatal piglets given fish oil monotherapy during parenteral nutrition (PN). The purpose of this study was to determine if abnormal fatty acid composition of the platelets could explain the prior observed antiplatelet effect. Neonatal piglets were assigned to 2 treatments: PN with fish oil monotherapy (FO; n = 4) or PN with soy oil (SO; n = 5). On day 14, plasma was collected and platelets isolated by centrifuging. The fatty acid content in plasma and platelet plug were measured using gas liquid chromatography and compared with controls (CON; n = 5). The arachidonic acid (AA) content in the FO group was on average half that of the SO group, in both the platelets (FO, 3.5% vs SO, 7.6%; P = .021; CON, 4.5%-11%) and the plasma (FO, 3.8% vs SO, 9.2%; P = .002; CON, 6.1%-9.5%). No bleeding complications were observed for any piglets during PN treatment. Using platelet mapping, we have previously shown that neonatal piglets given fish oil monotherapy have abnormal platelet function in the AA pathway. This report demonstrates that such an abnormality can be explained by platelet AA deficiency. Platelet mapping and platelet fatty acid analysis should be undertaken in human infants treated with fish oil monotherapy during PN. © 2015 American Society for Parenteral and Enteral Nutrition.

  10. Incidence of laryngeal cancer and exposure to acid mists.

    PubMed Central

    Steenland, K; Schnorr, T; Beaumont, J; Halperin, W; Bloom, T

    1988-01-01

    To determine the relation between exposure to acid mist and laryngeal cancer, the smoking habits, drinking habits, and incidence of laryngeal cancer of 879 male steelworkers exposed to acid mists during pickling operations was ascertained. Sulphuric acid mist was the primary exposure for most men in this cohort. These men had all worked in a pickling operation for a minimum of six months before 1965, with an average duration of exposure of 9.5 years. Exposures to sulphuric acid in the 1970s averaged about 0.2 mg/m3, and earlier exposures were probably similar. Interviews were conducted with all cohort members or their next of kin in 1986 and medical records of decedents were reviewed. Nine workers were identified who had been diagnosed as having laryngeal cancer, using a conservative case definition that required medical record confirmation for any case among decedents and confirmation by a physician for any case among live individuals. Using data from national surveys of cancer incidence as referent rates, 3.44 laryngeal cancers would have been expected. Excess smoking by the exposed cohort compared with the United States population resulted in an upward adjustment of the expected number of cases of laryngeal cancer to 3.92. The standardised incidence rate ratio for laryngeal cancer was 2.30 (9/3.92), with a one sided p value of 0.01 (assuming a Poisson distribution). The finding of excess laryngeal cancer in this cohort is consistent with four other studies published since 1981. PMID:3203082

  11. 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

  12. Understanding potential exposure sources of perfluorinated carboxylic acids in the workplace.

    PubMed

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

    2010-11-01

    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.

  13. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Maternal exposure to silver nanoparticles are associated with behavioral abnormalities in adulthood: Role of mitochondria and innate immunity in developmental toxicity.

    PubMed

    Amiri, Shayan; Yousefi-Ahmadipour, Aliakbar; Hosseini, Mir-Jamal; Haj-Mirzaian, Arya; Momeny, Majid; Hosseini-Chegeni, Heshmat; Mokhtari, Tahmineh; Kharrazi, Sharmin; Hassanzadeh, Gholamreza; Amini, Seyed Mohammad; Jafarinejad, Somayeh; Ghazi-Khansari, Mahmoud

    2018-05-01

    Silver nanoparticles (Ag-NPs) are currently used in a wide range of consumer products. Considering the small size of Ag-NPs, they are able to pass through variety of biological barriers and exert their effects. In this regard, the unique physicochemical properties of Ag-NPs along with its high application in the industry have raised concerns about their negative effects on human health. Therefore, it investigated whether prenatal exposure to low doses of Ag-NPs is able to induce any abnormality in the cognitive and behavioral performance of adult offspring. We gavaged pregnant NMRI mice with, 1) Deionized water as vehicle, 2) Ag-NPs 10 nm (0.26 mg/kg/day), 3) Ag-NPs 30 nm (0.26 mg/kg/day), and 4) AgNO 3 (0.26 mg/kg/day) from gestational day (GD) 0 until delivery day. At the postnatal day (PD) 1, our results showed that high concentration of silver is present in the brain of pups. Further, we observed mitochondrial dysfunction and upregulation of the genes relevant to innate immune system in the brain. At PD 60, results revealed that prenatal exposure to Ag-NPs provoked severe cognitive and behavioral abnormalities in male offspring. In addition, we found that prenatal exposure to Ag-NPs was associated with abnormal mitochondrial function and significant up-regulation of the genes relevant to innate immunity in the brain. Although the Ag-NPs have been considered as safe compounds at low doses, our results indicate that prenatal exposure to low doses of Ag-NPs is able to induce behavioral and cognitive abnormalities in adulthood. Also, we found that these effects are at least partly associated with hippocampal mitochondrial dysfunction and the activation of sterile inflammation during early stages of life. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. A Prospective Cohort Study of the Prevalence of Growth, Facial, and Central Nervous System Abnormalities in Children with Heavy Prenatal Alcohol Exposure

    PubMed Central

    Kuehn, Devon; Aros, Sofía; Cassorla, Fernando; Avaria, Maria; Unanue, Nancy; Henriquez, Cecilia; Kleinsteuber, Karin; Conca, Barbara; Avila, Alejandra; Carter, Tonia C.; Conley, Mary R.; Troendle, James; Mills, James L.

    2014-01-01

    Background Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. Methods This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. Results One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. Conclusions After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and

  16. Exposure assessment of oxidant gases and acidic aerosols

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

    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 themore » 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.« less

  17. Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

    PubMed

    Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

    2016-06-01

    Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

  18. Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

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

    Chase, K.H.; Wong, O.; Thomas, D.

    1982-02-01

    A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p < .00001), correlating well with age and duration of employment. Thesemore » correlations were stronger for fat (p < .001) than for plasma (p < .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p < .00001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p < .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

  19. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

    PubMed Central

    Brady, Roscoe O; McCarthy, Julie M; Prescot, Andrew P; Jensen, J Eric; Cooper, Alissa J; Cohen, Bruce M; Renshaw, Perry F; Ongür, Dost

    2017-01-01

    Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition. PMID:23634979

  20. 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.

  1. 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

  2. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans

    PubMed Central

    Hulver, Matthew W.; Berggren, Jason R.; Carper, Michael J.; Miyazaki, Makoto; Ntambi, James M.; Hoffman, Eric P.; Thyfault, John P.; Stevens, Robert; Dohm, G. Lynis; Houmard, Joseph A.; Muoio, Deborah M.

    2014-01-01

    Summary Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. PMID:16213227

  3. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

    PubMed

    Hulver, Matthew W; Berggren, Jason R; Carper, Michael J; Miyazaki, Makoto; Ntambi, James M; Hoffman, Eric P; Thyfault, John P; Stevens, Robert; Dohm, G Lynis; Houmard, Joseph A; Muoio, Deborah M

    2005-10-01

    Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

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

    PubMed

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

    2016-04-14

    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.

  5. Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

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

    Chase, K.H.; Wong, O.; Thomas, D.

    1982-02-01

    A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p less than .0001), correlating well with age and duration of employment.more » These correlations were stronger for fat (p less than .001) than for plasma (p less than .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p less than .0001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p less than .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

  6. Induction and persistence of abnormal testicular germ cells following gestational exposure to di-(n-butyl) phthalate in p53-null mice.

    PubMed

    Saffarini, Camelia M; Heger, Nicholas E; Yamasaki, Hideki; Liu, Tao; Hall, Susan J; Boekelheide, Kim

    2012-01-01

    Phthalate esters are commonly used plasticizers found in many household items, personal care products, and medical devices. Animal studies have shown that in utero exposure to di-(n-butyl) phthalate (DBP) within a critical window during gestation causes male reproductive tract abnormalities resembling testicular dysgenesis syndrome. Our studies utilized p53-deficient mice for their ability to display greater resistance to apoptosis during development. This model was chosen to determine whether multinucleated germ cells (MNG) induced by gestational DBP exposure could survive postnatally and evolve into testicular germ cell cancer. Pregnant dams were exposed to DBP (500 mg/kg/day) by oral gavage from gestational day 12 until birth. Perinatal effects were assessed on gestational day 19 and postnatal days 1, 4, 7, and 10 for the number of MNGs present in control and DBP-treated p53-heterozygous and null animals. As expected, DBP exposure induced MNGs, with greater numbers found in p53-null mice. Additionally, there was a time-dependent decrease in the incidence of MNGs during the early postnatal period. Histologic examination of adult mice exposed in utero to DBP revealed persistence of abnormal germ cells only in DBP-treated p53-null mice, not in p53-heterozygous or wild-type mice. Immunohistochemical staining of perinatal MNGs and adult abnormal germ cells was negative for both octamer-binding protein 3/4 and placental alkaline phosphatase. This unique model identified a role for p53 in the perinatal apoptosis of DBP-induced MNGs and provided insight into the long-term effects of gestational DBP exposure within a p53-null environment.

  7. Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids.

    PubMed

    Wei, Yongyue; Wang, Zhaoxi; Chang, Chiung-yu; Fan, Tianteng; Su, Li; Chen, Feng; Christiani, David C

    2013-01-01

    Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans. To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure. The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry. Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5) exposure (p<0.05). The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [β(95% CI) = -0.013(-0.022 ≈ -0.004); p = 0.005], docosapentaenoic acid n3 [β(95% CI) = -0.010(-0.018 ≈ -0.002); p = 0.017], and docosapentaenoic acid n6 [β(95% CI) = -0.007(-0.013 ≈ -0.001); p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study-2011 = 0.025; p Study-2012 = 0.021; p Combined = 0.009). The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders. High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.

  8. 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.

  9. Soil microbial community responses to acid exposure and neutralization treatment.

    PubMed

    Shin, Doyun; Lee, Yunho; Park, Jeonghyun; Moon, Hee Sun; Hyun, Sung Pil

    2017-12-15

    Changes in microbial community induced by acid shock were studied in the context of potential release of acids to the environment due to chemical accidents. The responses of microbial communities in three different soils to the exposure to sulfuric or hydrofluoric acid and to the subsequent neutralization treatment were investigated as functions of acid concentration and exposure time by using 16S-rRNA gene based pyrosequencing and DGGE (Denaturing Gradient Gel Electrophoresis). Measurements of soil pH and dissolved ion concentrations revealed that the added acids were neutralized to different degrees, depending on the mineral composition and soil texture. Hydrofluoric acid was more effectively neutralized by the soils, compared with sulfuric acid at the same normality. Gram-negative ß-Proteobacteria were shown to be the most acid-sensitive bacterial strains, while spore-forming Gram-positive Bacilli were the most acid-tolerant. The results of this study suggest that the Gram-positive to Gram-negative bacterial ratio may serve as an effective bio-indicator in assessing the impact of the acid shock on the microbial community. Neutralization treatments helped recover the ratio closer to their original values. The findings of this study show that microbial community changes as well as geochemical changes such as pH and dissolved ion concentrations need to be considered in estimating the impact of an acid spill, in selecting an optimal remediation strategy, and in deciding when to end remedial actions at the acid spill impacted site. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Global Metabolomic Profiling Reveals an Association of Metal Fume Exposure and Plasma Unsaturated Fatty Acids

    PubMed Central

    Chang, Chiung-yu; Fan, Tianteng; Su, Li; Chen, Feng; Christiani, David C.

    2013-01-01

    Background Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans. Objectives To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure. Methods The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry. Results Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5) exposure (p<0.05). The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [(95% CI) = −0.013(−0.022∼−0.004); p = 0.005], docosapentaenoic acid n3 [(95% CI) = −0.010(−0.018∼−0.002); p = 0.017], and docosapentaenoic acid n6 [(95% CI) = −0.007(−0.013∼−0.001); p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study−2011 = 0.025; p Study−2012 = 0.021; p Combined = 0.009). The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders. Conclusions High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders. PMID:24143234

  11. Waist circumference, body mass index, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal liver function tests in the Taiwanese population.

    PubMed

    Hsieh, Meng-Hsuan; Lin, Wen-Yi; Chien, Hsu-Han; Chien, Li-Ho; Huang, Chao-Kuan; Yang, Jeng-Fu; Chang, Ning-Chia; Huang, Chung-Feng; Wang, Chao-Ling; Chuang, Wan-Long; Yu, Ming-Lung; Dai, Chia-Yen; Ho, Chi-Kung

    2012-09-01

    Several studies have found that metabolic syndrome and uric acid level are related to abnormal liver function test results. The aim of this study was to explore the associations of risk factors [including blood pressure, blood sugar, total cholesterol, triglyceride, uric acid, waist circumference and body mass index (BMI) measurements] with abnormal liver function in the Taiwanese population.In total, 11,411 Taiwanese adults were enrolled in this study. Blood pressure was assessed according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, fasting blood sugar level according to the Bureau of Health Promotion, Department of Health, R.O.C., criteria, total cholesterol and triglyceride levels according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel III criteria, BMI according to the Asia-Pacific criteria, and waist circumference according to the Revised Diagnostic Criteria of Metabolic Syndrome in Taiwan. The prevalence of a past history of hypertension and diabetes mellitus was 17.7% and 6.5%, respectively, and the rates of abnormal measurements of blood pressure, BMI, waist circumference, fasting blood sugar, triglyceride, total cholesterol, uric acid (male/female), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were 76.2%, 67.6%, 40.0%, 28.6%, 30.6%, 57.3%, 37.9%/21.9%, 14.6% and 21.3%, respectively. Multivariate analysis showed that waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels were related to abnormal AST and ALT (p<0.05), but the odds ratio for waist circumference was larger than that for BMI. In conclusion, waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal AST and ALT readings in Taiwanese adults. Waist circumference might be a better indicator of risk of abnormal liver function than BMI. Copyright © 2012

  12. 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.

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

    PubMed

    Do, D; Orrego, S; Majd, H; Ryou, H; Mutluay, M M; Xu, Hockin H K; Arola, 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. © 2013 Elsevier Ltd. All rights reserved.

  14. Acid-base and hormonal abnormalities in dogs with naturally occurring diabetes mellitus.

    PubMed

    Durocher, Lawren L; Hinchcliff, Kenneth W; DiBartola, Stephen P; Johnson, Susan E

    2008-05-01

    To examine acid-base and hormonal abnormalities in dogs with diabetes mellitus. Cross-sectional study. 48 dogs with diabetes mellitus and 17 healthy dogs. Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups. Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 micromol/L had a serum insulin concentration < 5 microU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum beta-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased. Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

  15. The relationship between environmental exposures and hormonal abnormalities in pregnant women: An epidemiological study in Yazd, Iran.

    PubMed

    Askari, Sahar Ghale; Khatbasreh, Masomeh; Ehrampoush, Mohammad Hassan; Sheikhha, Mohammad Hassan; Eslami, Hadi; Taghavi, Mahmoud; Shahrokhi, Samira; Andishmand, Sodeh

    2018-06-01

    The process of industrialization and lifestyle changes have gradually exposed human ‎societies to a larger number of environmental risk factors, which may cause hormonal ‎abnormalities and congenital anomalies. The current study aimed to investigate the relationship ‎between environmental factors and hormonal abnormalities among pregnant women in Yazd, ‎Iran. A hundred participants were randomly selected from among a group of pregnant women. According to the screening tests (AFP, free β-‎HCG, uE3, PAPP-A, and inhibin-A) performed at the genome clinic in Yazd in 2016, the risk of Down Syndrome (DS) was sufficiently high in this group of pregnant women from which the participants were selected. A ‎questionnaire was used to collect data on the degree of the participants' exposure to pesticides ‎at home, use of canned and fast foods, and consumption of greenhouse fruits. The collected data were ‎analyzed by One-way ANOVA and Kruskal-Wallis Test. The mean of Multiple of Median (MoM) for inhibin-A was significantly higher among pregnant ‎women who often or always used pesticides at home (p=0.047). The mean MoM ‎for free β-HCG was significantly higher among pregnant women who often or always used canned ‎foods (p=0.024). Finally, the mean MoM for uE3 (1.85±1.30) was significantly higher among ‎pregnant women who never consumed greenhouse fruits (p=0.003). It can be concluded that it is possible to reduce environmental exposures affecting hormonal abnormalities among pregnant women by improving nutritional patterns, minimizing the use of pesticides at home, and reducing the intake of canned foods and greenhouse fruits. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  16. Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice

    EPA Science Inventory

    AbstractEnvironmental exposures occurring early in life may have an important influence on cancer risk later in life. Here we investigated carryover effects of young-adult exposure to dichloroacetic acid (DCA), a small molecule analog of pyruvate and low-level environmental cont...

  17. [Examination of laser-treated tooth surfaces after exposure to acid].

    PubMed

    Beeking, P O; Herrmann, C; Zuhrt, R

    1990-12-01

    In principle it is possible to homogenize the enamel surface by melting structural elements with the continuous wave CO2 laser. An experimental caries model was used for testing the acid resistance of the laser exposed tooth surfaces. Laser-treatment and measured exposure to acid produced zones of homogeneous smelting with microcracks and disintegration symptoms. Underneath the melted region the heat leakage obviously causes photo-thermic++ effects determined by increased resistance to acid.

  18. Abnormal synergistic effects between Lewis acid-base interaction and halogen bond in F3B···NCX···NCM

    NASA Astrophysics Data System (ADS)

    Tang, Qingjie; Li, Qingzhong

    2015-12-01

    An abnormal synergistic effect was found between the Lewis acid-base interaction and halogen bond in triads F3B···NCX···NCM (X and M are halogen atoms), where the strong Lewis acid-base interaction between F3B and NCX has a larger enhancement than the weak halogen bond between NCX and NCM. This is in contrast with the traditional cooperative effect. It is interesting that the alkali-metal substituent as well as the heavier halogen atom play a more remarkable role in the enhancement of the interaction F3B···NCX than that of NCX···NCM, particularly, the alkali-metal substituent makes the abnormal synergistic effect be the traditional cooperative one.

  19. Cellular Effects of Perfluorinated Fatty Acids (PFDA).

    DTIC Science & Technology

    This is a proposal to investigate the effects of perfluorinated decanoic acid ( PFDA ) on the cell surface of liver cells and tissue. The major method...summarized as follows: (a) differentiated liver tissue culture cells in vitro do have the membrane fluidity affected by PFDA whereas undifferentiated, non...d) the effect on mobility occurs within 24 hours of exposure without further increase with time of exposure; (e) scanning EM demonstrates no gross structural abnormality of the surface as a result of the non-toxic levels of PFDA .

  20. Frequency of metabolic abnormalities in urinary stones patients.

    PubMed

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-11-01

    To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

  1. Behavioral alterations induced in rats by a pre- and postnatal exposure to 2,4-dichlorophenoxyacetic acid.

    PubMed

    Bortolozzi, A A; Duffard, R O; Evangelista de Duffard, A M

    1999-01-01

    The purpose of this study was to determine whether the behavioral development pattern was altered by a pre- and postnatal exposure to 2,4-Dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postnatal day (PND) 23. After weaning, the pups were assigned to one of the two subgroups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Effects on offsprings were evaluated with a neurotoxicological test battery. Neuromotor reflexes, spontaneous motor activity, serotonin syndrome, circling, and catalepsy were analyzed during various postnatal ages. 2,4-D neonatal exposure induced delay of the ontogeny of righting reflex and negative geotaxis accompanied by motor abnormalities, stereotypic behaviors (excessive grooming and vertical head movements), and hyperactivity in the open field. Adult rats of both sexes (T2 group) showed a diminution of ambulation and rearing, while excessive grooming responses were only observed in T2 males. Besides, these animals manifested serotonin syndrome behaviors, catalepsy, and right-turning preference. Some behaviors were reversible, but others were permanent, and some were only expressed after pharmacological challenges.

  2. Case-control study: soft-tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols.

    PubMed Central

    Hardell, L.; Sandström, A.

    1979-01-01

    In 1977 a number of patients with soft-tissue sarcomas and previous exposure to phenoxyacetic acids were described. Following from these observations a matched case-control study was made. Exposure to chlorophenols was also included in this study. The results showed that exposure to phenoxyacetic acids or chlorophenols gave an approximately 6-fold increase in the risk for this type of tumour. It was not possible to determine, however, whether the carcinogenic effect was exerted by these compounds or by impurities such as chlorinated dibenzodioxins and dibenzofurans that in almost all cases were part of the commercial preparations. PMID:444410

  3. Comparison of ion-pair chromatography and capillary zone electrophoresis for the assay of organic acids as markers of abnormal metabolism.

    PubMed

    Wang, Shu-Ping; Liao, Chiou-Shyi

    2004-10-08

    The abnormal organic acids in urine are closely related with physiological metabolism. To determinate the low-molecular-mass metabolites in human biological fluids, although there were some previous reports by both of capillary electrophoresis and ion-exchange high-performance liquid chromatography, but it was rarely found by reverse phase of liquid chromatography using ion pair reagent. The objective of this study was aimed to suggest and compare two methods, an additional chromatographic method-ion-pair chromatography (IPC) and a sharp capillary zone electrophoresis (CZE), to determinate organic acids, acting as the abnormal metabolic markers, namely uric acid, orotic acid, pyruvic acid, alpha-ketoglutaric acid, fumaric acid, and hippuric acid. The proposed method of IPC possessed both the extreme stability for column and the good results of reproducibility, linearity and detection limit. The optimum mobile phase was 22% methanol and 10 mM tetra-n-butyl ammonium hydrogen sulfate (pH 4) by gradient elution. As well as the optimum condition of CZE was 5% acetonitrile and 0.5 mM CTAB in phosphate buffer. From the results, CZE showed better recovery and sharp lucid electropherogram. Finally, the two proposed analytical methods were applied to assay human urine with direct and spiked analysis. CZE showed good potency to overcome the sample-to sample variation with standard deviation less than 10%. By comparison results of urinary spiked analysis between IPC and CZE by statistical paired t-test, the results were evaluated no significant difference under P < 0.05. The quantitative linearity of both methods was fitted in application of clinical biological analysis even with 50-fold dilution.

  4. Occupational dental erosion from exposure to acids: a review.

    PubMed

    Wiegand, Annette; Attin, Thomas

    2007-05-01

    Dental erosion is characterized as a disorder with a multifactorial aetiology including environmental acid exposure. The purpose of this article was to summarize and discuss the available information concerning occupational dental erosion. Information from original scientific papers, case reports and reviews with additional case reports listed in PubMed, Medline or EMBASE [search term: (dental OR enamel OR dentin) AND (erosion OR tooth wear) AND (occupational OR worker)] were included in the review. References from the identified publications were manually searched to identify additional relevant articles. The systematic search resulted in 59 papers, of which 42 were suitable for the present review. Seventeen papers demonstrated evidence that battery, galvanizing and associated workers exposed to sulphuric or hydrochloric acid were at higher risk of dental erosion. For other industrial workers, wine tasters and competitive swimmers, only a few clinical studies exist and these do not allow the drawing of definitive conclusions. Occupational acid exposure might increase the risk of dental erosion. Evidence for occupational dental erosion is limited to battery and galvanizing workers, while data for other occupational groups need to be confirmed by further studies.

  5. Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.

    PubMed

    Miyara, Masatsugu; Kotake, Yaichiro; Tokunaga, Wataru; Sanoh, Seigo; Ohta, Shigeru

    2016-10-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP + suggest autophagy involvement in the pathogenesis of PD, the effect of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP + exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP + toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP + exposure predominantly inhibited autophagosome degradation, whereas acute MPP + exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP + exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP + exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP + exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP + exposure and mechanistic differences between mild and acute MPP + toxicities. Mild MPP + toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP + exposure. Mechanistic differences between acute and mild MPP + toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson

  6. AMMONIA ABATEMENT SYSTEM FOR WHOLE-BODY SMALL ANIMAL INHALATION EXPOSURES TO ACID MODELS

    EPA Science Inventory

    Conducting whole-body acid aerosol inhalation exposures of laboratory animals is complicated by ammonia arising from the excrement of the test animals which is sufficient to completely neutralize much of the acid aerosol. he neutralization of acid by ammonia con only be controlle...

  7. [Liver enzyme abnormalities among oil refinery workers].

    PubMed

    Carvalho, Fernando Martins; Silvany Neto, Annibal Muniz; Mendes, João Luiz Barberino; Cotrim, Helma Pinchemel; Nascimento, Ana Lísia Cunha; Lima Júnior, Alberto Soares; Cunha, Tatiana Oliveira Bernardo da

    2006-02-01

    Occupational exposure typical of an oil refinery may alter liver function among the workers. Thus, the objective of the study was to identify risk factors for liver enzyme abnormalities among oil refinery workers. The workers at an oil refinery in Northeastern Brazil underwent routine annual medical examination from 1982 to 1998. This case-control study investigated all the 150 cases of individuals with simultaneous gamma-glutamyltransferase and alanine aminotransferase abnormalities of at least 10% above reference levels. As controls, 150 workers without any liver enzyme or bilirubin abnormalities since starting to work there were selected. Odds ratios and the respective 95% confidence intervals were calculated from logistic regression models. In all the production sectors, the risk of liver enzyme abnormalities was significantly higher than in the administrative sector (OR=5.7; 95% CI: 1.7-18.4), even when the effects of alcohol, obesity and medical history of hepatitis were controlled for. During the period from 1992 to 1994, 88 out of the 89 cases occurred among workers from the various production sectors. Occupational exposure plays an important role in causing liver enzyme abnormalities among oil refinery workers. This is in addition to the specifically biological and/or behavioral risk factors such as obesity and alcohol consumption.

  8. Frequency of metabolic abnormalities in urinary stones patients

    PubMed Central

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-01-01

    Objective: To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Methods: Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Results: Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. Conclusion: This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients. PMID:24550954

  9. Radiographic abnormalities among construction workers exposed to quartz containing dust

    PubMed Central

    Tjoe, N; Burdorf, A; Parker, J; Attfield, M; van Duivenbooden, C; Heederik, D

    2003-01-01

    Background: Construction workers are exposed to quartz containing respirable dust, at levels that may cause fibrosis in the lungs. Studies so far have not established a dose-response relation for radiographic abnormalities for this occupational group. Aims: To measure the extent of radiographic abnormalities among construction workers primarily exposed to quartz containing respirable dust. Methods: A cross sectional study on radiographic abnormalities indicative of pneumoconiosis was conducted among 1339 construction workers mainly involved in grinding, (jack)-hammering, drilling, cutting, sawing, and polishing. Radiological abnormalities were determined by median results of the 1980 International Labour Organisation system of three certified "B" readers. Questionnaires were used for assessment of occupational history, presence of respiratory diseases, and symptoms and smoking habits. Results: An abnormality of ILO profusion category 1/0 and greater was observed on 10.2% of the chest radiographs, and profusion category of 1/1 or greater on 2.9% of the radiographs. The average duration of exposure of this group was 19 years and the average age was 42. The predominant type of small opacities (irregularly shaped) is presumably indicative of mixed dust pneumoconiosis. The prevalence of early signs of nodular silicosis (small rounded opacities of category 1/0 or greater) was low (0.8%). Conclusions: The study suggests an elevated risk of radiographic abnormalities among these workers with expected high exposure. An association between radiographic abnormalities and cumulative exposure to quartz containing dust from construction sites was observed, after correction for potentially confounding variables. PMID:12771392

  10. 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

  11. Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123

    PubMed Central

    Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M

    2011-01-01

    Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. PMID:21653798

  12. Mechanisms and consequences of paternally transmitted chromosomal abnormalities

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

    Marchetti, F; Wyrobek, A J

    Paternally transmitted chromosomal damage has been associated with pregnancy loss, developmental and morphological defects, infant mortality, infertility, and genetic diseases in the offspring including cancer. There is epidemiological evidence linking paternal exposure to occupational or environmental agents with an increased risk of abnormal reproductive outcomes. There is also a large body of literature on germ cell mutagenesis in rodents showing that treatment of male germ cells with mutagens has dramatic consequences on reproduction producing effects such as those observed in human epidemiological studies. However, we know very little about the etiology, transmission and early embryonic consequences of paternally-derived chromosomal abnormalities.more » The available evidence suggests that: (1) there are distinct patterns of germ cell-stage differences in the sensitivity of induction of transmissible genetic damage with male postmeiotic cells being the most sensitive; (2) cytogenetic abnormalities at first metaphase after fertilization are critical intermediates between paternal exposure and abnormal reproductive outcomes; and, (3) there are maternally susceptibility factors that may have profound effects on the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and directly affect the risk for abnormal reproductive outcomes.« less

  13. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

    PubMed

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2014-01-01

    Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation

  14. 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

  15. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The effects of obesity on oesophageal function, acid exposure and the symptoms of gastro-oesophageal reflux disease.

    PubMed

    Anggiansah, R; Sweis, R; Anggiansah, A; Wong, T; Cooper, D; Fox, M

    2013-03-01

    Obese patients have an increased risk of gastro-oesophageal reflux disease; however, the mechanism underlying this association is uncertain. To test the hypothesis that mechanical effects of obesity on oesophageal function increase acid exposure and symptoms. Height, weight and waist circumference (WC) were measured in patients with typical reflux symptoms referred for manometry and 24 h ambulatory pH studies. Symptom severity was assessed by questionnaire. The association between obesity [WC, body mass index (BMI)], oesophageal function, acid exposure and reflux symptoms was assessed. Physiological measurements were obtained from 582 patients (median age 48, 56% female) of whom 406 (70%) completed symptom questionnaires. The prevalence of general obesity was greater in women (BMI ≥ 30 kg/m(2) ; F 23%:M 16%; P = 0.056), however more men had abdominal obesity (WC ≥ 99 cm (M 41%:F 28%; P = 0.001)). Oesophageal acid exposure increased with obesity (WC: R = 0.284, P < 0.001) and was associated also with lower oesophageal sphincter (LOS) pressure, reduced abdominal LOS length and peristaltic dysfunction (all P < 0.001). Univariable regression showed a negative association of WC with both LOS pressure and abdominal LOS length (R = -0.221 and -0.209 respectively; both P < 0.001). However, multivariable analysis demonstrated that the effects of increasing WC on oesophageal function do not explain increased acid reflux in obese patients. Instead, independent effects of obesity and oesophageal dysfunction on acid exposure were present. Reflux symptoms increased with acid exposure (R = 0.300; P < 0.001) and this association explained increased symptom severity in obese patients. Abdominal obesity (waist circumference) is associated with oesophageal dysfunction, increased acid exposure and reflux symptoms; however, this analysis does not support the mechanical hypothesis that the effects of obesity on oesophageal function are the cause of increased acid exposure in obese

  17. Psychological stress exposure to aged mice causes abnormal feeding patterns with changes in the bout number.

    PubMed

    Yamada, Chihiro; Mogami, Sachiko; Hattori, Tomohisa

    2017-11-09

    Stress responses are affected by aging. However, studies on stress-related changes in feeding patterns with aging subject are minimal. We investigated feeding patterns induced by two psychological stress models, revealing characteristics of stress-induced feeding patterns as "meal" and "bout" (defined as the minimum feeding behavior parameters) in aged mice. Feeding behaviors of C57BL/6J mice were monitored for 24 h by an automatic monitoring device. Novelty stress reduced the meal amount over the 24 h in both young and aged mice, but as a result of a time course study it was persistent in aged mice. In addition, the decreased bout number was more pronounced in aged mice than in young mice. The 24-h meal and bout parameters did not change in either the young or aged mice following water avoidance stress (WAS). However, the meal amount and bout number increased in aged mice for 0-6 h after WAS exposure but remained unchanged in young mice. Our findings suggest that changes in bout number may lead to abnormal stress-related feeding patterns and may be one tool for evaluating eating abnormality in aged mice.

  18. The spectrum of motor function abnormalities in gastroesophageal reflux disease and Barrett's esophagus.

    PubMed

    Ang, D; Blondeau, K; Sifrim, D; Tack, J

    2009-01-01

    Barrett's esophagus has traditionally been regarded as the most severe end of the spectrum of gastroesophageal reflux disease and is of great clinical importance in view of the association with esophageal adenocarcinoma. Studies have documented high levels of esophageal acid exposure in Barrett's esophagus. Various pathogenetic mechanisms underlie this phenomenon. These include abnormalities in esophageal peristalsis, defective lower esophageal sphincter pressures, gastric dysmotility and bile reflux. Whilst these factors provide evidence for an acquired cause of Barrett's esophagus, an underlying genetic predisposition cannot be ruled out. Although the past decade has brought about many new discoveries in the pathogenesis of Barrett's esophagus, it has also added further controversy to this complex disorder. A detailed analysis of the gastrointestinal motor abnormalities occurring in Barrett's esophagus follows, with a review of the currently available literature and an update on this condition that continues to be of interest to the gastroenterologist.

  19. Inhalation exposure of rats to metal aerosol. I. Effects on pulmonary surfactant and ascorbic acid.

    PubMed

    Kováciková, Z; Chorvatovicová, D

    1992-02-01

    Female albino Wistar rats were exposed to less than 5 microns particles separated from nickel refinery waste. The generated aerosol of 50 mg m-3 mainly consisted of metal oxides, the most toxic being NiO and Cr2O3. The exposure of 5 h per day, 5 days per week, lasted for 4 weeks or 4 months. At the end of the exposure period the amounts of pulmonary surfactant and ascorbic acid were estimated in both exposed and control rats. The amount of pulmonary surfactant was elevated after both exposure times, while ascorbic acid increased significantly (P less than 0.02) only after 4 weeks of exposure.

  20. The induction of chromosomal abnormalities by inhalational anaesthetics.

    PubMed

    Grant, C J; Powell, J N; Radford, S G

    1977-06-01

    When Vicia faba root tips are exposed for 2 h to clinically useful concentrations of halothane or methoxyflurane in air, or to halothane in 80% nitrous oxide/20% oxygen, there is a transient increase in mitotic index and then abnormal interphase cells are produced in proportion to the anaesthetic concentrations. After exposure there is a period of mitotic inhibition during which the cells become partially synchronised. When colchicine-metaphase cells collected 28 h after exposure are compared with controls and with metaphases collected only 4 h after exposure, they show a significant increase in the incidence of aneuploidy, tetraploidy and the results of chromosome breakage. It is suggested that all the abnormalities seen can be accounted for by the effects of the anaesthetics on spindle movements, and that at the concentrations used the anaesthetics have no mutagenic effects on chromosomes in interphase.

  1. Urinary trans-trans muconic acid (exposure biomarker to benzene) and hippuric acid (exposure biomarker to toluene) concentrations in Mexican women living in high-risk scenarios of air pollution.

    PubMed

    Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Maldonado, Iván N

    2017-11-02

    This study aimed to determine t,t-muconic acid (t,t-MA; exposure biomarker for benzene) and hippuric acid (HA; exposure biomarker for toluene) concentrations in the urine of women living in Mexico. In a cross-sectional study, apparently healthy women (n = 104) were voluntarily recruited from localities with a high risk of air pollution; t,t-MA and HA in urine were quantified using a high-performance liquid chromatography (HPLC) technique. Mean urinary levels of t,t-MA ranged from 680 to 1,310 μg/g creatinine. Mean values of HA ranged from 0.38 to 0.87 g/g creatinine. In conclusion, compared to data recently reported in literature, we found high urinary levels of t,t-MA and HA in assessed women participating in this study. We therefore deem the implementation of a strategy aimed at the reduction of exposure as a necessary measure for the evaluated communities.

  2. Mildly abnormal general movement quality in infants is associated with higher Mead acid and lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio.

    PubMed

    van Goor, S A; Schaafsma, A; Erwich, J J H M; Dijck-Brouwer, D A J; Muskiet, F A J

    2010-01-01

    We showed that docosahexaenoic acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic acid (AA), DHA/AA and Mead acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable. Copyright 2009 Elsevier Ltd. All rights reserved.

  3. Tongue Abnormalities Are Associated to a Maternal Folic Acid Deficient Diet in Mice

    PubMed Central

    Maldonado, Estela; López-Gordillo, Yamila; Varela-Moreiras, Gregorio; Martínez-Álvarez, Concepción; Pérez-Miguelsanz, Juliana

    2017-01-01

    It is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2–16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes. PMID:29283374

  4. Tongue Abnormalities Are Associated to a Maternal Folic Acid Deficient Diet in Mice.

    PubMed

    Maldonado, Estela; López-Gordillo, Yamila; Partearroyo, Teresa; Varela-Moreiras, Gregorio; Martínez-Álvarez, Concepción; Pérez-Miguelsanz, Juliana

    2017-12-28

    It is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2-16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes.

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

    EPA Science Inventory


    Title:

    Effects Of Perfluorooctanoic Acid Exposure During Pregnancy In The Mouse

    Authors & affiliations:
    Lau, C., J.R. Thibodeaux*, R.G. Hanson* and J.M. Rogers. Reproductive Toxicology Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC
    Abstract:<...

  6. Significance of urinary hippuric acid determination as an index of toluene exposure

    PubMed Central

    Ikeda, Masayuki; Ohtsuji, Hatsue

    1969-01-01

    Ikeda, Masayuki, and Ohtsuji, Hatsue (1969).Brit. J. industr. Med.,26, 244-246. Significance of urinary hippuric acid determination as an index of toluene exposure. Urine samples from 118 male workers in photogravure printing factories were analysed for hippuric acid. The urinary levels of hippuric acid were proportional to the environmental concentrations of toluene, although within wide variations. The urinary concentration of hippuric acid corresponding to 200 p.p.m. of toluene was 3·5 g./litre (specific gravity 1·016) or 4·3 g./g. creatinine. PMID:5794951

  7. 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. Copyright © 2012 Elsevier GmbH. All rights reserved.

  8. Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS.

    PubMed

    Bajor, Antal; Törnblom, Hans; Rudling, Mats; Ung, Kjell-Arne; Simrén, Magnus

    2015-01-01

    Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs. 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8). Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

    PubMed

    Ly, Lundi; Chan, Donovan; Aarabi, Mahmoud; Landry, Mylène; Behan, Nathalie A; MacFarlane, Amanda J; Trasler, Jacquetta

    2017-07-01

    Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation. There is increasing evidence that disruptions in male germ cell epigenetic reprogramming are associated with offspring abnormalities and intergenerational disease. The fetal period is the critical time of DNA methylation pattern acquisition for developing male germ cells and an adequate supply of methyl donors is required. In addition, DNA methylation patterns continue to be remodeled during postnatal spermatogenesis. Previous studies have shown that lifetime (prenatal and postnatal) folic acid deficiency can alter the sperm epigenome and increase the incidence of fetal morphological abnormalities. Female BALB/c mice (F0) were placed on one of four amino-acid defined diets for 4 weeks before pregnancy and throughout pregnancy and lactation: folic acid control (Ctrl; 2 mg/kg), 7-fold folic acid deficient (7FD; 0.3 mg/kg), 10-fold high FS (10FS, 20 mg/kg) or 20-fold high FS (20FS, 40 mg/kg) diets. F1 males were weaned to their respective prenatal diets to allow for diet exposure during all windows of germline epigenetic reprogramming: the erasure, re-establishment and maintenance phases. F0 females were mated with chow-fed males to produce F1 litters whose germ cells were exposed to the diets throughout embryonic development. F1 males were subsequently mated with chow-fed female mice. Two F2 litters, unexposed to the experimental diets, were generated from each F1 male; one litter was collected at embryonic day (E)18.5 and one delivered and followed postnatally. DNA

  10. Preadaptation to Cold Stress in Salmonella enterica Serovar Typhimurium Increases Survival during Subsequent Acid Stress Exposure

    PubMed Central

    Shah, Jigna; Desai, Prerak T.; Chen, Dong; Stevens, John R.

    2013-01-01

    Salmonella is an important cause of bacterial food-borne gastroenteritis. Salmonella encounters multiple abiotic stresses during pathogen elimination methods used in food processing, and these stresses may influence its subsequent survivability within the host or in the environment. Upon ingestion, Salmonella is exposed to gastrointestinal acidity, a first line of the host innate defense system. This study tested the hypothesis that abiotic stresses encountered during food processing alter the metabolic mechanisms in Salmonella that enable survival and persistence during subsequent exposure to the host gastrointestinal acidic environment. Out of the four different abiotic stresses tested, viz., cold, peroxide, osmotic, and acid, preadaptation of the log-phase culture to cold stress (5°C for 5 h) significantly enhanced survival during subsequent acid stress (pH 4.0 for 90 min). The gene expression profile of Salmonella preadapted to cold stress revealed induction of multiple genes associated with amino acid metabolism, oxidative stress, and DNA repair, while only a few of the genes in the above-mentioned stress response and repair pathways were induced upon exposure to acid stress alone. Preadaptation to cold stress decreased the NAD+/NADH ratio and hydroxyl (OH·) radical formation compared with those achieved with the exposure to acid stress alone, indicating alteration of aerobic respiration and the oxidative state of the bacteria. The results from this study suggest that preadaptation to cold stress rescues Salmonella from the deleterious effect of subsequent acid stress exposure by induction of genes involved in stress response and repair pathways, by modification of aerobic respiration, and by redox modulation. PMID:24056458

  11. Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid.

    PubMed

    Rinaldi, Tania; Silberberg, Gilad; Markram, Henry

    2008-04-01

    Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render cortical modules more sensitive to stimulation and once activated, more autonomous, isolated, and more difficult to command. This could underlie some of the core symptoms observed in humans prenatally exposed to valproic acid.

  12. Prenatal Ethanol Exposure Causes Glucose Intolerance with Increased Hepatic Gluconeogenesis and Histone Deacetylases in Adult Rat Offspring: Reversal by Tauroursodeoxycholic Acid

    PubMed Central

    Yao, Xing-Hai; Nguyen, Hoa K.; Nyomba, B. L. Grégoire

    2013-01-01

    Prenatal ethanol exposure results in increased glucose production in adult rat offspring and this may involve modulation of protein acetylation by cellular stress. We used adult male offspring of dams given ethanol during gestation days 1–7 (early), 8–14 (mid) and 15–21 (late) compared with those from control dams. A group of ethanol offspring was treated with tauroursodeoxycholic acid (TUDCA) for 3 weeks. We determined gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, hepatic free radicals, histone deacetylases (HDAC), acetylated foxo1, acetylated PEPCK, and C/EBP homologous protein as a marker of endoplasmic reticulum stress. Prenatal ethanol during either of the 3 weeks of pregnancy increased gluconeogenesis, gluconeogenic genes, oxidative and endoplasmic reticulum stresses, sirtuin-2 and HDAC3, 4, 5, and 7 in adult offspring. Conversely, prenatal ethanol reduced acetylation of foxo1 and PEPCK. Treatment of adult ethanol offspring with TUDCA reversed all these abnormalities. Thus, prenatal exposure of rats to ethanol results in long lasting oxidative and endoplasmic reticulum stresses explaining increased expression of gluconeogenic genes and HDAC proteins which, by deacetylating foxo1 and PEPCK, contribute to increased gluconeogenesis. These anomalies occurred regardless of the time of ethanol exposure during pregnancy, including early embryogenesis. As these anomalies were reversed by treatment of the adult offspring with TUDCA, this compound has therapeutic potentials in the treatment of glucose intolerance associated with prenatal ethanol exposure. PMID:23544086

  13. The medical management of abnormal uterine bleeding in reproductive-aged women.

    PubMed

    Bradley, Linda D; Gueye, Ndeye-Aicha

    2016-01-01

    In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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...

  15. 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

  16. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Modeling and Experimental Studies of Obeticholic Acid Exposure and the Impact of Cirrhosis Stage

    PubMed Central

    LaCerte, C; Peyret, T; Gosselin, NH; Marier, JF; Hofmann, AF; Shapiro, D

    2016-01-01

    Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment. There was good agreement between predicted and observed increases in systemic OCA exposure in subjects with mild, moderate, and severe hepatic impairment, which were 1.4‐, 8‐, and 13‐fold relative to healthy volunteers. Predicted liver exposure for subjects with mild, moderate, and severe hepatic impairment were increased only 1.1‐, 1.5‐, and 1.7‐fold. In subjects with cirrhosis, OCA exposure in the liver, the primary site of pharmacological activity along with the intestine, is increased marginally (∼2‐fold). PMID:27743502

  18. The effect of lead exposure on fatty acid composition in mouse brain analyzed using pseudo-catalytic derivatization.

    PubMed

    Jung, Jong-Min; Lee, Jechan; Kim, Ki-Hyun; Jang, In Geon; Song, Jae Gwang; Kang, Kyeongjin; Tack, Filip M G; Oh, Jeong-Ik; Kwon, Eilhann E; Kim, Hyung-Wook

    2017-03-01

    We performed toxicological study of mice exposed to lead by quantifying fatty acids in brain of the mice. This study suggests that the introduced analytical method had an extremely high tolerance against impurities such as water and extractives; thus, it led to the enhanced resolution in visualizing the spectrum of fatty acid profiles in animal brain. Furthermore, one of the biggest technical advantages achieved in this study was the quantitation of fatty acid methyl ester profiles of mouse brain using a trace amount of sample (e.g., 100 μL mixture). Methanol was screened as the most effective extraction solvent for mouse brain. The behavioral test of the mice before and after lead exposure was conducted to see the effect of lead exposure on fatty acid composition of the mice' brain. The lead exposure led to changes in disease-related behavior of the mice. Also, the lead exposure induced significant alterations of fatty acid profile (C16:0, C 18:0, and C 18:1) in brain of the mice, implicated in pathology of psychiatric diseases. The alteration of fatty acid profile of brain of the mice suggests that the derivatizing technique can be applicable to most research fields associated with the environmental neurotoxins with better resolution in a short time, as compared to the current protocols for lipid analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Dermal exposure to chromium in the grinding of stainless and acid-proof steel.

    PubMed

    Mäkinen, Milja; Linnainmaa, Markku

    2004-04-01

    The aim of the study was to measure the dermal exposure levels of chromium dust during grinding of stainless and acid-proof steel parts. The potential dermal exposure of the body was measured with a patch sampling method and the actual exposure of hands with a hand-wash method. Simultaneously, personal air samples were also collected. The range of body and hand exposure to chromium dust was 4.04-3406 and 0.72-79.7 mg/h, respectively. Dust was distributed quite evenly to different body parts. Workers using hand-held grinding tools were more exposed than those using band grinders. It was judged that the sampling methods applied in this study gave a realistic estimation of exposure levels, because of the uniform distribution of contamination during grinding. Respiratory exposure was high compared to Finnish occupational exposure limit values.

  20. 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...

  1. 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 (...

  2. Fetal exposure to teratogens: evidence of genes involved in autism.

    PubMed

    Dufour-Rainfray, Diane; Vourc'h, Patrick; Tourlet, Sébastien; Guilloteau, Denis; Chalon, Sylvie; Andres, Christian R

    2011-04-01

    Environmental challenges during the prenatal period can result in behavioral abnormalities and cognitive deficits that appear later in life such as autism. Prenatal exposure to valproic acid, ethanol, thalidomide and misoprostol has been shown to be associated with an increased incidence of autism. In addition, rodents exposed in utero to some of these drugs show autism-like abnormalities, including brain changes and lifelong behavior dysfunction. Our aim is to summarize current understanding of the relationship between in utero exposure to these drugs and autism in humans and in autism-like animal model phenotypes. It also highlights the importance of these models to understanding the neurobiology of autism, particularly in the identification of susceptibility genes. These drugs are able to modulate the expression of many genes involved in processes such as proliferation, apoptosis, neuronal differentiation and migration, synaptogenesis and synaptic activity. It seems essential to focus research on genes expressed during early neurodevelopment which may be the target of mutations or affected by drugs such as those included in this review. Copyright © 2011. Published by Elsevier Ltd.

  3. 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

  4. Exposure to phthalic acid, phthalate diesters and phthalate monoesters from foodstuffs: UK total diet study results.

    PubMed

    Bradley, Emma L; Burden, Richard A; Bentayeb, Karim; Driffield, Malcolm; Harmer, Nick; Mortimer, David N; Speck, Dennis R; Ticha, Jana; Castle, Laurence

    2013-01-01

    Phthalates are ubiquitous in the environment and thus exposure to these compounds can occur in various forms. Foods are one source of such exposure. There are only a limited number of studies that describe the levels of phthalates (diesters, monoesters and phthalic acid) in foods and assess the exposure from this source. In this study the levels of selected phthalate diesters, phthalate monoesters and phthalic acid in total diet study (TDS) samples are determined and the resulting exposure estimated. The methodology for the determination of phthalic acid and nine phthalate monoesters (mono-isopropyl phthalate, mono-n-butyl phthalate, mono-isobutyl phthalate, mono-benzyl phthalate, mono-cyclohexyl phthalate, mono-n-pentyl phthalate, mono-(2-ethylhexyl) phthalate, mono-n-octyl phthalate and mono-isononyl phthalate) in foods is described. In this method phthalate monoesters and phthalic acid are extracted from the foodstuffs with a mixture of acidified acetonitrile and dichloromethane. The method uses isotope-labelled phthalic acid and phthalate monoester internal standards and is appropriate for quantitative determination in the concentration range of 5-100 µg kg⁻¹. The method was validated in-house and its broad applicability demonstrated by the analysis of high-fat, high-carbohydrate and high-protein foodstuffs as well as combinations of all three major food constituents. The methodology used for 15 major phthalate diesters has been reported elsewhere. Phthalic acid was the most prevalent phthalate, being detected in 17 food groups. The highest concentration measured was di-(2-ethylhexyl) phthalate in fish (789 µg kg⁻¹). Low levels of mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate were detected in several of the TDS animal-based food groups and the highest concentrations measured corresponded with the most abundant diesters (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate). The UK Committee on Toxicity of Chemicals in Food, Consumer Products

  5. 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

  6. Dietary Glutamate Supplementation Ameliorates Mycotoxin-Induced Abnormalities in the Intestinal Structure and Expression of Amino Acid Transporters in Young Pigs

    PubMed Central

    Wu, Miaomiao; Liao, Peng; Deng, Dun; Liu, Gang; Wen, Qingqi; Wang, Yongfei; Qiu, Wei; Liu, Yan; Wu, Xingli; Ren, Wenkai; Tan, Bie; Chen, Minghong; Xiao, Hao; Wu, Li; Li, Tiejun; Nyachoti, Charles M.; Adeola, Olayiwola; Yin, Yulong

    2014-01-01

    The purpose of this study was to investigate the hypothesis that dietary supplementation with glutamic acid has beneficial effects on growth performance, antioxidant system, intestinal morphology, serum amino acid profile and the gene expression of intestinal amino acid transporters in growing swine fed mold-contaminated feed. Fifteen pigs (Landrace×Large White) with a mean body weight (BW) of 55 kg were randomly divided into control group (basal feed), mycotoxin group (contaminated feed) and glutamate group (2% glutamate+contaminated feed). Compared with control group, mold-contaminated feed decreased average daily gain (ADG) and increased feed conversion rate (FCR). Meanwhile, fed mold-contaminated feed impaired anti-oxidative system and intestinal morphology, as well as modified the serum amino acid profile in growing pigs. However, supplementation with glutamate exhibited potential positive effects on growth performance of pigs fed mold-contaminated feed, ameliorated the imbalance antioxidant system and abnormalities of intestinal structure caused by mycotoxins. In addition, dietary glutamate supplementation to some extent restored changed serum amino acid profile caused by mold-contaminated feed. In conclusion, glutamic acid may be act as a nutritional regulating factor to ameliorate the adverse effects induced by mycotoxins. PMID:25405987

  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. Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome

    PubMed Central

    Bagic, Anto; Simmons, Janine M.; Mari, Zoltan; Bonne, Omer; Xu, Ben; Kazuba, Diane; Herscovitch, Peter; Carson, Richard E.; Murphy, Dennis L.; Drevets, Wayne C.; Hallett, Mark

    2012-01-01

    Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive–compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [11C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABAA receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABAA receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABAA receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics. PMID:22577221

  9. Profiles of Amino Acids and Acylcarnitines Related with Insecticide Exposure in Culex quinquefasciatus (Say)

    PubMed Central

    Martin-Park, Abdiel; Gomez-Govea, Mayra A.; Lopez-Monroy, Beatriz; Treviño-Alvarado, Víctor Manuel; Torres-Sepúlveda, María del Rosario; López-Uriarte, Graciela Arelí; Villanueva-Segura, Olga Karina; Ruiz-Herrera, María del Consuelo; Martinez-Fierro, Margarita de la Luz; Delgado-Enciso, Ivan; Flores-Suárez, Adriana E.; White, Gregory S.; Martínez de Villarreal, Laura E.; Ponce-Garcia, Gustavo; Black, William C.; Rodríguez-Sanchez, Irám Pablo

    2017-01-01

    Culex quinquefasciatus Say is a vector of many pathogens of humans, and both domestic and wild animals. Personal protection, reduction of larval habitats, and chemical control are the best ways to reduce mosquito bites and, therefore, the transmission of mosquito-borne pathogens. Currently, to reduce the risk of transmission, the pyrethroids, and other insecticide groups have been extensively used to control both larvae and adult mosquitoes. In this context, amino acids and acylcarnitines have never been associated with insecticide exposure and or insecticide resistance. It has been suggested that changes in acylcarnitines and amino acids profiles could be a powerful diagnostic tool for metabolic alterations. Monitoring these changes could help to better understand the mechanisms involved in insecticide resistance, complementing the strategies for managing this phenomenon in the integrated resistance management. The purpose of the study was to determine the amino acids and acylcarnitines profiles in larvae of Cx. quinquefasciatus after the exposure to different insecticides. Bioassays were performed on Cx. quinquefasciatus larvae exposed to the diagnostic doses (DD) of the insecticides chlorpyrifos (0.001 μg/mL), temephos (0.002 μg/mL) and permethrin (0.01 μg/mL). In each sample, we analyzed the profile of 12 amino acids and 31 acylcarnitines by LC-MS/MS. A t-test was used to determine statistically significant differences between groups and corrections of q-values. Results indicates three changes, the amino acids arginine (ARG), free carnitine (C0) and acetyl-carnitine (C2) that could be involved in energy production and insecticide detoxification. We confirmed that concentrations of amino acids and acylcarnitines in Cx. quinquefasciatus vary with respect to different insecticides. The information generated contributes to understand the possible mechanisms and metabolic changes occurring during insecticide exposure. PMID:28085898

  10. Profiles of Amino Acids and Acylcarnitines Related with Insecticide Exposure in Culex quinquefasciatus (Say).

    PubMed

    Martin-Park, Abdiel; Gomez-Govea, Mayra A; Lopez-Monroy, Beatriz; Treviño-Alvarado, Víctor Manuel; Torres-Sepúlveda, María Del Rosario; López-Uriarte, Graciela Arelí; Villanueva-Segura, Olga Karina; Ruiz-Herrera, María Del Consuelo; Martinez-Fierro, Margarita de la Luz; Delgado-Enciso, Ivan; Flores-Suárez, Adriana E; White, Gregory S; Martínez de Villarreal, Laura E; Ponce-Garcia, Gustavo; Black, William C; Rodríguez-Sanchez, Irám Pablo

    2017-01-01

    Culex quinquefasciatus Say is a vector of many pathogens of humans, and both domestic and wild animals. Personal protection, reduction of larval habitats, and chemical control are the best ways to reduce mosquito bites and, therefore, the transmission of mosquito-borne pathogens. Currently, to reduce the risk of transmission, the pyrethroids, and other insecticide groups have been extensively used to control both larvae and adult mosquitoes. In this context, amino acids and acylcarnitines have never been associated with insecticide exposure and or insecticide resistance. It has been suggested that changes in acylcarnitines and amino acids profiles could be a powerful diagnostic tool for metabolic alterations. Monitoring these changes could help to better understand the mechanisms involved in insecticide resistance, complementing the strategies for managing this phenomenon in the integrated resistance management. The purpose of the study was to determine the amino acids and acylcarnitines profiles in larvae of Cx. quinquefasciatus after the exposure to different insecticides. Bioassays were performed on Cx. quinquefasciatus larvae exposed to the diagnostic doses (DD) of the insecticides chlorpyrifos (0.001 μg/mL), temephos (0.002 μg/mL) and permethrin (0.01 μg/mL). In each sample, we analyzed the profile of 12 amino acids and 31 acylcarnitines by LC-MS/MS. A t-test was used to determine statistically significant differences between groups and corrections of q-values. Results indicates three changes, the amino acids arginine (ARG), free carnitine (C0) and acetyl-carnitine (C2) that could be involved in energy production and insecticide detoxification. We confirmed that concentrations of amino acids and acylcarnitines in Cx. quinquefasciatus vary with respect to different insecticides. The information generated contributes to understand the possible mechanisms and metabolic changes occurring during insecticide exposure.

  11. 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 ...

  12. Prolonged restraint stressor exposure in outbred CD-1 mice impacts microbiota, colonic inflammation, and short chain fatty acids.

    PubMed

    Maltz, Ross M; Keirsey, Jeremy; Kim, Sandra C; Mackos, Amy R; Gharaibeh, Raad Z; Moore, Cathy C; Xu, Jinyu; Bakthavatchalu, Vasudevan; Somogyi, Arpad; Bailey, Michael T

    2018-01-01

    Stressor-exposure has been shown to exacerbate inflammation and change the composition of the gastrointestinal microbiota; however stressor-induced effects on microbiota-derived metabolites and their receptors are unknown. Thus, bacterial-produced short chain fatty acids (SCFAs), as well as microbial community composition, were assessed in the colons of mice exposed to stress during infection with Citrobacter rodentium. Mice were exposed to overnight restraint on 7 consecutive nights, or left undisturbed as a control. After the first exposure of restraint, mice were orally challenged with C. rodentium or with vehicle. Microbial community composition was assessed using 16S rRNA gene sequencing and SCFA levels measured using gas chromatography-mass spectrometry (GC-MS). Pathogen levels and colonic inflammation were also assessed 6 days post-infection. Results demonstrated that the microbial community structure and SCFA production were significantly affected by both stressor exposure and C. rodentium-infection. Exposure to prolonged restraint in the absence of infection significantly reduced SCFAs (acetic acid, butyric acid, and propionic acid). Multiple bacterial taxa were affected by stressor exposure, with the relative abundance of Lactobacillus being significantly reduced and directly correlated with propionic acid. Lactobacillus abundances were inversely correlated with colonic inflammation, supporting the contention that Lactobacillus helps to regulate mucosal inflammatory responses. Our data indicates that restraint stressor can have significant effects on pathogen-induced colonic inflammation and suggest that stressor-induced changes in the microbiota, microbial-produced SCFAs and their receptors may be involved.

  13. Pretreatment with human serum butyrylcholinesterase alone prevents cardiac abnormalities, seizures, and death in Göttingen minipigs exposed to sarin vapor.

    PubMed

    Saxena, Ashima; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Hastings, Nicholas B; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2011-12-15

    Human serum butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a prophylactic countermeasure against organophosphorus nerve agents. This study was designed to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male Göttingen minipigs were subjected to: air exposure, GB vapor exposure, or pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection 24 h prior to exposure to 4.1 mg/m(3) of GB vapor for 60 min. Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were recorded throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB present. Untreated animals exposed to GB vapor exhibited cardiac abnormalities and generalized seizures, ultimately succumbing to respiratory failure. Pretreatment with 3.0 or 6.5 mg/kg of Hu BChE delayed blood gas and acid-base disturbances and the onset of cardiac and neural toxic signs, but failed to increase survivability. Pretreatment with 7.5 mg/kg of Hu BChE, however, completely prevented toxic signs, with blood chemistry and ECG and EEG parameters indistinguishable from control during and after GB exposure. GB bound in plasma was 200-fold higher than plasma from pigs that did not receive Hu BChE, suggesting that Hu BChE scavenged GB in blood and prevented it from reaching other tissues. Thus, prophylaxis with Hu BChE alone not only increased survivability, but also prevented cardiac abnormalities and neural toxicity in minipigs exposed to a lethal dose of GB vapor. Published by Elsevier Inc.

  14. 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. Published by Oxford University Press on behalf of the

  15. Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice

    PubMed Central

    Joshi, Mandar A.; Jeoung, Nam Ho; Obayashi, Mariko; Hattab, Eyas M.; Brocken, Eric G.; Liechty, Edward A.; Kubek, Michael J.; Vattem, Krishna M.; Wek, Ronald C.; Harris, Robert A.

    2006-01-01

    The BCKDH (branched-chain α-keto acid dehydrogenase complex) catalyses the rate-limiting step in the oxidation of BCAAs (branched-chain amino acids). Activity of the complex is regulated by a specific kinase, BDK (BCKDH kinase), which causes inactivation, and a phosphatase, BDP (BCKDH phosphatase), which causes activation. In the present study, the effect of the disruption of the BDK gene on growth and development of mice was investigated. BCKDH activity was much greater in most tissues of BDK−/− mice. This occurred in part because the E1 component of the complex cannot be phosphorylated due to the absence of BDK and also because greater than normal amounts of the E1 component were present in tissues of BDK−/− mice. Lack of control of BCKDH activity resulted in markedly lower blood and tissue levels of the BCAAs in BDK−/− mice. At 12 weeks of age, BDK−/− mice were 15% smaller than wild-type mice and their fur lacked normal lustre. Brain, muscle and adipose tissue weights were reduced, whereas weights of the liver and kidney were greater. Neurological abnormalities were apparent by hind limb flexion throughout life and epileptic seizures after 6–7 months of age. Inhibition of protein synthesis in the brain due to hyperphosphorylation of eIF2α (eukaryotic translation initiation factor 2α) might contribute to the neurological abnormalities seen in BDK−/− mice. BDK−/− mice show significant improvement in growth and appearance when fed a high protein diet, suggesting that higher amounts of dietary BCAA can partially compensate for increased oxidation in BDK−/− mice. Disruption of the BDK gene establishes that regulation of BCKDH by phosphorylation is critically important for the regulation of oxidative disposal of BCAAs. The phenotype of the BDK−/− mice demonstrates the importance of tight regulation of oxidative disposal of BCAAs for normal growth and neurological function. PMID:16875466

  16. 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.

  17. Occupational exposure to herbs containing aristolochic acids increases the risk of urothelial carcinoma in Chinese herbalists.

    PubMed

    Yang, Hsiao-Yu; Wang, Jung-Der; Lo, Tsai-Chang; Chen, Pau-Chung

    2013-01-01

    Aristolochic acid can cause urothelial carcinoma. Herbal remedies containing aristolochic acids were previously categorized as proven group 1 human carcinogens by the WHO cancer agency, the International Agency for Research on Cancer. However, the health effect on workers exposed to aristolochic acid is unclear. Fangchi, a representative herb containing aristolochic acid, is commonly used in the Chinese herbal medicine industry. We determined whether workers exposed to fangchi are at increased risk for urothelial carcinoma. We designed a case-control study based in a national representative cohort of Chinese herbalists. This study analyzed 6,564 Chinese herbalists employed between 1985 and 1998. All incident cases of urothelial carcinoma that occurred between 1988 and 2001 were defined as the case group. Controls were selected from the baseline cohort in a randomized manner. A total of 24 cases and 140 controls were included in analysis. Information about fangchi exposure was obtained in a questionnaire survey administered in 2002. Processing, selling or dispensing herbs containing fangchi significantly increased the risk of urothelial carcinoma (HR 2.4, 95% CI 1.1-5.3, p = 0.03). This relationship was independent of cigarette smoking or potential arsenic exposure from drinking water from deep wells. Exposure to the Chinese herbal drug fangchi increases the risk of urothelial carcinoma in herbalists. Appropriate medical monitoring is warranted for workers who have similar exposure. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  18. Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

    PubMed Central

    Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

    2013-01-01

    Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

  19. Fetal Alcohol Spectrum Disorders and Abnormal Neuronal Plasticity

    PubMed Central

    Medina, Alexandre E.

    2012-01-01

    The ingestion of alcohol during pregnancy can result in a group of neurobehavioral abnormalities collectively known as fetal alcohol spectrum disorders (FASD). During the past decade, studies using animal models indicated that early alcohol exposure can dramatically affect neuronal plasticity, an essential property of the central nervous system responsible for the normal wiring of the brain and involved in processes such as learning and memory. The abnormalities in neuronal plasticity caused by alcohol can explain many of the neurobehavioral deficits observed in FASD. Conversely, improving neuronal plasticity may have important therapeutic benefits. In this review, the author discuss the mechanisms that lead to these abnormalities and comment on recent pharmacological approaches that have been showing promising results in improving neuronal plasticity in FASD. PMID:21383101

  20. The normal squamocolumnar junction is circumferentially even and minimal irregularities are manifestations of gastroesophageal acid reflux.

    PubMed

    Guerrero Garcia Hall, Mats; Wenner, Jörgen; Öberg, Stefan

    2017-03-01

    The macroscopic appearance of the normal squamocolumnar junction (SCJ) is often described as serrated with short projections of columnar mucosa that extend into the esophagus. As studies of the normal SCJ are sparse, the aim of this study was to test the hypothesis that the normal SCJ is even and that irregularities are manifestations of acid reflux. Fifty asymptomatic subjects and 149 patients with symptoms suggestive of gastroesophageal reflux disease underwent endoscopy and 48-h pH monitoring with a pH electrode positioned immediately above the SCJ. The shape of the SCJ was assessed according to the Z-line appearance classification and correlated with clinical characteristics and the degree of esophageal acid exposure in the most distal esophagus. Even SCJs without irregularities were significantly more common in asymptomatic subjects compared with patients (50% versus 10%, p < .001) and were never found in patients with erosive esophagitis. The median degree of distal esophageal acid exposure in individuals with an even SCJ was within normal limits. With increasing degree of irregularity of the SCJ, the frequency and duration of reflux episodes, the degree of distal esophageal acid exposure, and the prevalence of abnormal acid exposure increased progressively and significantly. The shape of the normal SCJ is even and also minimal irregularities are a consequence of acid reflux, likely due to the formation of small areas of metaplastic columnar mucosa.

  1. Acute hydrofluoric acid exposure reported to Taiwan Poison Control Center, 1991-2010.

    PubMed

    Wu, M-L; Yang, C-C; Ger, J; Tsai, W-J; Deng, J-F

    2014-05-01

    Hydrofluoric acid (HF) is a dangerous chemical that can cause severe cutaneous burns as well as possible systemic toxicity. We retrospectively analyzed all human HF exposure cases reported to the National Poison Control Center of Taiwan between 1991 and 2010. In this 20-year survey, 324 calls were identified, with a majority of dermal exposure (84%). Occupational exposure accounted for 80% of all cases, with workers in semiconductor industry (61%), cleaning industry (15%), chemical or metal industry (13%), and other industries (11%). Electrolyte imbalances were uncommon, hypocalcemia, hypomagnesemia, and hypokalemia were recorded in 8.6%, 1.2%, and 1.5% of all cases, respectively. Most cases (64%) of dermal exposure received antidotal treatment. Treatment modalities of dermal exposure included calcium gluconate soaking, 49.8%; intravenous calcium, 20.6%; and topical use of calcium gluconate gel, 13.9%. Twenty patients (7%) received surgery. Following HF exposure, the majority of patients presented with mild (56.5%) or moderate (36.7%) toxic effects. However, four patients were severely intoxicated; two patients died of HF-related dysrhythmia and shock. Significant symptomology may occur following HF exposure, and most of the HF exposure required hospitals evaluation. Calcium gluconate soaks appear to be effective in reducing local pain and tissue damage. Hyperkalemia should not be overemphasized as a common finding in HF exposure, hypokalemia tends to occur in cases of severe HF poisoning.

  2. The effect of theobromine 200 mg/l topical gel exposure duration against surface enamel hardness resistance from 1% citric acid

    NASA Astrophysics Data System (ADS)

    Herisa, H. M.; Noerdin, A.; Eriwati, Y. K.

    2017-08-01

    Theobromine can be used to prevent the demineralization of enamel and can stimulate the growth of new enamels. This study analyzes the effect of theobromine’s gel duration exposure on enamel hardness resistance from 1% citric acid. Twenty-eight specimens were divided into three experimental groups; were exposed to theobromine gel 200 mg/l for 16, 48, and 96 minutes; and were then immersed in 1% citric acid. The control group was only immersed in 1% citric acid. Results: A Wilcoxon test showed a significant increase and decrease in enamel microhardness after exposure to theobromine gel and citric acid (p < 0.05). A Mann-Whitney test showed a significant increase and decrease in enamel microhardness between different durations of exposure to theobromine gel and immersion in citric acid (p < 0.05). The application of theobromine gel 200mg/L increased enamel microhardness but did not contribute to the enamel’s hardness resistance after immersion in 1% citric acid. The duration of theobromine gel application affected enamel microhardness and acid resistance.

  3. 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...

  4. Normal human gingival fibroblasts undergo cytostasis and apoptosis after long-term exposure to butyric acid.

    PubMed

    Shirasugi, Michihiro; Nishioka, Keisuke; Yamamoto, Toshiro; Nakaya, Takaaki; Kanamura, Narisato

    2017-01-22

    The causes of periodontal disease are complex. Butyric acid, a metabolite of periodontopathic bacteria such as Porphyromonas gingivalis, acts as a histone deacetylase inhibitor that has a direct effect on mRNA expression. Butyric acid produced by Clostridium butyricum in the intestinal tract induces differentiation of regulatory T cells, thereby suppressing inflammation in the gut. Mice lacking Clostridium butyricum in the intestinal tract suffer from colitis. By contrast, butyric acid in the oral cavity worsens periodontal disease. Periodontal disease is a chronic condition in which periodontal tissue is exposed to virulence factors (such as butyric acid); however, no study has examined the effects of long-term exposure to butyric acid. The present study demonstrated that long-term exposure of human gingival fibroblasts (HGFs) to butyric acid induced cytostasis and apoptosis via the intrinsic and extrinsic pathways. Butyric acid inhibited the division of HGFs by altering expression of mRNAs encoding cyclins. Butyric acid induced apoptosis in HGFs via the intrinsic pathway, followed by activation of caspase 9; there was no DNA damage or p53 activation. Butyric acid also upregulated expression of TNF-α mRNA and protein by HGFs. Furthermore TNF-α induced apoptosis by activating caspase 8 (the extrinsic pathway) and by inducing production of pro-inflammatory cytokines. Taken together, the results show that butyric acid induced cytostasis and apoptosis in HGFs, accompanied by production of pro-inflammatory cytokines. It thus acts as a death ligand and plays a critical role as a prophlogistic substance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Assessment of occupational exposure to gaseous peracetic acid.

    PubMed

    Dugheri, Stefano; Bonari, Alessandro; Pompilio, Ilenia; Colpo, Marco; Montalti, Manfredi; Mucci, Nicola; Arcangeli, Giulio

    2018-02-07

    In order to assess short-term exposure to peracetic acid (PAA) in disinfection processes, the Authors compared 4 industrial hygiene monitoring methods to evaluate their proficiency in measuring airborne PAA concentrations. An active sampling by basic silica gel impregnated with methyl p-tolyl sulfoxide (MTSO), a passive solid phase micro-extraction technique using methyl p-tolyl sulfide (MTS) as on-fiber derivatization reagent, an electrochemical direct-reading PAA monitor, and a novel visual test strip PAA detector doped with 2,2'-azino-bis (3-ethylbenzothiazoline)-6-sulfonate were evaluated and tested over the range of 0.06-16 mg/m3, using dynamically generated PAA air concentrations. The linear regression analysis of linearity and accuracy showed that the 4 methods were suitable for PAA monitoring. Peracetic acid monitoring in several use applications showed that the PAA concentration (1.8 mg/m3) was immediately dangerous to life or health as proposed by the National Institute of Occupational Safety and Health, and was frequently exceeded in wastewater treatment (up to 7.33 mg/m3), and sometimes during food and beverage processes and hospital high-level disinfection operations (up to 6.8 mg/m3). The methods were suitable for the quick assessment of acute exposure in PAA environmental monitoring and can assist in improving safety and air quality in the workplace where this disinfectant is used. These monitoring methods allowed the evaluation of changes to work out practices to reduce PAA vapor concentrations during the operations when workers are potentially overexposed to this strong antioxidant agent. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  6. Domestic Asbestos Exposure: A Review of Epidemiologic and Exposure Data

    PubMed Central

    Goswami, Emily; Craven, Valerie; Dahlstrom, David L.; Alexander, Dominik; Mowat, Fionna

    2013-01-01

    Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48–10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers’ exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically. PMID:24185840

  7. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

    PubMed Central

    Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

  8. Neural autoantibodies and neurophysiologic abnormalities in patients exposed to molds in water-damaged buildings.

    PubMed

    Campbell, Andrew W; Thrasher, Jack D; Madison, Roberta A; Vojdani, Aristo; Gray, Michael R; Johnson, Al

    2003-08-01

    Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

  9. Asbestotic radiological abnormalities among United States merchant marine seamen.

    PubMed

    Selikoff, I J; Lilis, R; Levin, G

    1990-05-01

    There has been limited information concerning the prevalence of radiologically evident parenchymal and pleural fibrosis consistent with prior exposure to asbestos among merchant marine seamen, despite the wide use of asbestos in ship construction until the late 1970s and subsequent exposure of seamen to the asbestos that had been installed. A total of 3324 chest radiographs (1985-7) of long term United States seamen were reviewed. One third (34.8%) had parenchymal or pleural abnormalities, or both (ILO classification); pleural changes were predominant. Abnormalities increased with longer duration from onset of shipboard exposure (as defined by first year at sea). The prevalence of asbestotic changes was greater among seamen who had served in the engine department (391/420; 42.5%) compared with seamen in other departments, including deck (301/820; 36.6%), steward (278/981; 28.4%), or with service in multiple departments (167/541; 30.9%). Since many vessels, particularly those built before 1978, contain asbestos materials, appropriate engineering controls (including complete removal, if possible) are required as well as appropriate medical surveillance for those who served aboard such ships.

  10. Assessment of skin exposure to nickel, chromium and cobalt by acid wipe sampling and ICP-MS.

    PubMed

    Lidén, Carola; Skare, Lizbet; Lind, Birger; Nise, Gun; Vahter, Marie

    2006-05-01

    There is a great need to accurately assess skin exposure to contact allergens. We have developed a technique for assessment of skin exposure to nickel, chromium and cobalt using acid wipe sampling by cellulose wipes with 1% nitric acid. Chemical analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS). The recovery of nickel, chromium and cobalt from arms and palms was 93%. The analytical result is expressed in terms of mass per unit area (microg/cm(2)). The developed acid wipe sampling technique is suitable for determination of nickel, chromium and cobalt deposited on the skin. The technique may be used in workplace studies, in studies of individuals in the general population, in dermatitis patients, in identification of risk groups, as well as in developing preventive strategies and in follow-up after intervention.

  11. Nicotinic Acid Receptor Abnormalities in Human Skin Cancer: Implications for a Role in Epidermal Differentiation

    PubMed Central

    Bermudez, Yira; Benavente, Claudia A.; Meyer, Ralph G.; Coyle, W. Russell; Jacobson, Myron K.; Jacobson, Elaine L.

    2011-01-01

    Background Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through Gi-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells. Results Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional Gi-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional. Conclusions The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s) of nicotinic acid receptors in human skin homeostasis. PMID:21655214

  12. 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

  13. Influence of long-term exposure to simulated acid rain on development, reproduction and acaricide susceptibility of the carmine spider mite, Tetranychus cinnabarinus

    PubMed Central

    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°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 pH4.0, 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. PMID:19537978

  14. Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet.

    PubMed

    Umezawa, Masakazu; Nakamura, Masayuki; El-Ghoneimy, Ashraf A; Onoda, Atsuto; Shaheen, Hazem M; Hori, Hiroshi; Shinkai, Yusuke; El-Sayed, Yasser S; El-Far, Ali H; Takeda, Ken

    2018-01-01

    Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease, and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol accumulation, but many daily diets are deficient in this nutrient. Therefore, the effect of DE exposure in mice fed n-3 PUFA-deficient diet was investigated. Mice were fed control chow or n-3 PUFA-deficient diet for 4 weeks, then exposed to clean air or DE by inhalation for further 4 weeks. Liver histology, plasma parameters, and expression of fatty acid synthesis-related genes were evaluated. N-3 PUFA-deficient diet increased hepatic lipid droplets accumulation and expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE further increased the plasma leptin and the expression of fatty acid synthesis-related genes: Acacb, Fasn, and Scd1. N-3 PUFA-deficient diet and DE exposure potentially enhanced hepatic fatty acid synthesis and subsequently accumulation of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA-deficient diet may be an additional risk factor for the incidence of non-alcoholic fatty liver disease. The present study suggests an important mechanism for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs in the diet. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-01-01

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

  16. Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?

    PubMed

    Bakshi, Vaishali P; Alsene, Karen M; Roseboom, Patrick H; Connors, Elenora E

    2012-02-01

    A deficit in prepulse inhibition (PPI) can be one of the clinically observed features of post-traumatic stress disorder (PTSD) that is seen long after the acute traumatic episode has terminated. Thus, reduced PPI may represent an enduring psychophysiological marker of this illness in some patients. PPI is an operational measure of sensorimotor gating and refers to the phenomenon in which a weak stimulus presented immediately before an intense startling stimulus inhibits the magnitude of the subsequent startle response. The effects of stress on PPI have been relatively understudied, and in particular, there is very little information on PPI effects of ethologically relevant psychological stressors. We aimed to develop a paradigm for evaluating stress-induced sensorimotor gating abnormalities by comparing the effects of a purely psychological stressor (predator exposure) to those of a nociceptive physical stressor (footshock) on PPI and baseline startle responses in rats over an extended period of time following stressor presentation. Male Sprague-Dawley rats were exposed (within a protective cage) to ferrets for 5 min or left in their homecage and then tested for PPI immediately, 24 h, 48 h, and 9 days after the exposure. The effects of footshock were evaluated in a separate set of rats. The effects seen with stressor presentation were compared to those elicited by corticotropin-releasing factor (CRF; 0.5 and 3 μg/6 μl, intracerebroventricularly). Finally, the effects of these stressors and CRF administration on plasma corticosterone were measured. PPI was disrupted 24 h after ferret exposure; in contrast, footshock failed to affect PPI at any time. CRF mimicked the predator stress profile, with the lowdose producing a PPI deficit 24 h after infusion. Interestingly, the high dose also produced a PPI deficit 24 h after infusion, but with this dose, the PPI deficit was evident even 9d later. Plasma corticosterone levels were elevated acutely (before PPI deficits

  17. Growth and physiological responses of beech seedlings to long-term exposure of acid fog.

    PubMed

    Shigihara, Ado; Matsumoto, Kiyoshi; Sakurai, Naoki; Igawa, Manabu

    2008-02-25

    Seven-year-old beech seedlings (Fagus crenata) were exposed to simulated acid fog (SAF) at pH 3 or pH 5 (as control) prepared by adding a 2:1:1 mixture (molar ratio) of nitric acid, ammonium sulfate, and sodium chloride to ultrapure water from September 2004 to July 2006 in a mobile fog chamber. In comparison to control seedlings, seedlings from the pH 3 treatment displayed inferior plant height, stem diameter, number of leaves, and dry matter production, but greater leaf area. Furthermore, exposure to SAF induced early falling of leaves with a nearly two-times-greater normalized leaf number index than control. The starch levels in the stems of seedlings of the pH 3 treatment were much lower than those of control at the harvest. The acid fog-induced reduction of the starch accumulation is considered to occur mainly because of fewer leaves during the growth phase. Results of laboratory experiments demonstrate that the amount of base cations leached from the beech leaves increased with decreasing pH of SAF; the leaching amount of calcium ion from the beech was high relative to that of conifers such as fir and cedar. These results imply that chronic acid fog exposure suppresses growth and physiological activity of beech seedlings.

  18. THE TIME-COURSE AND SENSITIVITY OF MUCONIC ACID AS A BIOMARKER FOR HUMAN ENVIRONMENTAL EXPOSURE TO BENZENE

    EPA Science Inventory

    Preliminary results are presented that show the effect of an increased benzene exposure on the urinary elimination of trans,trans-muconic acid (MA) for an adult male. These results were generated from a controlled exposure experiment where by an individual was exposed to benzene ...

  19. Moderate folic acid supplementation and MTHFD1-synthetase deficiency in mice, a model for the R653Q variant, result in embryonic defects and abnormal placental development.

    PubMed

    Christensen, Karen E; Hou, Wenyang; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga V; Arning, Erland; Bottiglieri, Teodoro; Caudill, Marie A; Jerome-Majewska, Loydie A; Rozen, Rima

    2016-11-01

    Moderately high folic acid intake in pregnant women has led to concerns about deleterious effects on the mother and fetus. Common polymorphisms in folate genes, such as methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) R653Q, may modulate the effects of elevated folic acid intake. We investigated the effects of moderate folic acid supplementation on reproductive outcomes and assessed the potential interaction of the supplemented diet with MTHFD1-synthetase (Mthfd1S) deficiency in mice, which is a model for the R653Q variant. Female Mthfd1S +/+ and Mthfd1S +/- mice were fed a folic acid-supplemented diet (FASD) (5-fold higher than recommended) or control diets before mating and during pregnancy. Embryos and placentas were assessed for developmental defects at embryonic day 10.5 (E10.5). Maternal folate and choline metabolites and gene expression in folate-related pathways were examined. The combination of FASD and maternal MTHFD1-synthetase deficiency led to a greater incidence of defects in E10.5 embryos (diet × maternal genotype, P = 0.0016; diet × embryonic genotype, P = 0.054). The methylenetetrahydrofolate reductase (MTHFR) protein and methylation potential [ratio of S-adenosylmethionine (major methyl donor):S-adenosylhomocysteine) were reduced in maternal liver. Although 5-methyltetrahydrofolate (methylTHF) was higher in maternal circulation, the methylation potential was lower in embryos. The presence of developmental delays and defects in Mthfd1S +/- embryos was associated with placental defects (P = 0.003). The labyrinth layer failed to form properly in the majority of abnormal placentas, which compromised the integration of the maternal and fetal circulation and presumably the transfer of methylTHF and other nutrients. Moderately higher folate intake and MTHFD1-synthetase deficiency in pregnant mice result in a lower methylation potential in maternal liver and embryos and a greater

  20. 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.

  1. Bicarbonate availability for vocal fold epithelial defense to acidic challenge.

    PubMed

    Durkes, Abigail; Sivasankar, M Preeti

    2014-01-01

    Bicarbonate is critical for acid-base tissue homeostasis. In this study we investigated the role of bicarbonate ion transport in vocal fold epithelial defense to acid challenges. Acidic insults to the larynx are common in gastric reflux, carcinogenesis and metastasis, and acute inflammation. Ion transport was measured in viable porcine vocal fold epithelium. First, 18 vocal folds were exposed to either the carbonic anhydrase antagonist acetazolamide or to vehicle. Second, 32 vocal folds were exposed to either a control buffer or a bicarbonate-free buffer on their luminal or basolateral surface or both. Third, 32 vocal folds were challenged with acid in the presence of bicarbonate-free or control buffer. The vocal fold transepithelial resistance was greater than 300 Ω*cm(2), suggesting robust barrier integrity. Ion transport did not change after exposure to acetazolamide (p > 0.05). Exposure to bicarbonate-free buffer did not compromise vocal fold ion transport (p > 0.05). Ion transport increased after acid challenge. This increase approached statistical significance and was the greatest for the control buffer and for the bicarbonate-free buffer applied to the basolateral surface. Bicarbonate secretion may contribute to vocal fold defense against acid challenge. Our data offer a potential novel role for bicarbonate as a therapeutic agent to reduce pH abnormalities in the larynx and prevent associated pathological changes.

  2. Bicarbonate Availability for Vocal Fold Epithelial Defense to Acidic Challenge

    PubMed Central

    Durkes, Abigail; Sivasankar, M. Preeti

    2014-01-01

    Objectives Bicarbonate is critical for acid-base tissue homeostasis. In this study we investigated the role of bicarbonate ion transport in vocal fold epithelial defense to acid challenges. Acidic insults to the larynx are common in gastric reflux, carcinogenesis and metastasis, and acute inflammation. Methods Ion transport was measured in viable, porcine vocal fold epithelium. First, 18 vocal folds were exposed to either the carbonic anhydrase antagonist acetazolamide or to vehicle. Second, 32 vocal folds were exposed to either a control buffer or a bicarbonate-free buffer on their luminal or basolateral surface or both. Third, vocal folds were challenged with acid in the presence of bicarbonate-free or control buffer. Results The vocal fold transepithelial resistance was greater than 300 Ω*cm2, suggesting robust barrier integrity. Ion transport did not change after exposure to acetazolamide (p > 0.05). Exposure to bicarbonate-free buffer did not compromise vocal fold ion transport (p > 0.05). Ion transport increased after acid challenge. This increase approached statistical significance and was the greatest for the control buffer and for the bicarbonate-free buffer applied to the basolateral surface. Conclusions Bicarbonate secretion may contribute to vocal fold defense against acid challenge. Our data offer a potential novel role for bicarbonate as a therapeutic agent to reduce pH abnormalities in the larynx and prevent associated pathological changes. PMID:24574427

  3. Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions.

    PubMed

    Sethi, M; Lehmann, A R; Fawcett, H; Stefanini, M; Jaspers, N; Mullard, K; Turner, S; Robson, A; McGibbon, D; Sarkany, R; Fassihi, H

    2013-12-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair. It is divided into eight complementation groups: XP-A to XP-G (classical XP) and XP variant (XP-V). Severe and prolonged sunburn reactions on minimal sun exposure have been considered a cardinal feature of classical XP. However, it has recently become clear that not all patients have abnormal sunburn reactions. To examine sunburn reactions in a cohort of patients with XP and correlate this to the complementation group. Sixty patients with XP attending the U.K. National XP Service from 2010 to 2012 were studied. Their history of burning after minimal sun exposure was assessed using a newly developed sunburn severity score. The age at which the first skin cancer was histologically diagnosed in each patient, and the presence of any neurological abnormality, was also recorded. Sunburn severity scores were abnormally high in patients with XP-A, XP-D, XP-F and XP-G compared with non-XP controls. There was no significant difference in sunburn score of patients with XP-C, XP-E and XP-V compared with controls (P > 0·05). Patients with XP-C, XP-E and XP-V were more likely to have skin cancer diagnosed at an earlier age than those with severe sunburn on minimal sun exposure. In addition, patients with XP with severe sunburn had an increased frequency of neurological abnormalities. Not all patients with XP have a history of severe and prolonged sunburn on minimal sun exposure. The normal sunburn response of patients with XP-C, XP-E and XP-V may relate to the preservation of transcription-coupled DNA repair in these groups. Those with a history of severe sunburn on minimal sun exposure developed their first skin cancer at an older age compared with patients with XP-C, XP-E and XP-V, but they had an increased frequency of neurological abnormalities. Physicians need to be aware that about half of all patients with XP will present without a history of abnormal sunburn. © 2013 British Association of

  4. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.

    PubMed Central

    Zhou, Y P; Grill, V E

    1994-01-01

    We tested effects of long-term exposure of pancreatic islets to free fatty acids (FFA) in vitro on B cell function. Islets isolated from male Sprague-Dawley rats were exposed to palmitate (0.125 or 0.25 mM), oleate (0.125 mM), or octanoate (2.0 mM) during culture. Insulin responses were subsequently tested in the absence of FFA. After a 48-h exposure to FFA, insulin secretion during basal glucose (3.3 mM) was several-fold increased. However, during stimulation with 27 mM glucose, secretion was inhibited by 30-50% and proinsulin biosynthesis by 30-40%. Total protein synthesis was similarly affected. Conversely, previous palmitate did not impair alpha-ketoisocaproic acid (5 mM)-induced insulin release. Induction and reversibility of the inhibitory effect on glucose-induced insulin secretion required between 6 and 24 h. Addition of the carnitine palmitoyltransferase I inhibitor etomoxir (1 microM) partially reversed (by > 50%) FFA-associated decrease in secretory as well as proinsulin biosynthetic responses to 27 mM glucose. The inhibitory effect of previous palmitate was similar when co-culture was performed with 5.5, 11, or 27 mM glucose. Exposure to palmitate or oleate reduced the production of 14CO2 from D-[U-14C]glucose, and of 14CO2 from D-[3,4-14C]-glucose, both effects being reversed by etomoxir. Conclusions: long-term exposure to FFA inhibits glucose-induced insulin secretion and biosynthesis probably through a glucose fatty acid cycle. PMID:8113418

  5. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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. © 2014 International Society for Diseases of the Esophagus.

  7. Asbestotic radiological abnormalities among United States merchant marine seamen.

    PubMed Central

    Selikoff, I J; Lilis, R; Levin, G

    1990-01-01

    There has been limited information concerning the prevalence of radiologically evident parenchymal and pleural fibrosis consistent with prior exposure to asbestos among merchant marine seamen, despite the wide use of asbestos in ship construction until the late 1970s and subsequent exposure of seamen to the asbestos that had been installed. A total of 3324 chest radiographs (1985-7) of long term United States seamen were reviewed. One third (34.8%) had parenchymal or pleural abnormalities, or both (ILO classification); pleural changes were predominant. Abnormalities increased with longer duration from onset of shipboard exposure (as defined by first year at sea). The prevalence of asbestotic changes was greater among seamen who had served in the engine department (391/420; 42.5%) compared with seamen in other departments, including deck (301/820; 36.6%), steward (278/981; 28.4%), or with service in multiple departments (167/541; 30.9%). Since many vessels, particularly those built before 1978, contain asbestos materials, appropriate engineering controls (including complete removal, if possible) are required as well as appropriate medical surveillance for those who served aboard such ships. PMID:2357448

  8. Two-year cortical trajectories are abnormal in children and adolescents with prenatal alcohol exposure

    PubMed Central

    Hendrickson, Timothy J.; Mueller, Bryon A.; Sowell, Elizabeth R.; Mattson, Sarah N.; Coles, Claire D.; Kable, Julie A.; Jones, Kenneth L.; Boys, Christopher J.; Lee, Susanne; Lim, Kelvin O.; Riley, Edward P.; Wozniak, Jeffrey R.

    2018-01-01

    Objectives Cortical abnormalities in prenatal alcohol exposure (PAE) are known, including in gyrification (LGI), thickness (CT), volume (CV), and surface area (CS). This study provides longitudinal and developmental context to the PAE cortical development literature. Experimental design Included: 58 children with PAE and 52 controls, ages 6–17 at enrollment, from four Collaborative Initiative on FASD (CIFASD) sites. Participants underwent a formal evaluation of physical anomalies and dysmorphic facial features associated with PAE. MRI data were collected on three platforms (Siemens, GE, and Philips) at four sites. Scans were spaced two years apart. Change in LGI, CT, CS, and CV were examined. Principal observations Several significant regional age-by-diagnosis linear and quadratic interaction effects in LGI, CT, and CV were found, indicating atypical developmental trajectories in PAE. No significant correlations were observed between cortical measures and IQ. Conclusions Regional differences were seen longitudinally in CT, CV, and LGI in those with PAE. The findings represent important insights into developmental trajectories and may have implications for the timing of assessments and interventions in this population. It is noteworthy that cortical metrics did not correlate with IQ, suggesting that more specific aspects of cognitive development may need to be explored to provide further context. PMID:29486453

  9. Two-year cortical trajectories are abnormal in children and adolescents with prenatal alcohol exposure.

    PubMed

    Hendrickson, Timothy J; Mueller, Bryon A; Sowell, Elizabeth R; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lee, Susanne; Lim, Kelvin O; Riley, Edward P; Wozniak, Jeffrey R

    2018-04-01

    Cortical abnormalities in prenatal alcohol exposure (PAE) are known, including in gyrification (LGI), thickness (CT), volume (CV), and surface area (CS). This study provides longitudinal and developmental context to the PAE cortical development literature. Included: 58 children with PAE and 52 controls, ages 6-17 at enrollment, from four Collaborative Initiative on FASD (CIFASD) sites. Participants underwent a formal evaluation of physical anomalies and dysmorphic facial features associated with PAE. MRI data were collected on three platforms (Siemens, GE, and Philips) at four sites. Scans were spaced two years apart. Change in LGI, CT, CS, and CV were examined. Several significant regional age-by-diagnosis linear and quadratic interaction effects in LGI, CT, and CV were found, indicating atypical developmental trajectories in PAE. No significant correlations were observed between cortical measures and IQ. Regional differences were seen longitudinally in CT, CV, and LGI in those with PAE. The findings represent important insights into developmental trajectories and may have implications for the timing of assessments and interventions in this population. It is noteworthy that cortical metrics did not correlate with IQ, suggesting that more specific aspects of cognitive development may need to be explored to provide further context. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Micronuclei and other erythrocyte nuclear abnormalities in fishes from the Great Lakes Basin, USA

    USGS Publications Warehouse

    Braham, Ryan P.; Blazer, Vicki S.; Shaw, Cassidy H.; Mazik, Patricia M.

    2017-01-01

    Biological markers (biomarkers) sensitive to genotoxic and mutagenic contamination in fishes are widely used to identify exposure effects in aquatic environments. The micronucleus assay was incorporated into a suite of indicators to assess exposure to genotoxic and mutagenic contamination at five Great Lakes Areas of Concern (AOCs), as well as one non-AOC (reference) site. The assay allowed enumeration of micronuclei as well as other nuclear abnormalities for both site and species comparisons. Erythrocyte abnormality data was also compared to skin and liver tumor prevalence and hepatic transcript abundance. Erythrocyte abnormalities were observed at all sites with variable occurrence and severity among sites and species. Benthic-oriented brown bullhead (Ameiurus nebulosus) and white sucker (Catostomus commersonii) expressed lower rates of erythrocyte abnormalities, but higher rates of skin and liver neoplasms, when compared to pelagic-oriented largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) at the same site. The reduced erythrocyte abnormalities, increased transcript abundance associated with Phase I and II toxicant responsive pathways, and increased neoplastic lesions among benthic-oriented taxa may indicate the development of contaminant resistance of these species to more acute effects.

  11. Radiation induced abnormalities in early in vitro mouse embryos

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

    Kirkpatrick, J.F.

    1973-08-01

    Female mice were superovulated and mated, and the two-cell embryos were collected and cultured in vitro. The embryos were exposed to x-irradiation (0 to 491 rads) during the two-cell stage before the appearance of the next cleavage plate, placed in new unirradiated culture medium and observed during subsequent development. Morphological abnormalities, which occurred as a result of irradiation, included fragmentation, disintegration, granlation, incomplete cleavage, cleavage cessation, nuclear degeneration and pycnosis and cytoplasmic vacuolization. There was no damage to the zona pellucida. The types of abnormalities indicate an agreement with the results of previous in vivo studies. A distinct correlation existedmore » between morphological abnormalities and embryo death. The greatest number of abnormalities resulted within five hours following irradiation, but increased through 20 hours post-exposure. At doses above 300 rads, the magnitude of damage was greater in the in vitro embryos than that shown in previous in vivo studies. (auth)« less

  12. Escherichia albertii Inactivation following l-Lactic Acid Exposure or Cooking in Ground Beef.

    PubMed

    Jones-Ibarra, Amie M; Wall, Kayley R; Vuia-Riser, Jennifer; Kerth, Chris R; Castillo, Alejandro; Taylor, T Matthew

    2016-09-01

    Escherichia albertii is an emerging foodborne pathogen recovered from young children and adults exhibiting symptoms of gastroenteritis via pathogenesis factors including attaching and effacing lesions, cytolethal distending toxin, and Shiga toxin variants. Study objectives were to determine E. albertii survival following (i) exposure to lactic acid as a function of solution pH and incubation period and (ii) cooking ground beef patties to different endpoint temperatures. E. albertii was incubated in phosphate buffer containing 3.0% l-lactic acid adjusted to pH 3.0, 4.0, 5.0, or 7.0; survivors were determined every 30 min for 150 min. Ground beef patties (80% lean) were cooked to temperature endpoints simulating undercooking (62°C), the minimum temperature for safe cooking (71.1°C), and cooking to well done (76°C). Maximal pathogen reduction was observed after a 30-min exposure to pH 3.0 l-lactic acid. Reductions of 3.9, 4.4, and 4.9 log CFU/g were obtained following cooking ground beef patties to 62, 71.1, and 76°C, respectively, but the reductions did not differ as a function of the endpoint cooking temperature (P ≥ 0.05). E. albertii may be controlled on beef through the proper application of antimicrobial interventions and cooking.

  13. Geographical Differences in Dietary Exposure to Perfluoroalkyl Acids between Manufacturing and Application Regions in China.

    PubMed

    Zhang, Haiyan; Vestergren, Robin; Wang, Thanh; Yu, Junchao; Jiang, Guibin; Herzke, Dorte

    2017-05-16

    Emissions of perfluoroalkyl acids (PFAAs) have increased in China over the past decade, but human exposure pathways are poorly understood. Here we analyzed 15 PFAAs in commonly consumed food items and calculated body weight normalized dietary intake rates (estimated dietary intake, EDIs) in an area with ongoing PFAA production (Hubei province; n = 121) and an urbanized coastal area (Zhejiang province; n = 106). Geographical differences in concentrations were primarily observed for perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) in animal food items and short-chain PFAAs in vegetable food items. The average EDI of ∑PFAAs for adults in Hubei (998 ng kg -1 day -1 ) was more than 2 orders of magnitude higher than that in Zhejiang (9.03 ng kg -1 day -1 ). In Hubei province, the average EDI of PFOS for adults (87 ng kg -1 day -1 ) was close to or exceeded advisory guidelines used in other countries indicating health risks for the population from long-term exposure. Yet, PFOS could only account for about 10% of the EDI of ∑PFAAs in the Hubei province, which was dominated by short-chain PFAAs through consumption of vegetables. The large contribution of short-chain PFAAs to the total EDIs in manufacturing areas emphasize the need for improved exposure and hazard assessment tools of these substances.

  14. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation.

    PubMed Central

    López-Soriano, F J; Fernández-López, J A; Mampel, T; Villarroya, F; Iglesias, R; Alemany, M

    1988-01-01

    The net uptake/release of glucose, lactate and amino acids from the bloodstream by the interscapular brown adipose tissue of control, cold-exposed and cold-acclimated rats was estimated by measurement of arteriovenous differences in their concentrations. In the control animals amino acids contributed little to the overall energetic needs of the tissue; glucose uptake was more than compensated by lactate efflux. Cold-exposure resulted in an enhancement of amino acid utilization and of glucose uptake, with high lactate efflux. There was a net glycine and proline efflux that partly compensated the positive nitrogen balance of the tissue; amino acids accounted for about one-third of the energy supplied by glucose to the tissue. Cold-acclimation resulted in a very high increase in glucose uptake, with a parallel decrease in lactate efflux and amino acid consumption. Branched-chain amino acids, however, were more actively utilized. This was related with a much higher alanine efflux, in addition to that of glycine and proline. It is suggested that most of the glucose used during cold-exposure is returned to the bloodstream as lactate under conditions of active lipid utilization, amino acids contributing their skeletons largely in anaplerotic pathways. On the other hand, cold-acclimation resulted in an important enhancement of glucose utilization, with lowered amino acid oxidation. Amino acids are thus used as metabolic substrates by the brown adipose tissue of rats under conditions of relatively scarce substrate availability, but mainly as anaplerotic substrates, in parallel to glucose. Cold-acclimation results in a shift of the main substrates used in thermogenesis from lipid to glucose, with a much lower need for amino acids. PMID:3421924

  16. Color stability of CAD/CAM Zirconia ceramics following exposure to acidic and staining drinks.

    PubMed

    Colombo, Marco; Cavallo, Marco; Miegge, Matteo; Dagna, Alberto; Beltrami, Riccardo; Chiesa, Marco; Poggio, Claudio

    2017-11-01

    The aim of this in vitro study was to evaluate the color stability of CAD/CAM Zirconia ceramics following exposure to acidic drink (Coca Cola) and after exposure to staining solution (coffee). All the samples were immersed in different staining solutions over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. Shapiro Wilk test and Kruskal-Wallis ANOVA were applied to assess significant differences among restorative materials. Paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. One week immersion in acidic drink did not cause a perceivable discoloration for all restorative materials (ΔE < 3.3). Subsequent immersion in coffee affected color stability of all Zirconia samples, even if Kruskal-Wallis ANOVA found significant differences among the various restorative materials. The ∆Es of CAD/CAM Zirconia ceramics after immersion in coffee varied among the products, but color integrity is not affected by contact with acidic drinks. Key words: CAD/CAM restorative materials, CIE Lab, Zirconia ceramics.

  17. 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

  18. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

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

    Gamboa da Costa, Gonçalo, E-mail: goncalo.gamboa@fda.hhs.gov; Jacob, Cristina C.; Von Tungeln, Linda S.

    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 weremore » 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.« less

  19. Amino Acid Concentrations in the Hamster Central Auditory System and Long-Term Effects of Intense Tone Exposure

    PubMed Central

    Godfrey, Donald A.; Kaltenbach, James A.; Chen, Kejian; Ilyas, Omer; Liu, Xiaochen; Licari, Frank; Sacks, Justin; McKnight, Darwin

    2015-01-01

    Exposure to intense sounds often leads to loss of hearing of environmental sounds and hearing of a monotonous tonal sound not actually present, a condition known as tinnitus. Chronic physiological effects of exposure to intense tones have been reported for animals and should be accompanied by chemical changes present at long times after the intense sound exposure. By using a microdissection mapping procedure combined with high-performance liquid chromatography (HPLC), we have measured concentrations of nine amino acids, including those used as neurotransmitters, in the cochlear nucleus, inferior colliculus, medial geniculate, and auditory cortex of hamsters 5 months after exposure to an intense tone, compared with control hamsters of the same age. No very large differences in amino acid concentrations were found between exposed and control hamsters. However, increases of glutamate and γ-aminobutyrate (GABA) in some parts of the inferior colliculus of exposed hamsters were statistically significant. The most consistent differences between exposed and control hamsters were higher aspartate and lower taurine concentrations in virtually all regions of exposed hamsters, which reached statistical significance in many cases. Although these amino acids are not considered likely neurotransmitters, they indirectly have roles in excitatory and inhibitory neurotransmission, respectively. Thus, there is evidence for small, widespread, long-term increases in excitatory transmission and decreases in inhibitory transmission after a level of acoustic trauma previously shown to produce hearing loss and tinnitus. PMID:22715056

  20. The occurrence, exposure and risk assessment of perfluoroalkyl acids in food from mainland, China.

    PubMed

    Wang, Xinxuan; Zhang, Ruobing; Zhang, Hong; Wang, Yanping

    2017-11-01

    To study the contamination of perfluoroalkyl acids (PFAAs) in Chinese food and the risk of dietary exposure for the Chinese population, the data of 17 PFAAs covering 38 cities throughout China in 15 groups of foods were collected for meta-analysis from published and available research literature. Using food consumption and body weight parameters, estimated dietary intakes (EDIs) were calculated for evaluation using the Scenario-Based Risk Assessment (SceBRA) modelling. Among food groups, the highest ΣPFAAs concentrations and EDI contributions were both found in poultry (363 ng/g), fish and shrimp (313 ng/g), dark vegetables (309 ng/g), fruits (116 ng/g) and pork (25 ng/g). The EDI of adults in the high-exposure scenario was about twice that of the intermediate-exposure scenario, while the EDI of children was about twice that of adults' EDI in the intermediate-exposure scenario. In addition, the PFOS EDI for children under high exposure approached its tolerable daily intake (TDI). Therefore high dietary exposure to PFAAs is giving rise to an increased health risk, especially for children.

  1. Morphological abnormalities during early-life development of the estuarine mummichog, Fundulus heteroclitus, as an indicator of androgenic and anti-androgenic endocrine disruption.

    PubMed

    Boudreau, Monica; Courtenay, Simon C; Maclatchy, Deborah L; Bérubé, Céline H; Hewitt, L Mark; Van Der Kraak, Glen J

    2005-03-04

    We tested the hypothesis that gross morphological abnormalities are a sensitive indicator of exposure to waterborne androgenic and anti-androgenic compounds during embryonic, larval and juvenile stages of development in the common estuarine killifish, the mummichog (Fundulus heteroclitus; Pisces: Cyprinodontidae). Static exposures with daily renewal were carried out with 10-100,000 ng/L of the androgen agonist, 17alpha-methyltestosterone (MT), or the androgen antagonist, cyproterone acetate (CA), for 60 days post-fertilization (PF) in duplicate exposures. Measured concentrations were 78.4-155.8% of nominal concentrations for MT and 13.5-168.1% for CA. No dose-related or consistent effects of MT or CA were observed before hatch. In 60 days PF juveniles, incidence of skeletal abnormalities (scoliosis, lordosis, head, facial and fin), soft tissue abnormality (anal swelling) and hemorrhaging were significantly increased by MT but only at high concentrations (> or =1000 ng/L). The 10,000 and 100,000 ng/L concentrations of MT produced a wider range of abnormalities than 1000ng/L. Over 90% of fish exposed to 10,000 or 100,000 ng/L were abnormal with an average of over 3.5 abnormalities per fish. CA did not increase the incidence of any type of abnormality. Survival of juveniles to the end of the exposure was reduced by MT at concentrations of 1000 ng/L and greater in the first experiment and at concentrations of 10,000 ng/L and greater in the second experiment. Juvenile length was reduced by high concentrations of MT (> or =10,000 ng/L) in the first experiment and by most concentrations in the second experiment. We conclude that morphological abnormalities in early-life stages of mummichogs are not a sensitive indicator of exposure to androgenic or anti-androgenic waterborne EDSs at environmentally relevant concentrations.

  2. Gastroesophageal pressure gradients in gastroesophageal reflux disease: relations with hiatal hernia, body mass index, and esophageal acid exposure.

    PubMed

    de Vries, Durk R; van Herwaarden, Margot A; Smout, André J P M; Samsom, Melvin

    2008-06-01

    The roles of intragastric pressure (IGP), intraesophageal pressure (IEP), gastroesophageal pressure gradient (GEPG), and body mass index (BMI) in the pathophysiology of gastroesophageal reflux disease (GERD) and hiatal hernia (HH) are only partly understood. In total, 149 GERD patients underwent stationary esophageal manometry, 24-h pH-metry, and endoscopy. One hundred three patients had HH. Linear regression analysis showed that each kilogram per square meter of BMI caused a 0.047-kPa increase in inspiratory IGP (95% confidence interval [CI] 0.026-0.067) and a 0.031-kPa increase in inspiratory GEPG (95% CI 0.007-0.055). Each kilogram per square meter of BMI caused expiratory IGP to increase with 0.043 kPa (95% CI 0.025-0.060) and expiratory IEP with 0.052 kPa (95% CI 0.027-0.077). Each added year of age caused inspiratory IEP to decrease by 0.008 kPa (95% CI -0.015-0.001) and inspiratory GEPG to increase by 0.008 kPa (95% CI 0.000-0.015). In binary logistic regression analysis, HH was predicted by inspiratory and expiratory IGP (odds ratio [OR] 2.93 and 2.62, respectively), inspiratory and expiratory GEPG (OR 3.19 and 2.68, respectively), and BMI (OR 1.72/5 kg/m(2)). In linear regression analysis, HH caused an average 5.09% increase in supine acid exposure (95% CI 0.96-9.22) and an average 3.46% increase in total acid exposure (95% CI 0.82-6.09). Each added year of age caused an average 0.10% increase in upright acid exposure and a 0.09% increase in total acid exposure (95% CI 0.00-0.20 and 0.00-0.18). BMI predicts IGP, inspiratory GEPG, and expiratory IEP. Age predicts inspiratory IEP and GEPG. Presence of HH is predicted by IGP, GEPG, and BMI. GEPG is not associated with acid exposure.

  3. Occupational exposure to perfluoroalkyl substances and serum levels of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in an aging population from upstate New York: a retrospective cohort study.

    PubMed

    Tanner, Eva M; Bloom, Michael S; Wu, Qian; Kannan, Kurunthachalam; Yucel, Recai M; Shrestha, Srishti; Fitzgerald, Edward F

    2018-02-01

    Perfluoroalkyl substances (PFASs) are environmentally persistent amphiphilic compounds. Exposure to two PFASs, perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) is linked to specific occupations and industries. This study examines the contribution of past occupational PFAS exposure to serum PFOS and PFOA levels among 154 older adults in New York State. Serum PFOS and PFOA levels were compared to data from the National Health and Nutrition Examination Survey (NHANES). Potential occupational exposure to any PFAS was determined from work histories, reviewed by an industrial hygienist, and assessed in relation to current serum PFOS and PFOA levels using exposure probability, duration and cumulative exposure. We observed 25% higher serum PFOS and 80% higher PFOA levels in study participants compared to NHANES. No participants reported PFAS chemical manufacturing work, but n = 68 reported work in occupations and industries known to use PFASs. We found that participants with high cumulative workplace exposure had 34% higher serum PFOS levels compared to participants without occupational exposure, adjusted for age, sex and income. Serum PFOS levels were 26% higher for participants with longer occupational exposure durations. The probability of occupational PFAS exposure metric was not associated with serum PFOS. Serum PFOA was not associated with any measure of occupational exposure. Occupational exposure may contribute to total PFOS body burden in this study population, even among workers not directly involved in manufacturing PFASs. PFAS exposure assessments should evaluate the workplace as a potential source, even when workplace exposures are assumed to be low or moderate.

  4. Dose-related cerebellar abnormality in rats with prenatal exposure to X-irradiation by magnetic resonance imaging volumetric analysis.

    PubMed

    Sawada, Kazuhiko; Saito, Shigeyoshi; Horiuchi-Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

    2013-09-01

    Cerebellar abnormalities in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T2 W-MRI anatomical sequence with high-spatial resolution at 11.7-tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose-dependently. Multiple linear regression analysis revealed that the cortical volume (standardized β=0.901; P<0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X-irradiation dose. The present MRI volumetric analysis revealed a dose-related cerebellar cortical hypoplasia by prenatal exposure to X-irradiation on E15. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

  5. 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 ...

  6. 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.

  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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism.

    PubMed

    Purcell, A E; Jeon, O H; Zimmerman, A W; Blue, M E; Pevsner, J

    2001-11-13

    Studies examining the brains of individuals with autism have identified anatomic and pathologic changes in regions such as the cerebellum and hippocampus. Little, if anything, is known, however, about the molecules that are involved in the pathogenesis of this disorder. To identify genes with abnormal expression levels in the cerebella of subjects with autism. Brain samples from a total of 10 individuals with autism and 23 matched controls were collected, mainly from the cerebellum. Two cDNA microarray technologies were used to identify genes that were significantly up- or downregulated in autism. The abnormal mRNA or protein levels of several genes identified by microarray analysis were investigated using PCR with reverse transcription and Western blotting. alpha-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)- and NMDA-type glutamate receptor densities were examined with receptor autoradiography in the cerebellum, caudate-putamen, and prefrontal cortex. The mRNA levels of several genes were significantly increased in autism, including excitatory amino acid transporter 1 and glutamate receptor AMPA 1, two members of the glutamate system. Abnormalities in the protein or mRNA levels of several additional molecules in the glutamate system were identified on further analysis, including glutamate receptor binding proteins. AMPA-type glutamate receptor density was decreased in the cerebellum of individuals with autism (p < 0.05). Subjects with autism may have specific abnormalities in the AMPA-type glutamate receptors and glutamate transporters in the cerebellum. These abnormalities may be directly involved in the pathogenesis of the disorder.

  9. Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio).

    PubMed

    Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

    2017-01-01

    Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi-static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 βestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017. © 2015 Wiley Periodicals, Inc.

  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.

  11. Health effects of acid aerosols on North American children: air pollution exposures.

    PubMed

    Spengler, J D; Koutrakis, P; Dockery, D W; Raizenne, M; Speizer, F E

    1996-05-01

    Air pollution measurements were conducted over a 1-year period in 24 North American communities participating in a respiratory health study. Ozone, particle strong acidity, sulfate, and mass (PM10 and PM2.1) were measured in all communities. In 20 of the communities, sulfur dioxide, ammonia, nitric acid, nitrous acid, and particulate nitrate were measured. The sampler was located centrally in the community whenever possible and samples were collected every other day. Concentrations of particle strong acidity, mass, sulfate, and ozone were highly correlated both in the region of the country defined as a high-sulfur source area and in the downwind transport regions. These regions of the eastern United States and southern Canada experienced the greatest particle strong acidity, sulfate, and particle mass concentrations during the spring and summer months (May-September). The particle strong acidity concentrations were highest in regions close to the high sulfur emission areas of the United States; that is, in the area immediately to the west of the Appalachian Plateau and west of the Allegheny Mountains (western Pennsylvania, eastern Ohio, and West Virginia) up through southern Ontario. The frequency of particle strong acidity events decreased with transport distance from the region of highest sulfur emissions. Low particle strong acidity and sulfates were found at the western and midwestern sites of both the United States and Canada. Substantial concentrations of nitric acid were found in two of the California sites as well as many sites in the northeastern portion of the United States. Sites selected for the epidemiologic study provide a range of annual mean particle strong acidity exposures from below the limit of detection to more than 50 nmol/m3.

  12. The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities.

    PubMed Central

    Kimm-Brinson, K L; Ramsdell, J S

    2001-01-01

    Brevetoxins are lipophilic polyether toxins produced by the red tide dinoflagellate Gymnodinium breve, and their neurotoxic effects on adult animals have been documented. In this study, we characterized adverse developmental effects of brevetoxin-1 (PbTx-1) using an exposure paradigm that parallels the maternal oocyte transfer of toxin. Medaka fish (Oryzias latipes) embryos were exposed to PbTx-1 via microinjection of toxin reconstituted in a triolein oil droplet. Embryos microinjected with doses of 0.1-8.0 ng/egg (ppm) of brevetoxin-1 exhibited pronounced muscular activity (hyperkinesis) after embryonic day 4. Upon hatching, morphologic abnormalities were commonly found in embryos at the following lowest adverse effect levels: 1.0-3.0 ppm, lateral curvature of the spinal column; 3.1-3.4 ppm, herniation of brain meninges through defects in the skull; and 3.4-4.0 ppm, malpositioned eye. Hatching abnormalities were also commonly observed at brevetoxin doses of 2.0 ppm and higher with head-first, as opposed to the normal tail-first, hatching, and doses > 4.1 ng/egg produced embryos that developed but failed to hatch. Given the similarity of developmental processes found between higher and lower vertebrates, teratogenic effects of brevetoxins have the potential to occur among different phylogenetic classes. The observation of developmental abnormalities after PbTx-1 exposure identifies a new spectrum of adverse effects that may be expected to occur following exposure to G. breve red tide events. PMID:11335186

  13. Color stability of CAD/CAM Zirconia ceramics following exposure to acidic and staining drinks

    PubMed Central

    Colombo, Marco; Cavallo, Marco; Miegge, Matteo; Dagna, Alberto; Beltrami, Riccardo; Chiesa, Marco

    2017-01-01

    Background The aim of this in vitro study was to evaluate the color stability of CAD/CAM Zirconia ceramics following exposure to acidic drink (Coca Cola) and after exposure to staining solution (coffee). Material and Methods All the samples were immersed in different staining solutions over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. Shapiro Wilk test and Kruskal-Wallis ANOVA were applied to assess significant differences among restorative materials. Paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. Results One week immersion in acidic drink did not cause a perceivable discoloration for all restorative materials (ΔE < 3.3). Subsequent immersion in coffee affected color stability of all Zirconia samples, even if Kruskal-Wallis ANOVA found significant differences among the various restorative materials. Conclusions The ∆Es of CAD/CAM Zirconia ceramics after immersion in coffee varied among the products, but color integrity is not affected by contact with acidic drinks. Key words:CAD/CAM restorative materials, CIE Lab, Zirconia ceramics. PMID:29302281

  14. Late onset deficits in synaptic plasticity in the valproic acid rat model of autism.

    PubMed

    Martin, Henry G S; Manzoni, Olivier J

    2014-01-01

    Valproic acid (VPA) is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC) physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP) due to an up-regulation of NMDA receptor (NMDAR) expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDARs during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general.

  15. Perfluorooctanoic Acid Exposure and Pregnancy Outcome in a Highly Exposed Community

    PubMed Central

    Savitz, David A.; Stein, Cheryl R.; Bartell, Scott M.; Elston, Beth; Gong, Jian; Shin, Hyeong-Moo; Wellenius, Gregory A.

    2012-01-01

    Background We assessed the association between perfluorooctanoic acid (PFOA) and pregnancy outcome in an area with elevated exposure to PFOA from drinking water contaminated by chemical plant releases. Methods Serum PFOA was measured and reproductive and residential histories were obtained in 2005 – 2006. We estimated serum PFOA levels at the time of pregnancy for 11,737 pregnancies occurring between 1990 and 2006 based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We assessed the association between PFOA and the odds of miscarriage, stillbirth, preeclampsia, preterm birth, term low birthweight, and birth defects controlling for calendar time, age, parity, education, and smoking. PFOA exposure was evaluated as a continuous measure (with and without log-transformation) and in quintiles, combining the lowest two quintiles (<6.8 ng/mL) as the referent. Results Measures of association between PFOA and miscarriage, preterm birth, term low birthweight, and birth defects were close to the null. Odds of stillbirth were elevated in the 4th quintile only. For preeclampsia, the odds ratio was 1.13 (95% confidence interval = 1.00 – 1.28) for an interquartile shift in log-transformed PFOA, and the odds ratios were 1.1 – 1.2 across the upper three quintiles of exposure. Conclusions In this large, population-based study in a region with markedly elevated PFOA exposure, we found no associations between estimated serum PFOA levels and adverse pregnancy outcomes other than possibly preeclampsia. Conclusions are tempered by inherent limitations in exposure reconstruction and self-reported pregnancy outcome information. PMID:22370857

  16. Association of lead exposure, serum uric acid and parameters of renal function in Nigerian lead-exposed workers.

    PubMed

    Alasia, D D; Emem-Chioma, P C; Wokoma, F S

    2010-10-01

    The presence of hyperuricemia and renal function impairment, especially in the absence of urate stone formation is strongly suggestive of lead nephropathy. The evaluation of this association is essential in areas where lead exposure is still prevalent and uncontrolled. To determine the relationship between serum uric acid and renal function indices in lead-exposed workers. A cross-sectional study of 190 adults with occupational lead exposure and 80 adults (comparison group), matched for age and sex was performed in Port Harcourt, South-south Nigeria. Blood lead was used as the biomarker of lead exposure while serum urea, serum creatinine, urine albumin (using urine albumin:creatinine ratio), estimated glomerular filtration rate (GFR) and serum uric acid were the renal function indices measured. Occupationally lead-exposed subjects had a significantly (p = 0.008) higher mean±SD blood lead levels (50.37±24.58 μg/dL) than the comparison group (41.40±26.85). The mean±SD serum urea (8.6±2.3 mg/dL), creatinine (1.0±0.2 mg/dL) and serum uric acid (4.6±1.2 mg/dL) were significantly (p < 0.01) higher in the study subjects than the comparison group (7.6±2.4, 0.9±0.2, and 3.9±1.1 mg/dL, respectively). The mean±SD creatinine clearance was significantly (p = 0.002) lower in the study subjects than the comparison group (98.9±21.3 vs. 108.2±25.2 mL/min/1.72 m2). Serum uric acid level correlated positively with serum creatinine (r = 0.134) and negatively with GFR (r = -0.151). People with occupational lead exposure are at risk of developing hyperuricemia and renal impairment.

  17. Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy.

    PubMed

    Hatlebakk, Jan G; Zerbib, Frank; Bruley des Varannes, Stanislas; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Galmiche, Jean-Paul; Eklund, Stefan; Långström, Göran; Lind, Tore; Lundell, Lars R

    2016-05-01

    patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show/NCT00251927). Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Personal exposure of dairy workers to dust, endotoxin, muramic acid, ergosterol, and ammonia on large-scale dairies in the high plains Western United States.

    PubMed

    Davidson, Margaret E; Schaeffer, Joshua; Clark, Maggie L; Magzamen, Sheryl; Brooks, Elizabeth J; Keefe, Thomas J; Bradford, Mary; Roman-Muniz, Noa; Mehaffy, John; Dooley, Gregory; Poole, Jill A; Mitloehner, Frank M; Reed, Sue; Schenker, Marc B; Reynolds, Stephen J

    2018-03-01

    Dairy workers experience a high degree of bioaerosol exposure, composed of an array of biological and chemical constituents, which have been tied to adverse health effects. A better understanding of the variation in the magnitude and composition of exposures by task is needed to inform worker protection strategies. To characterize the levels and types of exposures, 115 dairy workers grouped into three task categories on nine farms in the high plains Western United States underwent personal monitoring for inhalable dust, endotoxin, 3-hydroxy fatty acids (3-OHFA), muramic acid, ergosterol, and ammonia through one work shift. Eighty-nine percent of dairy workers were exposed to endotoxin at concentrations exceeding the recommended exposure guidelines (adjusted for a long work shift). The proportion of workers with exposures exceeding recommended guidelines was lower for inhalable dust (12%), and ammonia (1%). Ergosterol exposures were only measurable on 28% of samples, primarily among medical workers and feed handlers. Milking parlor workers were exposed to significantly higher inhalable dust, endotoxin, 3-OHFA, ammonia, and muramic acid concentrations compared to workers performing other tasks. Development of large modern dairies has successfully made progress in reducing worker exposures and lung disease prevalence. However, exposure to endotoxin, dust, and ammonia continues to present a significant risk to worker health on North American dairies, especially for workers in milking parlors. This study was among the first to concurrently evaluate occupational exposure to assayable endotoxin (lipid A), 3-hydroxy fatty acids or 3-OHFA (a chemical measure of cell bound and noncell-bound endotoxins), muramic acid, ergosterol, and ammonia among workers on Western U.S. dairies. There remains a need for cost-effective, culturally acceptable intervention strategies integrated in OHS Risk Management and production systems to further optimize worker health and farm productivity.

  19. Detection of low level benzene exposure in supermarket wrappers by urinary muconic acid.

    PubMed

    E S Johnson S Halabi G Netto G Lucier W Bechtold R Henderson

    1999-01-01

    Women who use the 'hot wire' and 'cool rod' machines to wrap meat in supermarkets are potentially exposed to low levels of benzene and polycyclic aromatic hydrocarbons present in fumes emitted during the thermal decomposition of the plastic used to wrap meat. In order to evaluate whether the benzene metabolite trans, trans-muconic acid (MA) can be used to monitor these low levels, we collected urine samples from supermarket workers, and assayed the urine for MA. Geometric mean after-shift MA levels were highest for subjects who used the 'hot wire' machine, i.e. > 300 ng mg-1 creatinine (Cr). The corresponding levels for subjects who used the 'cool rod' machine were similar to those for subjects who did not use either type of machine, and were much lower. These results indicate that urinary muconic acid has some potential for use in monitoring benzene exposures of less than 1 part per million (ppm). The study detected very high background MA levels (exceeding 2000 ng mg-1 Cr) in some subjects, suggesting that individuals in the general population without occupational exposure to benzene may have urinary MA levels equivalent to exposure to up to 2 ppm benzene in ambient air. However, since non-benzene sources of the metabolite cannot be completely ruled out as partially responsible for these high levels, the public health significance of this finding is not known at the moment.

  20. Effect of occupational silica exposure on pulmonary function.

    PubMed

    Hertzberg, Vicki Stover; Rosenman, Kenneth D; Reilly, Mary Jo; Rice, Carol H

    2002-08-01

    To assess the effect of occupational silica exposure on pulmonary function. Epidemiologic evaluation based on employee interview, plant walk-through, and information abstracted from company medical records, employment records, and industrial hygiene measurements. Drawn from 1,072 current and former hourly wage workers employed before January 1, 1986. Thirty-six individuals with radiographic evidence of parenchymal changes consistent with asbestosis or silicosis were excluded. In addition, eight individuals whose race was listed as other than white or black were excluded. Analysis of spirometry data (FVC, FEV1, FEV1/FVC) only using the test results that met American Thoracic Society criteria for reproducibility and acceptability shows decreasing percent-predicted FVC and FEV1 and decreasing FEV1/FVC in relationship to increasing silica exposure among smokers. Logistic regression analyses of abnormal FVC and abnormal FEV1 values (where abnormal is defined as < 95% confidence limit for predicted using the Knudson prediction equations) show odds ratios of 1.49 and 1.68, respectively, for occurrence of abnormal result with 40 years of exposure at the Occupational Safety and Health Administration (OSHA)-allowable level of 0.1 mg/m3. Longitudinal analyses of FVC and FEV1 measurements show a 1.6 mL/yr and 1.1 mL/yr, respectively, decline per milligram/cubic meter mean silica exposure (p = 0.011 and p = 0.001, respectively). All analyses were adjusted for weight, height, age, ethnicity, smoking status, and other silica exposures. Systematic problems leading to measurement error were possible, but would have been nondifferential in effect and not related to silica measurements. There is a consistent association between increased pulmonary function abnormalities and estimated measures of cumulative silica exposure within the current allowable OSHA regulatory level. Despite concerns about the quality control of the pulmonary function measurements use in these analyses, our

  1. Leaf surface and histological perturbations of leaves of Phaseolus vulgaris and Helianthus annuus after exposure to simulated acid rain

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

    Evans, L.S.; Gmur, N.F.; Da Costa, F.

    1977-08-01

    Initial injury to adaxial leaf surfaces of Phaseolus vulgaris and Helianthus annuus occurred near trichomes and stomata after exposure to simulated sulfate acid rain. Lesion frequency was not correlated with density of either stomata or trichomes but was correlated with degree of leaf expansion. The number of lesions per unit area increased with total leaf area. Results suggest that characteristics of the leaf indumentum such as development of trichomes and guard cells and/or cuticle thickness near these structures may be involved in lesion development. Adaxial epidermal cell collapse was the first event in lesion development. Palisade cells and eventually spongymore » mesophyll cells collapsed after continued, daily exposure to simulated rain of low pH. Lesion development on Phaseolus vulgaris followed a specific course of events after exposure to simulated rain of known composition, application rate, drop size frequency, drop velocities, and frequency of exposures. These results allow development of further experiments to observe accurately other parameters, such as nutrient inputs and nutrient leaching from foliage, after exposure to simulated sulfate acid rain.« less

  2. Health effects of acid aerosols on North American children: air pollution exposures.

    PubMed Central

    Spengler, J D; Koutrakis, P; Dockery, D W; Raizenne, M; Speizer, F E

    1996-01-01

    Air pollution measurements were conducted over a 1-year period in 24 North American communities participating in a respiratory health study. Ozone, particle strong acidity, sulfate, and mass (PM10 and PM2.1) were measured in all communities. In 20 of the communities, sulfur dioxide, ammonia, nitric acid, nitrous acid, and particulate nitrate were measured. The sampler was located centrally in the community whenever possible and samples were collected every other day. Concentrations of particle strong acidity, mass, sulfate, and ozone were highly correlated both in the region of the country defined as a high-sulfur source area and in the downwind transport regions. These regions of the eastern United States and southern Canada experienced the greatest particle strong acidity, sulfate, and particle mass concentrations during the spring and summer months (May-September). The particle strong acidity concentrations were highest in regions close to the high sulfur emission areas of the United States; that is, in the area immediately to the west of the Appalachian Plateau and west of the Allegheny Mountains (western Pennsylvania, eastern Ohio, and West Virginia) up through southern Ontario. The frequency of particle strong acidity events decreased with transport distance from the region of highest sulfur emissions. Low particle strong acidity and sulfates were found at the western and midwestern sites of both the United States and Canada. Substantial concentrations of nitric acid were found in two of the California sites as well as many sites in the northeastern portion of the United States. Sites selected for the epidemiologic study provide a range of annual mean particle strong acidity exposures from below the limit of detection to more than 50 nmol/m3. Images p492-a Figure 1. Figure 2. Figure 3. Figure 4. Figure 4. Figure 4. PMID:8743436

  3. Waist to hip ratio is a better predictor of esophageal acid exposure than body mass index.

    PubMed

    Ringhofer, C; Lenglinger, J; Riegler, M; Kristo, I; Kainz, A; Schoppmann, S F

    2017-07-01

    Obesity and gastroesophageal reflux disease (GERD) are major health problems showing an inconstant relationship in the literature. Therefore, anthropometric parameters which are predictive and can simply be assessed at first patient presentation may lead to a better patient selection for ambulatory reflux monitoring. We aimed to examine the association of body mass index (BMI) and waist to hip ratio (WHR) with gastroesophageal reflux activity during 24 hour-pH-impedance monitoring. Seven hundred and seventy-one patients with GERD symptoms underwent 24 hour-pH-impedance monitoring and high resolution manometry off proton pump inhibitors. Patients with known primary motility disorders of the esophagus and pre-existing endoscopic or operative procedure on esophagus or stomach were excluded from the study. Reflux parameters and anthropometric and demographic data from our prospectively gathered database were analyzed. We performed univariate and multivariate regression analysis to evaluate the associations of BMI and WHR with reflux parameters measured with 24 hour-pH-impedance monitoring. WHR showed a significantly stronger association with esophageal acid exposure than BMI (P<.001). Our data show that 6.9% of the percentage of endoluminal pH<4 in the distal esophagus is attributable to WHR. Furthermore, an association of WHR with impaired esophageal acid clearance was observed. Additionally, we observed an inverse relationship between lower esophageal sphincter integrity (P=.05) and esophageal acid exposure. WHR is a better predictor for esophageal acid exposure than BMI. Biomechanical and metabolic mechanisms of central fat distribution may influence reflux parameters in 24 hour pH impedance monitoring, which may affect patient selection for ambulatory reflux monitoring. © 2017 John Wiley & Sons Ltd.

  4. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Micronuclei and other erythrocyte nuclear abnormalities in fishes from the Great Lakes Basin, USA

    PubMed Central

    Braham, Ryan P.; Shaw, Cassidy H.; Mazik, Patricia M.; Umbuzeiro, G.

    2017-01-01

    Biological markers (biomarkers) sensitive to genotoxic and mutagenic contamination in fishes are widely used to identify exposure effects in aquatic environments. The micronucleus assay was incorporated into a suite of indicators to assess exposure to genotoxic and mutagenic contamination at five Great Lakes Areas of Concern (AOCs), as well as one non‐AOC (reference) site. The assay allowed enumeration of micronuclei as well as other nuclear abnormalities for both site and species comparisons. Erythrocyte abnormality data was also compared to skin and liver tumor prevalence and hepatic transcript abundance. Erythrocyte abnormalities were observed at all sites with variable occurrence and severity among sites and species. Benthic‐oriented brown bullhead (Ameiurus nebulosus) and white sucker (Catostomus commersonii) expressed lower rates of erythrocyte abnormalities, but higher rates of skin and liver neoplasms, when compared to pelagic‐oriented largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) at the same site. The reduced erythrocyte abnormalities, increased transcript abundance associated with Phase I and II toxicant responsive pathways, and increased neoplastic lesions among benthic‐oriented taxa may indicate the development of contaminant resistance of these species to more acute effects. Environ. Mol. Mutagen. 58:570–581, 2017. © 2017 This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:28868735

  6. Delivery of extraterrestrial amino acids to the primitive Earth. Exposure experiments in Earth orbit.

    PubMed

    Barbier, B; Bertrand, M; Boillot, F; Chabin, A; Chaput, D; Henin, O; Brack, A

    1998-06-01

    A large collection of micrometeorites has been recently extracted from Antarctic old blue ice. In the 50 to 100 micrometers size range, the carbonaceous micrometeorites represent 80% of the samples and contain 2% of carbon. They might have brought more carbon to the surface of the primitive Earth than that involved in the present surficial biomass. Amino acids such as "-amino isobutyric acid have been identified in these Antarctic micrometeorites. Enantiomeric excesses of L-amino acids have been detected in the Murchison meteorite. A large fraction of homochiral amino acids might have been delivered to the primitive Earth via meteorites and micrometeorites. Space technology in Earth orbit offers a unique opportunity to study the behaviour of amino acids required for the development of primitive life when they are exposed to space conditions, either free or associated with tiny mineral grains mimicking the micrometeorites. Our objectives are to demonstrate that porous mineral material protects amino acids in space from photolysis and racemization (the conversion of L-amino acids into a mixture of L- and D-molecules) and to test whether photosensitive amino acids derivatives can polymerize in mineral grains under space conditions. The results obtained in BIOPAN-1 and BIOPAN-2 exposure experiments on board unmanned satellite FOTON are presented.

  7. 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.

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

    PubMed Central

    BHATTI, PARVEEN; BLAIR, AARON; BELL, ERIN M.; ROTHMAN, NATHANIEL; LAN, QING; BARR, DANA B.; NEEDHAM, LARRY L.; PORTENGEN, LUTZEN; FIGGS, LARRY W.; VERMEULEN, ROEL

    2009-01-01

    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. PMID:19319162

  9. 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. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Exposure to the cytokine EGF leads to abnormal hyperactivity of pallidal GABA neurons: implications for schizophrenia and its modeling.

    PubMed

    Sotoyama, Hidekazu; Namba, Hisaaki; Chiken, Satomi; Nambu, Atsushi; Nawa, Hiroyuki

    2013-08-01

    Previous studies on a cytokine model for schizophrenia reveal that the hyperdopaminergic innervation and neurotransmission in the globus pallidus (GP) is involved in its behavioral impairments. Here, we further explored the physiological consequences of the GP abnormality in the indirect pathway, using the same schizophrenia model established by perinatal exposure to epidermal growth factor (EGF). Single-unit recordings revealed that the neural activity from the lateral GP was elevated in EGF-treated rats in vivo and in vitro (i.e., slice preparations), whereas the central area of the GP exhibited no significant differences. The increase in the pallidal activity was normalized by subchronic treatment with risperidone, which is known to ameliorate their behavioral deficits. We also monitored extracellular GABA concentrations in the substantia nigra, one of the targets of pallidal efferents. There was a significant increase in basal GABA levels in EGF-treated rats, whereas high potassium-evoked GABA effluxes and glutamate levels were not affected. A neurotoxic lesion in the GP of EGF-treated rats normalized GABA concentrations to control levels. Corroborating our in vivo results, GABA release from GP slices was elevated in EGF-treated animals. These findings suggest that the hyperactivity and enhanced GABA release of GP neurons represent the key pathophysiological features of this cytokine-exposure model for schizophrenia. © 2013 International Society for Neurochemistry.

  11. Phenotypic Dichotomy Following Developmental Exposure to ...

    EPA Pesticide Factsheets

    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 sera of wildlife and humans throughout the world, but is especially high in the sera of children. These studies in CD-1 mice aim to determine the latent health effects of PFOA following an in utero exposure, a developmental exposure followed by ovariectomy (ovx), or exposure as an adult. Mice were exposed to 0, 0.01, 0.1, 0.3, 1, 3, or 5 mg PFOA/kg BW for 17 days of pregnancy or as an adult. Body weight was reduced in the highest doses on postnatal day (PND) 1 and at weaning. However, the lowest exposures (0.01-0.3 mg/kg) induced excessive weight gain between 20-40 weeks, as well as a significant increase in serum leptin (0.01-0.1 mg/kg). Although body weight was significantly increased due to ovx, there was no longer a body weight effect of PFOA in ovx animals. Further, there was no effect of adult exposure to PFOA on body weight gain. At 18 months of age, the effects of PFOA on body weight were no longer detected. The white adipose tissue and spleen weights were decreased at high doses of PFOA in intact developmentally exposed mice, and spleen weight was reduced in ovx mice. But, brown adipose tissue weight was significantly increased in both ovx and intact mice at high doses. Liver weigh

  12. Effect on the growth and development and induction of abnormalities by a glyphosate commercial formulation and its active ingredient during two developmental stages of the South-American Creole frog, Leptodactylus latrans.

    PubMed

    Bach, Nadia Carla; Natale, Guillermo Sebastián; Somoza, Gustavo Manuel; Ronco, Alicia Estela

    2016-12-01

    We evaluated the acute lethal and sublethal effects of technical-grade glyphosate (GLY) and the GLY-based commercial formulation Roundup ULTRA MAX® (RU) on two Gosner stages (Gss) 25 and 36 of the South-American Creole frog, Leptodactylus latrans. Bioassays were performed following standardized methods within a wide range of concentrations (0.0007-9.62 mg of acid equivalents per liter-a.e./L-of RU and 3-300 mg/L of GLY). The endpoints evaluated were mortality, swimming activity, growth, development, and the presence of morphologic abnormalities, especially in the mouthparts. No lethal effects were observed on larvae exposed to GLY during either Gs-25 or Gs-36. The concentrations inducing 50 % lethality in RU-exposed larvae at different exposure times and Gss ranged from 3.26 to 9.61 mg a.e./L. Swimming activity was affected by only RU. Effects on growth and development and the induction of morphologic abnormalities-like oral abnormalities and edema-were observed after exposure to either GLY or RU. Gs-25 was the most sensitive stage to both forms of the herbicide. The commercial formulation was much more toxic than the active ingredient on all the endpoints assessed. Effects on growth, development, and the induction of morphologic abnormalities observed in the range of environmental concentrations reported for agroecosystems of Argentina constitute an alert to the potential detrimental effects of the herbicide that could be affecting the fitness and survival of anurans in agroecosystems.

  13. Prevention of congenital abnormalities by periconceptional multivitamin supplementation.

    PubMed Central

    Czeizel, A E

    1993-01-01

    OBJECTIVE--To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities. DESIGN--Randomised controlled trial of supplementation with multivitamins and trace elements. SETTING--Hungarian family planning programme. SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life. INTERVENTIONS--A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception. MAIN OUTCOME MEASURES--Number of major and mild congenital abnormalities. RESULTS--The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference cannot be explained totally by the significant reduction of neural tube defects. The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group; relative risk 1.85 (95% confidence interval 1.02 to 3.38); difference, 7.6/1000. The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group; relative risk 1.95 (1.23 to 3.09); difference, 13.6/1000. The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant. CONCLUSIONS--Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities. Further studies are needed to differentiate the chance effect and vitamin dependent effect. PMID:8324432

  14. Elevated Prostaglandin E Metabolites and Abnormal Plasma Fatty Acids at Baseline in Pediatric Cystic Fibrosis Patients: A Pilot Study

    PubMed Central

    O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam

    2016-01-01

    Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care

  15. Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

    PubMed

    O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

    2016-10-01

    Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further

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

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

    Mohamed, A.A.E.K.; Hamed, A.A.S.; Elhaimi, Y.A.A.

    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<.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 weremore » 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.« less

  17. 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.

  18. Abnormal characteristics of binary molecular clusters in DMSO–ethanol mixtures under external electric fields

    NASA Astrophysics Data System (ADS)

    Wu, Zhiyan; Huang, Kama

    2018-05-01

    For the nonlinearly phenomena on the dielectric properties of dimethyl sulfoxide (DMSO)-ethanol mixtures under a low intensity microwave field, we propose a conjecture that there exist some abnormal molecular clusters. To interpret the mechanism of abnormal phenomena and confirm our conjecture about the existence of abnormal molecular clusters, an in-depth investigation about the structure evolutions of (DMSO)m(C2H5OH)n (m = 0-4; n = 0-4; m + n ≤ 4) molecular clusters induced by external electric fields has been given by using density functional theory. The results show that there exist some binary molecular clusters with large cluster radii in mixtures, and some of them are unstable under exposure of electric fields. It implies that the existence of certain abnormal molecular clusters in DMSO-ethanol mixtures results in their abnormality of dielectric properties.

  19. Biochemical abnormalities in workers exposed to molybdenum dust.

    PubMed

    Walravens, P A; Moure-Eraso, R; Solomons, C C; Chappell, W R; Bentley, G

    1979-01-01

    Exposure to molybdenum in dust was measured in a molybdenite roasting plant. This exposure was accompanied by large elevations of serum ceruloplasmin and smaller increases in mean serum uric acid levels in the workers. Absorption of molybdenum from the dust was demonstrated by increases in plasma and urinary molybdenum levels. It remains necessary to demonstrate whether such exposure results in long-term health effects.

  20. Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

    PubMed

    Hamazaki, Kei; Hamazaki, Tomohito; Inadera, Hidekuni

    2013-11-30

    Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Biomonitoring of 2,4-Dichlorophenoxyacetic Acid Exposure and Dose in Farm Families

    PubMed Central

    Alexander, Bruce H.; Mandel, Jack S.; Baker, Beth A.; Burns, Carol J.; Bartels, Michael J.; Acquavella, John F.; Gustin, Christophe

    2007-01-01

    Objective We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm. Methods Farm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application. Results Median urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 μ g/L for applicators, below the limit of detection, and 1.2 μ g/L for spouses, and 1.5 and 2.9 μ g/L for children. The younger children (4–11 years of age) had higher median post-application concentrations than the older children (≥ 12 years of age) (6.5 vs. 1.9 μ g/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4–11 years of age), and 0.12 (children ≥ 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators. Conclusions We observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D–exposed agricultural populations. PMID:17431485

  2. Estimating human exposure to PFOS isomers and PFCA homologues: the relative importance of direct and indirect (precursor) exposure.

    PubMed

    Gebbink, Wouter A; Berger, Urs; Cousins, Ian T

    2015-01-01

    Contributions of direct and indirect (via precursors) pathways of human exposure to perfluorooctane sulfonic acid (PFOS) isomers and perfluoroalkyl carboxylic acids (PFCAs) are estimated using a Scenario-Based Risk Assessment (SceBRA) modelling approach. Monitoring data published since 2008 (including samples from 2007) are used. The estimated daily exposures (resulting from both direct and precursor intake) for the general adult population are highest for PFOS and perfluorooctanoic acid (PFOA), followed by perfluorohexanoic acid (PFHxA) and perfluorodecanoic acid (PFDA), while lower daily exposures are estimated for perfluorobutanoic acid (PFBA) and perfluorododecanoic acid (PFDoDA). The precursor contributions to the individual perfluoroalkyl acid (PFAA) daily exposures are estimated to be 11-33% for PFOS, 0.1-2.5% for PFBA, 3.7-34% for PFHxA, 13-64% for PFOA, 5.2-66% for PFDA, and 0.7-25% for PFDoDA (ranges represent estimated precursor contributions in a low- and high-exposure scenario). For PFOS, direct intake via diet is the major exposure pathway regardless of exposure scenario. For PFCAs, the dominant exposure pathway is dependent on perfluoroalkyl chain length and exposure scenario. Modelled PFOS and PFOA concentrations in human serum using the estimated intakes from an intermediate-exposure scenario are in agreement with measured concentrations in different populations. The isomer pattern of PFOS resulting from total intakes (direct and via precursors) is estimated to be enriched with linear PFOS (84%) relative to technical PFOS (70% linear). This finding appears to be contradictory to the observed enrichment of branched PFOS isomers in recent human serum monitoring studies and suggests that either external exposure is not fully understood (e.g. there are unknown precursors, missing or poorly quantified exposure pathways) and/or that there is an incomplete understanding of the isomer-specific human pharmacokinetic processes of PFOS, its precursors and

  3. Gestational exposure to perfluorooctanoic acid (PFOA): alterations in motor related behaviors

    PubMed Central

    Goulding, David R.; White, Sally S.; McBride, Sandra J.; Fenton, Suzanne E.; Harry, G. Jean

    2016-01-01

    Perfluoroalkyl and polyfluoroalkyl substances are used in commercial applications and developmental exposure has been implicated in alterations in neurobehavioral functioning. While associations between developmental perfluorooctanoic acid (PFOA) exposure and human outcomes have been inconsistent, studies in experimental animals suggest alterations in motor related behaviors. To examine a dose-response pattern of neurobehavioral effects following gestational exposure to PFOA, pregnant CD-1 mice received PFOA (0, 0.1, 0.3, 1.0 mg/kg/day) via oral gavage from gestational day 1–17 and the male offspring examined. Motor activity assessments on postnatal day (PND)18, 19, and 20 indicated a shift in the developmental pattern with an elevated activity level observed in the 1.0 mg/kg/day dose group on PND18. In the adult, no alterations were observed in body weights, activity levels, diurnal pattern of running wheel activity, startle response, or pre-pulse startle inhibition. In response to a subcutaneous injection of saline or nicotine (80 µg/kg), all animals displayed a transient increase in activity likely associated with handling with no differences observed across dose groups. Inhibition of motor activity over 18 days of 400µg/kg nicotine injection was not significantly different across dose groups. Hyperactivity induced by 2mg/kg (+)-methamphetamine hydrochloride intraperitoneal injection was significantly lower in the 1.0 mg/kg/day PFOA dose group as compared to controls. Taken together, these data suggest that the effects on motor-related behaviors with gestational PFOA exposure do not mimic those reported for acute postnatal exposure. Changes were not observed at dose level under 1.0 mg/kg/day PFOA. Further examination of pathways associated with methamphetamine-induced activity is warranted. PMID:27888120

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

    PubMed

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

    2016-08-01

    Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers. We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease. 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). 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). 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 diagnosed liver disease. Darrow LA, Groth AC, Winquist A, Shin HM

  5. Valproic Acid in Women and Girls of Childbearing Age.

    PubMed

    Gotlib, Dorothy; Ramaswamy, Rachel; Kurlander, Jacob E; DeRiggi, Alana; Riba, Michelle

    2017-09-01

    The aim of this paper is to evaluate recent literature on valproic acid (VPA) in women and girls of childbearing age and to emphasize new findings. Recent research confirms VPAs teratogenicity and risk of hormone disruption. VPA exposure in utero increases the risk for a variety of major congenital malformations (MCMs), reduced IQ and behavioral problems. In girls and women, VPA increases the risk of hormone abnormalities, obesity, and polycystic ovarian syndrome (PCOS). Despite guidelines recommending caution, VPA use continues to be prescribed to reproductive-aged women and girls. Despite significant and well-documented risk, adherence to guidelines in VPA use in reproductive-aged girls and women remains low.

  6. Lung volumes and emphysema in smokers with interstitial lung abnormalities.

    PubMed

    Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

    2011-03-10

    Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation

  7. Dysregulation of major functional genes in frontal cortex by maternal exposure to carbon black nanoparticle is not ameliorated by ascorbic acid pretreatment.

    PubMed

    Onoda, Atsuto; Takeda, Ken; Umezawa, Masakazu

    2018-09-01

    Recent cohort studies have revealed that perinatal exposure to particulate air pollution, including carbon-based nanoparticles, increases the risk of brain disorders. Although developmental neurotoxicity is currently a major issue in the toxicology of nanoparticles, critical information for understanding the mechanisms underlying the developmental neurotoxicity of airway exposure to carbon black nanoparticle (CB-NP) is still lacking. In order to investigate these mechanisms, we comprehensively analyzed fluctuations in the gene expression profile of the frontal cortex of offspring mice exposed maternally to CB-NP, using microarray analysis combined with Gene Ontology information. We also analyzed differences in the enriched function of genes dysregulated by maternal CB-NP exposure with and without ascorbic acid pretreatment to refine specific alterations in gene expression induced by CB-NP. Total of 652 and 775 genes were dysregulated by CB-NP in the frontal cortex of 6- and 12-week-old offspring mice, respectively. Among the genes dysregulated by CB-NP, those related to extracellular matrix structural constituent, cellular response to interferon-beta, muscle organ development, and cysteine-type endopeptidase inhibitor activity were ameliorated by ascorbic acid pretreatment. A large proportion of the dysregulated genes, categorized in hemostasis, growth factor, chemotaxis, cell proliferation, blood vessel, and dopaminergic neurotransmission, were, however, not ameliorated by ascorbic acid pretreatment. The lack of effects of ascorbic acid on the dysregulation of genes following maternal CB-NP exposure suggests that the contribution of oxidative stress to the effects of CB-NP on these biological functions, i.e., cell migration and proliferation, blood vessel maintenance, and dopaminergic neuron system, may be limited. At least, ascorbic acid pretreatment is hardly likely to be able to protect the brain of offspring from developmental neurotoxicity of CB-NP. The

  8. 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.

  9. 5-Mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities.

    PubMed

    Shi, Yu; Li, Jiejing; Chen, Chunjiang; Gong, Manzi; Chen, Yuan; Liu, Youxue; Chen, Jie; Li, Tingyu; Song, Weihong

    2014-09-16

    Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis. Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies. Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.

  10. Impact of desiccation and heat exposure stress on Salmonella tolerance to acidic conditions.

    PubMed

    Richardson, Kurt E; Cox, Nelson A; Cosby, Douglas E; Berrang, Mark E

    2018-02-01

    In a recent study, the pH of commonly used Salmonella pre-enrichment media became acidic (pH 4.0 to 5.0) when feed or feed ingredients were incubated for 24 h. Acidic conditions have been reported to injure or kill Salmonella. In this study, cultures of four known feed isolates (S. montevideo, S. senftenberg, S. tennessee, and S. schwarzengrund) and four important processing plant isolates (S. typhimurium, S. enteritidis, S. infantis, and S. heidelberg) were grown on meat and bone meal and later subjected to desiccation and heat exposure to stress the microorganism. The impact of stress on the isolates ability to survive in acidic conditions ranging from pH 4.0 to 7.0 was compared to the non-stressed isolate. Cell injury was determined on xylose lysine tergitol 4 (XLT4) and cell death determined on nutrient agar (NA). When measured by cell death in non-stressed Salmonella, S. typhimurium was the most acid tolerant and S. heidelberg was the most acid sensitive whereas in stressed Salmonella, S. senftenberg was the most acid tolerant and S. tennessee was the most acid sensitive. The pH required to cause cell injury varied among isolates. With some isolates, the pH required for 50% cell death and 50% cell injury was similar. In other isolates, cell injury occurred at a more neutral pH. These findings suggest that the pH of pre-enrichment media may influence the recovery and bias the serotype of Salmonella recovered from feed during pre-enrichment.

  11. A biological indicator of inorganic arsenic exposure using the sum of urinary inorganic arsenic and monomethylarsonic acid concentrations

    PubMed Central

    Hata, Akihisa; Kurosawa, Hidetoshi; Endo, Yoko; Yamanaka, Kenzo; Fujitani, Noboru; Endo, Ginji

    2016-01-01

    Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure. Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m3 of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure. Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m3 iAs exposure, respectively. PMID:27010090

  12. Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice.

    PubMed

    Maekawa, Motoko; Iwayama, Yoshimi; Watanabe, Akiko; Nozaki, Yayoi; Ohnishi, Tetsuo; Ohba, Hisako; Toyoshima, Manabu; Hamazaki, Kei; Osumi, Noriko; Aruga, Jun; Yoshikawa, Takeo

    2010-11-12

    The eyes are rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid [ARA; 20:4 (n-6)] and docosahexaenoic acid [DHA; 22:6 (n-3)]. Despite their abundance in the eyes, ARA and DHA cannot be sufficiently synthesized de novo in mammals. During gestation, eye development is exceptionally rapid, and substantial amounts of LC-PUFAs are needed to ensure proper eye development. Here, we studied the influences of dietary LC-PUFAs in dams (C57BL/6 and C3H/He) on the eye morphogenesis and organogenesis of their pups. Intriguingly, fetuses and newborn mice from C57BL/6 dams fed an LC-PUFA (particularly ARA)-enriched diet displayed a much higher incidence of eye abnormalities such as microphthalmia (small eye) and corneal opacity than those from dams fed an LC-PUFA-poor diet. The effects of LC-PUFAs on eye anomalies were evident only in the female pups of C57BL/6 inbred mice, not in those of C3H/He mice or male C57BL/6 mice. These results demonstrate a gene-by-environment (GxE) interaction in eye development in mice. Furthermore, our molecular analysis suggested the potential roles of Pitx3 and Pax6 in the above interaction involving ARA. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Bisphenol A Exposure Disrupts Genomic Imprinting in the Mouse

    PubMed Central

    Susiarjo, Martha; Sasson, Isaac; Mesaros, Clementina; Bartolomei, Marisa S.

    2013-01-01

    Exposure to endocrine disruptors is associated with developmental defects. One compound of concern, to which humans are widely exposed, is bisphenol A (BPA). In model organisms, BPA exposure is linked to metabolic disorders, infertility, cancer, and behavior anomalies. Recently, BPA exposure has been linked to DNA methylation changes, indicating that epigenetic mechanisms may be relevant. We investigated effects of exposure on genomic imprinting in the mouse as imprinted genes are regulated by differential DNA methylation and aberrant imprinting disrupts fetal, placental, and postnatal development. Through allele-specific and quantitative real-time PCR analysis, we demonstrated that maternal BPA exposure during late stages of oocyte development and early stages of embryonic development significantly disrupted imprinted gene expression in embryonic day (E) 9.5 and 12.5 embryos and placentas. The affected genes included Snrpn, Ube3a, Igf2, Kcnq1ot1, Cdkn1c, and Ascl2; mutations and aberrant regulation of these genes are associated with imprinting disorders in humans. Furthermore, the majority of affected genes were expressed abnormally in the placenta. DNA methylation studies showed that BPA exposure significantly altered the methylation levels of differentially methylated regions (DMRs) including the Snrpn imprinting control region (ICR) and Igf2 DMR1. Moreover, exposure significantly reduced genome-wide methylation levels in the placenta, but not the embryo. Histological and immunohistochemical examinations revealed that these epigenetic defects were associated with abnormal placental development. In contrast to this early exposure paradigm, exposure outside of the epigenetic reprogramming window did not cause significant imprinting perturbations. Our data suggest that early exposure to common environmental compounds has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta. PMID

  14. 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.

  15. Respiratory Acid-Base Disorders in the Critical Care Unit.

    PubMed

    Hopper, Kate

    2017-03-01

    The incidence of respiratory acid-base abnormalities in the critical care unit (CCU) is unknown, although respiratory alkalosis is suspected to be common in this population. Abnormal carbon dioxide tension can have many physiologic effects, and changes in Pco 2 may have a significant impact on outcome. Monitoring Pco 2 in CCU patients is an important aspect of critical patient assessment, and identification of respiratory acid-base abnormalities can be valuable as a diagnostic tool. Treatment of respiratory acid-base disorders is largely focused on resolution of the primary disease, although mechanical ventilation may be indicated in cases with severe respiratory acidosis. Published by Elsevier Inc.

  16. Perivascular Accumulation of β-Sheet-Rich Proteins in Offspring Brain following Maternal Exposure to Carbon Black Nanoparticles.

    PubMed

    Onoda, Atsuto; Kawasaki, Takayasu; Tsukiyama, Koichi; Takeda, Ken; Umezawa, Masakazu

    2017-01-01

    Environmental stimulation during brain development is an important risk factor for the development of neurodegenerative disease. Clinical evidence indicates that prenatal exposure to particulate air pollutants leads to diffuse damage to the neurovascular unit in the developing brain and accelerates neurodegeneration. Maternal exposure to carbon black nanoparticles (CB-NPs), used as a model for particulate air pollution, induces long-lasting diffuse perivascular abnormalities. We aimed to comprehensively characterize the perivascular abnormalities related to maternal NPs exposure using Fourier transform infrared microspectroscopy ( in situ FT-IR) and classical staining analysis. Pregnant ICR mice were intranasally treated with a CB-NPs suspension (95 μg/kg at a time) on gestational days 5 and 9. Brains were collected 6 weeks after birth and sliced to prepare 10-μm-thick serial sections. Reflective spectra of in situ FT-IR were acquired using lattice measurements ( x -axis: 7, y -axis: 7, 30-μm apertures) around a centered blood vessel. We also performed mapping analysis of protein secondary structures. Serial sections were stained with using periodic acid-Schiff or immunofluorescence to examine the phenotypes of the perivascular areas. Peaks of amide I bands in spectra from perivascular areas were shifted by maternal NPs exposure. However, there were two types of peak-shift in one mouse in the exposure group. Some vessels had a large peak-shift and others had a small peak-shift. In situ FT-IR combined with traditional staining revealed that the large peak-shift was induced around blood vessel adjacent to astrocytes with glial fibrillary acidic protein and aquaporin-4 over-expression and perivascular macrophages (PVMs) with enlarged lysosome granules. Furthermore, protein secondary structural analysis indicated that maternal NPs exposure led to increases in β-sheet content and decreases in α-helix content in areas that are mostly close to the centered blood

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

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

    Lu, S.-T; Brown, D.O.; Johnson, C.E.

    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 themore » 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.« less

  18. 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. Copyright © 2016. Published by Elsevier B.V.

  19. Low levels of exposure to libby amphibole asbestos and localized pleural thickening.

    PubMed

    Christensen, Krista Yorita; Bateson, Thomas F; Kopylev, Leonid

    2013-11-01

    To explore the relationship between low levels of exposure to Libby amphibole asbestos (LAA) and pleural abnormalities, specifically localized pleural thickening (LPT). Three studies presenting the risks associated with quantitative LAA exposure estimates were reviewed, paying particular attention to lower exposure ranges. Studies reviewed were conducted among workers exposed to LAA at mining and milling operations in Libby, Montana, at a vermiculite processing facility in Marysville, Ohio, and community residents exposed to LAA from a vermiculite processing facility in Minneapolis, Minnesota. Pleural abnormalities were evaluated using radiographs. Despite differences in study populations and design, each study found that cumulative inhalation LAA exposure was associated with increased risk of LPT even at low levels of exposure. Inhalation exposure to LAA is associated with increased risk of LPT even at the lowest levels of exposure in each study.

  20. Micronuclei and other erythrocyte nuclear abnormalities in fishes from the Great Lakes Basin, USA.

    PubMed

    Braham, Ryan P; Blazer, Vicki S; Shaw, Cassidy H; Mazik, Patricia M

    2017-10-01

    Biological markers (biomarkers) sensitive to genotoxic and mutagenic contamination in fishes are widely used to identify exposure effects in aquatic environments. The micronucleus assay was incorporated into a suite of indicators to assess exposure to genotoxic and mutagenic contamination at five Great Lakes Areas of Concern (AOCs), as well as one non-AOC (reference) site. The assay allowed enumeration of micronuclei as well as other nuclear abnormalities for both site and species comparisons. Erythrocyte abnormality data was also compared to skin and liver tumor prevalence and hepatic transcript abundance. Erythrocyte abnormalities were observed at all sites with variable occurrence and severity among sites and species. Benthic-oriented brown bullhead (Ameiurus nebulosus) and white sucker (Catostomus commersonii) expressed lower rates of erythrocyte abnormalities, but higher rates of skin and liver neoplasms, when compared to pelagic-oriented largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) at the same site. The reduced erythrocyte abnormalities, increased transcript abundance associated with Phase I and II toxicant responsive pathways, and increased neoplastic lesions among benthic-oriented taxa may indicate the development of contaminant resistance of these species to more acute effects. Environ. Mol. Mutagen. 58:570-581, 2017. © 2017 This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

  1. Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill.

    PubMed Central

    Chung, K S; Madar, D A; Goldsmith, J C; Kingdon, H S; Roberts, H R

    1978-01-01

    Human Factor IX (Christmas factor) was isolated from the plasma of a patient with mild hemophilia B. The patient's plasma contained 5% Factor IX clotting activity but 100% Factor IX antigenic activity as determined by immunological assays, which included inhibitor neutralization and a radioimmunoassay for Factor IX. This abnormal Factor IX is called Factor IX Chapel Hill (Factor IXCH). Both normal Factor IX and Factor IXCH have tyrosine as the NH2-terminal amino acid. The two proteins have a similar molecular weight, a similar amino acid analysis, the same number of gamma-carboxyglutamic acid residues (10 gamma-carboxyglutamic acid residues), and a similar carbohydrate content. Both exist as a single-chain glycoprotein in plasma. The major difference between normal Factor IX and Factor IXCH is that the latter exhibits delayed activation to Factor IXa in the presence of Factor XIa and Ca2+. Thus, Factor IXCH differs from other previously described abnormal Factor IX molecules. Images PMID:711853

  2. Neurotoxicity produced by dibromoacetic acid in drinking water of rats.

    PubMed

    Moser, V C; Phillips, P M; Levine, A B; McDaniel, K L; Sills, R C; Jortner, B S; Butt, M T

    2004-05-01

    An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids.

  3. Continuous animal exposure to dichloromethane

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.; Haun, C. C.

    1972-01-01

    Continuous exposures of dogs, monkeys, rats and mice to 5000 ppm and 1000 ppm of dichloromethane vapor (CH2Cl2) produced severe toxic effects on dogs, rats and mice. Dogs died after 3 weeks exposure to 1000 ppm and after 6 weeks exposure to 5000 ppm. Thirty percent of the mice also succumbed during four weeks exposure to 5000 ppm CH2Cl2. Although rats survived 14 weeks exposure to 5000 ppm, they experienced subnormal weight gains. Significant gross and histopathological hepatic lesions were noted in all 3 species at death or experimental termination in 14 weeks. In addition, rats showed abnormal kidney histopathology. Fat stains disclosed mild fatty increase in monkey livers after 14 weeks exposure to 1000 ppm CH2Cl2.

  4. Acid-base metabolism: implications for kidney stones formation.

    PubMed

    Hess, Bernhard

    2006-04-01

    The physiology and pathophysiology of renal H+ ion excretion and urinary buffer systems are reviewed. The main focus is on the two major conditions related to acid-base metabolism that cause kidney stone formation, i.e., distal renal tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid stone formation. Both the entities can be seen on the background of disturbances of the major urinary buffer system, NH3+ <--> NH4+. On the one hand, reduced distal tubular secretion of H+ ions results in an abnormally high urinary pH and either incomplete or complete dRTA. On the other hand, reduced production/availability of NH4+ is the cause of an abnormally low urinary pH, which predisposes to uric acid stone formation. Most recent research indicates that the latter abnormality may be a renal manifestation of the increasingly prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH values, both the dRTA and uric acid stone formation due to low urinary pH require the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the body's buffer capacity, whereas the goal of alkali treatment in uric acid stone formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid crystallization.

  5. (2-methoxyethoxy)acetic acid: a urinary biomarker of exposure for jet fuel JP-8.

    PubMed

    B'hymer, Clayton; Mathias, Patricia; Krieg, Edward; Cheever, Kenneth L; Toennis, Christine A; Clark, John C; Kesner, James S; Gibson, Roger L; Butler, Mary Ann

    2012-05-01

    To demonstrate the utility of the urinary metabolite (2-methoxyethoxy)acetic acid (MEAA) as a biomarker of exposure. 2-(2-methoxyethoxy)ethanol [diethylene glycol monomethyl ether] is an anti-icing agent used in the formulation of JP-8, and it is added at a known uniform 0.1% (v/v) concentration to each batch lot. JP-8 is a kerosene-based fuel containing different compounds that vary in the content of every batch/lot of fuel; thus, MEAA has the potential to be a more specific and a consistent quantitative biomarker for JP-8 exposure. MEAA was used to measure exposure of jet propulsion fuel 8 (JP-8) in United States Air Force (USAF) personnel working at six airbases within the United States. Post-shift urine specimens from various personnel including high (n = 98), moderate (n = 38), and low (n = 61) exposure workgroup categories were collected and analyzed by a gas chromatographic-mass spectrometric test method. The three exposure groups were evaluated for the number per group positive for MEAA, and a statistical analysis consisted of pair-wise t-tests for unequal variances was used to test for the differences in mean MEAA concentrations between the exposure groups. The number of samples detected as positive for MEAA exposure, that is, those above the test method's limit of detection (LOD = 0.1 μg/ml), were 92 (93.9%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure workgroup categories, respectively. The mean urinary MEAA level was significantly greater in the high exposure category (6.8 μg/ml), compared to the moderate (0.42 μg/ml) and the low (0.07 μg/ml) exposure categories. The maximum concentration of urinary MEAA was 110 μg/ml for the high exposure category, while 4.8 μg/ml and 0.2 μg/ml maximum levels were found in the moderate and low exposure categories, respectively. This study demonstrated that urinary MEAA can be used as an accurate biomarker of exposure for JP-8 workers and clearly distinguished the differences in JP-8

  6. The effect of duration of exposure on sulfuric acid-induced pulmonary function changes in asthmatic adolescent subjects: A dose-response study

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

    Koenig, J.Q.; Covert, D.S.; Larson, T.V.

    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). Themore » 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.« less

  7. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  8. Abnormal Uterine Bleeding

    MedlinePlus

    ... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

  9. Use of Virtual Reality Technology to Enhance Undergraduate Learning in Abnormal Psychology

    ERIC Educational Resources Information Center

    Stark-Wroblewski, Kim; Kreiner, David S.; Boeding, Christopher M.; Lopata, Ashley N.; Ryan, Joseph J.; Church, Tina M.

    2008-01-01

    We examined whether using virtual reality (VR) technology to provide students with direct exposure to evidence-based psychological treatment approaches would enhance their understanding of and appreciation for such treatments. Students enrolled in an abnormal psychology course participated in a VR session designed to help clients overcome the fear…

  10. 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

  11. 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...

  12. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).

    PubMed

    Wozniak, Jeffrey R; Mueller, Bryon A; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Sowell, Elizabeth R

    2017-10-01

    Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

  14. Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects.

    PubMed

    Kessing, B F; Smout, A J P M; Bennink, R J; Kraaijpoel, N; Oors, J M; Bredenoord, A J

    2014-08-01

    The 5-HT4 receptor agonist prucalopride is a prokinetic drug which improves colonic motility. Animal data and in vitro studies suggest that prucalopride also affects gastric and esophageal motor function. We aimed to assess the effect of prucalopride on gastric emptying, esophageal motility, and gastro-esophageal reflux in man. In this double-blind, placebo-controlled, randomized, crossover study, we included 21 healthy volunteers who received 4 mg prucalopride or placebo per day for 6 days. We performed high-resolution manometry (HRM) followed by 120-min HRM-pH-impedance monitoring after a standardized meal, ambulatory 24-h pH-impedance monitoring, and gastric emptying for solids. Prucalopride decreased (median [IQR]) total acid exposure time (3.4 [2.5-5.6] vs 1.7 [0.8-3.5] %, p < 0.05). The total number of reflux events was unaffected by prucalopride, however, the number of reflux events extending to the proximal esophagus was reduced by prucalopride (15.5 [9.8-25.5] vs 10.5 [5.3-17.5], p < 0.05). Furthermore, prucalopride improved acid clearance time (77.5 [47.8-108.8] vs 44.0 [30.0-67.8] s, p < 0.05). Prucalopride did not affect the number of transient lower esophageal sphincter (LES) relaxations or their association with reflux events. Esophageal motility and basal pressure of the LES were not affected by prucalopride. Prucalopride increased gastric emptying (T1/2 ; 32.7 [27.9-44.6] vs 49.8 [37.7-55.0] min, p < 0.05) and decreased residue after 120 min (8.8 [4.4-14.8] vs 2.7 [1.3-5.4] %, p < 0.05). Prucalopride reduces esophageal acid exposure and accelerates gastric emptying in healthy male volunteers. These findings suggest that the drug could be effective for treatment of patients with reflux disease and functional dyspepsia. © 2014 John Wiley & Sons Ltd.

  15. 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.

  16. 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).

  17. Nervous system disruption and concomitant behavioral abnormality in early hatched pufferfish larvae exposed to heavy oil.

    PubMed

    Kawaguchi, Masahumi; Sugahara, Yuki; Watanabe, Tomoe; Irie, Kouta; Ishida, Minoru; Kurokawa, Daisuke; Kitamura, Shin-Ichi; Takata, Hiromi; Handoh, Itsuki C; Nakayama, Kei; Murakami, Yasunori

    2011-08-01

    Spills of heavy oil (HO) over the oceans have been proven to have an adverse effect on marine life. It has been hypothesized that exposure of early larvae of sinking eggs to HO leads largely to normal morphology, whereas abnormal organization of the developing neural scaffold is likely to be found. HO-induced disruption of the nervous system, which controls animal behavior, may in turn cause abnormalities in the swimming behavior of hatched larvae. To clarify the toxicological effects of HO, we performed exposure experiments and morphological and behavioral analyses in pufferfish (Takifugu rubripes) larvae. Fertilized eggs of pufferfish were exposed to 50 mg/L of HO for 8 days and transferred to fresh seawater before hatching. The hatched larvae were observed for their swimming behavior, morphological appearance, and construction of muscles and nervous system. In HO-exposed larvae, we did not detect any anomaly of body morphology. However, they showed an abnormal swimming pattern and disorganized midbrain, a higher center controlling movement. Our results suggest that HO-exposed fishes suffer developmental disorder of the brain that triggers an abnormal swimming behavior and that HO may be selectively toxic to the brain and cause physical disability throughout the life span of these fishes.

  18. 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.

  19. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

    PubMed Central

    Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr -/- and in utero TCDD-exposed Ahr +/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr -/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  20. Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid.

    PubMed

    Kim, Pitna; Park, Jin Hee; Kwon, Kyoung Ja; Kim, Ki Chan; Kim, Hee Jin; Lee, Jong Min; Kim, Hahn Young; Han, Seol-Heui; Shin, Chan Young

    2013-01-01

    Ginseng is one of the most widely used medicinal plants, which belongs to the genus Panax. Compared to uncured white ginseng, red ginseng has been generally regarded to produce superior pharmacological effects with lesser side/adverse effects, which made it popular in a variety of formulation from tea to oriental medicine. Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring. VPA-induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng (KRG) in a dose dependent manner. Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open-field test. KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level. These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities of glucose and uric acid metabolisms.

    PubMed

    Zhang, Jian-Liang; Yu, Hui; Hou, Ying-Wei; Wang, Ke; Bi, Wen-Shan; Zhang, Liang; Wang, Qian; Li, Pan; Yu, Man-Li; Zhao, Xian-Xian

    2018-04-01

    Treatment of hypertension with thiazide diuretics may trigger hypokalemia, hyperglycemia, and hyperuricemia. Some studies suggest simultaneous potassium supplementation in hypertensive patients using thiazide diuretics. However, few clinical studies have reported the impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities in blood glucose and uric acid (UA) metabolisms. One hundred hypertensive patients meeting the inclusion criteria were equally randomized to two groups: IND group receiving indapamide (1.25-2.5 mg daily) alone, and IND/KCI group receiving IND (1.25-2.5 mg daily) plus potassium chloride (40 mmol daily), both for 24 weeks. At the end of 24-week follow-up, serum K + level in IND group decreased from 4.27 ± 0.28 to 3.98 ± 0.46 mmol/L (P < 0.001), and fasting plasma glucose (FPG) and UA increased from 5.11 ± 0.52 to 5.31 ± 0.57 mmol/L (P < 0.05), and from 0.404 ± 0.078 to 0.433 ± 0.072 mmol/L (P < 0.05), respectively. Serum K + level in IND/KCl group decreased from 4.27 ± 0.36 to 3.89 ± 0.28 mmol/L (P < 0.001), and FPB and UA increased from 5.10 ± 0.41 to 5.35 ± 0.55 mmol/L (P < 0.01), and from 0.391 ± 0.073 to 0.457 ± 0.128 mmol/L (P < 0.001), respectively. The difference value between the serum K + level and FPG before and after treatment was not statistically significant between the two groups. However, the difference value in UA in IND/KCl group was significantly higher than that in IND group (0.066 (95% confidence interval (CI): 0.041-0.090)  mmol/L vs. 0.029 (95% CI: 0.006-0.058) mmol/L, P < 0.05). The results showed that long-term routine potassium supplementation could not prevent or attenuate thiazide diuretic-induced abnormalities of glucose metabolism in hypertensive patients; rather, it may aggravate the UA metabolic abnormality.

  2. Esophageal hypermotility: cause or effect?

    PubMed

    Crespin, O M; Tatum, R P; Yates, R B; Sahin, M; Coskun, K; Martin, A V; Wright, A; Oelschlager, B K; Pellegrini, C A

    2016-07-01

    Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients' symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring

  3. Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury

    PubMed Central

    Mo, Yiqun; Chen, Jing; Humphrey, David M.; Fodah, Ramy A.; Warawa, Jonathan M.

    2014-01-01

    Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium. PMID:25398987

  4. Nanosecond pulsed electric field suppresses development of eyes and germ cells through blocking synthesis of retinoic acid in Medaka (Oryzias latipes).

    PubMed

    Shiraishi, Eri; Hosseini, Hamid; Kang, Dong K; Kitano, Takeshi; Akiyama, Hidenori

    2013-01-01

    Application of nanosecond pulsed electric fields (nsPEFs) has attracted rising attention in various scientific fields including medical, pharmacological, and biological sciences, although its effects and molecular mechanisms leading to the effects remain poorly understood. Here, we show that a single, high-intensity (10-30 kV/cm), 60-ns PEF exposure affects gene expression and impairs development of eyes and germ cells in medaka (Oryzias latipes). Exposure of early blastula stage embryos to nsPEF down-regulated the expression of several transcription factors which are essential for eye development, causing abnormal eye formation. Moreover, the majority of the exposed genetic female embryos showed a fewer number of germ cells similar to that of the control (unexposed) genetic male at 9 days post-fertilization (dpf). However, all-trans retinoic acid (atRA) treatment following the exposure rescued proliferation of germ cells and resumption of normal eye development, suggesting that the phenotypes induced by nsPEF are caused by a decrease of retinoic acid levels. These results confirm that nsPEFs induce novel effects during embryogenesis in medaka.

  5. Perfluorooctanoic acid exposure induces endoplasmic reticulum stress in the liver and its effects are ameliorated by 4-phenylbutyrate.

    PubMed

    Yan, Shengmin; Zhang, Hongxia; Wang, Jianshe; Zheng, Fei; Dai, Jiayin

    2015-10-01

    Perfluoroalkyl acids (PFAAs) are a group of widely used anthropogenic compounds. As one of the most dominant PFAAs, perfluorooctanoic acid (PFOA) has been suggested to induce hepatotoxicity and several other toxicological effects. However, details on the mechanisms for PFOA-induced hepatotoxicity still need to be elucidated. In this study, we observed the occurrence of endoplasmic reticulum (ER) stress in mouse livers and HepG2 cells after PFOA exposure using several familiar markers for the unfolded protein response (UPR). ER stress in HepG2 cells after PFOA exposure was not significantly influenced by autophagy inhibition or stimulation. The antioxidant defense system was significantly disturbed in mouse livers after PFOA exposure, and reactive oxygen species (ROS) were increased in cells exposed to PFOA for 24 h. However, N-acetyl-L-cysteine (NAC) pretreatment did not satisfactorily alleviate the UPR in cells exposed to PFOA even though the increase of ROS was less evident. Furthermore, exposure of HepG2 cells to PFOA in the presence of sodium 4-phenylbutyrate (4-PBA), a chemical chaperone and ER stress inhibitor, suggested that 4-PBA alleviated the UPR and autophagosome accumulation induced by PFOA in cells. In addition, several toxicological effects attributed to PFOA exposure, including cell cycle arrest, proteolytic activity impairment, and neutral lipid accumulation, were also improved by 4-PBA cotreatment in cells. In vivo study demonstrated that PFOA-induced lipid metabolism perturbation and liver injury were partially ameliorated by 4-PBA in mice after 28 days of exposure. These findings demonstrated that PFOA-induced ER stress leading to UPR might play an important role in PFOA-induced hepatotoxic effects, and chemical chaperone 4-PBA could ameliorate the effects. Copyright © 2015. Published by Elsevier Inc.

  6. Meiotic abnormalities

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

    NONE

    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.

  7. Induction of Salivary Proteins Modifies Measures of Both Orosensory and Postingestive Feedback during Exposure to a Tannic Acid Diet

    PubMed Central

    Torregrossa, Ann-Marie; Nikonova, Larissa; Bales, Michelle B.; Villalobos Leal, Maria; Smith, James C.; Contreras, Robert J.; Eckel, Lisa A.

    2014-01-01

    There are hundreds of proteins in saliva. Although it has long been hypothesized that these proteins modulate taste by interacting with taste receptors or taste stimuli, the functional impact of these proteins on feeding remains relatively unexplored. We have developed a new technique for saliva collection that does not interfere with daily behavioral testing and allows us to explore the relationship between feeding behavior and salivary protein expression. First, we monitored the alterations in salivary protein expression while simultaneously monitoring the animals' feeding behavior and meal patterns on a custom control diet or on the same diet mixed with 3% tannic acid. We demonstrated that six protein bands increased in density with dietary tannic acid exposure. Several of these bands were significantly correlated with behaviors thought to represent both orosensory and postingestive signaling. In a follow-up experiment, unconditioned licking to 0.01–3% tannic acid solutions was measured during a brief-access taste test before and after exposure to the tannic acid diet. In this experiment, rats with salivary proteins upregulated found the tannin solution less aversive (i.e., licked more) than those in the control condition. These data suggest a role for salivary proteins in mediating changes in both orosensory and postingestive feedback. PMID:25162297

  8. Abnormal branching and regression of the notochord and its relationship to foregut abnormalities.

    PubMed

    Vleesch Dubois, V N; Quan Qi, B; Beasley, S W; Williams, A

    2002-04-01

    An abnormally positioned notochord has been reported in embryos that develop foregut abnormalities, vertebral defects and other abnormalities of the VATER association. This study examines the patterns of regression of the abnormal notochord in the rat model of the VATER association and investigates the relationship between developmental abnormalities of the notochord and those of the vertebra and foregut. Timed-pregnant Sprague-Dawley rats were given daily intraperitoneal injections of 1.75 mg/kg adriamycin on gestational days 6 - 9 inclusive. Rats were sacrificed between days 14 and 20 and their embryos harvested, histologically sectioned and stained and examined serially. The location and appearance of the degenerating notochord and its relationship to regional structural defects were analysed. All 26 embryos exposed to adriamycin developed foregut abnormalities and had an abnormal notochord. The notochord disappeared by a process of apoptotic degeneration that lagged behind that of the normal embryo: the notochord persisted in the abnormal embryo beyond day 17, whereas in the normal rat it had already disappeared. Similarly, formation of the nucleus pulposus was delayed. Vertebral abnormalities occurred when the notochord was ventrally-positioned. The notochord disappears during day 16 in the normal embryo whereas abnormal branches of the notochord persist until day 19 in the adriamycin-treated embryo. Degeneration of the notochord is dominated by apoptosis. An excessively ventrally-placed notochord is closely associated with abnormalities of the vertebral column, especially hemivertebrae.

  9. Family, Friends, and Self: The Real-Life Context of an Abnormal Psychology Class.

    ERIC Educational Resources Information Center

    Connor-Greene, Patricia A.

    2001-01-01

    Presents results from a survey of students in two sections of an abnormal psychology course. Assessed the number of students who had firsthand exposure to a psychiatric disorder (friend, family member, or themselves), the nature of the relationship, the average number of personal relationships with people with psychiatric disorders, and the…

  10. HISTOPATHOLOGICAL ANALYSIS OF THE F344 RAT LUNG UPON EXPOSURE TO RETENOIC ACID, OVALBUMIN, MOLD SPORES AND CITRAL.

    PubMed

    Farah, Ibrahim O; Holt-Gray, Carlene; Cameron, Joseph A; Tucci, Michelle; Benghuzzi, Hamed

    2017-01-01

    The paradoxical role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of allergic and/or inflammatory complications in contrast to a therapeutic modality for lung pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function; a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2), in the reversal of retinoic acid, ovalbumin and allergic mold spore pathophysiology is also not well ascertained under an in vivo setting. Therefore, it is hypothesized that exposure of F344 lung tissues to supra-physiologic levels of retinoic acid, ovalbumin and mold spores individually or in combination with each other will lead to inflammatory tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoic acid have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate the histopathological implications of such exposure in vivo. This IACUC approved in vivo study used Fischer 344 rats ( n = 80 ; 229 to 273g), which were randomly assigned to controls as well as ovalbumin and mold-sensitized treatment groups (0.80 mg/kg and 1×10 9 mold spores combined from 4 strains/100 μl intra-tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent all four chemicals and mold spores treatments. Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light-dark cycle. A standard rodent diet and water access were provided ad libidum. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Slides were prepared and

  11. Auditory Brainstem Response (ABR) Abnormalities across the Life Span of Rats Prenatally Exposed to Alcohol

    PubMed Central

    Church, Michael W.; Hotra, John W.; Holmes, Pamela A.; Anumba, Jennifer I.; Jackson, Desmond A.; Adams, Brittany R.

    2011-01-01

    Background Fetal Alcohol Syndrome is a leading cause of neurodevelopmental impairments (NDI) in developed countries. Sensory deficits can play a major role in NDI, yet few studies have investigated the effects of prenatal alcohol exposure on sensory function. In addition, there is a paucity of information on the life-long effects of prenatal alcohol exposure. Thus, we sought to investigate the effects of prenatal alcohol exposure on auditory function across the life span in an animal model. Based on prior findings with prenatal alcohol exposure and other forms of adverse prenatal environments, we hypothesized that animals prenatally exposed to alcohol would show an age-dependent pattern of (A) hearing and neurological abnormalities as post-weanling pups, (B) a substantial dissipation of such abnormalities in young adulthood, and (C) a resurgence of such abnormalities in middle-aged adulthood. Method Pregnant rats were randomly assigned to an untreated control (CON), a pair-fed control (PFC) or an alcohol treated group (ALC). The ALC dams were gavaged with 6 mg/kg alcohol daily from gestation day (GD) 6 to 21. The PFC dams were gavaged daily from GD6-21 with an isocaloric and isovolumetric water-based solution of Maltose-Dextrins and pair-fed to the ALC dams. The CON dams were the untreated group to which the ALC and CON groups were compared. Hearing and neurological functions in the offspring were assessed with the Auditory Brainstem Response (ABR) at the postnatal ages of 22, 220 and 520 days of age. Results & Conclusions In accord with our hypothesis, ABR abnormalities were first observed in the post-weanling pups, largely dissipated in young adulthood, and then resurged in middle-aged adulthood. This age-related pattern suggests that the ALC pups had a developmental delay that dissipated in young adulthood and an enhanced age-related deterioration that occurred in middle-aged adulthood. Such a pattern is consistent with the fetal programming hypothesis of adult

  12. Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3.

    PubMed

    Jiang, Yi-Ming; Huang, Chen; Peng, Zhong; Han, Shao-Ling; Li, Wei-Guang; Zhu, Michael Xi; Xu, Tian-Le

    2017-01-01

    Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SL-NH 2 ) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH 2 to the same site. Notably, co-application of acid and SL-NH 2 following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis.

  13. Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3

    PubMed Central

    Jiang, Yi-Ming; Huang, Chen; Peng, Zhong; Han, Shao-Ling; Li, Wei-Guang; Zhu, Michael Xi; Xu, Tian-Le

    2017-01-01

    Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH2 to the same site. Notably, co-application of acid and SL-NH2 following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis. PMID:28745101

  14. Effect of acid tolerance response (ATR) on attachment of Listeria monocytogenes Scott A to stainless steel under extended exposure to acid or/and salt stress and resistance of sessile cells to subsequent strong acid challenge.

    PubMed

    Chorianopoulos, Nikos; Giaouris, Efstathios; Grigoraki, Ioanna; Skandamis, Panagiotis; Nychas, George-John

    2011-02-28

    The aim of this study was to investigate the potential effect of adaptive stationary phase acid tolerance response (ATR) of Listeria monocytogenes Scott A cells on their attachment to stainless steel (SS) under low pH or/and high salt conditions and on the subsequent resistance of sessile cells to strong acid challenge. Nonadapted or acid-adapted stationary-phase L. monocytogenes cells were used to inoculate (ca. 10⁸ CFU/ml) Brain Heart (BH) broth (pH 7.4, 0.5% w/v NaCl) in test tubes containing vertically placed SS coupons (used as abiotic substrates for bacterial attachment). Incubation was carried out at 16 °C for up to 15 days, without any nutrient refreshment. L. monocytogenes cells, prepared as described above, were also exposed to low pH (4.5; adjusted with HCl) or/and high salt (5.5% w/v NaCl) stresses, during attachment. On the 5th, 10th and 15th day of incubation, cells attached to SS coupons were detached (through bead vortexing) and enumerated (by agar plating). Results revealed that ATR significantly (p<0.05) affected bacterial attachment, when the latter took place under moderate acidic conditions (pH 4.5, 0.5 or 5.5% w/v NaCl), with the acid-adapted cells adhering slightly more than the nonadapted ones. Regardless of acidity/salinity conditions during attachment, ATR also enhanced the resistance of sessile cells to subsequent lethal acid challenge (exposure to pH 2 for 6 min; pH adjusted with either hydrochloric or lactic acid). The trend observed with viable count data agreed well with conductance measurements, used to indirectly quantify remaining attached bacteria (following the strong acid challenge) via their metabolic activity. To sum, this study demonstrates that acid adaptation of L. monocytogenes cells during their planktonic growth enhances their subsequent attachment to SS under extended exposure (at 16 °C for up to 15 days) to mild acidic conditions (pH 4.5), while it also improves the resistance of sessile cells to extreme acid

  15. Symptomatic benign pleural effusions among asbestos insulation workers: residual radiographic abnormalities.

    PubMed Central

    Lilis, R; Lerman, Y; Selikoff, I J

    1988-01-01

    During a cross sectional medical survey of 2815 insulation workers with 30 years or more from onset of asbestos exposure conducted from 1981 to 1983, a positive history of benign pleural effusion was found in 20 (0.71%). Two or three such episodes had occurred in four of these 20 subjects. The chest x ray abnormalities in these cases were characterised by pleural fibrosis in 19 and diffuse pleural fibrosis with blunting of the corresponding costophrenic angle in 16. In the total group of 2815 insulation workers diffuse pleural fibrosis was found in 142 (5.0%). Thus diffuse pleural fibrosis with blunting of the corresponding costophrenic angle is a frequent residual abnormality after benign pleural effusion. Its impact on pulmonary function can be pronounced. Images PMID:3260799

  16. The effect of time in the exposure of theobromine gel to enamel and surface hardness after demineralization with 1% citric acid

    NASA Astrophysics Data System (ADS)

    Irawan, M. I. P.; Noerdin, A.; Eriwati, Y. K.

    2017-08-01

    Theobromine is one of the alkaloid compounds that can be found in cacao (Theobroma cacao). It is said that theobromine can prevent enamel demineralization. The aim of this research was to evaluate the effect of different exposure times to 200 mg/L theobromine gel on enamel microhardness after demineralization in 1% citric acid. Twenty-eight specimens of human premolar teeth were divided into four groups and were immersed in 1% citric acid (pH 4) for 2.5 minutes. Then 200 mg/L theobromine gel was exposed to the specimens for 16 minutes (n = 7), 48 minutes (n = 7), and 96 minutes (n = 7). Enamel microhardness (KHN) values were tested using the Knoop Microhardness Tester (Shimadzu, Japan) using a 50-gram load for 5 seconds. A statistical test was performed using the Friedman test, Wilcoxon test, Kruskal-Wallis test, and Mann-Whitney test. The results showed a significant decrease, of microhardness values after demineralization with 1% citric acid. There was also a significant increase in hardness (p<0.05) after exposure of the demineralized specimens to theobromine gel for 16 minutes (32.3%), 48 minutes (39.8%), and 96 minutes (43.7%). It can be concluded that exposure to 200 mg/L theobromine gel for 16, 48, and 96 minutes increased enamel microhardness.

  17. Effect of one anesthetic exposure on long-term behavioral changes in children.

    PubMed

    Chemaly, Maen; El-Rajab, Mariam A; Ziade, Fouad M; Naja, Zoher M

    2014-11-01

    To determine the association between one anesthetic exposure and behavioral outcome at age 10 to 12 years. Retrospective comparative study. University-affiliated pediatrics department. The medical records of children who underwent anesthesia between January 2004 and December 2005 at our institution were reviewed. The records of 292 children were included in the study group and 300 children in the control group. The study group involved children who had one anesthetic exposure before age of 4 years and the control group had children who were not exposed to anesthesia. The primary outcome was behavioral change as assessed by the Eyberg Child Behavior Inventory (ECBI) questionnaire. The rate of behavioral abnormalities before the age of 11 years was 28.4% in the study group (P<0.001) and 5.7% in the control group. The risk of developing behavioral abnormalities was prominent in children being exposed to surgery versus those exposed during a diagnostic procedure (32.4% vs 4.8%; P<0.0001). Eighty-three point nine percent of the children who were exposed to longer duration anesthesia (more than 3 hrs) had behavioral abnormalities (P<0.0001), while 48.8% of children who received anesthesia at younger ages (0 - 6 mos) had behavioral abnormalities (P<0.0001). Exposure to multiple anesthetic agents versus one anesthetic agent was a significant risk factor for development of behavioral abnormalities (P<0.0001). The incidence of behavioral abnormalities increased when anesthesia and surgery were accompanied by younger age, longer duration of surgery, and use of multiple anesthetic agents. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury.

    PubMed

    Mo, Yiqun; Chen, Jing; Humphrey, David M; Fodah, Ramy A; Warawa, Jonathan M; Hoyle, Gary W

    2015-01-15

    Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium. Copyright © 2015 the American Physiological Society.

  19. Toxicological studies on pipemidic acid. V. Effect on diarthrodial joints of experimental animals.

    PubMed

    Tatsumi, H; Senda, H; Yatera, S; Takemoto, Y; Yamayoshi, M; Ohnishi, K

    1978-11-01

    Pipemidic acid (PPA) orally given in a dose of 100 mg/kg/day or more was found to cause lame gait in immature beagle dogs of about 3 months old. Their diarthrodial joints were abnormal with increased synovial fluid and blister formation under the outer layer of the articular cartilage. However, such an abnormality was not found in dogs younger than 2 weeks or older than 12 months. The blisters were formed at the joint areas bearing the body weight at a time when PPA was considered to be present there. Nalidixic and piromidic acids, structural analogues of PPA, also caused abnormality similar to PPA. The severity of the arthropathy was slight with piromidic acid as compared with PPA and nalidixic acid. The gait abnormality was almost disappeared spontaneously even if medication was continued. The incidence of the arthropathy was not or rarely observed in any young rats, rabbits and monkeys.

  20. Sampling and analysis of hexavalent chromium during exposure to chromic acid mist and welding fumes.

    PubMed

    Blomquist, G; Nilsson, C A; Nygren, O

    1983-12-01

    Sampling and analysis of hexavalent chromium during exposure to chromic acid mist and welding fumes. Scand j work environ & health 9 (1983) 489-495. In view of the serious health effects of hexavalent chromium, the problems involved in its sampling and analysis in workroom air have been the subject of much concern. In this paper, the stability problems arising from the reduction of hexavalent to trivalent chromium during sampling, sample storage, and analysis are discussed. Replacement of sulfuric acid by a sodium acetate buffer (pH 4) as a leaching solution prior to analysis with the diphenylcarbazide (DPC) method is suggested and is demonstrated to be necessary in order to avoid reduction. Field samples were taken from two different industrial processes-manual metal arc welding on stainless steel without shield gas and chromium plating. A comparison was made of the DPC method, acidic dissolution with atomic absorption spectrophotometric (AAS) analysis, and the carbonate method. For chromic acid mist, the DPC method and AAS analysis were shown to give the same results. In the analysis of welding fumes, the modified DPC method gave the same results as the laborious and less sensitive carbonate method.

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

    PubMed Central

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

    2017-01-01

    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 (3.5 g/kg, i.p.), VPA (200 mg/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

  2. Changes on lipid peroxidation,enzymatic activities and gene expression in planarian (Dugesia japonica) following exposure to perfluorooctanoic acid.

    PubMed

    Yuan, Zuoqing; Miao, Zili; Gong, Xiaoning; Zhao, Baoying; Zhang, Yuanyuan; Ma, Hongdou; Zhang, Jianyong; Zhao, Bosheng

    2017-11-01

    We investigated perfluorooctanoic acid (PFOA)-induced stress response in planarians. We administered different concentrations of PFOA to planarians for up to 10 d. PFOA exposure resulted in significant concentration-dependent elevations in lipid peroxidation, glutathione S-transferase and caspase-3 protease activities, and a significant decline in glutathione peroxidase activities compared with control groups. Exposure to PFOA significantly up-regulated the heat shock proteins hsp70 and hsp90, and p53, and down-regulated hsp40 compared with controls. PFOA exposure also increased HSP70 protein levels, as demonstrated by western blot analysis. These alterations indicated that PFOA exposure induced a stress response and affected the regulation of oxidative stress, enzymatic activities and gene expression. These results suggest that these sensitive parameters, together with other biomarkers, could be used for evaluating toxicity, for ecological risk assessment of PFOA in freshwaters. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Evaluation of sampling methods for measuring exposure to volatile inorganic acids in workplace air. Part 1: sampling hydrochloric acid (HCl) and nitric acid (HNO₃) from a test gas atmosphere.

    PubMed

    Howe, Alan; Musgrove, Darren; Breuer, Dietmar; Gusbeth, Krista; Moritz, Andreas; Demange, Martine; Oury, Véronique; Rousset, Davy; Dorotte, Michel

    2011-08-01

    Historically, workplace exposure to the volatile inorganic acids hydrochloric acid (HCl) and nitric acid (HNO(3)) has been determined mostly by collection on silica gel sorbent tubes and analysis of the corresponding anions by ion chromatography (IC). However, HCl and HNO(3) can be present in workplace air in the form of mist as well as vapor, so it is important to sample the inhalable fraction of airborne particles. As sorbent tubes exhibit a low sampling efficiency for inhalable particles, a more suitable method was required. This is the first of two articles on "Evaluation of Sampling Methods for Measuring Exposure to Volatile Inorganic Acids in Workplace Air" and describes collaborative sampling exercises carried out to evaluate an alternative method for sampling HCl and HNO(3) using sodium carbonate-impregnated filters. The second article describes sampling capacity and breakthrough tests. The method was found to perform well and a quartz fiber filter impregnated with 500 μL of 1 M Na(2)CO(3) (10% (m/v) Na(2)CO(3)) was found to have sufficient sampling capacity for use in workplace air measurement. A pre-filter is required to remove particulate chlorides and nitrates that when present would otherwise result in a positive interference. A GSP sampler fitted with a plastic cone, a closed face cassette, or a plastic IOM sampler were all found to be suitable for mounting the pre-filter and sampling filter(s), but care has to be taken with the IOM sampler to ensure that the sampler is tightly closed to avoid leaks. HCl and HNO(3) can react with co-sampled particulate matter on the pre-filter, e.g., zinc oxide, leading to low results, and stronger acids can react with particulate chlorides and nitrates removed by the pre-filter to liberate HCl and HNO(3), which are subsequently collected on the sampling filter, leading to high results. However, although there is this potential for both positive and negative interferences in the measurement, these are unavoidable

  4. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Volume 2. First Followup Examination Results.

    DTIC Science & Technology

    1987-10-01

    Ranch Hand Enlisted Flyers ... .......... ... R-14 R-1O Cross Tabulation of Pleurisy - (Abnormal, Total) by- Exposure Index Category-by-Age Category-by...by-Pack-Year Category for Ranch Hand Enlisted Groundcrew ........... .. R-19 R-15 Cross Tabulation of Pleurisy - (Abnormal, Total) by- Exposure Index

  5. Acetaminophen and Acetylsalicylic Acid Exposure in a Preterm Infant after Maternal Overdose.

    PubMed

    Pavlek, Leeann; Kraft, Monica; Simmons, Caitlyn; Ryan, Mary; Prusakov, Pavel; Campbell, Amanda; Brandehoff, Nicklaus; Ng, Patrick C; Russell, Jason; Ciciora, Steven L; Fathi, Omid

    2018-06-26

    Here, we review the case of a 26 1/7 weeks' gestation premature female infant born to a mother who intentionally ingested a large quantity of Tylenol, aspirin, quetiapine, and prenatal vitamins. The neonate subsequently had markedly elevated levels of both Tylenol and aspirin when checked on the first day of life. While overall clinically stable, the neonate did demonstrate coagulopathy as evidenced by abnormal coagulation studies. Both poison control and a pediatric gastroenterologist/hepatologist were consulted. She successfully tolerated a course of N-acetylcysteine; her subsequent Tylenol level was markedly decreased and the neonate exhibited no further effects of toxicity. The salicylate level decreased on its own accord. To our knowledge, this is the first report of a neonate at 26 weeks' gestation that has been successfully managed for supratherapeutic concentrations of acetaminophen and acetylsalicylic acid secondary to maternal ingestion. While rare, this case may serve as a reference for the effectiveness of N-acetylcysteine in premature infants in such instances. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Surface characterisation of ethylene propylene diene rubber upon exposure to aqueous acidic solution

    NASA Astrophysics Data System (ADS)

    Mitra, Susanta; Ghanbari-Siahkali, Afshin; Kingshott, Peter; Hvilsted, Søren; Almdal, Kristoffer

    2006-07-01

    Two types of pure ethylene propylene diene rubbers were exposed to two different acids for varying period of time. Surface characterisation was carried out using X-ray photoelectron spectroscopy (XPS). Two EPDM rubbers selected for this study were comparable in co-monomer compositions but significantly different with respect to molar mass and the presence of long chain branching. Both rubbers contained 5-ethylidene-2-norbornene (ENB) as diene. Solution cast films of pure EPDM samples were exposed in two different acidic solutions, viz. chromosulphuric (Cr (VI)/H 2SO 4) and sulphuric acid (H 2SO 4) (20%, v/v) at ambient temperature from 1 to 12 weeks. XPS analysis indicated that several oxygenated species were formed on the surface of both rubbers after exposure. It was postulated from the XPS analyses that both aqueous acidic solutions attacked the olefinic double bonds (C dbnd C) of ENB. Furthermore, 20% Cr (VI)/H 2SO 4 also attacked the allylic carbon-hydrogen (C sbnd H) bonds of ENB resulting in more oxygenated species on the surface compared to 20% H 2SO 4 under identical conditions. Cr (VI) in the 20% Cr (VI)/H 2SO 4 was found to play an important role in alteration of surface chemistry. Studies using a model system consisting of EPDM mixed with Cr (VI) and Cr (III) salts revealed that the change of oxidation state from Cr (VI) to Cr (III) as a consequence of direct involvement of Cr (VI) in the chemical alteration of EPDM surfaces. Interestingly, the presence of long chain branching and molar mass did not significantly influence the chemical processes owing to the acid treatment.

  7. Radiographic abnormalities and the risk of lung cancer among workers exposed to silica dust in Ontario.

    PubMed Central

    Finkelstein, M M

    1995-01-01

    OBJECTIVE: To determine whether workers in Ontario who had been exposed to silica dust and who have radiographic abnormalities are at increased risk of lung cancer. DESIGN: Cohort and case-control studies of rates of death from lung cancer and cancer incidence rates; data were obtained from the Ontario Silicosis Surveillance Registry. Follow-up was through linkage to the Ontario mortality and cancer registries. SETTING: Ontario. PARTICIPANTS: A total of 523 workers with radiographic abnormalities and 1568 control subjects with normal radiographic findings who had been exposed to silica dust. Matching criteria were year of birth and the requirement that the control subject have a normal radiographic finding either later than or in the same year that the radiographic abnormality was identified in the silicosis subject. OUTCOME MEASURES: Standardized mortality ratios (SMRs), standardized incidence ratios (SIRs) and odds ratios for lung cancer. RESULTS: In the cohort analysis, with the Ontario population rates as reference, the all-cause SMR was 0.96 among the workers with radiographic abnormalities and 0.51 among the control subjects. The corresponding SIRs for lung cancer were 2.49 and 0.87 (p < 0.001). In the case-control analysis the workers with silicosis were more likely than the control subjects to have been smokers, but this difference likely accounted for only a small part of the difference in the incidence of lung cancer. The relative risk of lung cancer was elevated among the workers with silicosis from the foundry, mining and nonmetallic-minerals industries; however, the number of subjects was too small for a significant difference to be detected. Among the miners exposure to radon daughters did not affect the risk of lung cancer attributable to radiographic abnormalities. CONCLUSIONS: Radiographic abnormalities suggestive of exposure to silica dust are markers for increased risk of lung cancer. Physicians might thus wish to warn their patients with silica

  8. Embryonic exposure to propylthiouracil disrupts left-right patterning in Xenopus embryos.

    PubMed

    van Veenendaal, Nicole R; Ulmer, Bärbel; Boskovski, Marko T; Fang, Xiefan; Khokha, Mustafa K; Wendler, Christopher C; Blum, Martin; Rivkees, Scott A

    2013-02-01

    Antithyroid medications are the preferred therapy for the treatment of Graves' disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole (MMI) due to potential teratogenic concerns with MMI. This study was to determine the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or vehicle control (water) from stages 2 to 45. Treated embryos were examined for gross morphological defects, ciliary function, and gene expression by in situ hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping defects and shortening along the anterior-posterior axis. PTU exposure during gastrulation (stage 8-12.5) was identified as the critical period of exposure leading to left-right (LR) patterning defects. Abnormal cilia polarization, abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and aberrant expression of both Coco and Pitx2c were associated with abnormal LR symmetry observed following PTU exposure. PTU is teratogenic during late blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary-driven flow and disrupts the normal genetic program involved in LR axis determination. These studies have important implications for women taking PTU during early pregnancy.

  9. DEVELOPMENTAL NEUROTOXICITY FOLLOWING NEONATAL EXPOSURE TO 3,3'-IMINODIPROPIONITRILE IN THE RAT

    EPA Science Inventory

    Adult exposure to the neurotoxicant 3,3'-iminodipropionitrile (IDPN) induces a hyperkinetic syndrome consisting of spontaneous head movements, abnormal circling, backwards locomotion, and sensory disruption. e report here the behavioral effects of developmental exposure to IDPN i...

  10. Ursolic acid improves podocyte injury caused by high glucose.

    PubMed

    Xu, Li; Fan, Qiuling; Wang, Xu; Li, Lin; Lu, Xinxing; Yue, Yuan; Cao, Xu; Liu, Jia; Zhao, Xue; Wang, Lining

    2017-08-01

    Autophagy plays an important role in the maintenance of podocyte homeostasis. Reduced autophagy may result in limited renal cell function during exposure to high glucose conditions. In this study we investigated the effects of ursolic acid (UA) on autophagy and podocyte injury, which were induced by high glucose. Conditionally immortalized murine podocytes were cultured in media supplemented with high glucose and the effects of the PI3K inhibitor LY294002 and UA on protein expression were determined. miR-21 expression was detected by real-time RT-PCR. Activation of the PTEN-PI3K/Akt/mTOR pathway, expression of autophagy-related proteins and expression of podocyte marker proteins were determined by western blot. Immunofluorescence was used to monitor the accumulation of LC3 puncta. Autophagosomes were also observed by transmission electron microscopy. During exposure to high glucose conditions, the normal level of autophagy was reduced in podocytes, and this defective autophagy induced podocyte injury. Increased miR-21 expression, decreased PTEN expression and abnormal activation of the PI3K/Akt/mTOR pathway were observed in cells that were cultured in high glucose conditions. UA and LY294002 reduced podocyte injury through the restoration of defective autophagy. Our data suggest that UA inhibits miR-21 expression and increases PTEN expression, which in turn inhibits Akt and mTOR and restores normal levels of autophagy. Our data suggest that podocyte injury is associated with reduced levels of autophagy during exposure to high glucose conditions, UA attenuated podocyte injury via an increase in autophagy through miR-21 inhibition and PTEN expression, which inhibit the abnormal activation of the PI3K/Akt/mTOR pathway. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  11. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...

  12. Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

    PubMed

    Zimmer, Alex M; Wood, Chris M

    2014-01-01

    The effects of acute moderate (20% air O2 saturation; 6-h exposure) and severe (5% air O2 saturation; 4-h exposure) hypoxia on N-waste, acid-base, and ion balance in dogfish sharks (Squalus acanthias suckleyi) were evaluated. We predicted that the synthesis and/or retention of urea, which are active processes, would be inhibited by hypoxia. Exposure to moderate hypoxia had negligible effects on N-waste fluxes or systemic physiology, except for a modest rise in plasma lactate. Exposure to severe hypoxia led to a significant increase in urea excretion (Jurea), while plasma, liver, and muscle urea concentrations were unchanged, suggesting a loss of urea retention. Ammonia excretion (Jamm) was elevated during normoxic recovery. Moreover, severe hypoxia led to disruptions in acid-base balance, indicated by a large increase in plasma [lactate] and substantial decreases in arterial pHa and plasma [Formula: see text], as well as loss of ionic homeostasis, indicated by increases in plasma [Mg(2+)], [Ca(2+)], and [Na(+)]. We suggest that severe hypoxia in dogfish sharks leads to a reduction in active gill homeostatic processes, such as urea retention, acid-base regulation and ionoregulation, and/or an osmoregulatory compromise due to increased functional gill surface area. Overall, the results provide a comprehensive picture of the physiological responses to a severe degree of hypoxia in an ancient fish species.

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

    PubMed

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

    2017-01-01

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

  14. An Analysis of Sound Exposure in a University Music Rehearsal

    ERIC Educational Resources Information Center

    Farmer, Joe; Thrasher, Michael; Fumo, Nelson

    2014-01-01

    Exposure to high sound levels may lead to a variety of hearing abnormalities, including Noise-Induced Hearing Loss (NIHL). Pre-professional university music majors may experience frequent exposure to elevated sound levels, and this may have implications on their future career prospects (Jansen, Helleman, Dreschler & de Laat, 2009). Studies…

  15. Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans.

    PubMed

    Deline, Marshall; Keller, Julia; Rothe, Michael; Schunck, Wolf-Hagen; Menzel, Ralph; Watts, Jennifer L

    2015-10-21

    Dietary fats are not created equally, slight differences in structure lead to crucial differences in function. Muticellular organisms use polyunsaturated fatty acid as substrates to produce potent signaling molecules crucial for many physiological processes, including reproduction. Here we explored the mechanism responsible for germ cell loss induced by dietary supplementation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6) in the roundworm Caenorhabditis elegans. In this study we found that C. elegans CYP-33E2 activity produces a range of epoxy and hydroxy metabolites from dietary DGLA. Knockdown of cyp-33E2 suppressed the DGLA-induced sterility phenotype. Additionally, direct exposure of two specific DGLA-derived epoxy products, 8,9- and 14,15-epoxyeicosadienoic acids, produced germ cell abnormalities in the C. elegans gonad. We propose that sterility is mediated by the production of toxic DGLA-derived epoxides that trigger germ cell destruction. These studies are the first to establish a biological activity for a CYP-produced metabolite of DGLA.

  16. Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.

    PubMed

    Schmidt, Rebecca J; Kogan, Vladimir; Shelton, Janie F; Delwiche, Lora; Hansen, Robin L; Ozonoff, Sally; Ma, Claudia C; McCanlies, Erin C; Bennett, Deborah H; Hertz-Picciotto, Irva; Tancredi, Daniel J; Volk, Heather E

    2017-09-08

    Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. In this study population, associations between

  17. Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder

    PubMed Central

    Kogan, Vladimir; Shelton, Janie F.; Delwiche, Lora; Hansen, Robin L.; Ozonoff, Sally; Ma, Claudia C.; McCanlies, Erin C.; Bennett, Deborah H.; Hertz-Picciotto, Irva; Tancredi, Daniel J.; Volk, Heather E.

    2017-01-01

    Background: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. Objective: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Methods: Participants were California children born from 2000–2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case–control study at age 2–5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003–2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers’ addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. Results: High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive

  18. Physiological effects and tissue residues from exposure of leopard frogs to commercial naphthenic acids.

    PubMed

    Smits, Judit E G; Hersikorn, Blair D; Young, Rozlyn F; Fedorak, Phillip M

    2012-10-15

    Naphthenic acids (NAs) have been cited as one of the main causes of the toxicity related to oil sands process-affected materials and have recently been measured in biological tissues (fish). However, adverse effects have not been a consistent finding in toxicology studies on vertebrates. This study set out to determine two factors: 1) whether exposure to commercial NAs (Refined Merichem) resulted in detectable tissue residues in native amphibians (northern leopard frogs, Lithobates pipiens), and 2) whether such exposure would produce clinical or subclinical toxicity. Frogs were kept in NA solutions (0, 20, or 40 mg/L) under saline conditions comparable to that on reclaimed wetlands in the Athabasca oil sands for 28 days. These exposures resulted in proportional NA concentrations in muscle tissue of the frogs, estimated by gas chromatography-mass spectrometry analyses. Detailed studies determined if the increasing concentrations of NAs, and subsequently increased tissue NA levels, caused a proportional compromise in the health of the experimental animals. Physiological investigations included innate immune function, thyroid hormone levels, and hepatic detoxification enzyme induction, none of which differed in response to increased exposures or tissue concentrations of NAs. Body mass did increase in both the salt- and NA-exposed animals, likely related to osmotic pressure and uptake of water through the skin. Our results demonstrate that commercial NAs are absorbed and deposited in muscle tissue, yet they show few negative physiological or toxicological effects on the frogs. Copyright © 2012. Published by Elsevier B.V.

  19. 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...

  20. Adult-onset glutaric aciduria type I presenting with white matter abnormalities and subependymal nodules.

    PubMed

    Pierson, T M; Nezhad, Mani; Tremblay, Matthew A; Lewis, Richard; Wong, Derek; Salamon, Noriko; Sicotte, Nancy

    2015-10-01

    A 55-year-old female presented with a 6-year history of paresthesias, incontinence, spasticity, and gait abnormalities. Neuroimaging revealed white matter abnormalities associated with subependymal nodules. Biochemical evaluation noted increased serum C5-DC glutarylcarnitines and urine glutaric and 3-hydroxyglutaric acids. Evaluation of the glutaryl-CoA dehydrogenase (GCDH) gene revealed compound heterozygosity consisting of a novel variant (c.1219C>G; p.Leu407Val) and pathogenic mutation (c.848delT; p.L283fs). Together, these results were consistent with a diagnosis of adult-onset type I glutaric aciduria.

  1. Urine - abnormal color

    MedlinePlus

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  2. Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

    NASA Technical Reports Server (NTRS)

    Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A 2nd; Lieberman, Michael W.; Karsenty, Gerard

    2003-01-01

    Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

  3. Effect of air breathing on acid-base and ion regulation after exhaustive exercise and during low pH exposure in the bowfin, Amia calva.

    PubMed

    Gonzalez, R J; Milligan, L; Pagnotta, A; McDonald, D G

    2001-01-01

    To explore a potential conflict between air breathing and acid-base regulation in the bowfin (Amia calva), we examined how individuals with access to air differed from fish without air access in their response to acidosis. After exhaustive exercise, bowfin with access to air recovered significantly more slowly from the acidosis than fish without air access. While arterial blood pH (pH(a)) of fish without air access recovered to resting levels by 8 h, pH(a) was still significantly depressed in fish having access to air. In addition, Pco(2) was slightly more elevated in fish having air access than those without it. Fish with access to air still had a significant metabolic acid load after 8-h recovery, while those without air access completely cleared the load within 4 h. These results suggest that bowfin with access to air were breathing air and, consequently, were less able to excrete CO(2) and H(+) and experienced a delayed recovery. In contrast, during exposure to low pH, air breathing seemed to have a protective effect on acid-base status in bowfin. During exposure to low pH water, bowfin with access to air developed a much milder acidosis than bowfin without air access. The more severe acidosis in fish without air access was caused by an increased rate of lactic acid production. It appears that enhanced O(2) delivery allowed air-breathing bowfin to avoid acidosis-induced anaerobic metabolism and lactic acid production. In addition, during low pH exposure, plasma Na(+) and Cl(-) concentrations of fish without air access fell slightly more rapidly than those in fish with air access, indicating that the branchial ventilatory changes associated with air breathing limited, to some degree, ion losses associated with low pH exposure.

  4. Light exposure during storage preserving soluble sugar and l-ascorbic acid content of minimally processed romaine lettuce (Lactuca sativa L.var. longifolia).

    PubMed

    Zhan, Lijuan; Hu, Jinqiang; Ai, Zhilu; Pang, Lingyun; Li, Yu; Zhu, Meiyun

    2013-01-01

    Minimally processed romaine lettuce (MPRL) leaves were stored in light condition (2500lux) or darkness at 4°C for 7d. Light exposure significantly delayed the degradation of chlorophyll and decrease of glucose, reducing sugar, and sucrose content, and thus preserved more total soluble solid (TSS) content at the end of storage in comparison with darkness. While, it did not influenced starch content that progressively decreased over time. The l-ascorbic acid (AA) accumulated in light-stored leaves, but deteriorated in dark-stored leaves during storage. The dehydroascorbic acid (DHA) increased in all leaves stored in both light and dark condition, of which light condition resulted in less DHA than darkness. In addition, the fresh weight loss and dry matter significantly increased and these increases were accelerated by light exposure. Conclusively, light exposure in applied intensity effectively alleviated MPRL quality deterioration by delaying the decreases of pigments, soluble sugar, TSS content and accumulating AA. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Reduction of Phosphorylated Synapsin I (Ser-553) Leads to Spatial Memory Impairment by Attenuating GABA Release after Microwave Exposure in Wistar Rats

    PubMed Central

    Qiao, Simo; Peng, Ruiyun; Yan, Haitao; Gao, Yabing; Wang, Changzhen; Wang, Shuiming; Zou, Yong; Xu, Xinping; Zhao, Li; Dong, Ji; Su, Zhentao; Feng, Xinxin; Wang, Lifeng; Hu, Xiangjun

    2014-01-01

    Background Abnormal release of neurotransmitters after microwave exposure can cause learning and memory deficits. This study investigated the mechanism of this effect by exploring the potential role of phosphorylated synapsin I (p-Syn I). Methods Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal) PC12 cells were exposed to microwave radiation for 5 min at a mean power density of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically treated and acted as controls for all of the following post-exposure analyses. Spatial learning and memory in rats was assessed using the Morris Water Maze (MWM) navigation task. The protein expression and presynaptic distribution of p-Syn I and neurotransmitter transporters were examined via western blotting and immunoelectron microscopy, respectively. Levels amino acid neurotransmitter release from rat hippocampal synaptosomes and PC12 cells were measured using high performance liquid chromatograph (HPLC) at 6 hours after exposure, with or without synapsin I silencing via shRNA transfection. Results In the rat experiments, there was a decrease in spatial memory performance after microwave exposure. The expression of p-Syn I (ser-553) was decreased at 3 days post-exposure and elevated at later time points. Vesicular GABA transporter (VGAT) was significantly elevated after exposure. The GABA release from synaptosomes was attenuated and p-Syn I (ser-553) and VGAT were both enriched in small clear synaptic vesicles, which abnormally assembled in the presynaptic terminal after exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553) and GABA release were both attenuated at 6 hours after exposure. Both microwave exposure and p-Syn I silencing reduced GABA release and maximal reduction was found for the combination of the two, indicating a synergetic effect. Conclusion p-Syn I (ser-553) was found to play a key role in the impaired GABA release and cognitive dysfunction that was

  6. Reduction of phosphorylated synapsin I (ser-553) leads to spatial memory impairment by attenuating GABA release after microwave exposure in Wistar rats.

    PubMed

    Qiao, Simo; Peng, Ruiyun; Yan, Haitao; Gao, Yabing; Wang, Changzhen; Wang, Shuiming; Zou, Yong; Xu, Xinping; Zhao, Li; Dong, Ji; Su, Zhentao; Feng, Xinxin; Wang, Lifeng; Hu, Xiangjun

    2014-01-01

    Abnormal release of neurotransmitters after microwave exposure can cause learning and memory deficits. This study investigated the mechanism of this effect by exploring the potential role of phosphorylated synapsin I (p-Syn I). Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal) PC12 cells were exposed to microwave radiation for 5 min at a mean power density of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically treated and acted as controls for all of the following post-exposure analyses. Spatial learning and memory in rats was assessed using the Morris Water Maze (MWM) navigation task. The protein expression and presynaptic distribution of p-Syn I and neurotransmitter transporters were examined via western blotting and immunoelectron microscopy, respectively. Levels amino acid neurotransmitter release from rat hippocampal synaptosomes and PC12 cells were measured using high performance liquid chromatograph (HPLC) at 6 hours after exposure, with or without synapsin I silencing via shRNA transfection. In the rat experiments, there was a decrease in spatial memory performance after microwave exposure. The expression of p-Syn I (ser-553) was decreased at 3 days post-exposure and elevated at later time points. Vesicular GABA transporter (VGAT) was significantly elevated after exposure. The GABA release from synaptosomes was attenuated and p-Syn I (ser-553) and VGAT were both enriched in small clear synaptic vesicles, which abnormally assembled in the presynaptic terminal after exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553) and GABA release were both attenuated at 6 hours after exposure. Both microwave exposure and p-Syn I silencing reduced GABA release and maximal reduction was found for the combination of the two, indicating a synergetic effect. p-Syn I (ser-553) was found to play a key role in the impaired GABA release and cognitive dysfunction that was induced by microwave exposure.

  7. In utero exposure to valproic acid and autism--a current review of clinical and animal studies.

    PubMed

    Roullet, Florence I; Lai, Jonathan K Y; Foster, Jane A

    2013-01-01

    Valproic acid (VPA) is both an anti-convulsant and a mood stabilizer. Clinical studies over the past 40 years have shown that exposure to VPA in utero is associated with birth defects, cognitive deficits, and increased risk of autism. Two recent FDA warnings related to use of VPA in pregnancy emphasize the need to reevaluate its use clinically during child-bearing years. The emerging clinical evidence showing a link between VPA exposure and both cognitive function and risk of autism brings to the forefront the importance of understanding how VPA exposure influences neurodevelopment. In the past 10 years, animal studies have investigated anatomical, behavioral, molecular, and physiological outcomes related to in utero VPA exposure. Behavioral studies show that VPA exposure in both rats and mice leads to autistic-like behaviors in the offspring, including social behavior deficits, increased repetitive behaviors, and deficits in communication. Based on this work VPA maternal challenge in rodents has been proposed as an animal model to study autism. This model has both face and construct validity; however, like all animal models there are limitations to its translation to the clinical setting. Here we provide a review of clinical studies that examined pregnancy outcomes of VPA use as well as the related animal studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. 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

  9. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus

    PubMed Central

    Bandara, Suren B.; Eubig, Paul A.; Sadowski, Renee N.; Schantz, Susan L.

    2016-01-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID:26543103

  10. Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

    PubMed Central

    Juliandi, Berry; Tanemura, Kentaro; Igarashi, Katsuhide; Tominaga, Takashi; Furukawa, Yusuke; Otsuka, Maky; Moriyama, Noriko; Ikegami, Daigo; Abematsu, Masahiko; Sanosaka, Tsukasa; Tsujimura, Keita; Narita, Minoru; Kanno, Jun; Nakashima, Kinichi

    2015-01-01

    Summary Prenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running. PMID:26677766

  11. 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

  12. 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 (10 mg/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. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults.

    PubMed

    Virtanen, J K; Siscovick, D S; Longstreth, W T; Kuller, L H; Mozaffarian, D

    2008-08-05

    To investigate the association between fish consumption and subclinical brain abnormalities. In the population-based Cardiovascular Health Study, 3,660 participants age > or =65 underwent an MRI scan in 1992-1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish > or =3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54-1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.

  14. Exposure to 2,4-dichlorophenoxyacetic acid induced PPARβ-dependent disruption of glucose metabolism in HepG2 cells.

    PubMed

    Sun, Haidong; Shao, Wentao; Liu, Hui; Jiang, Zhaoyan

    2018-04-09

    2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its impact on health is increasingly attracting great attentions. This study aimed to investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4-dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells presented more extracellular glucose consumption and glycogen content after exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related genes, FoxO1, and CREB is significantly elevated. Moreover, PPARβ was up-regulated dose-dependently. SiRNA knockdown of PPARβ completely rescued the increase of glycogen accumulation and glucose uptake, and the up-regulation of FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4-dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARβ in HepG2 cells.

  15. Crop bioaccumulation and human exposure of perfluoroalkyl acids through multi-media transport from a mega fluorochemical industrial park, China.

    PubMed

    Liu, Zhaoyang; Lu, Yonglong; Shi, Yajuan; Wang, Pei; Jones, Kevin; Sweetman, Andrew J; Johnson, Andrew C; Zhang, Meng; Zhou, Yunqiao; Lu, Xiaotian; Su, Chao; Sarvajayakesavaluc, Suriyanarayanan; Khan, Kifayatullah

    2017-09-01

    Significant quantities of perfluoroalkyl acids (PFAAs) are released to the environment from fluorochemical manufacturing processes through wastewater discharge and air emission in China, which may lead to human exposure and health risks through crop bioaccumulation from PFAAs-contaminated soil and irrigation water. This paper systematically studied the distribution and transport of PFAAs in agricultural soil, irrigation water and precipitation, followed by crop bioaccumulation and finally human exposure of PFAAs within a 10km radius around a mega-fluorochemical industrial park (FIP). Hotspots of contamination by PFAAs were found near the FIP and downstream of the effluent discharge point with the maximum concentrations of 641ng/g in agricultural soil, 480ng/g in wheat grain, 58.8ng/g in maize grain and 4,862ng/L in precipitation. As the distance increased from the FIP, PFAAs concentrations in all media showed a sharp initial decrease followed by a moderate decline. Elevated PFAA concentrations in soil and grains were still present within a radius of 10 km of the FIP. The soil contamination was associated with the presence of PFAAs in irrigation water and precipitation, and perfluorooctanoic acid (PFOA) was the dominant PFAA component in soil. However, due to bioaccumulation preference, short-chain perfluoroalkyl carboxylic acids (PFCAs), especially perfluorobutanoic acid (PFBA), became the major PFAA contaminants in grains of wheat and maize. The bioaccumulation factors (BAFs) for both grains showed a decrease with increasing chain length of PFAAs (approximately 0.5 log decrease per CF 2 group). Compared to maize grain, wheat grain showed higher BAFs, possibly related to its higher protein content. The PFCA (C4-C8) concentrations (on a log 10 basis) in agricultural soil and grain were found to show a linear positive correlation. Local human exposure of PFOA via the consumption of contaminated grains represents a health risk for local residents, especially for

  16. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities.

    PubMed

    McNally, James M; McCarley, Robert W

    2016-05-01

    We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

  17. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities

    PubMed Central

    McNally, James M.; McCarley, Robert W.

    2016-01-01

    Purpose of review We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Recent findings Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Summary Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention. PMID:26900672

  18. A survey on abnormal uterine bleeding among radiographers with frequent MRI exposure using intrauterine contraceptive devices.

    PubMed

    Huss, A; Schaap, K; Kromhout, H

    2018-02-01

    Based on a previous case report of menometrorrhagia (prolonged/excessive uterine bleeding, occurring at irregular and/or frequent intervals) in MRI workers with intrauterine devices (IUDs), it was evaluated whether this association could be confirmed. A survey was performed among 381 female radiographers registered with their national association. Logistic regression was used to analyze associations of abnormal uterine bleeding with the frequency of working with MRI scanners, presence near the scanner/in the scanner room during image acquisition, and with scanner strength or type. A total of 68 women reported using IUDs, and 72 reported abnormal uterine bleeding. Compared with unexposed women not using IUDs, the odds ratio in women with IUDs working with MRI scanners was 2.09 (95% confidence interval 0.83-3.66). Associations were stronger if women working with MRI reported being present during image acquisition (odds ratio 3.43, 95% CI 1.26-9.34). Associations with scanner strength or type were not consistent. Radiographers using IUDs who are occupationally exposed to stray fields from MRI scanners report abnormal uterine bleeding more often than their co-workers without an IUD, or nonexposed co-workers with an IUD. In particular, radiographers present inside the scanner room during image acquisition showed an increased risk. Magn Reson Med 79:1083-1089, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  19. Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism.

    PubMed

    Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Katashiba, Keisuke; Hasebe, Shigeru; Takano, Erika; Onaka, Yusuke; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2016-09-01

    Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the α2 -adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. Autism Res 2016, 9: 926-939. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  20. Exposure of spermatozoa to dibutyl phthalate induces abnormal embryonic development in a marine invertebrate Galeolaria caespitosa (Polychaeta: Serpulidae).

    PubMed

    Lu, Yonggang; Lin, Minjie; Aitken, Robert John

    2017-10-01

    In this study, we have investigated the impact of dibutyl phthalate (DBP) on early embryogenesis in a sessile marine invertebrate, Galeolaria caespitosa. DBP was found to induce sperm dysfunction as well as impaired and defective embryogenesis characterised by a particular pattern of abnormality. Thus, after the first cleavage, one blastomere in these abnormal embryos was able to carry out further mitoses, while the other arrested. Analysis of microtubules, chromosomes and actin filaments demonstrated that the mitotic spindles in the abnormal embryos were irregularly bent, shortened and unable to anchor to the cortex, resulting in the defective segregation of chromosomes. Within the non-dividing blastomeres, karyokinesis was found to continue at a slow pace as indicated by the presence of multiple sets of abnormal mitotic spindles. However, cytokinesis had been disrupted in these arrested cells due to a failure to assemble the contractile actin ring, as a result of which one pole of the embryos remained as one large, undivided cell. DBP was found to suppress the activity of superoxide dismutase in spermatozoa and, in association with this change, DBP-treated cells experienced oxidative stress as indicated by the presence of lipid aldehydes, such as 4-hydroxynonenal (4-HNE) in the sperm acrosome and neck. Adduction of lipid aldehydes at the level of the acrosome would be expected to impede the acrosome reaction and account for the significant decrease in fertilisation rates. 4-HNE generated as a consequence of lipid peroxidation in the sperm neck resulted in alkylation of the sperm centrioles. Such paternally damaged centrioles were inherited by the embryos and disrupted cytoskeletal protein organisation during early cleavage, generating the observed abnormalities in embryonic development. This research emphasises the vulnerability of spermatozoa to oxidative damage and highlights novel potential mechanisms for reproductive toxicity involving the alkylation of

  1. Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat.

    PubMed

    Bhardwaj, S K; Forcelli, P A; Palchik, G; Gale, K; Srivastava, L K; Kondratyev, A

    2012-06-01

    Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat

    PubMed Central

    Bhardwaj, S.K.; Forcelli, P.A; Palchik, G.; Gale, K.; Srivastava, L.K.; Kondratyev, A.

    2012-01-01

    Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations. PMID:22366076

  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. Excess caffeine exposure impairs eye development during chick embryogenesis

    PubMed Central

    Ma, Zheng-lai; Wang, Guang; Cheng, Xin; Chuai, Manli; Kurihara, Hiroshi; Lee, Kenneth Ka Ho; Yang, Xuesong

    2014-01-01

    Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over-exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of HNK-1+ cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (ROS) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti-oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess ROS induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing ROS production and perturbs Pax6 expression. PMID:24636305

  5. Thyroid ultrasound abnormalities in persons exposed during childhood to 131I from the Hanford nuclear site.

    PubMed

    Kopecky, Kenneth J; Onstad, Lynn; Hamilton, Thomas E; Davis, Scott

    2005-06-01

    Approximately 740,000 Ci of 131I were released into the atmosphere from the Hanford Nuclear Site in Washington State during 1944-1957. The Hanford Thyroid Disease Study (HTDS), conducted to determine if thyroid disease is increased among persons exposed as children to that 131I, also investigated whether thyroid ultrasound (US) abnormalities might be increased. The HTDS cohort (n = 5199) was selected from 1940-1946 births to mothers with usual residence in seven Washington counties. Of these, 4350 were located alive, 3447 attended HTDS clinics (1992-1997), and 3440 (1747 females) had evaluable clinical results and sufficient data to characterize their Hanford 131I exposures. US abnormalities were observed in 55.5% of women and 37.4% of men. Thyroid radiation doses from Hanford 131I, which could be estimated for 3191 evaluable participants, ranged from 0.0029 to 2823 mGy (mean, 174 mGy). Estimated dose was not significantly associated with the prevalence of any US abnormality (p = 0.21), US nodules with maximum dimension 5 mm or more (p = 0.64), or average number of US nodules per person (p = 0.80 for nodules with maximum dimension 5 mm or more). These results remained unchanged after accounting for factors that might confound or modify dose-response relationships and for uncertainty of the dose estimates. This study does not support the hypothesis that 131I exposure at Hanford's dose levels and dose rates during infancy and childhood increases the prevalence of adult thyroid US abnormalities.

  6. Human exposure to per- and polyfluoroalkyl substances (PFASs) via house dust in Korea: Implication to exposure pathway.

    PubMed

    Tian, Zhexi; Kim, Seung-Kyu; Shoeib, Mahiba; Oh, Jeong-Eun; Park, Jong-Eun

    2016-05-15

    A wide range of per- and polyfluoroalkyl substances (PFASs), including fluorotelomer alcohols (FTOHs), perfluorooctane sulfonamidoethanols (FOSEs), perfluoroalkyl carboxylic acids (PFCAs), and perfluoroalkane sulfonic acids (PFSAs), were measured in fifteen house dust and two nonresidential indoor dust of Korea. Total concentrations of PFASs in house dust ranged from 29.9 to 97.6 ng g(-1), with a dominance of perfluorooctane sulfonic acid (PFOS), followed by 8:2 FTOH, N-Ethyl perfluorooctane sulfonamidoethanol (EtFOSE), perfluoroctanoic acid (PFOA). In a typical exposure scenario, the estimated daily intakes (EDIs) of total PFASs via house dust ingestion were 2.83 ng d(-1) for toddlers and 1.13 ng d(-1) for adults, which were within the range of the mean EDIs reported from several countries. For PFOA and PFOS exposure via house dust ingestion, indirect exposure (via precursors) was a minor contributor, accounting for 5% and 12%, respectively. An aggregated exposure (hereafter, overall-EDIs) of PFOA and PFOS occurring via all pathways, estimated using data compiled from the literature, were 53.6 and 14.8 ng d(-1) for toddlers, and 20.5 and 40.6 ng d(-1) for adults, respectively, in a typical scenario. These overall-EDIs corresponded to 82% (PFOA) and 92% (PFOS) of a pharmacokinetic model-based EDIs estimated from adults' serum data. Direct dietary exposure was a major contributor (>89% of overall-EDI) to PFOS in both toddlers and adults, and PFOA in toddlers. As for PFOA exposure of adults, however direct exposure via tap water drinking (37%) and indirect exposure via inhalation (22%) were as important as direct dietary exposure (41%). House dust-ingested exposure (direct+indirect) was responsible for 5% (PFOS in toddlers) and <1% (PFOS in adults, and PFOA in both toddlers and adults) of the overall-EDIs. In conclusion, house-dust ingestion was a minor contributor in this study, but should not be ignored for toddlers' PFOS exposure due to its significance in the

  7. Small Airway Dysfunction and Abnormal Exercise Responses

    PubMed Central

    Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

    2016-01-01

    Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987

  8. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  9. Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

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

    Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

    1989-04-01

    We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that inmore » control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.« less

  10. Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

    PubMed Central

    Son, Ji Yeon; Kang, Yoon Jong; Kim, Kyeong Seok; Kim, Tae Hyung; Lim, Sung Kwang; Lim, Hyun Jung; Jeong, Tae Cheon; Choi, Dal Woong; Chung, Kyu Hyuck; Lee, Byung Mu

    2014-01-01

    Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods. PMID:25071919

  11. Exposure to 2,4-dichlorophenoxyacetic acid induces oxidative stress and apoptosis in mouse testis.

    PubMed

    Zhang, Dalei; Wu, Yaling; Yuan, Yangyang; Liu, Wenwen; Kuang, Haibin; Yang, Jianhua; Yang, Bei; Wu, Lei; Zou, Weiying; Xu, Changshui

    2017-09-01

    The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide. It has been associated with a variety of toxicities in rodents. In this study, male mice were orally administered 2,4-D at 50, 100 or 200mg/kg/day to investigate testicular toxicity and the possible mechanisms of action. Exposure to 2,4-D at high concentrations (100 and 200mg/kg/day) for 14 consecutive days caused spermatogenic disruption and seminiferous epithelial destruction. Furthermore, 2,4-D administration (100 and 200mg/kg/day) increased the formation of the lipid peroxidation product malondialdehyde and decreased activities of the antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, 2,4-D exposure up-regulated the expression of p53 and Bax protein and down-regulated the expression of Bcl-2 protein in the testis. These results demonstrate that oxidative stress and apoptosis may be involved in testicular toxicity induced by high concentrations of 2,4-D in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Systemic exposure to benzoic acid and hippuric acid following topical application of clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel in Japanese patients with acne vulgaris.

    PubMed

    Ino, Hiroko; Takahashi, Naoki; Saenz, Alessandra Alio; Wakamatsu, Akira; Hashimoto, Hirofumi; Nakahara, Norie; Hasegawa, Setsuo

    2015-01-01

    Clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel (CLDM/BPO3%) is a topical product for the treatment of acne vulgaris. In this study, plasma and urine concentrations of benzoic acid (BA) and hippuric acid (HA) were analyzed to estimate the pharmacokinetics (PK) of BPO after application of CLDM/BPO3% twice-daily for 7 days in Japanese patients with acne vulgaris. Seven-day repeated application of CLDM/BPO3% appears to be safe in this patient population. Concentrations of plasma and urine BA were below the limit of quantification before and after repeated application in most of the 12 adult male patients. Mean difference in Cmax and AUC0-last for plasma HA indicated increased exposures after repeated application, but with wide 90% confidence intervals. Mean Ae0-12 for urine HA was similar before and after repeated application. Repeated application of CLDM/BPO3% is thus unlikely to result in accumulation of BA and HA. The study suggests negligible systemic exposure to BPO metabolites from CLDM/BPO3% after 7-day repeated application in male patients with acne vulgaris. © 2014, The American College of Clinical Pharmacology.

  13. The Effects of Subacute Exposure of Peracetic Acid on Lipid Peroxidation and Hepatic Enzymes in Wistar Rats

    PubMed Central

    Marjani, Abdoljalal; Golalipour, Mohammad J.; Gharravi, Anneh M.

    2010-01-01

    Objectives This study was undertaken to determine the effect of subacute exposure of peracetic acid on lipid peroxidation and hepatic enzymes in Wistar rats. Methods 48 male animals in Treatment Group I, II and III received 0.2%, 2% and 20% peracetic acid daily for 2 and 4 weeks. Results Serum malondialdehyde increased and Alanine Transaminase and Aspartate Transaminase decreased significantly in groups 2 and 3, compared to the control group. The malondialdehyde, Alanine Transaminase and Aspartate Transaminase with 0.2% and 2% doses of peracetic acid for 2 weeks do not lead to the alteration of malondialdehyde and enzyme activities. Conclusion This study demonstrated that the enhancement of malondialdehyde could provide an oxidative damage induced by disinfectant peroxidation at 20% and 2% doses at 2 and 4 weeks. The consumption of peroxidation with 20% for 2 weeks and 2% for 4 weeks can cause the increase of malondialdehyde and the decrease of enzyme activities, respectively. PMID:22043353

  14. Morphological alterations in the freshwater rotifer Brachionus calyciflorus Pallas 1766 (Rotifera: Monogononta) caused by vinclozolin chronic exposure.

    PubMed

    Alvarado-Flores, Jesús; Rico-Martínez, Roberto; Adabache-Ortíz, Araceli; Silva-Briano, Marcelo

    2015-05-01

    Vinclozolin (VZ) is a dicarboximide fungicide widely used on fruits, vegetables and wines, effective against fungi plagues. In this study we characterized the effects of VZ using a 4-day reproductive chronic assay with the freshwater rotifer Brachionus calyciflorus. The assay included observations of several features of asexual and sexual reproduction. Our results indicate that VZ: (a) increased asexual and sexual reproduction, (b) caused severe abnormality in females and (c) these abnormalities were inherited by sexual and asexual reproduction. At 1.2 mg/L three abnormal females were found out of 457 total females (0.66 %). This low percentage is consistent and reproducible according to further analysis, where we increased the number of replicates and total females exposed to 1.2 mg/L of VZ, and found 18 abnormal females out of 2868 total females (0.63 % abnormality). Interestingly, abnormal females found at 5.6 mg/L VZ exposure, were able to show mating behavior. Our results suggest that VZ behaves as a strong endocrine disruptor whose effects show the characteristic inverted-U-shape exposure concentration response curve regarding the intrinsic population increase and the percentage of abnormalities as endpoints.

  15. Abnormal movements in first-episode, nonaffective psychosis: dyskinesias, stereotypies, and catatonic-like signs

    PubMed Central

    Compton, Michael T.; Fantes, Francisco; Wan, Claire Ramsay; Johnson, Stephanie; Walker, Elaine F.

    2015-01-01

    Motor abnormalities represent a neurobehavioral domain of signs intrinsic to schizophrenia-spectrum disorders, though they are commonly attributed to medication side effects and remain understudied. Individuals with first-episode psychosis represent an ideal group to study innate movement disorders due to minimal prior antipsychotic exposure. We measured dyskinesias, stereotypies, and catatonic-like signs and examined their associations with: (1) age at onset psychotic symptoms and duration of untreated psychosis; (2) positive, negative, and disorganized symptoms; (3) neurocognition; and (4) neurological soft signs. Among 47 predominantly African American first-episode psychosis patients in a public-sector hospital, the presence and severity of dyskinesias, stereotypies, and catatonic-like features were assessed using approximately 30-minute video recordings. Movement abnormalities were rated utilizing three scales (Dyskinesia Identification System Condensed User Scale, Stereotypy Checklist, and Catatonia Rating Scale). Correlational analyses were conducted. Scores for each of three movement abnormality types were modestly inter-correlated (r=.29-.40). Stereotypy score was significantly associated with age at onset of psychotic symptoms (r=.32) and positive symptom severity scores (r=.29–.41). There were no meaningful or consistent associations with negative symptom severity, neurocognition, or neurological soft signs. Abnormal movements appear to represent a relatively distinct phenotypic domain deserving of further research. PMID:25619434

  16. Stearic Acid

    ERIC Educational Resources Information Center

    Young, Jay A.

    2004-01-01

    A chemical laboratory information profile (CLIP) is presented for the chemical, stearic acid. The profile lists the chemical's physical and harmful characteristics, exposure limits, and symptoms of major exposure, for the benefit of teachers and students, who use the chemical in the laboratory.

  17. Behaviour modification in the management of chronic habits of abnormal eye rubbing.

    PubMed

    McMonnies, Charles W

    2009-04-01

    To describe how and why many keratoconus patients do not comply with strong advice to control chronic habits of abnormal rubbing. To outline a behaviour modification approach for controlling chronic habits of abnormal rubbing. Common reasons for chronic habits of abnormal rubbing have been reviewed as a basis for specifying a behavioural modification approach to habit reversal. The methods described are organized into the classic behavioural modification structure of: (1) habit awareness, (2) competing responses, (3) development of motivation, and (4) social support. This structure is supported by the application of social influence principles to achieve optimum compliance. The use of take-home written information in the form of an Abnormal Rubbing Guide is the basis for the development of motivation. Family social support is based upon a widening of the responsibility for avoiding eye rubbing to all family members. Some patients will need minimal application of these principles with patient education being sufficient intervention to achieve habit reversal. For patients with strong provocation to rubbing and/or by having a well established rubbing habit, a greater exposure to the habit reversal program described is indicated. Successful habit reversal may slow the rate of ectasia progression. Prophylactic application of the methods described for patients who are at risk for developing keratoconus, or post-laser assisted in situ keratomileusis keratectasia, may show that some forms of keratectasia are preventable.

  18. Impacts of short-term acid and aluminum exposure on Atlantic salmon (Salmo salar) physiology: A direct comparison of parr and smolts

    USGS Publications Warehouse

    Monette, M.Y.; McCormick, S.D.

    2008-01-01

    Episodic acidification resulting in increased acidity and inorganic aluminum (Ali) is known to impact anadromous salmonids and has been identified as a possible cause of Atlantic salmon population decline. Sensitive life-stages such as smolts may be particularly vulnerable to impacts of short-term (days–week) acid/Al exposure, however the extent and mechanism(s) of this remain unknown. To determine if Atlantic salmon smolts are more sensitive than parr to short-term acid/Al, parr and smolts held in the same experimental tanks were exposed to control (pH 6.3–6.6, 11–37 μg l−1 Ali) and acid/Al (pH 5.0–5.4, 43–68 μg l−1 Ali) conditions in the lab, and impacts on ion regulation, stress response and gill Al accumulation were examined after 2 and 6 days. Parr and smolts were also held in cages for 2 and 6 days in a reference (Rock River, RR) and an acid/Al-impacted tributary (Ball Mountain Brook, BMB) of the West River in Southern Vermont. In the lab, losses in plasma Cl− levels occurred in both control parr and smolts as compared to fish sampled prior to the start of the study, however smolts exposed to acid/Al experienced additional losses in plasma Cl− levels (9–14 mM) after 2 and 6 days, and increases in plasma cortisol (4.3-fold) and glucose (2.9-fold) levels after 6 days, whereas these parameters were not significantly affected by acid/Al in parr. Gill Na+,K+-ATPase (NKA) activity was not affected by acid/Al in either life-stage. Both parr and smolts held at BMB (but not RR) exhibited declines in plasma Cl−, and increases in plasma cortisol and glucose levels; these differences were significantly greater in smolts after 2 days but similar in parr and smolts after 6 days. Gill NKA activity was reduced 45–54% in both life-stages held at BMB for 6 days compared to reference fish at RR. In both studies, exposure to acid/Al resulted in gill Al accumulation in parr and smolts, with parr exhibiting two-fold greater gill Al than smolts after 6

  19. Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline

    PubMed Central

    Weiden, Michael D.; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I.; Reibman, Joan; Rom, William N.; Prezant, David J.; Nolan, Anna

    2016-01-01

    Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung’s normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after World Trade Center (WTC) exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1exposure that were predictive of their FEV1 up to 7 years after their WTC exposure. Predicting future risk of airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services. PMID:26024341

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

    PubMed

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

    2018-07-01

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

  1. Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.

    PubMed

    Blondeau, Kathleen; Mertens, Veerle; Vanaudenaerde, Bart A; Verleden, Geert M; Van Raemdonck, Dirk E; Sifrim, Daniel; Dupont, Lieven J

    2009-02-01

    Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH <4) and weakly acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.

  2. Estimation of stress relaxation time for normal and abnormal breast phantoms using optical technique

    NASA Astrophysics Data System (ADS)

    Udayakumar, K.; Sujatha, N.

    2015-03-01

    Many of the early occurring micro-anomalies in breast may transform into a deadliest cancer tumor in future. Probability of curing early occurring abnormalities in breast is more if rightly identified. Even in mammogram, considered as a golden standard technique for breast imaging, it is hard to pick up early occurring changes in the breast tissue due to the difference in mechanical behavior of the normal and abnormal tissue when subjected to compression prior to x-ray or laser exposure. In this paper, an attempt has been made to estimate the stress relaxation time of normal and abnormal breast mimicking phantom using laser speckle image correlation. Phantoms mimicking normal breast is prepared and subjected to precise mechanical compression. The phantom is illuminated by a Helium Neon laser and by using a CCD camera, a sequence of strained phantom speckle images are captured and correlated by the image mean intensity value at specific time intervals. From the relation between mean intensity versus time, tissue stress relaxation time is quantified. Experiments were repeated for phantoms with increased stiffness mimicking abnormal tissue for similar ranges of applied loading. Results shows that phantom with more stiffness representing abnormal tissue shows uniform relaxation for varying load of the selected range, whereas phantom with less stiffness representing normal tissue shows irregular behavior for varying loadings in the given range.

  3. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Sampling and analysis of airborne resin acids and solvent-soluble material derived from heated colophony (rosin) flux: a method to quantify exposure to sensitizing compounds liberated during electronics soldering.

    PubMed

    Smith, P A; Son, P S; Callaghan, P M; Jederberg, W W; Kuhlmann, K; Still, K R

    1996-07-17

    Components of colophony (rosin) resin acids are sensitizers through dermal and pulmonary exposure to heated and unheated material. Significant work in the literature identifies specific resin acids and their oxidation products as sensitizers. Pulmonary exposure to colophony sensitizers has been estimated indirectly through formaldehyde exposure. To assess pulmonary sensitization from airborne resin acids, direct measurement is desired, as the degree to which aldehyde exposure correlates with that of resin acids during colophony heating is undefined. Any analytical method proposed should be applicable to a range of compounds and should also identify specific compounds present in a breathing zone sample. This work adapts OSHA Sampling and Analytical Method 58, which is designed to provide airborne concentration data for coal tar pitch volatile solids by air filtration through a glass fiber filter, solvent extraction of the filter, and gravimetric analysis of the non-volatile extract residue. In addition to data regarding total soluble material captured, a portion of the extract may be subjected to compound-specific analysis. Levels of soluble solids found during personal breathing zone sampling during electronics soldering in a Naval Aviation Depot ranged from below the "reliable quantitation limit" reported in the method to 7.98 mg/m3. Colophony-spiked filters analyzed in accordance with the method (modified) produced a limit of detection for total solvent-soluble colophony solids of 10 micrograms/filter. High performance liquid chromatography was used to identify abietic acid present in a breathing zone sample.

  5. 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

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

    PubMed

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

    2017-08-14

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

  7. Effects of sublethal exposure to boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta.

    PubMed

    Ali, Arshad; Xue, Rui-De; Barnard, Donald R

    2006-09-01

    Effects of sublethal exposure to 0.1% boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta were studied in the laboratory. Survival of males as well as females was significantly reduced when exposed to the bait, compared to control adults. The host-seeking and bloodfeeding activities in the baited females decreased, but the mean duration of blood engorgement (probing to voluntary withdrawal of proboscis) was not significantly different between the baited and control females. The landing and biting rates (human forearm) were significantly reduced in the baited females compared to nonbaited controls. Fecundity and fertility (based on number of laid eggs per female and percentage egg hatch, respectively) in the baited females were significantly reduced, and ovarian development was retarded. Sublethal exposure to sugar-based boric acid bait has the potential to reduce adult populations of St. albopicta.

  8. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

    PubMed Central

    Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

    2012-01-01

    Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

  9. Valproic acid exposure sequentially activates Wnt and mTOR pathways in rats.

    PubMed

    Qin, Liyan; Dai, Xufang; Yin, Yunhou

    2016-09-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, limited verbal communication and repetitive behaviors. Recent studies have demonstrated that Wnt signaling and mTOR signaling play important roles in the pathogenesis of ASD. However, the relationship of these two signaling pathways in ASD remains unclear. We assessed this question using the valproic acid (VPA) rat model of autism. Our results demonstrated that VPA exposure activated mTOR signaling and suppressed autophagy in the prefrontal cortex, hippocampus and cerebellum of autistic model rats, characterized by enhanced phospho-mTOR and phospho-S6 and decreased Beclin1, Atg5, Atg10, LC3-II and autophagosome formation. Rapamycin treatment suppressed the effect of VPA on mTOR signaling and ameliorated the autistic-like behaviors of rats in our autism model. The administration of VPA also activated Wnt signaling through up-regulating beta-catenin and phospho-GSK3beta. Suppression of the Wnt pathway by sulindac relieved autistic-like behaviors and attenuated VPA-induced mTOR signaling activation in autistic model rats. Our results demonstrate that VPA exposure sequentially activates Wnt signaling and mTOR signaling in rats. Suppression of the Wnt signaling pathway relieves autistic-like behaviors partially by deactivating the mTOR signaling pathway in VPA-exposed rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. [A cohort study of longer-term impact of melamine contaminated formula on infant health].

    PubMed

    Wang, Pei-xin; Li, Hong-tian; Wang, Lin-lin; Zhang, Long; Zhou, Yu-bo; Liu, Jian-meng

    2013-10-15

    To prospectively evaluate the health status of infants with exposure to melamine-contaminated milk formula prior to September 2008. The cohort study was conducted in an area close to the manufacturer of Sanlu dairy products. There were three groups (n = 47 each). In September 2008, the exposure group I included infants with exposure to melamine and a diagnosis of renal abnormalities, the exposure group IIhad exposure to melamine but there was no diagnosis of renal abnormalities and the non-exposure group had no exposure to melamine. The exposure II and non-exposure groups were matched with those of exposure group I by birthplaces, gender and date of birth ( ± 3 months). Kidney function tests (urea nitrogen, serum creatinine, uric acid, serum albumin, β2-microglobulin and cystatin C), liver function tests (alanine aminotransferase and aspartate aminotransferase), growth and development assessment and urinary system ultrasonography were implemented between November 2011 and June 2012. The analysis of covariance (least significant difference method) was performed to compare the differences of relevant variables among three groups. The urinary system ultrasonography showed that all abnormalities disappeared in exposure group I and all infants of another two groups had normal ultrasonography. There were statistically significant differences in serum uric acid and albumin of kidney function in exposure group I, exposure group II and non-exposure group ((344 ± 75) and (338 ± 98) and (282 ± 69) µmol/L , (47 ± 5) and (47 ± 6) and (43 ± 5) g/L, all P < 0.05) among three groups. However the differences in the remaining markers of kidney function, markers of liver function and Z scores of weight-for-age and height-for age were all statistically insignificant (all P > 0.05). Further pair-wise comparisons showed that the levels of serum uric acid and albumin in exposure group I were higher than those in non-exposure group (P = 0.001 and 0.010). And the levels of serum

  11. Human Plant Exposures Reported to a Regional (Southwestern) Poison Control Center Over 8 Years.

    PubMed

    Enfield, Ben; Brooks, Daniel E; Welch, Sharyn; Roland, Maureen; Klemens, Jane; Greenlief, Kim; Olson, Rachel; Gerkin, Richard D

    2018-03-01

    There is little published data about human plant exposures reported to US poison control centers (PCCs). A retrospective chart review of all reported plant exposures to a single regional PCC between January 1, 2003 and December 31, 2010 was done to understand better the characteristics of plant exposure cases. Specific generic plant codes were used to identify cases. Recorded variables included patient demographics, plant involved, exposure variables, symptoms, management site, treatments, and outcome. Univariate and multivariate regression was used to identify outcome predictors. A total of 6492 charts met inclusion criteria. The average age was 16.6 years (2 months-94 years); 52.4% were male. The most common exposure reason was unintentional (98%), and the majority (92.4%) occurred at the patient's home. Ingestions (58.3%) and dermal exposures (34.3%) accounted for most cases. Cactus (27.5%), oleander (12.5%), Lantana (5.7%), and Bougainvillea (3.8%) were most commonly involved. Symptoms developed in 47.1% of patients, and were more likely to occur following Datura (66.7%), and Morning Glory or Milkweed (25% each) exposures. Almost 94% of patients were managed onsite (home) and only 5.2% involved evaluation in a health care facility (HCF). Only 37 (0.6%) patients required hospital admission, and 2.9% of cases resulted in more than minimal effects. Exposures resulting in more than minimal clinical effects were predicted by several variables: abnormal vital signs (OR = 35.62), abnormal labs (OR = 14.87), and management at a HCF (OR = 7.37). Hospital admissions were increased for patients already at a HCF (OR = 54.01), abnormal vital signs (OR = 23.28), and intentional exposures (OR = 14.7). Plant exposures reported to our poison control center were typically unintentional ingestions occurring at home. Most patients were managed onsite and few developed significant symptoms.

  12. Preventive effect of a high fluoride toothpaste and arginine-carbonate toothpaste on dentinal tubules exposure followed by acid challenge: a dentine permeability evaluation

    PubMed Central

    2014-01-01

    Background Considering the current high use of high fluoride toothpastes, the aim of the study was to quantify alterations in the root dentine permeability submitted to treatment with a high fluoride toothpaste and 8% arginine, calcium carbonate, sodium monofluorophosphate toothpaste as a preventive treatment for dentinal tubules exposure followed by acid challenge. Methods Thirty-third molars were sectioned below the cementoenamel. The root segments were connected to a hydraulic pressure apparatus to measure dentine permeability after the following sequential steps (n = 10 per group): I) Baseline; II) treatment with phosphoric acid for 30 s (maximum permeability); III) Toothbrushing (1 min) according to the experimental groups (G1- control; G2- 5000 ppm fluoride toothpaste; G3- 8% arginine-calcium carbonate toothpaste); IV) acid challenge for 5 min (orange juice). The data were converted into percentage, considering stage II as 100%. Results The results have shown a statistically significant decreasing on dentine permeability after treatment with toothpaste (Friedman test and Dunn’s post hoc test). Comparison among groups demonstrated a high increasing on dentine permeability when acid challenge was performed after toothbrushing with distilled water (control group) (Kruskal-Wallis and Dunn’s post hoc test). Conclusion The toothpaste treatment may provide sufficient resistance on dentine surface, preventing dentinal tubules exposure after acid challenge. PMID:24958423

  13. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus.

    PubMed

    Bandara, Suren B; Eubig, Paul A; Sadowski, Renee N; Schantz, Susan L

    2016-02-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

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

    Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech

    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 andmore » 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.« less

  15. Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model.

    PubMed

    Wang, Wanjun; Zhou, Ji; Chen, Minjie; Huang, Xingke; Xie, Xiaoyun; Li, Weihua; Cao, Qi; Kan, Haidong; Xu, Yanyi; Ying, Zhekang

    2018-04-17

    Exposure to ambient fine particulate matter (PM 2.5 ) correlates with abnormal glucose homeostasis, but the underlying biological mechanism has not been fully understood. The gut microbiota is an emerging crucial player in the homeostatic regulation of glucose metabolism. Few studies have investigated its role in the PM 2.5 exposure-induced abnormalities in glucose homeostasis. C57Bl/6J mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) for 12 months using a versatile aerosol concentration enrichment system (VACES) that was modified for long-term whole-body exposures. Their glucose homeostasis and gut microbiota were examined and analysed by correlation and mediation analysis. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) showed that CAP exposure markedly impaired their glucose and insulin tolerance. Faecal microbiota analysis demonstrated that the impairment in glucose homeostasis was coincided with decreased faecal bacterial ACE and Chao-1 estimators (the indexes of community richness), while there was no significant change in all faecal fungal alpha diversity estimators. The Pearson's correlation analyses showed that the bacterial richness estimators were correlated with glucose and insulin tolerance, and the mediation analyses displayed a significant mediation of CAP exposure-induced glucose intolerance by the alteration in the bacterial Chao-1 estimator. LEfSe analyses revealed 24 bacterial and 21 fungal taxa differential between CAP- and FA-exposed animals. Of these, 14 and 20 bacterial taxa were correlated with IPGTT AUC and ITT AUC, respectively, and 5 fungal taxa were correlated with abnormalities in glucose metabolism. Chronic exposure to PM 2.5 causes gut dysbiosis and may subsequently contribute to the development of abnormalities in glucose metabolism.

  16. Metabolic differentiation and classification of abnormal Savda Munziq's pharmacodynamic role on rat models with different diseases by nuclear magnetic resonance-based metabonomics.

    PubMed

    Mamtimin, Batur; Xia, Guo; Mijit, Mahmut; Hizbulla, Mawlanjan; Kurbantay, Nazuk; You, Li; Upur, Halmurat

    2015-01-01

    Abnormal Savda Munziq (ASMq) is a traditional Uyghur herbal preparation used as a therapy for abnormal Savda-related diseases. In this study, we investigate ASMq's dynamic effects on abnormal Savda rat models under different disease conditions. Abnormal Savda rat models with hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), and asthma dosed of ASMq. Serum samples of each animal tested by nuclear magnetic resonance spectroscopy and analyzed by orthogonal projection to latent structure with discriminant analysis. Compared with healthy controls, HCC rats had higher concentrations of amino acids, fat-related metabolites, lactate, myoinositol, and citrate, but lower concentrations of α-glucose, β-glucose, and glutamine. Following ASMq treatment, the serum acetone very low-density lipoprotein (VLDL), LDL, unsaturated lipids, acetylcysteine, and pyruvate concentration decreased, but α-glucose, β-glucose, and glutamine concentration increased (P < 0.05). T2DM rats had higher concentrations of α- and β-glucose, but lower concentrations of isoleucine, leucine, valine, glutamine, glycoprotein, lactate, tyrosine, creatine, alanine, carnitine, and phenylalanine. After ASMq treated T2DM groups showed reduced α- and β-glucose and increased creatine levels (P < 0.05). Asthma rats had higher acetate, carnitine, formate, and phenylalanine levels, but lower concentrations of glutamine, glycoprotein, lactate, VLDL, LDL, and unsaturated lipids. ASMq treatment showed increased glutamine and reduced carnitine, glycoprotein, formate, and phenylalanine levels (P < 0.05). Low immune function, decreased oxidative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of abnormal Savda-related diseases. ASMq may improve the abnormal metabolism and immune function of rat models with different diseases combined abnormal Savda.

  17. The novel, peripherally restricted GABAB receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h pHmetry in dogs.

    PubMed

    Brändén, Lena; Fredriksson, Anita; Harring, Emelie; Jensen, Jörgen; Lehmann, Anders

    2010-05-25

    While patients with symptoms of gastroesophageal reflux disease generally respond well to proton pump inhibitors, 20-30% continue to experience troublesome symptoms. In such cases, agents that target transient lower esophageal sphincter (LES) relaxation may be useful as add-on therapy to proton pump inhibitors. The GABAB receptor agonist baclofen inhibits transient LES relaxation but it is not an ideal agent due to central nervous system activity. Lesogaberan (AZD3355) is a peripherally restricted GABAB receptor agonist with limited central nervous system activity that inhibits transient LES relaxation in dogs. In the present study, the comparative effects of lesogaberan (7 micromol/kg) and baclofen (2.8 micromol/kg) on reflux were studied in dogs using 24-h pHmetry. Drugs (or vehicle control) were administered orally prior to the first meal of the day, and the number of reflux episodes (pH<4 for > or = 5 s) and acid exposure time were computed for the 24-h monitoring period. The mean (S.E.M.) number of reflux episodes/24 h was 4.6 (0.4) and 6.4 (0.6) for lesogaberan and baclofen, respectively, versus 10.7 (0.5) for control (P<0.0001 for both). Acid exposure time was 51.2 (4.5) min for control versus 23.6 (3.8) min for lesogaberan (P<0.0001) and 35.4 (6.5) min with baclofen (P=0.05). It is concluded that lesogaberan significantly reduces acid reflux in dogs, with comparable efficacy to baclofen. Copyright 2010 Elsevier B.V. All rights reserved.

  18. Excitatory amino acid transmitters in epilepsy.

    PubMed

    Meldrum, B S

    1991-01-01

    For the majority of human epilepsy syndromes, the molecular and cellular basis for the epileptic activity remains largely conjectural. The principal hypotheses currently concern: defects in membrane ionic conductances or transport mechanisms; defects in gamma-aminobutyric acid (GABA)-mediated inhibitory processes; and enhanced or abnormal excitatory synaptic action. Substantial evidence exists in humans and animals for acquired abnormalities in excitatory amino acid neurotransmission that may participate in the abnormal patterns of neuronal discharge, and this could provide the morphological basis for a recurrent excitatory pathway sustaining seizure discharges in temporal lobe epilepsy. In practice, two approaches appear significant in the suppression of seizures. One is to act postsynaptically on receptors to decrease the excitation induced by glutamate, and the other is to decrease synaptic release of glutamate and aspartate. Agents acting upon adenosine or GABAB receptors decrease glutamate release in vitro but do not have significant anticonvulsant activity, probably because of their predominant actions at other sites. Lamotrigine blocks stimulated release of glutamate and shows anticonvulsant activity in a wide range of animal models.

  19. Effects of abnormal light-rearing conditions on retinal physiology in larvae zebrafish.

    PubMed

    Saszik, S; Bilotta, J

    1999-11-01

    Anatomic studies have found that zebrafish retinal neurons develop in a sequential fashion. In addition, exposure to abnormal light-rearing conditions produces deficits in visual behavior of larvae zebrafish, even though there appears to be little effect of the light-rearing conditions on the gross morphology of the retina. The purpose of this study was to assess the effects of abnormal light-rearing conditions on larvae zebrafish retinal physiology. Larvae zebrafish (Danio rerio) were exposed to constant light (LL), constant dark (DD), or normal cyclic light (LD) from fertilization to 6 days postfertilization (dpf). After 6 days, the animals were placed into normal cyclic light and tested at 6 to 8, 13 to 15, and 21 to 24 dpf. Electroretinogram (ERG) responses to visual stimuli, consisting of various wavelengths and irradiances, were recorded. Comparisons were made across the three age groups and the three light-rearing conditions. Deficits from the light-rearing conditions were seen immediately after exposure (6 8 dpf). The LL-condition subjects showed the greatest deficit in the UV and short-wavelength areas and the DD-condition subjects showed a slight deficit across the entire spectrum. At 13 to 15 dpf, the LL and DD groups showed an increase in sensitivity and by 21 to 24 dpf, the groups no longer differed from controls. Abnormal lighting environments can adversely influence the physiological development of the larvae zebrafish retina. The pattern of damage that was seen in zebrafish is similar to that found in other vertebrates, including higher vertebrates. However, unlike higher vertebrates, the zebrafish appears to be capable of regeneration. This suggests that the zebrafish would be a viable model for light environment effects and neural regeneration.

  20. Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis.

    PubMed

    Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

    2015-11-01

    The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. © 2015 The British Pharmacological Society.

  1. Impact of fetal alcohol exposure on body systems: A systematic review.

    PubMed

    Caputo, Courtney; Wood, Erin; Jabbour, Leila

    2016-06-01

    Review of published manuscripts on fetal alcohol exposure on several body systems. Articles in this review were found online using databases such as Medline, Medline Complete, PubMed, and Health Source: Nursing/Academic Edition. The following terms were searched: fetal alcohol spectrum disorders, fetal alcohol syndrome, prenatal alcohol exposure, and alcohol related birth defects. Thirteen articles were gathered, five original investigations and eight reviews. This review identified several abnormalities in the body systems discussed and their associations to fetal alcohol syndrome. Evidence shows that the brain was the most severely impacted organ of the body systems discussed. However, prenatal alcohol exposure causes several abnormalities within the heart, kidney, liver, gastrointestinal tract, and the endocrine systems. In addition, preventative measures need to be taken by mothers during pregnancy. Birth Defects Research (Part C), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part C) 108:174-180, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. White matter microstructural alterations in children with prenatal methamphetamine/polydrug exposure

    PubMed Central

    Colby, John B.; Smith, Lynne; O’Connor, Mary J.; Bookheimer, Susan Y.; Van Horn, John D.; Sowell, Elizabeth R.

    2013-01-01

    Little is known about the effects of prenatal methamphetamine exposure on white matter microstructure, and the impact of concomitant alcohol exposure. Diffusion tensor imaging and neurocognitive testing were performed on 21 children with prenatal methamphetamine exposure (age 9.8±1.8 years; 17 also exposed to alcohol), 19 children with prenatal alcohol but not methamphetamine exposure (age 10.8±2.3 years), and 27 typically-developing children (age 10.3±3.3 years). Whole-brain maps of fractional anisotropy (FA) were evaluated using tract-based spatial statistics. Relative to unexposed controls, children with prenatal methamphetamine exposure demonstrated higher FA mainly in left-sided regions, including the left anterior corona radiata (LCR) and corticospinal tract (P<0.05, corrected). Post-hoc analyses of these FA differences showed they likely result more from lower radial diffusivity (RD) than higher axial diffusivity (AD). Relative to the methamphetamine-exposed group, children with prenatal alcohol exposure showed lower FA in frontotemporal regions – particularly the right external capsule (P<0.05, corrected). We failed to find any group-performance interaction (on tests of executive functioning and visuomotor integration) in predicting FA; however, FA in the right external capsule was significantly associated with performance on a test of visuomotor integration across groups (P<0.05). This report demonstrates unique diffusion abnormalities in children with prenatal methamphetamine/polydrug exposure that are distinct from those associated with alcohol exposure alone, and illustrates that these abnormalities in brain microstructure are persistent into childhood and adolescence – long after the polydrug exposure in utero. PMID:23149028

  3. Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children.

    PubMed

    Chastang, Julie; Baïz, Nour; Cadwallader, Jean Sébastien; Cadwalladder, Jean Sébastien; Robert, Sarah; Dywer, John L; Dywer, John; Charpin, Denis André; Caillaud, Denis; de Blay, Frédéric; Raherison, Chantal; Lavaud, François; Annesi-Maesano, Isabella

    2015-01-01

    The purpose of this study was to examine the association between pre and post environmental tobacco smoke (ETS) exposure and behavioral problems in schoolchildren. In the cross-sectional 6 cities Study conducted in France, 5221 primary school children were investigated. Pre- and postnatal exposure to secondhand tobacco smoke at home was assessed using a parent questionnaire. Child's behavioral outcomes (emotional symptoms and conduct problems) were evaluated by the Strengths and Difficulties Questionnaire (SDQ) completed by the parents. ETS exposure during the postnatal period and during both pre- and postnatal periods was associated with behavioral problems in children. Abnormal emotional symptoms (internalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.72 (95% Confidence Interval (CI)= 1.36-2.17), whereas the OR was estimated to be 1.38 (95% CI= 1.12-1.69) in the case of postnatal exposure only. Abnormal conduct problems (externalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.94 (95% CI= 1.51-2.50), whereas the OR was estimated to be 1.47 (95% CI=1.17-1.84) in the case of postnatal exposure only. Effect estimates were adjusted for gender, study center, ethnic origin, child age, low parental education, current physician diagnosed asthma, siblings, preterm birth and single parenthood. Postnatal ETS exposure, alone or in association with prenatal exposure, increases the risk of behavioral problems in school-age children.

  4. Management of exposure to waste anesthetic gases.

    PubMed

    Smith, Francis Duval

    2010-04-01

    Anesthetic agents were developed in the 1700s, and nitrous oxide was first used in 1884. Research on the effects of waste anesthetic gas exposure started appearing in the literature in 1967. Short-term exposure causes lethargy and fatigue, and long-term exposure may be linked to spontaneous abortion, congenital abnormalities, infertility, premature births, cancer, and renal and hepatic disease. Today, perioperative staff members are exposed to trace amounts of waste anesthetic gas, and although this exposure cannot be eliminated, it can be controlled. Health care facilities are required to develop, implement, measure, and control practices to reduce anesthetic gas exposure to the lowest practical level. Exposure levels must be measured every six months and maintained at less than 25 parts per million for nitrous oxide and 2 parts per million for halogenated agents to be compliant with Occupational Safety and Health Administration standards. Copyright 2010 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  5. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

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

    Strecker, Ruben, E-mail: Ruben.Strecker@cos.uni-heidelberg.de; Weigt, Stefan, E-mail: stefan.weigt@merckgroup.com; Braunbeck, Thomas, E-mail: braunbeck@uni-hd.de

    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 fracturesmore » 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.« less

  6. 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

  7. Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.

    PubMed

    Negishi, Takayuki; Matsunaga, Yuki; Kobayashi, Yayoi; Hirano, Seishiro; Tashiro, Tomoko

    2013-12-01

    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.

  8. Electrocardiographic abnormalities in opiate addicts.

    PubMed

    Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

    2008-12-01

    To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P < 0.05), and in patients with positive than negative urine findings for cannabis (68 versus 57%, P < 0.05). Patients with ST abnormalities were more often males than females (21 versus 11%, P < 0.05), had a history of seizures less often (16 versus 27%, P < 0.05), had positive than negative urine findings for cannabis more often (26 versus 15%, P < 0.01) and had negative than positive urine findings for methadone more often (21 versus 11%, P < 0.05). QTc prolongation was more frequent in patients with high dosages of maintenance drugs than in patients with medium or low dosages (27 versus 12 versus 10%, P < 0.05) and in patients whose urine findings were positive than negative for methadone (23 versus 11%, P < 0.001) as well as for benzodiazepines (17 versus 9%, P < 0.05). Limitations of the data are that in most cases other risk factors for the cardiac abnormalities were not known. ECG abnormalities are frequent in opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation

  9. The AMINO experiment: exposure of amino acids in the EXPOSE-R experiment on the International Space Station and in laboratory

    NASA Astrophysics Data System (ADS)

    Bertrand, Marylène; Chabin, Annie; Colas, Cyril; Cadène, Martine; Chaput, Didier; Brack, Andre; Cottin, Herve

    2015-01-01

    In order to confirm the results of previous experiments concerning the chemical behaviour of organic molecules in the space environment, organic molecules (amino acids and a dipeptide) in pure form and embedded in meteorite powder were exposed in the AMINO experiment in the EXPOSE-R facility onboard the International Space Station. After exposure to space conditions for 24 months (2843 h of irradiation), the samples were returned to the Earth and analysed in the laboratory for reactions caused by solar ultraviolet (UV) and other electromagnetic radiation. Laboratory UV exposure was carried out in parallel in the Cologne DLR Center (Deutsches Zentrum für Luft und Raumfahrt). The molecules were extracted from the sample holder and then (1) derivatized by silylation and analysed by gas chromatography coupled to a mass spectrometer (GC-MS) in order to quantify the rate of degradation of the compounds and (2) analysed by high-resolution mass spectrometry (HRMS) in order to understand the chemical reactions that occurred. The GC-MS results confirm that resistance to irradiation is a function of the chemical nature of the exposed molecules and of the wavelengths of the UV light. They also confirm the protective effect of a coating of meteorite powder. The most altered compounds were the dipeptides and aspartic acid while the most robust were compounds with a hydrocarbon chain. The MS analyses document the products of reactions, such as decarboxylation and decarbonylation of aspartic acid, taking place after UV exposure. Given the universality of chemistry in space, our results have a broader implication for the fate of organic molecules that seeded the planets as soon as they became habitable as well as for the effects of UV radiation on exposed molecules at the surface of Mars, for example.

  10. Variations in collagen fibrils network structure and surface dehydration of acid demineralized intertubular dentin: effect of dentin depth and air-exposure time.

    PubMed

    Fawzy, Amr S

    2010-01-01

    The aim was to characterize the variations in the structure and surface dehydration of acid demineralized intertubular dentin collagen network with the variations in dentin depth and time of air-exposure (3, 6, 9 and 12 min). In addition, to study the effect of these variations on the tensile bond strength (TBS) to dentin. Phosphoric acid demineralized superficial and deep dentin specimens were prepared. The structure of the dentin collagen network was characterized by AFM. The surface dehydration was characterized by probing the nano-scale adhesion force (F(ad)) between AFM tip and intertubular dentin surface as a new experimental approach. The TBS to dentin was evaluated using an alcohol-based dentin self-priming adhesive. AFM images revealed a demineralized open collagen network structure in both of superficial and deep dentin at 3 and 6 min of air-exposure. However, at 9 min, superficial dentin showed more collapsed network structure compared to deep dentin that partially preserved the open network structure. Total collapsed structure was found at 12 min for both of superficial and deep dentin. The value of the F(ad) is decreased with increasing the time of air-exposure and is increased with dentin depth at the same time of air-exposure. The TBS was higher for superficial dentin at 3 and 6 min, however, no difference was found at 9 and 12 min. The ability of the demineralized dentin collagen network to resist air-dehydration and to preserve the integrity of open network structure with the increase in air-exposure time is increased with dentin depth. Although superficial dentin achieves higher bond strength values, the difference in the bond strength is decreased by increasing the time of air-exposure. The AFM probed F(ad) showed to be sensitive approach to characterize surface dehydration, however, further researches are recommended regarding the validity of such approach.

  11. Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence.

    PubMed

    Tolomeo, S; Gray, S; Matthews, K; Steele, J D; Baldacchino, A

    2016-10-01

    Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

  12. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  13. Biochemical abnormalities in neonatal seizures.

    PubMed

    Sood, Arvind; Grover, Neelam; Sharma, Roshan

    2003-03-01

    The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

  14. Evaluation of continuous 4-day exposure to peracetic acid as a treatment for Ichthyophthirius multifiliis.

    PubMed

    Sudová, Eliska; Straus, David L; Wienke, Andreas; Meinelt, Thomas

    2010-01-01

    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 found to be toxic to I. multifiliis theronts at low concentrations. I. multifiliis-infested carp were exposed to 1 mg/l PAA in a dynamic exposure by means of peristaltic pumps. Five days after infestation, gills, tail fins, and skin below the dorsal fin were observed microscopically for I. multifiliis abundance. After PAA exposure, PAA-treated fish showed lower infestation of I. multifiliis in all investigated tissues than the unexposed control fish. The infestation increased in the control group whereas the infestation in the PAA-exposed groups significantly decreased (p = 0.0083, Bonferroni correction). The fish in the two exposure groups showed a slight reinfestation with I. multifiliis. This might be caused by a peroxide degradation (hydrolysis) and/or reduction of the delivered PAA concentration. Thus, PAA concentrations were possibly too low to be effective on the released trophonts and/or the infective theronts. This hypothesis is corroborated by the fact that the I. multifiliis in the gills, skin, and fins of the PAA-exposed carp were in an early developmental stage.

  15. Abnormal movements in first-episode, nonaffective psychosis: dyskinesias, stereotypies, and catatonic-like signs.

    PubMed

    Compton, Michael T; Fantes, Francisco; Wan, Claire Ramsay; Johnson, Stephanie; Walker, Elaine F

    2015-03-30

    Motor abnormalities represent a neurobehavioral domain of signs intrinsic to schizophrenia-spectrum disorders, though they are commonly attributed to medication side effects and remain understudied. Individuals with first-episode psychosis represent an ideal group to study innate movement disorders due to minimal prior antipsychotic exposure. We measured dyskinesias, stereotypies, and catatonic-like signs and examined their associations with: (1) age at onset of psychotic symptoms and duration of untreated psychosis; (2) positive, negative, and disorganized symptoms; (3) neurocognition; and (4) neurological soft signs. Among 47 predominantly African American first-episode psychosis patients in a public-sector hospital, the presence and severity of dyskinesias, stereotypies, and catatonic-like features were assessed using approximately 30-min video recordings. Movement abnormalities were rated utilizing three scales (Dyskinesia Identification System Condensed User Scale, Stereotypy Checklist, and Catatonia Rating Scale). Correlational analyses were conducted. Scores for each of three movement abnormality types were modestly inter-correlated (r=0.29-0.40). Stereotypy score was significantly associated with age at onset of psychotic symptoms (r=0.32) and positive symptom severity scores (r=0.29-0.41). There were no meaningful or consistent associations with negative symptom severity, neurocognition, or neurological soft signs. Abnormal movements appear to represent a relatively distinct phenotypic domain deserving of further research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. 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...

  17. 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...

  18. High-resolution metabolomics of occupational exposure to trichloroethylene

    PubMed Central

    Walker, Douglas I; Uppal, Karan; Zhang, Luoping; Vermeulen, Roel; Smith, Martyn; Hu, Wei; Purdue, Mark P; Tang, Xiaojiang; Reiss, Boris; Kim, Sungkyoon; Li, Laiyu; Huang, Hanlin; Pennell, Kurt D; Jones, Dean P; Rothman, Nathaniel; Lan, Qing

    2016-01-01

    Background: Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin’s lymphoma and kidney and liver cancer; however, TCE’s mode of action for development of these diseases in humans is not well understood. Methods: Non-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppma)] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population. Results: Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10−5), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = −1.6, P-value = 0.0043), taurine (β = −2.4, P-value = 0.0011) and chenodeoxycholic acid (β = −1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations. Conclusions: High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure

  19. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Berberine exposure triggers developmental effects on planarian regeneration

    PubMed Central

    Balestrini, Linda; Isolani, Maria Emilia; Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria; Deri, Paolo; Batistoni, Renata

    2014-01-01

    The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians. PMID:24810466

  1. Early valproic acid exposure alters functional organization in the primary visual cortex

    PubMed Central

    Pohl-Guimaraes, Fernanda; Krahe, Thomas E.; Medina, Alexandre E.

    2018-01-01

    Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200 mg/kg), Lev (100 mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42–P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val-but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. PMID:21215743

  2. Early valproic acid exposure alters functional organization in the primary visual cortex.

    PubMed

    Pohl-Guimaraes, Fernanda; Krahe, Thomas E; Medina, Alexandre E

    2011-03-01

    Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200mg/kg), Lev (100mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42-P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val- but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Concentration variations of amino acids in mammalian fossils: effects of diagenesis and the implications for amino acid racemization analysis

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

    Blackwell, B.; Rutter, N.W.

    Detailed amino acid analysis of bones, teeth, and antler from several mammal species have shown that concentrations of several amino acids can be related to three factors: type of material analyzed, diagenetic alteration of the material, and relative age of the fossil. Concentrations of several amino acids are significantly different in enamel compared to those of dentine or cement. This can be used to check that no contamination of one material by another has occurred, which is critical for using the data for amino acid dating, since all three materials have different racemization rates for some acids. With increased inmore » growth of secondary minerals, generally reduced amino acid concentrations are observed. Interacid ratios and concentrations vary significantly the norms expected for the type of material with increasing degrees of alteration. These effects can be linked to abnormal racemization ratios observed in the same samples. Therefore, abnormal concentrations and/or interacid ratios can be used to detect samples in which the D/L amino acid ratios otherwise appear normal, thereby insuring better accuracy of amino acid racemization analysis. For unaltered fossils, with increasing sample age regardless the type of material, some amino acids steadily degrade, while others actually increase in concentration initially due to their generation as by-products of decay. Preliminary studies indicate that this progressive alteration can used to complement racemization data for determining relative stratigraphic sequences.« less

  4. Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes.

    PubMed

    Marshall, Nicole E; Fraley, Gwen; Feist, Cori; Burns, Michael J; Pereira, Leonardo

    2012-08-01

    To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity.

  5. Rat fertility and embryo fetal development: influence of exposure to the Wi-Fi signal.

    PubMed

    Poulletier de Gannes, Florence; Billaudel, Bernard; Haro, Emmanuelle; Taxile, Murielle; Le Montagner, Laureline; Hurtier, Annabelle; Ait Aissa, Saliha; Masuda, Hiroshi; Percherancier, Yann; Ruffié, Gilles; Dufour, Philippe; Veyret, Bernard; Lagroye, Isabelle

    2013-04-01

    In recent decades, concern has been growing about decreasing fecundity and fertility in the human population. Exposure to non-ionizing electromagnetic fields (EMF), especially radiofrequency (RF) fields used in wireless communications has been suggested as a potential risk factor. For the first time, we evaluated the effects of exposure to the 2450MHz Wi-Fi signal (1h/day, 6days/week) on the reproductive system of male and female Wistar rats, pre-exposed to Wi-Fi during sexual maturation. Exposure lasted 3 weeks (males) or 2 weeks (females), then animals were mated and couples exposed for 3 more weeks. On the day before delivery, the fetuses were observed for lethality, abnormalities, and clinical signs. In our experiment, no deleterious effects of Wi-Fi exposure on rat male and female reproductive organs and fertility were observed for 1h per days. No macroscopic abnormalities in fetuses were noted, even at the critical level of 4W/kg. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Therapeutic efficacy of DL-alpha-lipoic acid on cyclosporine A induced renal alterations.

    PubMed

    Amudha, Ganapathy; Josephine, Anthony; Mythili, Yenjerla; Sundarapandiyan, Rajaguru; Varalakshmi, Palaninathan

    2007-10-01

    The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.

  7. Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients.

    PubMed

    Emerenziani, S; Ribolsi, M; Guarino, M P L; Balestrieri, P; Altomare, A; Rescio, M P; Cicala, M

    2014-01-01

    Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure. © 2013 John Wiley & Sons Ltd.

  8. Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment.

    PubMed

    Sromicki, Jerzy Jan; Hess, Bernhard

    2017-06-01

    Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing

  9. Element uptake and physiological responses of Lactuca sativa upon co-exposures to tourmaline and dissolved humic acids.

    PubMed

    Jia, Weili; Wang, Cuiping; Ma, Chuanxin; Wang, Jicheng; Sun, Hongwen

    2018-06-01

    Element migration and physiological response in Lactuca sativa upon co-exposure to tourmaline (T) and dissolved humic acids (DHAs) were investigated. Different fractions of DHA 1 and DHA 4 and three different doses of T were introduced into Hoagland's solution. The results indicated that T enhanced the contents of elements such as N and C, Si and Al in the roots and shoots. The correlation between TF values of Si and Al (R 2  = 0.7387) was higher than that of Si and Mn (R 2  = 0.4961) without the presence of DHAs. However, both DHA 1 and DHA 4 increased the correlation between Si and Mn, but decreased the one between Si and Al. CAT activities in T treatments were positively correlated to the contents of N and Al in the shoots, whose R 2 was 0.9994 and 0.9897, respectively. In the co-exposure of DHAs and tourmaline, DHA 4 exhibited more impacts on element uptake, CAT activities, as well as ABA contents in comparison with the presence of DHA 1 , regardless of the T exposure doses. These results suggested that DHAs have effects on mineral element behaviors and physiological response in Lactuca sativa upon exposure to tourmaline for the first time, which had great use in guiding soil remediation.

  10. Lead exposure affects health indices in free-ranging ducks in Argentina.

    PubMed

    Ferreyra, Hebe; Beldomenico, Pablo M; Marchese, Krysten; Romano, Marcelo; Caselli, Andrea; Correa, Ana I; Uhart, Marcela

    2015-05-01

    Numerous experiments under controlled conditions and extensive investigation of waterfowl die-offs have demonstrated that exposure to lead from spent gunshot is highly detrimental to the health of waterfowl. However, few studies have focused on examining the more subtle sub-lethal effects of lead toxicity on ducks in non-experimental settings. In our study, the health of ducks exposed to varying amounts of lead under natural conditions was assessed by correlating individual lead exposure with relevant indices of health. Based on hunter-killed wild ducks in Argentina, we measured spleen mass, body condition, examined bone marrow smears, and determined Ca and P in bone tissue. In free-ranging live-trapped ducks we determined basic hematology and aminolevulinic acid dehydratase activity. Using multivariate analyses, we found that, when controlling for the potential confounding effect of site type, year, duck species, body mass and age, lead levels in the liver were negatively associated with body condition and spleen mass. Spleen mass was also lower in ducks with higher lead levels in their bones. In live ducks, high blood lead levels were associated with low packed cell volume and red cell morphologic abnormalities. These findings suggest that, despite the lack of recorded lead-induced mortality in the region, lead exposure results in less conspicuous but still significant impacts on the health of ducks, which could have serious implications for their conservation. Moreover, this evidence further supports the need for urgently banning lead shot in the region.

  11. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

    PubMed

    Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

    2010-10-01

    Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

  12. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow. (b) Classification. Class II. [52 FR 16122, May 1, 1987; 53 FR....1295 Folic acid test system. (a) Identification. A folic acid test system is a device intended to...

  13. Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux.

    PubMed

    López-Alonso, Manuel; Moya, Maria Jose; Cabo, Jose Antonio; Ribas, Juan; del Carmen Macías, Maria; Silny, Jiry; Sifrim, Daniel

    2006-08-01

    Gastroesophageal reflux is a physiologic process and is considered pathologic (gastroesophageal reflux disease) when it causes symptoms or results in complications. It is common in preterm infants and occurs in healthy neonates. Twenty-four-hour pH monitoring commonly is used in children for diagnosis of gastroesophageal reflux disease, and abnormal reflux is considered with detection of increased esophageal acid exposure. However, in neonates, relatively few gastroesophageal reflux episodes cause esophageal acidification to pH < 4. Premature infants receive frequent feeds, which can induce a weaker acid secretory response than that observed in older infants and adults. As a consequence, gastric pH may be > 4 for prolonged periods, and reflux of gastric contents might be less acidic or even alkaline. Esophageal impedance monitoring can detect weakly acidic and even alkaline gastroesophageal reflux. The role of weakly acidic reflux in the pathophysiology of gastroesophageal reflux disease in preterm infants is not clear. To date, studies that have used impedance-pH in neonates assessed the association between nonacid reflux and cardiorespiratory symptoms, but no impedance data from healthy preterm neonates have been available to determine whether those symptomatic neonates had an increased number of weakly acidic reflux episodes or increased reactivity to a physiologic number of reflux events. Our aim with this study was to provide impedance-pH values for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates. Esophageal impedance was recorded for 24 hours in 21 asymptomatic preterm neonates by replacing the conventional feeding tube with a specially designed feeding tube that included 9 impedance electrodes (8 French). All neonates were asymptomatic, with spontaneous breathing. Reflux monitoring was performed after comprehensive explanation and on receipt of written parental consent. Esophageal and gastric pH were monitored using a separate

  14. Morphological and behavioral responses of zebrafish after 24 h of ketamine embryonic exposure

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

    Félix, Luís M., E-mail: lfelix@utad.pt

    Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24 h-LC{sub 50} was calculated from percent survival using probit analysis. Based on the 24 h-LC{sub 50} (94.4 mg L{sup −1}), embryos (2 hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24 h to ketamine concentrations of 50, 70 or 90 mg L{supmore » −1}. Developmental parameters were evaluated on the course of the experimental period, and anatomical abnormalities and locomotor deficits were analyzed at 144 hpf. Although the portion of ketamine transferred into the embryo was higher in the lowest exposed group (about 0.056 ± 0.020 pmol per embryo), the results showed that endpoints such as increased mortality, edema, heart rate alterations, malformation and abnormal growth rates were significantly affected. At 144 hpf, the developmental abnormalities included thoracic and trunk abnormalities in the groups exposed to 70 and 90 mg L{sup −1}. Defects in cartilage (alcian blue) and bone (calcein) elements also corroborated the craniofacial anomalies observed. A significant up-regulation of the development-related gene nog3 was detected by qRT-PCR at 8 hpf. Early exposure to ketamine also resulted in long-term behavioral changes, such as an increase in thigmotaxis and disruption of avoidance behavior at 144 hpf. Altogether, this study provides new evidence on the ketamine teratogenic potential, indicating a possible pharmacological impact of ketamine in aquatic environments. - Highlights: • 24 h exposure to ketamine increases mortality. • Morphological changes were observed after exposure. • Exposure to ketamine leads to severe craniofacial anomalies. • Developmental gene

  15. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Exposure of tumor-bearing mice to extremely high-frequency electromagnetic radiation modifies the composition of fatty acids in thymocytes and tumor tissue.

    PubMed

    Gapeyev, Andrew B; Kulagina, Tatiana P; Aripovsky, Alexander V

    2013-08-01

    To test the participation of fatty acids (FA) in antitumor effects of extremely high-frequency electromagnetic radiation (EHF EMR), the changes in the FA composition in the thymus, liver, blood plasma, muscle tissue, and tumor tissue in mice with Ehrlich solid carcinoma exposed to EHF EMR were studied. Normal and tumor-bearing mice were exposed to EHF EMR with effective parameters (42.2 GHz, 0.1 mW/cm2, 20 min daily during five consecutive days beginning the first day after the inoculation of tumor cells). Fatty acid composition of various organs and tissues of mice were determined using a gas chromatography. It was shown that the exposure of normal mice to EHF EMR or tumor growth significantly increased the content of monounsaturated FA (MUFA) and decreased the content of polyunsaturated FA (PUFA) in all tissues examined. Exposure of tumor-bearing mice to EHF EMR led to the recovery of FA composition in thymocytes to the state that is typical for normal animals. In other tissues of tumor-bearing mice, the exposure to EHF EMR did not induce considerable changes that would be significantly distinguished between disturbances caused by EHF EMR exposure or tumor growth separately. In tumor tissue which is characterized by elevated level of MUFA, the exposure to EHF EMR significantly decreased the summary content of MUFA and increased the summary content of PUFA. The recovery of the FA composition in thymocytes and the modification of the FA composition in the tumor under the influence of EHF EMR on tumor-bearing animals may have crucial importance for elucidating the mechanisms of antitumor effects of the electromagnetic radiation.

  17. A Longitudinal Analysis of Prenatal Exposure to Methylmercury and Fatty Acids in the Seychelles

    PubMed Central

    Stokes-Riner, Abbie; Thurston, Sally W.; J.Myers, Gary; Duffy, Emeir M.; Wallace, Julie; Bonham, Maxine; Robson, Paula; Shamlaye, Conrad F.; Strain, J.J.; Watson, Gene

    2011-01-01

    Background Maternal fish consumption during pregnancy exposes the fetus simultaneously to methyl mercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n-3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing. Methods A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included. Results Maternal hair MeHg had a negative effect on BSID PDI, while maternal n-3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis. Conclusions The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure. PMID:21145963

  18. A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles.

    PubMed

    Stokes-Riner, Abbie; Thurston, Sally W; Myers, Gary J; Duffy, Emeir M; Wallace, Julie; Bonham, Maxine; Robson, Paula; Shamlaye, Conrad F; Strain, J J; Watson, Gene; Davidson, Philip W

    2011-01-01

    Maternal fish consumption during pregnancy exposes the fetus simultaneously to methylmercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n-3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing. A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included. Maternal hair MeHg had a negative effect on BSID PDI, while maternal n-3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis. The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Dialkyl phosphate urinary metabolites and chromosomal abnormalities in human sperm.

    PubMed

    Figueroa, Zaida I; Young, Heather A; Meeker, John D; Martenies, Sheena E; Barr, Dana Boyd; Gray, George; Perry, Melissa J

    2015-11-01

    The past decade has seen numerous human health studies seeking to characterize the impacts of environmental exposures, such as organophosphate (OP) insecticides, on male reproduction. Despite an extensive literature on OP toxicology, many hormone-mediated effects on the testes are not well understood. This study investigated environmental exposures to OPs and their association with the frequency of sperm chromosomal abnormalities (i.e., disomy) among adult men. Men (n=159) from a study assessing the impact of environmental exposures on male reproductive health were included in this investigation. Multi-probe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine XX18, YY18, XY18 and total disomy in sperm nuclei. Urine was analyzed using gas chromatography coupled with mass spectrometry for concentrations of dialkyl phosphate (DAP) metabolites of OPs [dimethylphosphate (DMP); dimethylthiophosphate (DMTP); dimethyldithiophosphate (DMDTP); diethylphosphate (DEP); diethylthiophosphate (DETP); and diethyldithiophosphate (DEDTP)]. Poisson regression was used to model the association between OP exposures and disomy measures. Incidence rate ratios (IRRs) were calculated for each disomy type by exposure quartiles for most metabolites, controlling for age, race, BMI, smoking, specific gravity, total sperm concentration, motility, and morphology. A significant positive trend was seen for increasing IRRs by exposure quartiles of DMTP, DMDTP, DEP and DETP in XX18, YY18, XY18 and total disomy. A significant inverse association was observed between DMP and total disomy. Findings for total sum of DAP metabolites concealed individual associations as those results differed from the patterns observed for each individual metabolite. Dose-response relationships appeared nonmonotonic, with most of the increase in disomy rates occurring between the second and third exposure quartiles and without additional increases between the third and fourth

  20. TWENTY WEEK EXPOSURES TO THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID: REPRODUCTIVE CYCLICITY AND STEROID CONCENTRATIONS IN THE FEMALE SPRAGUE-DAWLEY RAT

    EPA Science Inventory

    Abstract
    Elevated gavage exposures to the drinking water disinfection by-product dibromoacetic acid (DBA) have been found to disrupt estrous cyclicity in the rat and induce increases in estradiol concentrations in both cycling (day of estrus) and ovariectomized/estradiol-impla...

  1. Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

    PubMed

    Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

    1985-10-01

    We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

  2. Chromosomal abnormalities in human sperm

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

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhapsmore » reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.« less

  3. The risk of infertility and delayed conception associated with exposures in the Danish workplace

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

    Rachootin, P.; Olsen, J.

    1983-05-01

    The association between infertility and a number of occupations and occupational exposures was examined in a case-control study utilizing data collected from medical records and mailed questionnaires. The results suggest that male exposure to heat and female exposure to noise, textile dyes and lead, mercury, and cadmium are associated with infertility. Further research is needed to examine the entire spectrum of abnormal reproductive and developmental outcomes of exposure to these agents and to identify their full effects.

  4. 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...

  5. Relationship between umbilical cord essential fatty acid content and the quality of general movements of healthy term infants at 3 months.

    PubMed

    Bouwstra, Hylco; Dijck-Brouwer, Da Janneke; Decsi, Tamás; Boehm, Günther; Boersma, E Rudy; Muskiet, Frits A J; Hadders-Algra, Mijna

    2006-05-01

    Prenatal essential fatty acid (EFA) status might be an important factor in the development of the central nervous system (CNS). The aim of the present study was to evaluate the relationship between the fatty acid compositions of the umbilical blood vessels at birth, used as a proxy of prenatal EFA status, and quality of general movements (GMs) at 3 mo. Umbilical artery and vein fatty acid compositions were investigated in a mixed group of breastfed infants and infants fed with formula with or without long-chain polyunsaturated fatty acid (LCPUFA) supplementation. At the age of 3 mo, video assessment of the quality of GMs was performed to evaluate neurologic condition. The quality of GMs was scored by assessing the degree of variation, complexity, and fluency. Outcomes were classified as normal-optimal, normal suboptimal, mildly abnormal, and definitely abnormal movements. Information on potential confounders, including the type of postnatal feeding, was collected prospectively. Associations between fatty acid status at birth and quality of GMs were investigated, and multinomial logistic regression analyses were carried out. None of the infants showed definitely abnormal movements. Infants with mildly abnormal GMs had a lower EFA index, lower arachidonic acid (AA) content, higher total n-9 fatty acid, and higher total monounsaturated fatty acid (MUFA) content in the umbilical artery compared with infants with normal GMs. Multivariate analyses confirmed these findings. We conclude that mildly abnormal GMs are associated with a less favorable EFA status in the umbilical artery.

  6. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

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

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high inmore » most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.« less

  7. Correlation between urinary methoxyacetic acid and exposure of ethylene glycol dimethyl ether in a lithium battery plant.

    PubMed

    Yokota, Kozo; Ueno, Hiroshi; Ikeda, Naoko; Johyama, Yasushi; Michitsuji, Hiromi; Yamada, Seiji

    2007-10-01

    To examine the correlation between airborne ethylene glycol dimethyl ether (EGdiME) exposures and the urinary methoxyacetic acid (MAA) and to approach the issue of a permissible exposure limit for EGdiME. The survey was conducted on Thursday. Workers occupationally exposed to EGdiME, as well as nonexposed controls, were studied in combination with one of the authors, who was coincidentally exposed to EGdiME while carrying out the study. Air levels of EGdiME were determined by personal sampling on passive gas tubes. Urine was collected from nine control subjects and ten workers immediately before and after the shift, and from one of the authors at intervals during 12 h. The analyses of EGdiME in air and MAA in urine were performed by gas chromatography with flame ionization detection. The time-weighted average (TWA) air levels of EGdiME ranged from 0.7 to 10.5 ppm during 8 h work shifts. The urinary levels of MAA in one of the authors increased continuously during exposure and after the end of exposure. The levels of urinary MAA in the exposed workers were significantly higher than those in the control subjects. On the other hand, the postshift values were higher than the preshift values in the exposed workers, but the difference was not significant. A linear correlation was found between the TWA air levels of EGdiME and creatinine-adjusted MAA levels in urine collected at the end of the shift (r = 0.933; P < 0.0001). According to our equation, a linear extrapolation to the biological limit value recommended by Shih et al. (1999) of 40 mg MAA/g crea indicated an average inhalation exposure to EGdiME over the workweek of 12 ppm. These results indicate that the determination of MAA in urine is suitable for use in the biological monitoring of EGdiME exposure.

  8. Environmental Lead (Pb) Exposure Versus Fatty Acid Content in Blood and Milk of the Mother and in the Blood of Newborn Children.

    PubMed

    Baranowska-Bosiacka, Irena; Kosińska, Ida; Jamioł, Dominika; Gutowska, Izabela; Prokopowicz, Adam; Rębacz-Maron, Ewa; Goschorska, Marta; Olszowski, Tomasz; Chlubek, Dariusz

    2016-04-01

    Significant progress in understanding the effects of the neurotoxic action of lead (Pb) in young organisms had led to reduction of "safe" level in the blood (Pb-B) to 5 μg/dL in children and pregnant women. Prolonged exposure to relatively low levels of Pb, generally asymptomatic and subclinical (i.e., microintoxication), is currently the dominant form of environmental poisoning, and its negative effects on health may appear after many years, e.g., secondary contamination from Pb bone deposits released in pregnancy. Therefore, the aim of this study was to investigate the effect of environmental exposure (urban areas) of mothers to Pb, on its levels in their milk and blood and in the blood of newborns. Moreover, the aim was to determine the fatty acid profile in the mothers' blood and milk and in the blood of newborns. We also wanted to find if infant birth weight depends on Pb blood levels, as well as on Pb and fatty acid levels in the blood and milk of the mothers. Finally, we examined if the mothers' weight and body mass index (BMI) before pregnancy influenced the concentration of Pb and fatty acid profile in the blood and milk of mothers and in the blood of their children. Analysis of fatty acids elaidic (C18:1, 9t), oleic (C18:1, 9c), vaccenic (C18:1, 11t), cis-vaccenic (C18:1, 11c), linoleic (C18:2, cis), γ-linolenic (C18:3, n-6), α-linolenic (C18:3, n-3), arachidonic (C20:4, n-6), eicosapentaenoic (C20:5, n-3), and docosahexaenoic (C22:6, n-3) was conducted by gas chromatography. The concentration of Pb in the whole blood and milk were determined by atomic absorption spectrometry with graphite furnace atomization and Zeeman correction. Our study established a significant and strong correlation between the content of Pb in the blood of the mother and the child. This supports the assumption that the transport of Pb through the placenta is neither regulated nor selective. Environmental maternal exposure to lead resulting in Pb-B levels considered safe for

  9. Cyclopiazonic acid augments the hepatic and renal oxidative stress in broiler chicks.

    PubMed

    Malekinejad, H; Akbari, P; Allymehr, M; Hobbenaghi, R; Rezaie, A

    2011-08-01

    Generation of reactive oxygen species (ROS) leads to serious tissue injuries. The effect of cyclopiazonic acid (CPA) on oxidative stress markers in the liver and kidneys of broiler chicks was studied. Ten-day-old male broiler chicks (Ross 308) were assigned into the control and test groups, which received normal saline and 10, 25, and 50 μg/kg CPA, respectively, for 28 days. Body weight gain, serum level of alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), uric acid, creatinine, and blood urea nitrogen (BUN) were measured after 2 and 4 weeks exposure. Moreover, the total thiol molecules (TTM) and malondialdehyde (MDA) content of the liver and kidneys were assessed. No significant differences (p > 0.05) were found in body weight gain between the control and test groups. Whereas, the hepatic weight increased significantly (p < 0.05) in animals that received 25 and 50 μg/kg CPA. Both ALP and GGT level in serum were elevated in comparison to the control group. CPA also resulted in uric acid, creatinine, and BUN enhancement in broilers. The MDA content of the liver and kidneys showed remarkable increase. By contrast, the TTM levels in the liver and kidneys were significantly (p < 0.05) attenuated. Histopathological findings confirmed the biochemical changes in either organ characterized by inflammatory cells infiltration along with severe congestion and cell swelling, suggesting an inflammatory response. These data suggest that exposure to CPA resulted in hepatic and renal disorders, which were reflected as biochemical markers alteration and pathological injuries in either organ. The biochemical alteration and pathological abnormalities may be attributed to CPA-induced oxidative stress.

  10. Ultrastructural brain abnormalities and associated behavioral changes in mice after low-intensity blast exposure.

    PubMed

    Song, Hailong; Konan, Landry M; Cui, Jiankun; Johnson, Catherine E; Langenderfer, Martin; Grant, DeAna; Ndam, Tina; Simonyi, Agnes; White, Tommi; Demirci, Utkan; Mott, David R; Schwer, Doug; Hubler, Graham K; Cernak, Ibolja; DePalma, Ralph G; Gu, Zezong

    2018-07-16

    Explosive blast-induced mild traumatic brain injury (mTBI), a "signature wound" of recent military conflicts, commonly affects service members. While past blast injury studies have provided insights into TBI with moderate- to high-intensity explosions, the impact of primary low-intensity blast (LIB)-mediated pathobiology on neurological deficits requires further investigation. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a primary LIB injury murine model exposed to open field detonation of 350 g of high-energy explosive C4. We quantified ultrastructural and behavioral changes up to 30 days post blast injury (DPI). The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 PSI (46.6 kPa) at a 3-m distance from the center of the explosion, a positive phase duration of approximate 3.0 milliseconds (ms), a maximal impulse of 8.7 PSI × ms and a sharp rising time of 9 × 10 -3  ms, with no apparent impact/acceleration in exposed animals. Neuropathologically, myelinated axonal damage was observed in blast-exposed groups at 7 DPI. Using transmission electron microscopy, we observed and quantified myelin sheath defects and mitochondrial abnormalities at 7 and 30 DPI. Inverse correlations between blast intensities and neurobehavioral outcomes including motor activities, anxiety levels, nesting behavior, spatial learning and memory occurred. These observations uncover unique ultrastructural brain abnormalities and associated behavioral changes due to primary blast injury and provide key insights into its pathogenesis and potential treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. 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.

  12. Embryonic Exposure to Valproic Acid Impairs Social Predispositions of Newly-Hatched Chicks.

    PubMed

    Sgadò, Paola; Rosa-Salva, Orsola; Versace, Elisabetta; Vallortigara, Giorgio

    2018-04-12

    Biological predispositions to attend to visual cues, such as those associated with face-like stimuli or with biological motion, guide social behavior from the first moments of life and have been documented in human neonates, infant monkeys and domestic chicks. Impairments of social predispositions have been recently reported in neonates at high familial risk of Autism Spectrum Disorder (ASD). Using embryonic exposure to valproic acid (VPA), an anticonvulsant associated to increased risk of developing ASD, we modeled ASD behavioral deficits in domestic chicks. We then assessed their spontaneous social predispositions by comparing approach responses to a stimulus containing a face configuration, a stuffed hen, vs. a scrambled version of it. We found that this social predisposition was abolished in VPA-treated chicks, whereas experience-dependent mechanisms associated with filial imprinting were not affected. Our results suggest a specific effect of VPA on the development of biologically-predisposed social orienting mechanisms, opening new perspectives to investigate the neurobiological mechanisms involved in early ASD symptoms.

  13. Effect of seafood mediated PCB exposure on desaturase activity and PUFA profile in Faroese septuagenarians.

    PubMed

    Tøttenborg, Sandra Søgaard; Choi, Anna L; Bjerve, Kristian S; Weihe, Pal; Grandjean, Philippe

    2015-07-01

    Polychlorinated biphenyl (PCB) exposure may affect serum concentrations of polyunsaturated fatty acids (PUFAs) by inhibiting desaturases ∆5 and ∆6 that drive their synthesis from precursor fatty acids. Such changes in the composition of fatty acids may affect cardiovascular disease risk, which is thought to increase at elevated PCB exposures. This population-based cross-sectional study examined 712 Faroese men and women aged 70-74 years. The serum phospholipid fraction of fasting blood samples was used to determine the PUFA profile, including linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosatrienoic acid, and other relevant fatty acids. Ratios between precursor and metabolite fatty acids were used as proxies for ∆5 and ∆6 desaturase activity. Tertiles of serum-PCB concentrations were used in multiple regression analyses to determine the association between the exposure and desaturase activity. In multiple regression models, PCB exposure was inversely related to the estimated Δ6 desaturase activity resulting in accumulation of precursor fatty acids and decrease in the corresponding product PUFAs. A positive association between PCB and Δ5 desaturation was also found. A relative increase in EA was also observed, though only in the third tertile of PCB exposure. Non-linear relationships between the exposure and the desaturase activity were not found. Consuming fish and seafood may not be translated into beneficial fatty acid profiles if the diet simultaneously causes exposure to PCBs. Although the desaturase estimates were likely influenced by dietary intakes of product PUFAs, the association between PCB exposure and ∆6 desaturase activity is plausible and may affect cardiovascular disease risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Functional brain MRI in patients complaining of electrohypersensitivity after long term exposure to electromagnetic fields.

    PubMed

    Heuser, Gunnar; Heuser, Sylvia A

    2017-09-26

    Ten adult patients with electromagnetic hypersensitivity underwent functional magnetic resonance imaging (fMRI) brain scans. All scans were abnormal with abnormalities which were consistent and similar. It is proposed that fMRI brain scans be used as a diagnostic aid for determining whether or not a patient has electromagnetic hypersensitivity. Over the years we have seen an increasing number of patients who had developed multi system complaints after long term repeated exposure to electromagnetic fields (EMFs). These complaints included headaches, intermittent cognitive and memory problems, intermittent disorientation, and also sensitivity to EMF exposure. Regular laboratory tests were within normal limits in these patients. The patients refused to be exposed to radioactivity. This of course ruled out positron emission tomography (PET) and single-photon emission computed tomography (SPECT) brain scanning. This is why we ordered fMRI brain scans on these patients. We hoped that we could document objective abnormalities in these patients who had often been labeled as psychiatric cases. Ten patients first underwent a regular magnetic resonance imaging (MRI) brain scan, using a 3 Tesla Siemens Verio MRI open system. A functional MRI study was then performed in the resting state using the following sequences: A three-dimensional, T1-weighted, gradient-echo (MPRAGE) Resting state network. The echo-planar imaging (EPI) sequences for this resting state blood oxygenation level dependent (BOLD) scan were then post processed on a 3D workstation and the independent component analysis was performed separating out the various networks. Arterial spin labeling. Tractography and fractional anisotropy. All ten patients had abnormal functional MRI brain scans. The abnormality was often described as hyper connectivity of the anterior component of the default mode in the medial orbitofrontal area. Other abnormalities were usually found. Regular MRI studies of the brain were mostly

  15. Exposure misclassification due to residential mobility during pregnancy.

    PubMed

    Hodgson, Susan; Lurz, Peter W W; Shirley, Mark D F; Bythell, Mary; Rankin, Judith

    2015-06-01

    Pregnant women are a highly mobile group, yet studies suggest exposure error due to migration in pregnancy is minimal. We aimed to investigate the impact of maternal residential mobility on exposure to environmental variables (urban fabric, roads and air pollution (PM10 and NO₂)) and socio-economic factors (deprivation) that varied spatially and temporally. We used data on residential histories for deliveries at ≥ 24 weeks gestation recorded by the Northern Congenital Abnormality Survey, 2000-2008 (n=5399) to compare: (a) exposure at conception assigned to maternal postcode at delivery versus maternal postcode at conception, and (b) exposure at conception assigned to maternal postcode at delivery versus mean exposure based on residences throughout pregnancy. In this population, 24.4% of women moved during pregnancy. Depending on the exposure variable assessed, 1-12% of women overall were assigned an exposure at delivery >1 SD different to that at conception, and 2-25% assigned an exposure at delivery >1 SD different to the mean exposure throughout pregnancy. To meaningfully explore the subtle associations between environmental exposures and health, consideration must be given to error introduced by residential mobility. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

  16. Effects of pre- and postnatal exposure to chromium picolinate or picolinic acid on neurological development in CD-1 mice.

    PubMed

    Bailey, Melissa M; Boohaker, Jonathan G; Jernigan, Peter L; Townsend, Megan B; Sturdivant, John; Rasco, Jane F; Vincent, John B; Hood, Ronald D

    2008-07-01

    Chromium picolinate, Cr(pic)3, a popular dietary supplement marketed as an aid in fat loss and lean muscle gain, has also been suggested as a therapy for women with gestational diabetes. The current study investigated the effects of maternal exposure to Cr(pic)3 and picolinic acid during gestation and lactation on neurological development of the offspring. Mated female CD-1 mice were fed diets from implantation through weaning that were either untreated or that contained Cr(pic)3 (200 mg kg(-1) day(-1)) or picolinic acid (174 mg kg(-1) day(-1)). A comprehensive battery of postnatal tests was administered, including a modified Fox battery, straight-channel swim, open-field activity, and odor-discrimination tests. Pups exposed to picolinic acid tended to weigh less than either control or Cr(pic)3-exposed pups, although the differences were not significant. Offspring of picolinic acid-treated dams also appeared to display impaired learning ability, diminished olfactory orientation ability, and decreased forelimb grip strength, although the differences among the treatment groups were not significant. The results indicate that there were no significant effects on the offspring with regard to neurological development from supplementation of the dams with either Cr(pic)3 or picolinic acid.

  17. Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure

    PubMed Central

    Horan, Tegan S.; Marre, Alyssa; Hassold, Terry; Lawson, Crystal; Hunt, Patricia A.

    2017-01-01

    The hypothesis that developmental estrogenic exposure induces a constellation of male reproductive tract abnormalities is supported by experimental and human evidence. Experimental data also suggest that some induced effects persist in descendants of exposed males. These multi- and transgenerational effects are assumed to result from epigenetic changes to the germline, but few studies have directly analyzed germ cells. Typically, studies of transgenerational effects have involved exposing one generation and monitoring effects in subsequent unexposed generations. This approach, however, has limited human relevance, since both the number and volume of estrogenic contaminants has increased steadily over time, intensifying rather than reducing or eliminating exposure. Using an outbred CD-1 mouse model, and a sensitive and quantitative marker of germline development, meiotic recombination, we tested the effect of successive generations of exposure on the testis. We targeted the germline during a narrow, perinatal window using oral exposure to the synthetic estrogen, ethinyl estradiol. A complex three generation exposure protocol allowed us to compare the effects of individual, paternal, and grandpaternal (ancestral) exposure. Our data indicate that multiple generations of exposure not only exacerbate germ cell exposure effects, but also increase the incidence and severity of reproductive tract abnormalities. Taken together, our data suggest that male sensitivity to environmental estrogens is increased by successive generations of exposure. PMID:28727826

  18. Carbon disulfide exposure and neurotoxic sequelae among viscose rayon workers

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

    Aaserud, O.; Hommeren, O.J.; Tvedt, B.

    1990-01-01

    In Norway's only viscose rayon plant, carbon disulfide (CS2) concentrations in ambient air usually were between 30 and 50 mg/m3 during the first 23 years of production. From 1970/1971 until the factory was closed in 1982, corresponding values were 10-25 mg/m3. Through all of these years, high peak exposures of CS2 and H2S occurred. In 1986, 16 of the 24 men still at work in 1982 and with at least 10 years' experience in the spinning room agreed to participate in this study. Clinical neurological examination demonstrated abnormalities in 15; neuropsychological tests showed impairments of probable organic origin in 14.more » Thirteen had cerebral atrophy demonstrated by cerebral computed tomography (CT). Electromyography (EMG) was abnormal in six, neurography in 11. Regional cerebral blood flow measurements indicated flow asymmetries in eight, whereas Doppler investigation of the extracranial carotid and vertebral arteries, electroencephalography (EEG), and evoked response investigations were mostly normal. Based on these results and the exposure data, a diagnosis of CS2-induced encephalopathy was reached in eight workers; another six had an encephalopathy in which CS2 exposure was regarded as a partial cause. Correspondingly, seven had a neuropathy probably caused by CS2 exposure alone; in three others, CS2 was found to be the partial cause of a neuropathy. This indicates that long-term, relatively moderate exposure to CS2 in association with high peak exposures to CS2 and H2S involves a substantial risk of developing neurotoxic disease.« less

  19. Evaluation and Comparison of Changes in Microhardness of Primary and Permanent Enamel on Exposure to Acidic Center-filled Chewing Gum: An in vitro Study

    PubMed Central

    Muppa, Radhika; Srinivas, NCH; Kumar, Duddu Mahesh

    2014-01-01

    ABSTRACT Objectives: The study is to evaluate changes in microhardness of enamel after exposure to acidic center filled chewing gum on primary and permanent teeth. Methods: Thirty primary and 30 permanent molar extracted teeth were painted with acid resistant varnish except a small window over buccal surface. Teeth were divided into four groups according to type of teeth and type of chewing gum (Center fresh and Bubbaloo) (D1, P1, D2 and P2); each tooth was exposed to whole chewing gum mashed with 5 ml of artificial saliva for five minutes at room temperature twice a day for 5 days. After the exposure, teeth were stored in deionized water and submitted for microhardness tests. Results: Paired t-test and independent sample t-test were used for statistical analysis. A significant reduction in microhardness was found between exposed and unexposed areas in all groups. There was no statistically significant difference in reduction of microhardness to chewing gums, and between primary and permanent enamel. Conclusion: There is a definite reduction in microhardness in all groups exposed to chewing gums. Both the chewing gums are equally erosive; both permanent and primary teeth were affected. How to cite this article: Mudumba VL, Muppa R, Srinivas NCH, Kumar DM. Evaluation and Comparison of Changes in Microhardness of Primary and Permanent Enamel on Exposure to Acidic Center-filled Chewing Gum: An in vitro Study. Int J Clin Pediatr Dent 2014;7(1):24-29. PMID:25206233

  20. Abnormal Notochord Branching Is Associated with Foregut Malformations in the Adriamycin Treated Mouse Model

    PubMed Central

    Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

    2011-01-01

    Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities. PMID:22132119

  1. Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model.

    PubMed

    Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

    2011-01-01

    Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities.

  2. Abnormal stress responsivity in a rodent developmental disruption model of schizophrenia.

    PubMed

    Zimmerman, Eric C; Bellaire, Mark; Ewing, Samuel G; Grace, Anthony A

    2013-10-01

    Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.

  3. High-resolution metabolomics of occupational exposure to trichloroethylene.

    PubMed

    Walker, Douglas I; Uppal, Karan; Zhang, Luoping; Vermeulen, Roel; Smith, Martyn; Hu, Wei; Purdue, Mark P; Tang, Xiaojiang; Reiss, Boris; Kim, Sungkyoon; Li, Laiyu; Huang, Hanlin; Pennell, Kurt D; Jones, Dean P; Rothman, Nathaniel; Lan, Qing

    2016-10-01

    Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin's lymphoma and kidney and liver cancer; however, TCE's mode of action for development of these diseases in humans is not well understood. Non-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppm a )] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population. Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10 -5 ), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = -1.6, P-value = 0.0043), taurine (β = -2.4, P-value = 0.0011) and chenodeoxycholic acid (β = -1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations. High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology. © The Author 2016; all rights

  4. Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion

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

    Kajimoto, Masaki; Ledee, Dolena R.; Olson, Aaron K.

    Rationale: Deep hypothermic circulatory arrest (DHCA) is often required for the repair of complex congenital cardiac defects in infants. However, DHCA induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion (SCP) theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. Objectives: We tested the hypothesis that SCP modulates glucose entry into the citric acid cycle, and ameliorates abnormalities in glutamate flux which occur in association neuroapoptosis during DHCA. Methods and Results: Eighteen male Yorkshire piglets (age 34-44 days) were assigned randomly to 2 groups of 7 (DHCA or DHCAmore » with SCP for 60 minutes at 18 °C) and 4 control pigs without cardiopulmonary bypass support. After the completion of rewarming from DHCA, 13-Carbon-labeled (13C) glucose as a metabolic tracer was infused. We used gas chromatography-mass spectrometry (GCMS) and nuclear magnetic resonance for metabolic analysis in the frontal cortex. Following 2.5 hours of cerebral reperfusion, we observed similar cerebral ATP levels, absolute levels of lactate and citric acid cycle intermediates, and 13C-enrichment. However, DHCA induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid (GABA)/glutamate along with neuroapoptosis (TUNEL), which were all prevented by SCP. Conclusions: DHCA alone induces abnormalities in cycling of the major neurotransmitters in association with neuroapoptosis, but does not alter cerebral glucose utilization during reperfusion. The data suggest that SCP prevents these modifications in glutamate/glutamine/GABA cycling and protects the cerebral cortex from neuroapoptosis.« less

  5. Assessing human exposure to phthalic acid and phthalate esters from mineral water stored in polyethylene terephthalate and glass bottles.

    PubMed

    Montuori, P; Jover, E; Morgantini, M; Bayona, J M; Triassi, M

    2008-04-01

    Phthalic acid and phthalate esters are of growing interest due to their significant usage and potential toxicity. Polyethylene terephthalate (PET) and glass are both widely used materials for bottled drinking water. In this study, phthalic acid (PhA), bis(2-ethylhexyl) phthalate (DEHP), dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiisoBP) and dibutyl phthalate (DBP) were analysed in a large number of Italian bottled water samples. These samples showed different concentrations of phthalates are nearly 20 times higher in samples bottled in PET than those from glass bottles with total levels of phthalates of 3.52 and 0.19 microg l(-1), respectively. However, the observed levels do not represent a significant exposure pathway when considering the US Environmental Protection Agency (USEPA) reference dose (an estimate of a daily oral exposure to the human population, including sensitive subgroups, that is likely to be without an appreciable risk of deleterious effects during a lifetime). In addition, no significant correlation was found between the phthalate concentrations and the physicochemical properties of the different water samples, apart from the still/sparkling water parameter for the PET samples. In this instance, slightly higher concentrations were observed for the PET bottled still water samples than for the sparkling water samples, although no explanation has been found yet.

  6. Comparison of methods for acid quantification: impact of resist components on acid-generating efficiency

    NASA Astrophysics Data System (ADS)

    Cameron, James F.; Fradkin, Leslie; Moore, Kathryn; Pohlers, Gerd

    2000-06-01

    Chemically amplified deep UV (CA-DUV) positive resists are the enabling materials for manufacture of devices at and below 0.18 micrometer design rules in the semiconductor industry. CA-DUV resists are typically based on a combination of an acid labile polymer and a photoacid generator (PAG). Upon UV exposure, a catalytic amount of a strong Bronsted acid is released and is subsequently used in a post-exposure bake step to deprotect the acid labile polymer. Deprotection transforms the acid labile polymer into a base soluble polymer and ultimately enables positive tone image development in dilute aqueous base. As CA-DUV resist systems continue to mature and are used in increasingly demanding situations, it is critical to develop a fundamental understanding of how robust these materials are. One of the most important factors to quantify is how much acid is photogenerated in these systems at key exposure doses. For the purpose of quantifying photoacid generation several methods have been devised. These include spectrophotometric methods, ion conductivity methods and most recently an acid-base type titration similar to the standard addition method. This paper compares many of these techniques. First, comparisons between the most commonly used acid sensitive dye, tetrabromophenol blue sodium salt (TBPB) and a less common acid sensitive dye, Rhodamine B base (RB) are made in several resist systems. Second, the novel acid-base type titration based on the standard addition method is compared to the spectrophotometric titration method. During these studies, the make up of the resist system is probed as follows: the photoacid generator and resist additives are varied to understand the impact of each of these resist components on the acid generation process.

  7. Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats.

    PubMed

    Dwivedi, Nidhi; Flora, Govinder; Kushwaha, Pramod; Flora, Swaran J S

    2014-01-01

    We investigated protective efficacy of α-lipoic acid (LA), an antioxidant against arsenic and DDVP co-exposed rats. Biochemical variables suggestive of oxidative stress, neurological dysfunction, and tissue histopathological alterations were determined. Male rats were exposed either to 50 ppm sodium arsenite in drinking water or in combination with DDVP (4 mg/kg, subcutaneously) for 10 weeks. α-Lipoic acid (50mg/kg, pos) was also co-administered in above groups. Arsenic exposure led to significant oxidative stress along, hepatotoxicity, hematotoxicity and altered brain biogenic amines levels accompanied by increased arsenic accumulation in blood and tissues. These altered biochemical variables were supported by histopathological examinations leading to oxidative stress and cell death. These biochemical alterations were significantly restored by co-administration of α-lipoic acid with arsenic and DDVP alone and concomitantly. The results indicate that arsenic and DDVP induced oxidative stress and cholinergic dysfunction can be significantly protected by the supplementation of α-lipoic acid. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Alterations in the endocannabinoid system in the rat valproic acid model of autism.

    PubMed

    Kerr, D M; Downey, L; Conboy, M; Finn, D P; Roche, M

    2013-07-15

    The endocannabinoid system plays a crucial role in regulating emotionality and social behaviour, however it is unknown whether this system plays a role in symptoms associated with autism spectrum disorders. The current study evaluated if alterations in the endocannabinoid system accompany behavioural changes in the valproic acid (VPA) rat model of autism. Adolescent rats prenatally exposed to VPA exhibited impaired social investigatory behaviour, hypoalgesia and reduced lococmotor activity on exposure to a novel aversive arena. Levels of the endocananbinoids, anandamide (AEA) and 2-arachidonylglycerol (2-AG) in the hippocampus, frontal cortex or cerebellum were not altered in VPA- versus saline-exposed animals. However, the expression of mRNA for diacylglycerol lipase α, the enzyme primarily responsible for the synthesis of 2-AG, was reduced in the cerebellum of VPA-exposed rats. Furthermore, while the expression of mRNA for the 2-AG-catabolising enzyme monoacylglycerol lipase was reduced, the activity of this enzyme was increased, in the hippocampus of VPA-exposed animals. CB1 or CB2 receptor expression was not altered in any of the regions examined, however VPA-exposed rats exhibited reduced PPARα and GPR55 expression in the frontal cortex and PPARγ and GPR55 expression in the hippocampus, additional receptor targets of the endocannabinoids. Furthermore, tissue levels of the fatty acid amide hydrolase substrates, AEA, oleoylethanolamide and palmitoylethanolamide, were higher in the hippocampus of VPA-exposed rats immediately following social exposure. These data indicate that prenatal VPA exposure is associated with alterations in the brain's endocannabinoid system and support the hypothesis that endocannabinoid dysfunction may underlie behavioural abnormalities observed in autism spectrum disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Mycophenolic acid exposure and complement fraction C3 influence inosine 5'-monophosphate dehydrogenase activity in systemic lupus erythematosus.

    PubMed

    Mino, Yasuaki; Naito, Takafumi; Shimoyama, Kumiko; Ogawa, Noriyoshi; Kawakami, Junichi

    2017-07-01

    activity may be determined by mycophenolic acid exposure and complement fraction C3 in systemic lupus erythematosus patients.

  10. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Exposure estimates to disinfection by-products of chlorinated drinking water.

    PubMed

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

    1999-02-01

    Exposure to disinfection by-products (DBPs) of drinking water is multiroute and occurs in households serviced by municipal water treatment facilities that disinfect the water as a necessary step to halt the spread of waterborne infectious diseases. Biomarkers of the two most abundant groups of DBPs of chlorination, exhaled breath levels of trihalomethanes (THMs) and urinary levels of two haloacetic acids, were compared to exposure estimates calculated from in-home tap water concentrations and responses to a questionnaire related to water usage. Background THM breath concentrations were uniformly low. Strong relationships were identified between the THM breath concentrations collected after a shower and both the THM water concentration and the THM exposure from a shower, after adjusting for the postshower delay time in collecting the breath sample. Urinary haloacetic acid excretion rates were not correlated to water concentrations. Urinary trichloroacetic acid excretion rates were correlated with ingestion exposure, and that correlation was stronger in a subset of individuals who consumed beverages primarily within their home where the concentration measurements were made. No correlation was observed between an average 48-hr exposure estimate and the urinary dichloroacetic acid excretion rate, presumably because of its short biological half-life. Valid biomarkers were identified for DBP exposures, but the time between the exposure and sample collection should be considered to account for different metabolic rates among the DBPs. Further, using water concentration as an exposure estimate can introduce misclassification of exposure for DBPs whose primary route is ingestion due to the great variability in the amount of water ingested across a population.

  12. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

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

    Grossman, S.A.; Trump, D.L.; Chen, D.C.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizingmore » these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.« less

  13. Risk assessment of plant food supplements and other herbal products containing aristolochic acids using the margin of exposure (MOE) approach.

    PubMed

    Abdullah, Rozaini; Diaz, Leolean Nyle; Wesseling, Sebastiaan; Rietjens, Ivonne M C M

    2017-02-01

    After the incidences of induction of aristolochic acid nephropathy after consumption of herbal weight loss preparations that accidentally contained aristolochic acids (AAs), several countries defined national restrictions on the presence of AAs in food, including plant food supplements (PFS) and herbal products. This study investigates whether the risks associated with exposure to AAs via PFS and herbal products are at present indeed negligible. Data reported in literature on AA levels in PFS and other herbal products and also obtained from a new series of PFS in the present study were used to calculate the estimated daily intakes (EDIs) and corresponding margins of exposure (MOEs). Available literature data revealed that 206 out of 573 samples were found to contain aristolochic acid I (AAI) and/or aristolochic acid II (AAII). The results obtained from recently collected PFS revealed that both AAI and AAII were detected in three out of 18 analysed PFS at levels up to 594.8 and 235.3 µg g -1 , respectively, being in line with the levels reported in literature. The EDIs resulting from intake of these PFS resulted in MOEs that were generally below 10,000, corroborating the priority for risk management. Although these results refer to PFS collected by targeted sampling strategies, the data reveal that AA-containing PFS are still freely available. When considering that the use of these samples may be limited to shorter periods of time, the EDIs might be lower, but MOE values would still be lower than 10,000 for more than 50% of the AA-containing PFS and herbal products. In conclusion, the presence of AAs in PFS and herbal products even several years after instalment of the legal restrictions still raises concern, especially for people who frequently use the respective PFS and herbal products.

  14. Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

    PubMed

    Yuan, Yao Zong; Fang, Jing Yuan; Zou, Duo Wu; Levinson, Nigel; Jenner, Bartosz; Wilkinson, Joanne

    2016-11-01

    To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH <4. Secondary end-points were number of acid reflux episodes (pH <4), longest reflux time and DeMeester scores. All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH <4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs. DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  15. Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression

    PubMed Central

    Lenters, Virissa; Portengen, Lützen; Rignell-Hydbom, Anna; Jönsson, Bo A.G.; Lindh, Christian H.; Piersma, Aldert H.; Toft, Gunnar; Bonde, Jens Peter; Heederik, Dick; Rylander, Lars; Vermeulen, Roel

    2015-01-01

    Background Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts. Citation Lenters V, Portengen L, Rignell-Hydbom A, Jönsson BA, Lindh CH, Piersma AH, Toft G, Bonde JP

  16. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism.

    PubMed

    Gevi, Federica; Zolla, Lello; Gabriele, Stefano; Persico, Antonio M

    2016-01-01

    Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status. ASD-specific urinary metabolomic patterns were explored at an early age in 30 ASD children and 30 matched controls (age range 2-7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC and mass spectrometry, a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. Urinary metabolites displaying the largest differences between young ASD and control children belonged to the tryptophan and purine metabolic pathways. Also, vitamin B 6 , riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate and CoA, and pyrimidine metabolism differed significantly. ASD children preferentially transform tryptophan into xanthurenic acid and quinolinic acid (two catabolites of the kynurenine pathway), at the expense of kynurenic acid and especially of melatonin. Also, the gut microbiome contributes to altered tryptophan metabolism, yielding increased levels of indolyl 3-acetic acid and indolyl lactate. The metabolic pathways most distinctive of young Italian autistic children largely overlap with those found in rodent models of ASD following maternal immune activation or genetic manipulations. These results are consistent with the proposal of a purine-driven cell danger response, accompanied by overproduction of epileptogenic and

  17. Measuring water ingestion from spray exposures.

    PubMed

    Sinclair, Martha; Roddick, Felicity; Nguyen, Thang; O'Toole, Joanne; Leder, Karin

    2016-08-01

    Characterisation of exposure levels is an essential requirement of health risk assessment; however for water exposures other than drinking, few quantitative exposure data exist. Thus, regulatory agencies must use estimates to formulate policy on treatment requirements for non-potable recycled water. We adapted the use of the swimming pool chemical cyanuric acid as a tracer of recreational water ingestion to permit detection of small water volumes inadvertently ingested from spray exposures. By using solutions of 700-1000 mg/L cyanuric acid in an experimental spray exposure scenario, we were able to quantify inadvertent water ingestion in almost 70% of participants undertaking a 10 min car wash activity using a high pressure spray device. Skin absorption was demonstrated to be negligible under the experimental conditions, and the measured ingestion volumes ranged from 0.06 to 3.79 mL. This method could be applied to a range of non-potable water use activities to generate exposure data for risk assessment processes. The availability of such empirical measurements will provide greater assurance to regulatory agencies and industry that potential health risks from exposure to non-potable water supplies are well understood and adequately managed to protect public health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Prenatal Exposure to DEHP Induces Neuronal Degeneration and Neurobehavioral Abnormalities in Adult Male Mice.

    PubMed

    Barakat, Radwa; Lin, Po-Ching; Park, Chan Jin; Best-Popescu, Catherine; Bakery, Hatem H; Abosalum, Mohamed E; Abdelaleem, Nabila M; Flaws, Jodi A; Ko, CheMyong

    2018-04-23

    Phthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies. In this study, we tested the hypothesis that prenatal exposure to DEHP impairs neurobehavior and recognition memory in her male offspring and we investigated one possible mechanism-oxidative damage in the hippocampus. Pregnant CD-1 female mice were orally administered 200μg, 500mg, or 750mg/kg/day DEHP or vehicle from gestational day 11 until birth. The neurobehavioral impact of the prenatal DEHP exposure was assessed at the ages of 16 to 22 months. Elevated plus maze and open field tests were used to measure anxiety levels. Y-maze and novel object recognition tests were employed to measure memory function. The oxidative damage in the hippocampus was measured by the levels of oxidative DNA damage and by SLIM microscopic counting of hippocampal neurons. Adult male mice that were prenatally exposed to DEHP exhibited anxious behaviors and impaired spatial and short-term recognition memory. The number of hippocampal pyramidal neurons was significantly decreased in the DEHP mice. Furthermore, DEHP mice expressed remarkably high levels of cyclooxygenase-2, 8-hydroxyguanine, and thymidine glycol in their hippocampal neurons. DEHP mice also had lower circulating testosterone concentrations and displayed a weaker immunoreactivity than the control mice to androgen receptor expression in the brain. This study found that prenatal exposure to DEHP caused elevated anxiety behavior and impaired recognition memory. These behavioral changes may originate from neurodegeneration caused by oxidative damage and inflammation in the hippocampus. Decreased circulating testosterone concentrations and decreased expression of androgen receptor in the brain also may be factors contributing

  19. S-phenylmercapturic acid (S-PMA) levels in urine as an indicator of exposure to benzene in the Kinshasa population.

    PubMed

    Tuakuila, J

    2013-07-01

    Data on human exposure to chemicals in Africa are scarce. A biomonitoring study was conducted in a representative sample of the population in Kinshasa (Democratic Republic of Congo) to document exposure to benzene. S-phenylmercapturic acid (S-PMA) was measured by LC-MS/MS in spot urine samples from 220 individuals (50.5% women), aged 6-70 years living in the urban area and from 50 additional subjects from the sub-rural area of Kinshasa. Data were compiled as arithmetic means, geometric means, percentile 95th and range expressed in μg/L. Overall, living in urban Kinshasa was associated with increased levels of S-PMA in urine as compared to a population living in the sub-rural area. Increased levels were also found by comparison with some date from literature. This study reveals the high benzene exposure of the Kinshasa population requiring the determination of benzene concentrations in ambient air of Kinshasa and limit values for the protection of human health. Copyright © 2013 Elsevier GmbH. All rights reserved.

  20. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The effect of propionic acid and valeric acid on the cell cycle in root meristems of Pisum sativum

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

    Tramontano, W.A.; Yang, Shauyu; Delillo, A.R.

    1990-01-01

    Propionic acid and valeric acid at 1mM reduced the mitotic index of root meristem cells of Pisum sativum to < 1% after 12 hr in aerated White's medium. This effect varied with different acid concentrations. After a 12 hr exposure to either acid, seedlings transferred to fresh medium without either acid, resumed their normal mitotic index after 12 hr, with a burst of mitosis 8 hr post-transfer. Exposure of root meristem cells to either acid also inhibited ({sup 3}H)-TdR incorporation. Neither acid significantly altered the distribution of meristematic cells in G1 and G2 after 12 hr. The incorporation of ({supmore » 3}H) - uridine was also unaltered by the addition of either acid. This information suggests that propionic acid and valeric acid, limit progression through the cell cycle by inhibiting DNA synthesis and arresting cells in G1 and G2. These results were consistent with previous data which utilized butyric acid.« less

  2. LIPID ABNORMALITIES IN SUCCINATE SEMIALDEHYDE DEHYDROGENASE (Aldh5a1−/−) DEFICIENT MOUSE BRAIN PROVIDE ADDITIONAL EVIDENCE FOR MYELIN ALTERATIONS

    PubMed Central

    Barcelo-Coblijn, G.; Murphy, E. J.; Mills, K.; Winchester, B.; Jakobs, C.; Snead, O.C.; Gibson, KM

    2007-01-01

    Earlier work from our laboratory provided evidence for myelin abnormalities (decreased quantities of proteins associated with myelin compaction, decreased sheath thickness) in cortex and hippocampus of Aldh5a1−/− mice, which have a complete ablation of the succinate semialdehyde dehydrogenase protein [1]. In the current report, we have extended these findings via comprehensive analysis of brain phospholipid fractions, including quantitation of fatty acids in individual phospholipid subclasses and estimation of hexose-ceramide in Aldh5a1−/− brain. In comparison to wild-type littermates (Aldh5a1+/+), we detected a 20% reduction in the ethanolamine glycerophospholipid content of Aldh5a1−/− mice, while other brain phospholipids (choline glycerophospholipid, phosphatidylserine and phosphatidylinositol) were within normal limits. Analysis of individual fatty acids in each of these fractions revealed consistent alterations in n-3 fatty acids, primarily increased 22:6n-3 levels (docosahexaenoic acid; DHA). In the phosphatidyl serine fraction there were marked increases in the proportions of polyunsaturated fatty acids with corresponding decreases of monounsaturated fatty acids. Interestingly, the levels of hexose-ceramide (glucosyl- and galactosylceramide, principal myelin cerebrosides) were decreased in Aldh5a1−/− brain tissue (one-tailed t test, p=0.0449). The current results suggest that lipid and myelin abnormalities in this animal may contribute to the pathophysiology. PMID:17300923

  3. Birth Weight, Ethnicity, and Exposure to Trihalomethanes and Haloacetic Acids in Drinking Water during Pregnancy in the Born in Bradford Cohort

    PubMed Central

    Smith, Rachel B.; Edwards, Susan C.; Best, Nicky; Wright, John; Nieuwenhuijsen, Mark J.; Toledano, Mireille B.

    2015-01-01

    Background: Evidence for a relationship between trihalomethane (THM) or haloacetic acid (HAA) exposure and adverse fetal growth is inconsistent. Disinfection by-products exist as complex mixtures in water supplies, but THMs and HAAs have typically been examined separately. Objectives: We investigated joint exposure at the individual level to THMs and HAAs in relation to birth weight in the multi-ethnic Born in Bradford birth cohort. Methods: Pregnant women reported their water consumption and activities via questionnaire. These data were combined with area-level THM and HAA concentrations to estimate integrated uptake of THMs into blood and HAA ingestion, accounting for boiling/filtering. We examined the relationship between THM and HAA exposures and birth weight of up to 7,438 singleton term babies using multiple linear regression, stratified by ethnicity. Results: Among Pakistani-origin infants, mean birth weight was significantly lower in association with the highest versus lowest tertiles of integrated THM uptake (e.g., –53.7 g; 95% CI: –89.9, –17.5 for ≥ 1.82 vs. < 1.05 μg/day of total THM) and there were significant trends (p < 0.01) across increasing tertiles, but there were no associations among white British infants. Neither ingestion of HAAs alone or jointly with THMs was associated with birth weight. Estimated THM uptake via showering, bathing, and swimming was significantly associated with lower birth weight in Pakistani-origin infants, when adjusting for THM and HAA ingestion via water consumption. Conclusions: To our knowledge, this is the largest DBP and fetal growth study to date with individual water use data, and the first to examine individual-level estimates of joint THM–HAA exposure. Our findings demonstrate associations between THM, but not HAA, exposure during pregnancy and reduced birth weight, but suggest this differs by ethnicity. This study suggests that THMs are not acting as a proxy for HAAs, or vice-versa. Citation: Smith RB

  4. 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.

  5. Assessment of nuclear abnormalities in exfoliated cells from the oral epithelium of mobile phone users.

    PubMed

    Souza, Leonardo da Cunha Menezes; Cerqueira, Eneida de Moraes Marcílio; Meireles, José Roberto Cardoso

    2014-06-01

    Transmission and reception of mobile telephony signals take place through electromagnetic wave radiation, or electromagnetic radiofrequency fields, between the mobile terminal and the radio base station. Based on reports in the literature on adverse effects from exposure to this type of radiation, the objective of this study was to evaluate the genotoxic and cytotoxic potential of such exposure, by means of the micronucleus test on exfoliated cells from the oral epithelium. The sample included 45 individuals distributed in 3 groups according to the amount of time in hours per week (t) spent using mobile phones: group I, t > 5 h; group II, t > 1 h and ≤ 5 h; and group III, t ≤ 1 h. Cells from the oral mucosa were analyzed to assess the numbers of micronuclei, broken egg structures and degenerative nuclear abnormalities indicative of apoptosis (condensed chromatin, karyorrhexis and pyknosis) or necrosis (karyolysis in addition to these changes). The occurrences of micronuclei and degenerative nuclear abnormalities did not differ between the groups, but the number of broken egg (structures that may be associated with gene amplification) was significantly greater in the individuals in group I (p < 0.05).

  6. Neurologic abnormalities in murderers.

    PubMed

    Blake, P Y; Pincus, J H; Buckner, C

    1995-09-01

    Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

  7. Abnormal IgG4 antibody response to aeroallergens in allergic patients.

    PubMed

    Jeannin, P; Delneste, Y; Tillie-Leblond, I; Wallaert, B; carlier, A; Pestel, J; Tonnel, A B

    1994-01-01

    Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders.

  8. Duration-dependent effect of exposure to static electric field on learning and memory ability in mice.

    PubMed

    Xu, Yaqian; Gu, Xiaoyu; Di, Guoqing

    2018-06-07

    With the rapid development of ultra-high-voltage direct-current (UHVDC) transmission, the strength of environmental static electric field (SEF) around UHVDC transmission lines increased substantially, which has aroused widely public attention on the potential health effects of SEF. In this study, the effect of SEF exposure on learning and memory ability was investigated. Institute of Cancer Research mice were exposed to 56.3 kV/m SEF for a short term (7 days) or long term (49 days). Behaviors in the Morris water maze (MWM) test, hippocampal neurotransmitter contents, and oxidative stress indicators were examined. Results showed that short-term SEF exposure significantly prolonged escape latency and decreased the number of platform-site crossovers, as well as decreased the time spent in the target quadrant in the MWM test. Meanwhile, serotonin level and the ratio of glutamate level to γ-aminobutyric acid level changed significantly. Besides, malondialdehyde content and glutathione peroxidase activity increased significantly, while superoxide dismutase activity decreased significantly. After long-term SEF exposure, all indices above showed no significant differences between the SEF and sham exposure groups. These data indicated that short-term exposure to 56.3 kV/m SEF could cause abnormal neurotransmitter levels and oxidative stress in the hippocampus, which led to the decline in learning and memory ability. Under the condition of long-term exposure, the SEF-induced disturbances in neurotransmitter contents and redox balance were offset by the compensatory responses of mice, and thus, the learning and memory ability returned to normal level. The temporary and reversible decline in learning and memory ability was only a common biological effect of SEF rather than a health hazard.

  9. 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

  10. Dandy-Walker syndrome and chromosomal abnormalities.

    PubMed

    Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

    2007-12-01

    Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

  11. Exposure estimates to disinfection by-products of chlorinated drinking water.

    PubMed Central

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

    1999-01-01

    Exposure to disinfection by-products (DBPs) of drinking water is multiroute and occurs in households serviced by municipal water treatment facilities that disinfect the water as a necessary step to halt the spread of waterborne infectious diseases. Biomarkers of the two most abundant groups of DBPs of chlorination, exhaled breath levels of trihalomethanes (THMs) and urinary levels of two haloacetic acids, were compared to exposure estimates calculated from in-home tap water concentrations and responses to a questionnaire related to water usage. Background THM breath concentrations were uniformly low. Strong relationships were identified between the THM breath concentrations collected after a shower and both the THM water concentration and the THM exposure from a shower, after adjusting for the postshower delay time in collecting the breath sample. Urinary haloacetic acid excretion rates were not correlated to water concentrations. Urinary trichloroacetic acid excretion rates were correlated with ingestion exposure, and that correlation was stronger in a subset of individuals who consumed beverages primarily within their home where the concentration measurements were made. No correlation was observed between an average 48-hr exposure estimate and the urinary dichloroacetic acid excretion rate, presumably because of its short biological half-life. Valid biomarkers were identified for DBP exposures, but the time between the exposure and sample collection should be considered to account for different metabolic rates among the DBPs. Further, using water concentration as an exposure estimate can introduce misclassification of exposure for DBPs whose primary route is ingestion due to the great variability in the amount of water ingested across a population. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9924004

  12. Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia.

    PubMed

    Crowe, Elizabeth; Pandeya, Nirmala; Brotherton, Julia M L; Dobson, Annette J; Kisely, Stephen; Lambert, Stephen B; Whiteman, David C

    2014-03-04

    To measure the effectiveness of the quadrivalent human papillomavirus (HPV) vaccine against cervical abnormalities four years after implementation of a nationally funded vaccination programme in Queensland, Australia. Case-control analysis of linked administrative health datasets. Queensland, Australia. Women eligible for free vaccination (aged 12-26 years in 2007) and attending for their first cervical smear test between April 2007 and March 2011. High grade cases were women with histologically confirmed high grade cervical abnormalities (n = 1062) and "other cases" were women with any other abnormality at cytology or histology (n = 10,887). Controls were women with normal cytology (n = 96,404). Exposure odds ratio (ratio of odds of antecedent vaccination (one, two, or three vaccine doses compared with no doses) among cases compared with controls), vaccine effectiveness ((1-adjusted odds ratio) × 100), and number needed to vaccinate to prevent one cervical abnormality at first screening round. We stratified by four age groups adjusted for follow-up time, year of birth, and measures of socioeconomic status and remoteness. The primary analysis concerned women whose first ever smear test defined their status as a case or a control. The adjusted odds ratio for exposure to three doses of HPV vaccine compared with no vaccine was 0.54 (95% confidence interval 0.43 to 0.67) for high grade cases and 0.66 (0.62 to 0.70) for other cases compared with controls with normal cytology, equating to vaccine effectiveness of 46% and 34%, respectively. The adjusted numbers needed to vaccinate were 125 (95% confidence interval 97 to 174) and 22 (19 to 25), respectively. The adjusted exposure odds ratios for two vaccine doses were 0.79 (95% confidence interval 0.64 to 0.98) for high grade cases and 0.79 (0.74 to 0.85) for other cases, equating to vaccine effectiveness of 21%. The quadrivalent HPV vaccine conferred statistically significant protection against cervical abnormalities in

  13. Effect of nitrous acid on lung function in asthmatics: a chamber study.

    PubMed Central

    Beckett, W S; Russi, M B; Haber, A D; Rivkin, R M; Sullivan, J R; Tameroglu, Z; Mohsenin, V; Leaderer, B P

    1995-01-01

    Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. Because the usual assays for nitrogen dioxide measure several oxides of nitrogen (including nitrous acid) together, previous studies of indoor nitrogen dioxide may have included exposure to and health effects of nitrous acid. To assess the respiratory effects of nitrous acid exposure alone, we carried out a double-blinded crossover chamber exposure study with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. We conclude that this concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics. Images Figure 1. PMID:7607138

  14. Comprehensive genetic study of fatty acids helps explain the role of noncoding inflammatory bowel disease associated SNPs and fatty acid metabolism in disease pathogenesis.

    PubMed

    Jezernik, Gregor; Potočnik, Uroš

    2018-03-01

    Fatty acids and their derivatives play an important role in inflammation. Diet and genetics influence fatty acid profiles. Abnormalities of fatty acid profiles have been observed in inflammatory bowel diseases (IBD), a group of complex diseases defined by chronic gastrointestinal inflammation. IBD associated fatty acid profile abnormalities were observed independently of nutritional status or disease activity, suggesting a common genetic background. However, no study so far has attempted to look for overlap between IBD loci and fatty acid associated loci or investigate the genetics of fatty acid profiles in IBD. To this end, we conducted a comprehensive genetic study of fatty acid profiles in IBD using iCHIP, a custom microarray platform designed for deep sequencing of immune-mediated disease associated loci. This study identifies 10 loci associated with fatty acid profiles in IBD. The most significant associations were a locus near CBS (p = 7.62 × 10 -8 ) and a locus in LRRK2 (p = 1.4 × 10 -7 ). Of note, this study replicates the FADS gene cluster locus, previously associated with both fatty acid profiles and IBD pathogenesis. Furthermore, we identify 18 carbon chain trans-fatty acids (p = 1.12 × 10 -3 ), total trans-fatty acids (p = 4.49 × 10 -3 ), palmitic acid (p = 5.85 × 10 -3 ) and arachidonic acid (p = 8.58 × 10 -3 ) as significantly associated with IBD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. 2,4-dichlorophenoxyacetic acid (2,4-D) and risk of non-Hodgkin lymphoma: a meta-analysis accounting for exposure levels.

    PubMed

    Smith, Adam M; Smith, Martyn T; La Merrill, Michele A; Liaw, Jane; Steinmaus, Craig

    2017-04-01

    2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most commonly used selective herbicides in the world. A number of epidemiology studies have found an association between 2,4-D exposure and non-Hodgkin lymphoma (NHL) but these results are inconsistent and controversial. A previous meta-analysis found no clear association overall but did not specifically examine high-exposure groups. We conducted a systematic review and meta-analysis of the peer-reviewed epidemiologic studies of the associations between 2,4-D and NHL, with a particular focus on high-exposure groups, and evaluations of heterogeneity, dose-response, and bias. A total of 12 observational studies, 11 case-control studies, and one cohort study, were included. The summary relative risk for NHL using study results comparing subjects who were ever versus never exposed to 2,4-D was 1.38 (95% confidence interval (CI), 1.07-1.77). However, in analyses focusing on results from highly exposed groups, the summary relative risk for NHL was 1.73 (95% CI, 1.10-2.72). No clear bias based on study design, exposure assessment methodology, or outcome misclassification was seen. Overall, these findings provide new evidence for an association between NHL and exposure to the herbicide 2,4-D. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Animal Model Selection for Inhalational HCN Exposure

    DTIC Science & Technology

    2016-08-01

    temperature and pressure). Health Effects from CN Exposure Cardiovascular responses to CN are complex and include precordial pain and EKG abnormalities...thyroid) may be affected, the brain is selectively sensitive given its high oxygen consumption and low rhodanese content, an enzyme involved in CN...efficiency of oxygenation while in dorsal recumbency under anesthesia, is decreased slightly compared to humans. The alveolar ventilation and perfusion (VA/Q

  17. Chronic effects of clofibric acid in zebrafish (Danio rerio): a multigenerational study.

    PubMed

    Coimbra, Ana M; Peixoto, Maria João; Coelho, Inês; Lacerda, Ricardo; Carvalho, António Paulo; Gesto, Manuel; Lyssimachou, Angeliki; Lima, Daniela; Soares, Joana; André, Ana; Capitão, Ana; Castro, Luís Filipe C; Santos, Miguel M

    2015-03-01

    Clofibric acid (CA) is an active metabolite of the blood lipid lowering agent clofibrate, a pharmaceutical designed to work as agonist of peroxisome proliferator-activated receptor alpha (PPARa). It is the most commonly reported fibrate in aquatic environments with low degradation rate and potential environmental persistence. Previous fish exposures showed that CA may impact spermatogenesis, growth and the expression of fat binding protein genes. However, there are limited data on the effects of chronic multigenerational CA exposures. Here, we assessed chronic multigenerational effects of CA exposure using zebrafish (Danio rerio) as a teleost model. Zebrafish were exposed through the diet to CA (1 and 10mg/g) during their whole lifetime. Growth, reproduction-related parameters and embryonic development were assessed in the exposed fish (F1 generation) and their offspring (F2 generation), together with muscle triglyceride content and gonad histology. In order to study the potential underlying mechanisms, the transcription levels of genes coding for enzymes involved in lipid metabolism pathways were determined. The results show that chronic life-cycle exposure to CA induced a significant reduction in growth of F1 generation and lowered triglyceride muscle content (10mg/g group). Also, an impact in male gonad development was observed together with a decrease in the fecundity (10mg/g group) and higher frequency of embryo abnormalities in the offspring of fish exposed to the lowest CA dose. The profile of the target genes was sex- and tissue-dependent. In F1 an up-regulation of male hepatic pparaa, pparb and acox transcript levels was observed, suggesting an activation of the fatty acid metabolism (provided that transcript level change indicates also a protein level change). Interestingly, the F2 generation, raised with control diet, displayed a response pattern different from that observed in F1, showing an increase in weight in the descendants of CA exposed fish, in

  18. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

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

    Lamparter, Christina L.

    The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 hmore » induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase

  19. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  20. Combined effects of dietary polyunsaturated fatty acids and parasite exposure on eicosanoid-related gene expression in an invertebrate model.

    PubMed

    Schlotz, Nina; Roulin, Anne; Ebert, Dieter; Martin-Creuzburg, Dominik

    2016-11-01

    Eicosanoids derive from essential polyunsaturated fatty acids (PUFA) and play crucial roles in immunity, development, and reproduction. However, potential links between dietary PUFA supply and eicosanoid biosynthesis are poorly understood, especially in invertebrates. Using Daphnia magna and its bacterial parasite Pasteuria ramosa as model system, we studied the expression of genes coding for key enzymes in eicosanoid biosynthesis and of genes related to oogenesis in response to dietary arachidonic acid and eicosapentaenoic acid in parasite-exposed and non-exposed animals. Gene expression related to cyclooxygenase activity was especially responsive to the dietary PUFA supply and parasite challenge, indicating a role for prostanoid eicosanoids in immunity and reproduction. Vitellogenin gene expression was induced upon parasite exposure in all food treatments, suggesting infection-related interference with the host's reproductive system. Our findings highlight the potential of dietary PUFA to modulate the expression of key enzymes involved in eicosanoid biosynthesis and reproduction and thus underpin the idea that the dietary PUFA supply can influence invertebrate immune functions and host-parasite interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 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

  2. Effect of azithromycin on acid reflux, hiatus hernia and proximal acid pocket in the postprandial period.

    PubMed

    Rohof, W O; Bennink, R J; de Ruigh, A A; Hirsch, D P; Zwinderman, A H; Boeckxstaens, G E

    2012-12-01

    The risk for acidic reflux is mainly determined by the position of the gastric acid pocket. It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position. To study the effect of azithromycin (Azi) on acid pocket position and acid exposure in patients with gastro-oesophageal reflux disease (GORD). Nineteen patients with GORD were included, of whom seven had a large hiatal hernia (≥3 cm) (L-HH) and 12 had a small or no hiatal hernia (S-HH). Patients were randomised to Azi 250 mg/day or placebo during 3 days in a crossover manner. On each study day, reflux episodes were detected using concurrent high-resolution manometry and pH-impedance monitoring after a standardised meal. The acid pocket was visualised using scintigraphy, and its position was determined relative to the diaphragm. Azi reduced the number of acid reflux events (placebo 8.0±2.2 vs Azi 5.6±1.8, p<0.01) and postprandial acid exposure (placebo 10.5±3.8% vs Azi 5.9±2.5%, p<0.05) in all patients without affecting the total number of reflux episodes. Acid reflux occurred mainly when the acid pocket was located above, or at the level of, the diaphragm, rather than below the diaphragm. Treatment with Azi reduced hiatal hernia size and resulted in a more distal position of the acid pocket compared with placebo (below the diaphragm 39% vs 29%, p=0.03). Azi reduced the rate of acid reflux episodes in patients with S-HH (38% to 17%) to a greater extent than in patients with L-HH (69% to 62%, p=0.04). Azi reduces acid reflux episodes and oesophageal acid exposure. This effect was associated with a smaller hiatal hernia size and a more distal position of the acid pocket, further indicating the importance of the acid pocket in the pathogenesis of GORD. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1970 NTR1970.

  3. Arsenite promotes centrosome abnormalities under a p53 compromised status induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

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

    Liao, W.-T.; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    2010-02-15

    Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus an interaction between arsenite and cigarette smoking in lung carcinogenesis was suspected. In the present study, we investigated the interactions of a tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone, NNK) and arsenite on lung cell transformation. BEAS-2B, an immortalized human lung epithelial cell line, was selected to test the centrosomal abnormalities and colony formation by NNK and arsenite. We found that NNK, alone, could enhance BEAS-2B cell growth at 1-5 muM. Under NNK exposure, arsenite wasmore » able to increase centrosomal abnormality as compared with NNK or arsenite treatment alone. NNK treatment could also reduce arsenite-induced G2/M cell cycle arrest and apoptosis, these cellular effects were found to be correlated with p53 dysfunction. Increased anchorage-independent growth (colony formation) of BEAS-2B cells cotreated with NNK and arsenite was also observed in soft agar. Our present investigation demonstrated that NNK could provide a p53 compromised status. Arsenite would act specifically on this p53 compromised status to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenite under tobacco-specific carcinogen co-exposure.« less

  4. Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort.

    PubMed

    Viel, Jean-François; Rouget, Florence; Warembourg, Charline; Monfort, Christine; Limon, Gwendolina; Cordier, Sylvaine; Chevrier, Cécile

    2017-03-01

    The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Increased prenatal cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans -DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age. Published by the BMJ Publishing Group Limited. For permission

  5. Safety assessment of myristic acid as a food ingredient.

    PubMed

    Burdock, George A; Carabin, Ioana G

    2007-04-01

    Myristic acid is used in the food industry as a flavor ingredient. It is found widely distributed in fats throughout the plant and animal kingdom, including common human foodstuffs, such as nutmeg. Myristic acid (a 14-carbon, straight-chain saturated fatty acid) has been shown to have a low order of acute oral toxicity in rodents. It may be irritating in pure form to skin and eyes under exaggerated exposure conditions, but is not known or predicted to induce sensitization responses. Myristic acid did not induce a mutagenic response in either bacterial or mammalian systems in vitro. Relevant subchronic toxicity data are available on closely related fatty acid analogs. In particular, a NOEL of >6000mg/kg was reported for lauric acid (a 12-carbon, straight-chain saturated fatty acid) following dietary exposure to male rats for 18 weeks and a NOEL of >5000mg/kg was reported for palmitic acid (a 16-carbon, straight-chain saturated fatty acid) following dietary exposure to rats for 150 days. The data and information that are available indicate that at the current level of intake, food flavoring use of myristic acid does not pose a health risk to humans.

  6. Association Between Nocturnal Acid Reflux and Sleep Disturbance in Patients With Gastroesophageal Reflux Disease.

    PubMed

    Hung, Jui-Sheng; Lei, Wei-Yi; Yi, Chih-Hsun; Liu, Tso-Tsai; Chen, Chien-Lin

    2016-08-01

    This study was conducted to investigate whether there is a direct association between subjective sleep quality and esophageal acid reflux in patients with gastroesophageal reflux disease. We enrolled patients with classic reflux symptoms for endoscopy and ambulatory pH monitoring. The severity of esophageal mucosal injury was assessed by upper endoscopy. Distal esophageal acid exposure was determined by ambulatory 24-hour pH monitoring. Sleep disturbance was assessed by using the Pittsburgh Sleep Quality Index. In total, 103 patients (53 patients without sleep dysfunction and 50 patients with sleep dysfunction) were studied. Erosive esophagitis was found more in patients with sleep disturbance than in those without sleep disturbance (45% versus 31%, P = 0.04). Abnormal esophageal pH was found more in patients with dysfunction (22%) than in patients without sleep dysfunction (5.7%, P = 0.03). Recumbent acid contact time (%) was greater in patients with sleep disturbance than in those without sleep disturbance (3.7 ± 2.4 versus 1.9 ± 0.9, P = 0.04). Sleep quality score positively correlated with acid contact time (r = 0.32, P = 0.02), prolonged reflux events (r = 0.45, P = 0.008) and longer reflux event (r = 0.28, P = 0.03) during recumbent period. Patients with gastroesophageal reflux disease along with sleep dysfunction are characterized with greater nocturnal acid reflux and more erosive esophagitis. Our study suggests that increased nocturnal acid reflux may play a role in inducing sleep disturbance in patients with gastroesophageal reflux disease. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  7. Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli.

    PubMed

    Bhat, Supriya V; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E S

    2018-01-01

    Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro , and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force - laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage.

  8. Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli

    PubMed Central

    Bhat, Supriya V.; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E. S.

    2018-01-01

    Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro, and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force – laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage. PMID:29472899

  9. Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

    PubMed

    Kaminski, R; Powchick, P; Warne, P A; Goldstein, M; McQueeney, R T; Davidson, M

    1990-01-01

    1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

  10. In ovo exposure to omega-3 fatty acids does not enhance omega-3 long-chain polyunsaturated fatty acid metabolism in broiler chickens.

    PubMed

    Kanakri, K; Carragher, J; Muhlhausler, B; Hughes, R; Gibson, R

    2017-10-01

    The content of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in chicken meat can be boosted by feeding broilers a diet containing α-linolenic acid (ALA, from flaxseed oil), some of which is converted by hepatic enzymes to n-3 LCPUFA. However, most of the accumulated n-3 polyunsaturated fatty acid (PUFA) in meat tissues is still in the form of ALA. Despite this, the levels of chicken diets are being enhanced by the inclusion of vegetable and marine sources of omega-3 fats. This study investigated whether the capacity of chicken for n-3 LCPUFA accumulation could be enhanced or inhibited by exposure to an increased supply of ALA or n-3 LCPUFA in ovo. Breeder hens were fed either flaxseed oil (High-ALA), fish oil (high n-3 LCPUFA) or tallow- (low n-3 PUFA, Control) based diets. The newly hatched chicks in each group were fed either the High-ALA or the Control diets until harvest at 42 days' post-hatch. The n-3 PUFA content of egg yolk and day-old chick meat closely matched the n-3 PUFA composition of the maternal diet. In contrast, the n-3 PUFA composition of breast and leg meat tissues of the 42-day-old offspring closely matched the diet fed post-hatch, with no significant effect of maternal diet. Indeed, there was an inhibition of n-3 LCPUFA accumulation in meat of the broilers from the maternal Fish-Oil diet group when fed the post-hatch High-ALA diet. Therefore, this approach is not valid to elevate n-3 LCPUFA in chicken meat.

  11. High prevalence of heartburn and low acid sensitivity in patients with idiopathic achalasia.

    PubMed

    Ponce, Julio; Ortiz, Vicente; Maroto, Nuria; Ponce, Marta; Bustamante, Marco; Garrigues, Vicente

    2011-03-01

    Heartburn is frequently reported by patients with achalasia before treatment. However, the esophageal sensitivity to acid as a possible mediator of this symptom has not been previously evaluated. To evaluate the prevalence of gastroesophageal reflux symptoms and the esophageal sensitivity to acid perfusion in patients with untreated achalasia. Forty patients with achalasia were prospectively evaluated. Forty-three patients with gastroesophageal reflux disease comprised the control group (ten of them with Barrett's esophagus). Symptoms were evaluated by a structured clinical questionnaire. Objective assessment was performed by ambulatory 24-h esophageal pH monitoring and endoscopy. Esophageal sensitivity to acid was evaluated by esophageal perfusion of ClH 0.1 N. Fifteen (37%) of the 40 patients with achalasia presented heartburn, but only four of them had esophagitis and/or abnormal esophageal pH recording. Eight patients had abnormal pH recording. Three patients had esophagitis. The esophagus was sensitive to acid in seven (17%) patients with achalasia, three of them with heartburn and one with abnormal pH recording. In the control group, 40 of 43 (93%) presented heartburn. Acid perfusion was positive in 32 (74%). Sensitivity to acid was lower in patients with achalasia than in those with gastroesophageal reflux disease with or without Barrett's esophagus. The prevalence of heartburn in patients with achalasia is high, although its association with objective indicators of gastroesophageal reflux disease is weak. Patients with achalasia have lower esophageal sensitivity to acid than patients with GERD, suggesting that heartburn is does not arise from this condition.

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

    PubMed

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

    2014-06-01

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

  13. Pinna abnormalities and low-set ears

    MedlinePlus

    ... Pinna abnormalities; Genetic defect - pinna; Congenital defect - pinna Images Ear abnormalities Pinna of the newborn ear References Haddad J, Keesecker S. Congenital malformations. In: Kliegman RM, Stanton BF, ...

  14. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

    PubMed

    Fujiita, Takashi; Shimizu, Masami; Kaku, Bunji; Kanaya, Hounin; Horita, Yuki; Uno, Yoshihide; Yamazaki, Tsukasa; Ohka, Takio; Sakata, Kenji; Mabuchi, Hiroshi

    2005-07-01

    A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

  16. Natural levels of abnormalities in the trilling frog (neobactrachus centralis) at the Olympic dam mine

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

    Read, J.L.; Tyler, M.J.

    1994-07-01

    Frogs are more susceptible than most vertebrates to environmental contaminants. Unlike amniotes, the frog egg is not protected by a semi-impervious shell, and hence is readily exposed to pollutants. In addition, tadpoles develop in wetlands to which many noxious substances drain from the surrounding landscape. Coupled with this high exposure rate, frogs are also very sensitive to trace elements, some pesticides, heavy metals especially when coupled with exposure to low pH and ionizing radiation. Frogs commonly exhibit discernible deformities following exposure to teratogenic contaminants, and therefore are valuable indicators of the existence of noxious substances in the environment. The abundancemore » and ease of sampling of frogs, along with their sensitivity to environmental contaminants, makes them ideal organisms for environmental monitoring in the Australian arid zone. The study of abnormalities in frogs has become an integral part of the Environmental Management Programme of the Olympic Dam Operations (ODO) copper-uranium-gold-silver mine in northern South Australia. The Trilling Frog (Neobatrachus centralis) is the only frog species which has been recorded at Olympic Dam. It is likely that these frogs, are relatively sedentary, thus enhancing their value as indicator organisms. A pilot survey in 1989 documented frog deformity levels comparable to those found at undisturbed sites in Australia and in other countries. This paper reports on larger study conducted in February and March 1992 when heavy rains provided another opportunity to survey the frog population. The low levels of abnormalities support the conclusion that N. centralis at Olympic Dam does not appear to be accumulating or being influenced by the very low levels of radionuclides present here.« less

  17. Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad.

    PubMed

    Dorman, David C; Foster, Melanie L; Olesnevich, Brooke; Bolon, Brad; Castel, Aude; Sokolsky-Papkov, Marina; Mariani, Christopher L

    2018-06-01

    Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered "nontoxic" with acute oral median lethal doses (LD 50 ) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6-19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

  18. Inflammatory and genotoxic responses during 30-day welding-fume exposure period.

    PubMed

    Yu, Il Je; Song, Kyung Seuk; Maeng, Seung Hee; Kim, Soo Jin; Sung, Jae Hyuck; Han, Jeong Hee; Chung, Yong Hyun; Cho, Myung Haing; Chung, Kyu Hyuck; Han, Kuy Tae; Hyun, Jin Sook; Kim, Kwang Jong

    2004-12-01

    Welder's pneumoconiosis has generally been determined to be benign and unassociated with respiratory symptoms based on the absence of pulmonary-function abnormalities in welders with marked radiographic abnormalities. In previous studies, the current authors suggested a three-phase lung fibrosis process to study the pathological process of lung fibrosis and found that the critical point for recovery was after 30 days of welding-fume exposure at a high dose, at which point early and delicate fibrosis was observed in the perivascular and peribronchiolar regions. Accordingly, the current study investigated the inflammatory and genotoxic responses during a 30-day period of welding-fume exposure to elucidate the process of fibrosis. As such, rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes at concentrations of 65.6 +/- 2.9 (low dose) and 116.8 +/- 3.9 mg/m3 (high dose) total suspended particulate for 2 h per day in an inhalation chamber for 30 days. Animals were sacrificed after the initial 2 h exposure, and after 15 and 30 days of exposure. The rats exposed to the welding fumes exhibited a statistically significant (P < 0.05) decrease in body weight when compared to the control during the 30-day exposure period, yet an elevated cellular differential count and higher levels of albumin, LDH, and beta-NAG, but not elevated TNF-alpha, and IL-1beta in the acellular bronchoalveolar lavage fluid. In addition, the DNA damage resulting from 30 days of welding-fume exposure was confirmed by a comet assay and the inmmunohistochemistry for 8-hydroxydeoxyguanine (8-OH-dG). Consequently, the elevated inflammatory and genotoxic indicators confirmed the lung injury and inflammation caused by the MMA-SS welding-fume exposure.

  19. Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by δ-aminolevulinic acid dehydratase gene polymorphism.

    PubMed

    Tian, Liting; Zheng, Guang; Sommar, Johan Nilsson; Liang, Yihuai; Lundh, Tomas; Broberg, Karin; Lei, Lijian; Guo, Weijun; Li, Yulan; Tan, Mingguang; Skerfving, Staffan; Jin, Taiyi; Bergdahl, Ingvar A

    2013-08-14

    Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that δ-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), ALAD polymorphism (rs1800435, ALAD1/2; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary δ-aminolevulic acid), on the kidneys (urinary albumin, β2-microglobulin and N-acetyl-β-d-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27)μg/L, B-Pb 401 (110-950)μg/L, and U-Pb 188 (22-590)μg/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: rS=-0.10 to 0.79; B-Pb: rS=-0.08 to 0.75; all p<0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p=0.04) in ALAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb. (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Interactive effects of ambient acidity and salinity on thyroid function during acidic and post-acidic acclimation of air-breathing fish (Anabas testudineus Bloch).

    PubMed

    Peter, M C Subhash; Rejitha, V

    2011-11-01

    The interactive effects of ambient acidity and salinity on thyroid function are less understood in fish particularly in air-breathing fish. We, therefore, examined the thyroid function particularly the osmotic and metabolic competences of freshwater (FW) and salinity-adapted (SA; 20 ppt) air-breathing fish (Anabas testudineus) during acidic and post-acidic acclimation, i.e., during the exposure of fish to either acidified water (pH 4.2 and 5.2) for 48 h or clean water for 96 h after pre-exposure. A substantial rise in plasma T(4) occurred after acidic exposure of both FW and SA fish. Similarly, increased plasma T(3) and T(4) were found in FW fish kept for post-acidic acclimation and these suggest an involvement of THs in short-term acidic and post-acidic acclimation. Water acidification produced significant hyperglycaemia and hyperuremia in FW fish but not in SA fish. The SA fish when kept for post-acclimation, however, produced a significant hypouremia. In both FW and SA fish, gill Na(+), K(+)-ATPase activity decreased but kidney Na(+), K(+)-ATPase activity increased upon acidic acclimation. During post-acidic acclimation, gill Na(+), K(+)-ATPase activity of the FW fish showed a rise while decreasing its activity in the SA fish. Similarly, post-acidic acclimation reduced the Na(+), K(+)-ATPase activity of intestine but elevated its activity in the liver of SA fish. A higher tolerance of the SA fish to water acidification was evident in these fish as they showed tight plasma and tissue mineral status due to the ability of this fish to counteract the ion loss. In contrast, FW fish showed more sensitivity to water acidification as they loose more ions in that medium. The positive correlations of plasma THs with many tested metabolic and hydromineral indices of both FW and SA fish and also with water pH further confirm the involvement of THs in acidic and post-acidic acclimation in these fish. We conclude that thyroid function of this fish is more sensitive to

  1. An efficient analytical method for determination of S-phenylmercapturic acid in urine by HPLC fluorimetric detector to assessing benzene exposure.

    PubMed

    Mendes, Michele P Rocha; Silveira, Josianne Nicácio; Andre, Leiliane Coelho

    2017-09-15

    Benzene is an important occupational and environmental contaminant, naturally present in petroleum and as by-product in the steel industry. Toxicological studies showed pronounced myelotoxic action, causing leukemic and others blood cells disorders. Assessing of benzene exposure is performed by biomarkers as trans, trans-muconic acid (AttM) and S-phenylmercapturic acid (S-PMA) in urine. Due to specificity of S-PMA, this biomarker has been proposed to asses lower levels of benzene in air. The aim of this study was to validate an analytical method for the quantification of S-PMA by High-Performance Liquid Chromatography with fluorometric detector. The development of an analytical method of S-PMA in urine was carried out by solid phase extraction (SPE) using C-18 phase. The eluated were submitted to water bath at 75°C and nitrogen to analyte concentration, followed by alkaline hydrolysis and derivatization with monobromobimane. The chromatography conditions were reverse phase C-18 column (240mm, 4mm and 5μm) at 35°C; acetonitrile and 0.5% acetic acid (50:50) as mobile phase with a flow of 0.8mL/min. The limits of detection and quantification were 0.22μg/L and 0.68μg/L, respectively. The linearity was verified by simple linear regression, and the method exhibited good linearity in the range of 10-100μg/L. There was no matrix effect for S-PMA using concentrations of 40, 60, 80 and 100μg/L. The intra- and interassay precision showed coefficient of variation of less than 10% and the recovery ranged from 83.4 to 102.8% with an average of 94.4%. The stability of S-PMA in urine stored at -20°C was of seven weeks. The conclusion is that this method presents satisfactory results per their figures of merit. This proposed method for determining urinary S-PMA showed adequate sensitivity for assessment of occupational and environmental exposure to benzene using S-PMA as biomarker of exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid.

    PubMed

    Roullet, F I; Wollaston, L; Decatanzaro, D; Foster, J A

    2010-10-13

    Experiments in rodents have indicated that maternal valproic acid (VPA) exposure has permanent adverse effects upon neurological and behavioral development. In humans, prenatal exposure to VPA can induce fetal valproate syndrome, which has been associated with autism. The present study examined mouse pups exposed in utero to VPA, measuring physical development, olfactory discrimination, and social behavior as well as expression of plasticity-related genes, brain derived neurotrophic factor (BDNF) and NMDA receptor subunits NR2A and NR2B. VPA-exposed mice showed delayed physical development, impaired olfactory discrimination, and dysfunctional pre-weaning social behavior. In situ hybridization experiments revealed lower cortical expression of BDNF mRNA in VPA animals. These results support the validity of the VPA mouse model for human autism and suggest that alterations in plasticity-related genes may contribute to the behavioral phenotype. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. The effect of adriamycin exposure on the notochord of mouse embryos.

    PubMed

    Hajduk, Piotr; May, Alison; Puri, Prem; Murphy, Paula

    2012-04-01

    The notochord has important structural and signaling properties during vertebrate development with key roles in patterning surrounding tissues, including the foregut. The adriamycin mouse model is an established model of foregut anomalies where exposure of embryos in utero to the drug adriamycin leads to malformations including oesophageal atresia and tracheoesophageal fistula. In addition to foregut abnormalities, treatment also causes branching, displacement, and hypertrophy of the notochord. Here, we explore the hypothesis that the notochord may be a primary target of disruption leading to abnormal patterning of the foregut by examining notochord position and structure in early embryos following adriamycin exposure. Treated (n = 46) and control (n = 30) embryos were examined during the crucial period when the notochord normally delaminates away from the foregut endoderm (6-28 somite pairs). Transverse sections were derived from the anterior foregut and analyzed by confocal microscopy following immunodetection of extracellular matrix markers E-cadherin and Laminin. In adriamycin-treated embryos across all stages, the notochord was abnormally displaced ventrally with prolonged attachment to the foregut endoderm. While E-cadherin was normally detected in the foregut endoderm with no expression in the notochord of control embryos, treated embryos up to 24 somites showed ectopic notochordal expression indicating a change in characteristics of the tissue; specifically an increase in intracellular adhesiveness, which may be instrumental in structural changes, affecting mechanical and signaling properties. This is consistent with disruption of the notochord leading to altered signaling to the foregut causing abnormal patterning and congenital foregut malformations. © 2012 Wiley Periodicals, Inc.

  4. Dysmorphometrics: the modelling of morphological abnormalities.

    PubMed

    Claes, Peter; Daniels, Katleen; Walters, Mark; Clement, John; Vandermeulen, Dirk; Suetens, Paul

    2012-02-06

    The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited. A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram. We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities. The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.

  5. Association of Dyslipidemia and Glucose Abnormalities with Antiretroviral Treatment in a Cohort of HIV-infected Latin American Children

    PubMed Central

    Paganella, MP; Cohen, RA; Harris, DR; Kuchenbecker, RS; Sperhacke, RD; Kato, SK; Silva, CLO; Sturzbecher, FT; Oliveira, RHS; Pavía Ruz, N; Hazra, R

    2016-01-01

    Objective(s) To estimate the incidence of lipid and glucose abnormalities and assess their association with exposure to antiretroviral (ARV) regimens among perinatally HIV-infected Latin American children. Design Longitudinal cohort study. Methods Data were analyzed from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI) Pediatric Latin American Countries Epidemiologic Study (PLACES). The incidence of dyslipidemia (total cholesterol>200mg/dL, HDL<35mg/dL, LDL≥130mg/dL, triglycerides>110mg/dL [age<10 years] or >150mg/dL [≥10 years]) and fasting glucose abnormalities (homeostasis model assessment of insulin resistance >2.5 [Tanner Stage 1] or >4.0 [Tanner Stage>1]; impaired glucose: 110 to <126mg/dL; diabetes: ≥126 mg/dL) was estimated. Proportional hazards regression was used to evaluate the risk of abnormalities associated with ARV regimen, adjusted for covariates. Results There were 385 children eligible for analysis (mean age 6.6 years). Incident cholesterol abnormalities were reported in 18.1% of participants (95% confidence interval [CI] 14.1–22.8%), HDL and LDL cholesterol abnormalities in 19.6% (15.1–24.7%) and 15.0% (11.3–19.5%), respectively, and triglyceride abnormalities in 44.2% (37.7–50.8%). In multivariable analysis, ARV regimen was only associated with triglyceride abnormalities; participants receiving a protease inhibitor-containing (PI) regimen were 3.6 times as likely to experience a triglyceride abnormality as those receiving no ARVs (95% CI: 1.3–10.5; p=0.0167). The cumulative incidence of insulin resistance was 3.8% (1.8–7.1%); there were no incident cases of diabetes and only two of impaired fasting glucose. Conclusions Children receiving PI-containing regimens were at increased risk of developing triglyceride abnormalities. Continued monitoring of lipid levels in children receiving PI-containing regimens appears warranted. PMID:27570910

  6. Congenital Abnormalities

    MedlinePlus

    ... tube defects. However, there is also a genetic influence to this type of congenital anomaly. Unknown Causes The vast majority of congenital abnormalities have no known cause. This is particularly troubling for parents who plan to have more children, because there is no way to predict if ...

  7. Induced cytotoxic damage by exposure to gasoline vapors: a study in Sinaloa, Mexico.

    PubMed

    Martinez-Valenzuela, Carmen; Soto, Fernanda Balderrama; Waliszewski, Stefan M; Meza, Enrique; Arroyo, Sandra Gómez; Martínez, Luis Daniel Ortega; Meraz, Eliakym Arambula; Caba, Mario

    2017-01-01

    Gasoline is a blend of organic compounds used in internal combustion engines. Gasoline-station attendants are exposed to gasoline vapors, which pose a potentially mutagenic risk. According to the International Agency for Research on Cancer, exposure to gasoline and engine exhaust is possibly carcinogenic to humans. We determined the frequency of micronucleus and other nuclear abnormalities, such as pyknotic nuclei, chromatin condensation, cells with nuclear buds, karyolytic cells, karyorrhexis, and binucleated cells in buccal mucosal smears of 60 gasoline-station attendants and 60 unexposed controls. In addition, we explored if factors such as smoking habits, alcohol consumption, and worked years exert an additional synergistic cytotoxic effect. There were statistically significant higher frequencies (p < 0.05) of nuclear abnormalities among exposed attendants compared to the controls. No statistical significant (p > 0.05) additional effect of lifestyle habits such as smoking and alcohol consumption or worked years on the cytotoxicity was observed. The results showed that from the beginning exposure to gasoline vapors increased the frequency of nuclear abnormalities in buccal epithelial cells. Our results provide valuable information on cytotoxic damage for an early pre-symptomatic diagnosis.

  8. Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

    PubMed

    Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

    2017-05-01

    The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  9. Abnormal octadeca-carbon fatty acids distribution in erythrocyte membrane phospholipids of patients with gastrointestinal tumor.

    PubMed

    Lin, Shaohui; Li, Tianyu; Liu, Xifang; Wei, Shihu; Liu, Zequn; Hu, Shimin; Liu, Yali; Tan, Hongzhuan

    2017-06-01

    Fatty acid (FA) composition is closely associated with tumorigenesis and neoplasm metastasis. This study was designed to investigate the differences of phospholipid FA (PLFA) composition in erythrocyte and platelet cell membranes in both gastrointestinal (GI) tumor patients and healthy controls.In this prospective study, 50 GI tumor patients and 33 healthy volunteers were recruited between the years 2013 and 2015. Blood samples were collected from healthy volunteers and patients, and FA composition was assessed using gas chromatography-mass spectrometer (GC-MS), and data were analyzed by multifactor regression analysis.Compared with healthy controls, the percentages of C18:0 (stearic acid, SA), C22:6 (docosahexaenoic acid, DHA), and n-3 polyunsaturated FAs (n-3 PUFA) were significantly increased, while C18:1 (oleic acid, OA), C18:2 (linoleic acid, LA), and monounsaturated FAs (MUFA) decreased in erythrocyte membranes of GI tumor patients. Also, patient's platelets revealed higher levels of C20:4 (arachidonic acid, AA) and DHA, and lower levels of OA and MUFA.Our study displayed a remarkable change in the FA composition of erythrocyte and platelet membranes in GI tumor patients as compared with healthy controls. The octadeca-carbon FAs (SA, OA, and LA) in erythrocyte membranes could serve as a potential indicator for GI tumor detection.

  10. Abnormal Cervical Cancer Screening Test Results

    MedlinePlus

    ... FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test results? • What is the difference between the terms cervical ...

  11. Fatty acids are required for epidermal permeability barrier function.

    PubMed

    Mao-Qiang, M; Elias, P M; Feingold, K R

    1993-08-01

    The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis.

  12. Fatty acids are required for epidermal permeability barrier function.

    PubMed Central

    Mao-Qiang, M; Elias, P M; Feingold, K R

    1993-01-01

    The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis. Images PMID:8102380

  13. Occupational exposure of petroleum depot workers to BTEX compounds.

    PubMed

    Rezazadeh Azari, M; Naghavi Konjin, Z; Zayeri, F; Salehpour, S; Seyedi, M D

    2012-01-01

    Benzene, toluene, ethylbenzene and xylene (BTEX) are the most important toxic volatile compounds in the air and could be easily absorbed through the respiratory tract. In recent years, the risk of exposure to BTEX compounds, especially benzene as a carcinogen, has been considered in petroleum depot stations. To assess the occupational exposure of petroleum depot workers in Iran to BTEX compounds. After completing a questionnaire and assessing occupational exposure to BTEX compounds, 78 (46 exposed and 32 non-exposed) depot workers were randomly selected to participate in this study. Air sampling and analysis of BTEX was conducted according to the NIOSH method No. 1501. Analysis of urinary hippuric acid, as an indicator of toluene exposure, was carried out according to NIOSH method No. 8300. Personal monitoring of the high exposure group to BTEX compounds was repeated to verify the results obtained in the first phase of the monitoring. Among the 9 operating groups studied, occupational exposure to benzene and toluene was higher in quality control and gasoline loading operators-the median exposure ranged from 0.16 to 1.63 ppm for benzene and 0.2 to 2.72 ppm for toluene. Median exposure of other group members to BTEX compounds was below the detection limit of analytical method (0.07, 0.06, 0.05, and 0.05 ppm, respectively). The level of toluene exposure measured showed correlation with neither post-shift urinary hippuric acid (Spearman's rho = 0.128, p = 0.982) nor with the difference between post- and pre-shift urinary hippuric acid (Spearman's rho = 0.089, p = 0.847) in depot operational workers. Gasoline loading operators are exposed to a relatively high level of benzene.

  14. Acetylated sialic acid residues and blood group antigens localise within the epithelium in microvillous atrophy indicating internal accumulation of the glycocalyx

    PubMed Central

    Phillips, A D; Brown, A; Hicks, S; Schüller, S; Murch, S H; Walker-Smith, J A; Swallow, D M

    2004-01-01

    Background: Microvillous atrophy, a disorder of intractable diarrhoea in infancy, is characterised by the intestinal epithelial cell abnormalities of abnormal accumulation of periodic acid-Schiff (PAS) positive secretory granules within the apical cytoplasm and the presence of microvillous inclusions. The identity of the PAS positive material is not known, and the aim of this paper was to further investigate its composition. Methods: Formaldehyde fixed sections were stained with alcian blue/PAS to identify the acidic or neutral nature of the material, phenylhydrazine blocking was employed to stain specifically for sialic acid, and saponification determined the presence of sialic acid acetylation. The specificity of sialic acid staining was tested by digestion with mild sulphuric acid. Expression of blood group related antigens was tested immunochemically. Results: Alcian blue/PAS staining identified a closely apposed layer of acidic material on the otherwise neutral (PAS positive) brush border in controls. In microvillous atrophy, a triple layer was seen with an outer acidic layer, an unstained brush border region, and accumulation within the epithelium of a neutral glycosubstance that contained acetylated sialic acid. Blood group antigens were detected on the brush border, in mucus, and within goblet cells in controls. In microvillous atrophy they were additionally expressed within the apical cytoplasm of epithelial cells mirroring the PAS abnormality. Immuno electron microscopy localised expression to secretory granules. Conclusions: A neutral, blood group antigen positive, glycosubstance that contains acetylated sialic acid accumulates in the epithelium in microvillous atrophy. Previous studies have demonstrated that the direct and indirect constitutive pathways are intact in this disorder and it is speculated that the abnormal staining pattern reflects accumulation of glycocalyx related material. PMID:15542511

  15. 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 ...

  16. Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.

    PubMed

    Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A

    2016-11-01

    Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. © The Author(s) 2016.

  17. Sleep disorders and the prevalence of asymptomatic nocturnal acid and non-acid reflux.

    PubMed

    Herdman, Christine; Marzio, Dina Halegoua-De; Shah, Paurush; Denuna-Rivera, Susie; Doghramji, Karl; Cohen, Sidney; Dimarino, Anthony J

    2013-01-01

    Nocturnal acid reflux is associated with symptomatic and asymptomatic sleep arousals, leading to fragmented sleep. The frequency and influence of acid reflux in patients with various forms of insomnia has not been reported. The aim of this study was to quantify nocturnal acid and nonacid reflux in patients with primary sleep disorders as previously diagnosed by polysomnography. THIRTY ONE SUBJECTS WERE STUDIED: (A) 9 subjects with a polysomnographically diagnosed sleep disorder (1 with restless legs syndrome, 4 with narcolepsy, 4 with periodic limb movement disorder); (B) 12 subjects with primary insomnia (PI) and unrevealing polysomnography; and (C) 10 controls without disturbed sleep. All subjects underwent a physical examination and 24 h transnasal pH and impedance monitoring to detect acid and non-acid reflux. The 21 subjects with fragmented sleep due to a primary sleep disorder had significantly more recumbent acid exposure (>1.2% of time) as compared with control subjects (33% versus 0%). When fragmented sleep subjects were divided into two groups, 17% of PI subjects and 55% of subjects with a diagnosed sleep disorder had significant recumbent acid exposure (P=0.009). Likewise, the median recumbent nonacid events were increased in the sleep disordered group (P=0.011). This study indicates that patients with primary sleep disorders have prominent nocturnal acid reflux without symptoms of daytime acid reflux. Acid reflux is most prominent in patients with polysomnographic findings of disturbed sleep as compared to patients with PI; while non acid reflux is increased minimally in these patients.

  18. Glutamatergic system abnormalities in posttraumatic stress disorder.

    PubMed

    Nishi, Daisuke; Hashimoto, Kenji; Noguchi, Hiroko; Hamazaki, Kei; Hamazaki, Tomohito; Matsuoka, Yutaka

    2015-12-01

    Accumulating evidence suggests involvement of the glutamatergic system in the biological mechanisms of posttraumatic stress disorder (PTSD), but few studies have demonstrated an association between glutamatergic system abnormalities and PTSD diagnosis or severity. We aimed to examine whether abnormalities in serum glutamate and in the glutamine/glutamate ratio were associated with PTSD diagnosis and severity in severely injured patients at risk for PTSD and major depressive disorder (MDD). This is a nested case-control study in TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD were assessed 3 months after the accidents using the Clinician-Administered PTSD Scale. The associations of glutamate levels and the glutamine/glutamate ratio with diagnosis and severity of PTSD and MDD were investigated by univariate and multiple linear regression analyses. Ninety-seven of 110 participants (88 %) completed assessments at 3 months. Serum glutamate levels were significantly higher for participants with full or partial PTSD than for participants without PTSD (p = 0.049) and for participants with MDD than for participants without MDD (p = 0.048). Multiple linear regression analyses showed serum glutamate levels were significantly positively associated with PTSD severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio was also significantly inversely associated with PTSD severity (p = 0.03), but not with MDD severity (p = 0.07). These findings suggest that the glutamatergic system may play a major role in the pathogenesis of PTSD and the need for new treatments targeting the glutamatergic system to be developed for PTSD.

  19. Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

    PubMed

    Janer, Gemma; Navarro, Juan Carlos; Porte, Cinta

    2007-09-01

    Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARgamma receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

  20. What proportion of congenital abnormalities can be prevented?

    PubMed Central

    Czeizel, A E; Intôdy, Z; Modell, B

    1993-01-01

    OBJECTIVE--To estimate the proportion of preventable congenital abnormalities in Hungary. DESIGN--Analysis of available Hungarian data-bases and of the effectiveness of primary, secondary, and tertiary preventive methods. SETTING--Databases of ad hoc epidemiological studies and of the Hungarian congenital abnormality registry. MAIN OUTCOME MEASURES--Prevalence at birth and prevalence after prevention in 73 congenital abnormality types or groups. RESULTS--Preventive methods are available for 51 (70%) of the 73 congenital abnormality types or groups evaluated. The birth prevalence of all congenital abnormalities could be reduced from 65 to 26 per 1000; thus 39 per 1000 (60%) are preventable. Without congenital dislocation of the hip, which is unusually common in Hungary, the preventable proportion of congenital abnormalities is 52%. CONCLUSION--Many congenital abnormalities can be prevented, but as they do not represent a single pathological category there is no single strategy for their prevention. Images p502-a p503-a PMID:8448464