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Sample records for repeated acid exposure

  1. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

    Science.gov (United States)

    Main, Stacey L; Kulesza, Randy J

    2017-01-06

    Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Toxicological characteristics of petroleum products repeated exposure

    Directory of Open Access Journals (Sweden)

    V.M. Rubin

    2015-03-01

    Full Text Available Abstract. The ability of petroleum products to initiate cumulative effects was assessed in experimental intragastric admission to male albino rats for one month. The analysis of skin-resorptive effects was performed using "test-tube" method on the skin of rats’ tails. It has been established that petroleum products can penetrate the intact skin and, with repeated admission, cause a general toxic effect. There were reductions bodyweights, the negative effect on the function of the kidneys and liver, changes of hematological parameters, as well as activation of the antioksidatnoy system. Repeated intragastric administration does not lead to the death of the animals testifying to the lack of accumulation capacity for petroleum products at the level of functional mortal effects, the cumulation coefficient being > 5.1. Negative impact on urinary function and hepatobiliary system, changes in hematological parameters and activation of the «lipid peroxidation – antioksidant defense» were observed.

  3. Sweet and sour preferences in young children and adults: role of repeated exposure

    NARCIS (Netherlands)

    Liem, D.G.; Graaf, de C.

    2004-01-01

    The authors investigated the influence of repeated exposure to orangeades with added sucrose and different concentrations of citric acid, on the taste preferences of 6- to-11-year-old children and young adults. During an intervention study of 8 days, 59 children (9.2±0.9 years) and 46 young adults

  4. Increasing Positive Perceptions of Counseling: The Importance of Repeated Exposures

    Science.gov (United States)

    Kaplan, Scott A.; Vogel, David L.; Gentile, Douglas A.; Wade, Nathaniel G.

    2012-01-01

    This study assesses the effectiveness of repeated exposures to a video intervention based on the Elaboration Likelihood Model. The video was designed to increase help-seeking attitudes and perceptions of peer norms and to decrease the stigma associated with seeking counseling. Participants were 290 undergraduates who were randomly assigned to a…

  5. Absence of bacterial resistance following repeat exposure to photodynamic therapy

    Science.gov (United States)

    Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.

    2009-06-01

    The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

  6. Effects of repeated skin exposure to low nickel concentrations

    DEFF Research Database (Denmark)

    Nielsen, N H; Menné, T; Kristiansen, J

    1999-01-01

    and nickel allergy, either on normal or on SLS-treated forearm skin. The present study strongly suggests that the changes observed were specific to nickel exposure. Standardized methods to assess trace to moderate nickel exposure on the hands, and the associated effects in nickel-sensitized subjects......We studied the effects of repeated daily exposure to low nickel concentrations on the hands of patients with hand eczema and nickel allergy. The concentrations used were chosen to represent the range of trace to moderate occupational nickel exposure. The study was double-blinded and placebo...... controlled. Patients immersed a finger for 10 min daily into a 10-p.p.m. nickel concentration in water for the first week, and during the second week into a 100-p.p.m. nickel concentration. This regimen significantly increased (P = 0.05) local vesicle formation and blood flow (P = 0.03) as compared...

  7. Behavioral sensitization after repeated formaldehyde exposure in rats.

    Science.gov (United States)

    Sorg, B A; Hochstatter, T

    1999-01-01

    Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary

  8. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro.

    Science.gov (United States)

    Buist, Harrie E; van de Sandt, Johannes J M; van Burgsteden, Johan A; de Heer, Cees

    2005-10-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeated exposure. The influence of repeated and single exposure to representative biocidal active substances on the skin barrier was investigated in vitro. The biocidal active substances selected were alkyldimethylbenzylammonium chloride (ADBAC), boric acid, deltamethrin, dimethyldidecylammonium chloride (DDAC), formaldehyde, permethrin, piperonyl butoxide, sodium bromide, and tebuconazole. Of these nine compounds, only the quaternary ammonium chlorides ADBAC and DDAC had a clear and consistent influence on skin permeability of the marker compounds tritiated water and [(14)C]propoxur. For these compounds, repeated exposure increased skin permeability more than single exposure. At high concentrations the difference between single and repeated exposure was quantitatively significant: repeated exposure to 300 mg/L ADBAC increased skin permeability two to threefold in comparison to single exposure. Therefore, single and repeated exposure to specific biocidal products may significantly increase skin permeability, especially when used undiluted.

  9. Firefighting and mental health: Experiences of repeated exposure to trauma.

    Science.gov (United States)

    Jahnke, Sara A; Poston, Walker S Carlos; Haddock, Christopher K; Murphy, Beth

    2016-02-15

    Firefighters must be ready to respond to a broad range of emergencies every duty day. In the course of many of these emergencies, firefighters witness events which have the potential to induce emotional trauma, such as badly injured people, deceased children, and individuals who are highly distraught. Previous research suggests that repeated exposure to these traumas (RET) may have negative impacts on the emotional and mental health of fire service personnel. Research on the mental health of firefighters has been limited to small surveys reporting the prevalence of specific mental health problems such as depression and post-traumatic stress disorder among firefighters. Despite the likelihood that RET leads to negative outcomes in firefighters, data is lacking on how exposure impacts fire service personnel. The current study examines the experiences of firefighters related to RET. Using formative research methods, we examined the beliefs and experiences of firefighters and administrators from across the United States regarding the impact of RET on firefighter health. Study findings highlight the cumulative psychological toll of repeated exposure to traumatic events including desensitization, flashbacks, and irritability. Results of the current study suggest that RET is a significant concern for emergency responders that warrants additional research and attention. It is likely that the long term consequences of RET are closely intertwined with other mental health outcomes and general well-being of this important occupational group.

  10. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  11. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-01-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

  12. Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain.

    Science.gov (United States)

    Olutoye, Olutoyin A; Sheikh, Fariha; Zamora, Irving J; Yu, Ling; Akinkuotu, Adesola C; Adesina, Adekunle M; Olutoye, Oluyinka O

    2016-04-01

    Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2

  13. Micronucleus induction by repeated exposure of diagnostic X-ray on oral buccal mucosa

    International Nuclear Information System (INIS)

    Lohith Tejashvi, K.; Suchetha Kumari, N.; Shetty, Shishir Ram

    2012-01-01

    Radiography is the important diagnostic tools essential for diagnosis and planning of orthodontic treatment. X-ray is ionizing radiation which showed various effects include breaking the bond of biological molecules, inducing loss of ability of cell death, increases nuclear alterations. Micronuclei - x000D - (MN) are small chromatin bodies that appear in the cytoplasm by the - x000D - condensation of acrocentric chromosomal fragments or by whole chromosomes. This - x000D - is a sensitive indicator of genetic damage. - x000D - x000D - . To evaluate micronucleus induction by repeated exposure of diagnostic X-ray on human buccal cell. Methods: 25 patients who visiting to ABSMIDS, Department of Oral medicine and Radiology for dental checkup exposed to diagnostic X-ray more than 4 times have been selected for this study. The buccal cell for analysis was collected from the cheek mucosa by means of gentle scraping of epithelial using ice-cream sticks and placed in Buffer saline. This sample was smeared on glass slide and then fixed in methanol:glacial acetic acid (3:1). Air dried and stained with Giemsa for 15-25 minutes. Then 250 cells in each slides were analyzed under microscope and frequency of micronucleus was scored (n=4). Repeated X-ray exposed cells showed micronucleus (1.25%) and nuclear alteration (2.3%) compare to the control. Repeated X-ray exposure leads to induces detectable number of micronucleus and nuclear alterations. (author)

  14. Repeated Exposure to Conditioned Fear Stress Increases Anxiety and Delays Sleep Recovery Following Exposure to an Acute Traumatic Stressor

    OpenAIRE

    Greenwood, Benjamin N.; Thompson, Robert S.; Opp, Mark R.; Fleshner, Monika

    2014-01-01

    Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep–wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by human beings, but whether exposure to repeated fear can prime the develo...

  15. The Effects of Repeated Exposure to Graphic Fear Appeals on Cigarette Packages: A Field Experiment

    NARCIS (Netherlands)

    Dijkstra, A.; Bos, C.

    2015-01-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on

  16. The Effects of Repeated Exposure to Graphic Fear Appeals on Cigarette Packages : A Field Experiment

    NARCIS (Netherlands)

    Dijkstra, Arie; Colin, Bos,

    2015-01-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on

  17. Dealing with consumer differences in liking during repeated exposure to food; typical dynamics in rating behavior

    NARCIS (Netherlands)

    Horst, ter G.J.; Renken, R.; Nanneti, L.; Dalenberg, J.R.; Wijk, de R.A.

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in

  18. Dealing with Consumer Differences in Liking during Repeated Exposure to Food; Typical Dynamics in Rating Behavior

    NARCIS (Netherlands)

    Dalenberg, Jelle R.; Nanetti, Luca; Renken, Remco J.; de Wijk, Rene A.; ter Horst, Gert J.

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in

  19. Attenuated response to repeated daily ozone exposures in asthmatic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Gong, H. Jr.; Linn, W.S. [Rancho Low Amigos Medical Center, Downey, CA (United States); McManus, M.S. [Univ. of California, Los Angeles, CA (United States)

    1997-01-01

    The development of attenuated response ({open_quotes}tolerance{close_quotes}) to daily ozone (O{sub 3}) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures in unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O{sub 3} in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O{sub 3} exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 {degrees}C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O{sub 3} exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O{sub 3} day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O{sub 3} exposure and remained somewhat elevated after all subsequent O{sub 3} exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O{sub 3} predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O{sub 3} exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics. 27 refs., 3 figs., 4 tabs.

  20. Repeated exposure to conditioned fear stress increases anxiety and delays sleep recovery following exposure to an acute traumatic stressor

    Directory of Open Access Journals (Sweden)

    Benjamin N Greenwood

    2014-10-01

    Full Text Available Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by humans, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to either no, mild (10, or severe (100 acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced REM and NREM sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep / wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep / wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders.

  1. Repeated inhalation exposure of Beagle dogs to aerosols of 239PuO2. XII

    International Nuclear Information System (INIS)

    Diel, J.H.; Hahn, F.F.; Muggenburg, B.A.

    1988-01-01

    Beagle dogs were exposed once or semi-annually for 10 yr by inhalation to aerosols of 239 PuO 2 to study the relative doses and effects of these two types of exposures. All exposures have been completed. Dogs exposed at high levels died predominantly of radiation pneumonitis and pulmonary fibrosis. Dogs exposed at lower levels, either once or repeatedly, are dying of a variety of causes including lung cancer. Dogs have survived up to 11 yr after their first exposure. Preliminary results suggest that single and repeated exposures cause similar health effects for equal accumulated radiation doses. (author)

  2. Neonates' responses to repeated exposure to a still face.

    Science.gov (United States)

    Nagy, Emese; Pilling, Karen; Watt, Rachel; Pal, Attila; Orvos, Hajnalka

    2017-01-01

    The main aims of the study were to examine whether human neonates' responses to communication disturbance modelled by the still-face paradigm were stable and whether their responses were affected by their previous experience with the still-face paradigm. The still face procedure, as a laboratory model of interpersonal stress, was administered repeatedly, twice, to 84 neonates (0 to 4 day olds), with a delay of an average of 1.25 day. Frame-by-frame analysis of the frequency and duration of gaze, distressed face, crying, sleeping and sucking behaviours showed that the procedure was stressful to them both times, that is, the still face effect was stable after repeated administration and newborns consistently responded to such nonverbal violation of communication. They averted their gaze, showed distress and cried more during the still-face phase in both the first and the second administration. They also showed a carry-over effect in that they continued to avert their gaze and displayed increased distress and crying in the first reunion period, but their gaze behaviour changed with experience, in the second administration. While in the first administration the babies continued averting their gaze even after the stressful still-face phase was over, this carry-over effect disappeared in the second administration, and the babies significantly increased their gaze following the still-face phase. After excluding explanations of fatigue, habituation and random effects, a self-other regulatory model is discussed as a possible explanation for this pattern.

  3. Neonates’ responses to repeated exposure to a still face

    Science.gov (United States)

    Pilling, Karen; Watt, Rachel; Pal, Attila; Orvos, Hajnalka

    2017-01-01

    Aim The main aims of the study were to examine whether human neonates’ responses to communication disturbance modelled by the still-face paradigm were stable and whether their responses were affected by their previous experience with the still-face paradigm. Methods The still face procedure, as a laboratory model of interpersonal stress, was administered repeatedly, twice, to 84 neonates (0 to 4 day olds), with a delay of an average of 1.25 day. Results Frame-by-frame analysis of the frequency and duration of gaze, distressed face, crying, sleeping and sucking behaviours showed that the procedure was stressful to them both times, that is, the still face effect was stable after repeated administration and newborns consistently responded to such nonverbal violation of communication. They averted their gaze, showed distress and cried more during the still-face phase in both the first and the second administration. They also showed a carry-over effect in that they continued to avert their gaze and displayed increased distress and crying in the first reunion period, but their gaze behaviour changed with experience, in the second administration. While in the first administration the babies continued averting their gaze even after the stressful still-face phase was over, this carry-over effect disappeared in the second administration, and the babies significantly increased their gaze following the still-face phase. Conclusion After excluding explanations of fatigue, habituation and random effects, a self-other regulatory model is discussed as a possible explanation for this pattern. PMID:28771555

  4. Tumorigenic responses from single or repeated inhalation exposures to relatively insoluble aerosols of Ce-144

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1980-01-01

    Human occupational or environmental inhalation exposures may involve repeated or chronic exposures, but most laboratory studies of inhaled radionuclides have involved single exposures. This study was designed to compare the biological effects of repeated inhalation exposures of dogs to a relatively insoluble form of 144 Ce with existing data for singly-exposed dogs that had the same cumulative dose to the lungs two years after exposure. To date, the biological effects observed in these repeatedly-exposed dogs have been substantially different from those seen in singly-exposed dogs, particularly during the first 5 years after the initial exposure. Although pulmonary hemangiosarcoma was the prominent biological effect seen in singly-exposed dogs between 2 and 4 years after exposure, no lung tumors were seen during the 5 years after the first of the repeated exposures. This response plus other clinical observations are discussed in relation to the patterns of dose rate and cumulative dose for the different exposure conditions. (H.K.)

  5. The Effects of Repeated Low-Dose Sarin Exposure

    Science.gov (United States)

    2005-08-01

    support the idea that there is a triphasic NT model for onset and progression of seizures and subsequent brain damage upon acute exposure to OP ChE...An ACh microbore column (1x530 mm ID, 10 µm UniJet, BAS #MF-8904) coupled with AChE/choline oxidase immobilized enzyme reactor (BAS # MF-8903) was...peroxidase to the electrode for the reduction of hydrogen peroxide that was generated from the immobilized enzyme reactor . The detector was set at (-)1.0

  6. Repeated cue exposure effects on subjective and physiological indices of chocolate craving

    NARCIS (Netherlands)

    van Gucht, D.; Vansteenwegen, D.; Beckers, T.; Hermans, D.; Baeyens, F.; Van den Bergh, O.

    2008-01-01

    The aim of this study is to investigate the effects of repeated unreinforced exposure to chocolate cues in persons reporting chocolate craving. Participants in the experimental group (n ¼ 40) received 10 consecutive brief exposures to chocolate cues in each of two sessions, separated by 1-3 days.

  7. Repeated cue exposure effects on subjective and physiological indices of chocolate craving

    OpenAIRE

    Van Gucht, Dinska; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Baeyens, Frank; Van den Bergh, Omer

    2008-01-01

    The aim of this study is to investigate the effects of repeated unreinforced exposure to chocolate cues in persons reporting chocolate craving. Participants in the experimental group (n=40) received 10 consecutive brief exposures to chocolate cues in each of two sessions, separated by 1-3 days. Control participants (n=18) received two exposures at the start and end of each session. Chocolate craving was measured (alternately) through subjective report and the amount of saliva secretion to cho...

  8. The Role of Repeated Exposure to Multimodal Input in Incidental Acquisition of Foreign Language Vocabulary.

    Science.gov (United States)

    Bisson, Marie-Josée; van Heuven, Walter J B; Conklin, Kathy; Tunney, Richard J

    2014-12-01

    Prior research has reported incidental vocabulary acquisition with complete beginners in a foreign language (FL), within 8 exposures to auditory and written FL word forms presented with a picture depicting their meaning. However, important questions remain about whether acquisition occurs with fewer exposures to FL words in a multimodal situation and whether there is a repeated exposure effect. Here we report a study where the number of exposures to FL words in an incidental learning phase varied between 2, 4, 6, and 8 exposures. Following the incidental learning phase, participants completed an explicit learning task where they learned to recognize written translation equivalents of auditory FL word forms, half of which had occurred in the incidental learning phase. The results showed that participants performed better on the words they had previously been exposed to, and that this incidental learning effect occurred from as little as 2 exposures to the multimodal stimuli. In addition, repeated exposure to the stimuli was found to have a larger impact on learning during the first few exposures and decrease thereafter, suggesting that the effects of repeated exposure on vocabulary acquisition are not necessarily constant.

  9. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models

    International Nuclear Information System (INIS)

    Teng, S.; Tebby, C.; Barcellini-Couget, S.; De Sousa, G.; Brochot, C.; Rahmani, R.; Pery, A.R.R.

    2016-01-01

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro – in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. - Highlights: • We could predict cell response over repeated exposure to mixtures of cosmetics. • Compounds acted independently on the cells. • Metabolic interactions impacted exposure concentrations to the compounds.

  10. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models

    Energy Technology Data Exchange (ETDEWEB)

    Teng, S.; Tebby, C. [Models for Toxicology and Ecotoxicology Unit, INERIS, Parc Technologique Alata, BP 2, 60550 Verneuil-en-Halatte (France); Barcellini-Couget, S. [ODESIA Neosciences, Sophia Antipolis, 400 route des chappes, 06903 Sophia Antipolis (France); De Sousa, G. [INRA, ToxAlim, 400 route des Chappes, BP, 167 06903 Sophia Antipolis, Cedex (France); Brochot, C. [Models for Toxicology and Ecotoxicology Unit, INERIS, Parc Technologique Alata, BP 2, 60550 Verneuil-en-Halatte (France); Rahmani, R. [INRA, ToxAlim, 400 route des Chappes, BP, 167 06903 Sophia Antipolis, Cedex (France); Pery, A.R.R., E-mail: alexandre.pery@agroparistech.fr [AgroParisTech, UMR 1402 INRA-AgroParisTech Ecosys, 78850 Thiverval Grignon (France); INRA, UMR 1402 INRA-AgroParisTech Ecosys, 78850 Thiverval Grignon (France)

    2016-08-15

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro – in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. - Highlights: • We could predict cell response over repeated exposure to mixtures of cosmetics. • Compounds acted independently on the cells. • Metabolic interactions impacted exposure concentrations to the compounds.

  11. Effects of repeated exposure to white noise on central cholinergic activity in the rat.

    Science.gov (United States)

    Lai, H

    1988-03-01

    Acute (45 min) exposure to noise has been shown to decrease sodium-dependent high-affinity choline uptake activity in the frontal cortex and hippocampus of the rat. In the present experiment, the effects of repeated noise exposure on choline uptake in these two brain regions were studied. Rats were exposed to 100-dB white noise in ten 45-min sessions. Tolerance developed to the effects of noise on choline uptake. In addition, the effects were found to be classically conditionable to cues in the exposure environment. These data may have important implications in understanding the health hazard of noise exposure in both the public and occupational environments.

  12. Primary blast survival and injury risk assessment for repeated blast exposures.

    Science.gov (United States)

    Panzer, Matthew B; Bass, Cameron R Dale; Rafaels, Karin A; Shridharani, Jay; Capehart, Bruce P

    2012-02-01

    The widespread use of explosives by modern insurgents and terrorists has increased the potential frequency of blast exposure in soldiers and civilians. This growing threat highlights the importance of understanding and evaluating blast injury risk and the increase of injury risk from exposure to repeated blast effects. Data from more than 3,250 large animal experiments were collected from studies focusing on the effects of blast exposure. The current study uses 2,349 experiments from the data collection for analysis of the primary blast injury and survival risk for both long- and short-duration blasts, including the effects from repeated exposures. A piecewise linear logistic regression was performed on the data to develop survival and injury risk assessment curves. New injury risk assessment curves uniting long- and short-duration blasts were developed for incident and reflected pressure measures and were used to evaluate the risk of injury based on blast over pressure, positive-phase duration, and the number of repeated exposures. The risk assessments were derived for three levels of injury severity: nonauditory, pulmonary, and fatality. The analysis showed a marked initial decrease in injury tolerance with each subsequent blast exposure. This effect decreases with increasing number of blast exposures. The new injury risk functions showed good agreement with the existing experimental data and provided a simplified model for primary blast injury risk. This model can be used to predict blast injury or fatality risk for single exposure and repeated exposure cases and has application in modern combat scenarios or in setting occupational health limits. .Copyright © 2012 by Lippincott Williams & Wilkins

  13. Memory responses of jasmonic acid-associated Arabidopsis genes to a repeated dehydration stress.

    Science.gov (United States)

    Liu, Ning; Staswick, Paul E; Avramova, Zoya

    2016-11-01

    Dehydration stress activates numerous genes co-regulated by diverse signaling pathways. Upon repeated exposures, however, a subset of these genes does not respond maintaining instead transcription at their initial pre-stressed levels ('revised-response' genes). Most of these genes are involved in jasmonic acid (JA) biosynthesis, JA-signaling and JA-mediated stress responses. How these JA-associated genes are regulated to provide different responses to similar dehydration stresses is an enigma. Here, we investigate molecular mechanisms that contribute to this transcriptional behavior. The memory-mechanism is stress-specific: one exposure to dehydration stress or to abscisic acid (ABA) is required to prevent transcription in the second. Both ABA-mediated and JA-mediated pathways are critical for the activation of these genes, but the two signaling pathways interact differently during a single or multiple encounters with dehydration stress. Synthesis of JA during the first (S1) but not the second dehydration stress (S2) accounts for the altered transcriptional responses. We propose a model for these memory responses, wherein lack of MYC2 and of JA synthesis in S2 is responsible for the lack of expression of downstream genes. The similar length of the memory displayed by different memory-type genes suggests biological relevance for transcriptional memory as a gene-regulating mechanism during recurring bouts of drought. © 2016 John Wiley & Sons Ltd.

  14. A re-examination of the mere exposure effect: The influence of repeated exposure on recognition, familiarity, and liking.

    Science.gov (United States)

    Montoya, R Matthew; Horton, Robert S; Vevea, Jack L; Citkowicz, Martyna; Lauber, Elissa A

    2017-05-01

    To evaluate the veracity of models of the mere exposure effect and to understand the processes that moderate the effect, we conducted a meta-analysis of the influence of repeated exposure on liking, familiarity, recognition, among other evaluations. We estimated parameters from 268 curve estimates drawn from 81 articles and revealed that the mere exposure effect was characterized by a positive slope and negative quadratic effect consistent with an inverted-U shaped curve. In fact, such curves were associated with (a) all visual, but not auditory stimuli; (b) exposure durations shorter than 10 s and longer than 1 min; (c) both homogeneous and heterogeneous presentation types; and (d) ratings that were taken after all stimuli were presented. We conclude that existing models for the mere exposure effect do not adequately account for the findings, and we provide a framework to help guide future research. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Consumer acceptance of salt-reduced 'soy sauce' foods over rapidly repeated exposure

    NARCIS (Netherlands)

    Kremer, S.; Shimojo, R.; Holthuysen, N.T.E.; Köster, E.P.; Mojet, J.

    2013-01-01

    The stability of the liking for salt reduced products was tested in a rapidly repeated exposure study using soup and bread (with ham). Salt was partially replaced by naturally brewed soy sauce. First, 44 consumers performed 5 two-alternative forced choice tests to establish the exchange rate (ER) at

  16. Developmental differences in stress responding after repeated underwater trauma exposures in rats.

    Science.gov (United States)

    Altman, Daniel E; Simmons, Laurence P; Vuong, Chau T; Taylor, Rachel M; Sousa, Jason C; Marcsisin, Sean R; Zottig, Victor E; Moore, Nicole L T

    2018-05-01

    Adolescence is a distinct developmental period characterized by behavioral and physiological maturation. Rapid ongoing changes during neurodevelopment in particular present potential opportunities for stress to have lasting effects on longitudinal outcomes of behavioral and neuroendocrine function. While adult stress effects on outcomes during adulthood have been characterized, little is known about the lasting effects of adolescent repeated stressor exposure on outcomes during adolescence. We have previously reported different stress responses in adolescent rats relative to adult rats, including a blunted fear response outcome in adulthood in rats stressed during adolescence. The present study characterized the ontogeny of behavioral and neuroendocrine responses to eight underwater trauma (UWT) exposures in rats over a two week poststress time period during adolescence (P34) or adulthood (P83) relative to age-matched control groups that underwent eight swimming episodes without UWT. Repeated UWT exposures starting in adolescence, but not adulthood, resulted in adverse behavioral responses on the elevated plus maze 1 day post-stress. Corticosterone responses did not differ between UWT-exposed and controls for either age group at 1 day or at 7 days poststress, although there was an effect of age on corticosterone levels. We conclude that repeated UWT stress events have a lasting, negative behavioral effect on adolescent rats that is not observed in adult rats after the two-week exposure window. These results suggest that neurophysiological mechanisms underlying recovery from a repeated stressor are immature in adolescence relative to adulthood in rats.

  17. College in the Media: The Relationship between Repeated Exposure and College Expectations

    Science.gov (United States)

    Nuñez, Roland

    2018-01-01

    Media consumption can influence viewer perceptions and attitudes. Recent research on media's effect on college students has failed to address gender differences. Using Mere Repeated Exposure Theory (traditionally used in marketing research), this study aims to answer three research questions regarding college media consumption and college…

  18. Information technology-based approaches to reducing repeat drug exposure in patients with known drug allergies.

    Science.gov (United States)

    Cresswell, Kathrin M; Sheikh, Aziz

    2008-05-01

    There is increasing interest internationally in ways of reducing the high disease burden resulting from errors in medicine management. Repeat exposure to drugs to which patients have a known allergy has been a repeatedly identified error, often with disastrous consequences. Drug allergies are immunologically mediated reactions that are characterized by specificity and recurrence on reexposure. These repeat reactions should therefore be preventable. We argue that there is insufficient attention being paid to studying and implementing system-based approaches to reducing the risk of such accidental reexposure. Drawing on recent and ongoing research, we discuss a number of information technology-based interventions that can be used to reduce the risk of recurrent exposure. Proven to be effective in this respect are interventions that provide real-time clinical decision support; also promising are interventions aiming to enhance patient recognition, such as bar coding, radiofrequency identification, and biometric technologies.

  19. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models.

    Science.gov (United States)

    Teng, S; Tebby, C; Barcellini-Couget, S; De Sousa, G; Brochot, C; Rahmani, R; Pery, A R R

    2016-08-15

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro - in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery

    Science.gov (United States)

    Nicholson, John W.; Wilson, Alan

    2004-09-01

    This article describes the history of the reaction converting carboxylic acids to ketones. The reaction has been rediscovered several times, yet has actually been known for centuries. The best known version of the process is the Dakin West reaction (1928), which applies to α-amino acids and also involves the simultaneous conversion of the amine group to amido functionality. Unlike other examples, this particular reaction has attracted a reasonable amount of attention and it appears to be better known than the conversion of simple carboxylic acids to ketones. However, this reaction was described as long ago as 1612, when Beguin published an account of it in his book, Tyrocinium Chymicum . Since then, many chemists have rediscovered the reaction, apparently independently. One of the earliest modern accounts was by W. H. Perkin, Sr., in 1886, who made various simple ketones by refluxing the appropriate carboxylic acids with base. However, this work has been largely ignored, including by his son, W. H. Perkin, Jr., who used a more complicated base-catalyzed ketonization to prepare small ring compounds in the early years of the 20th century. Other articles detailing the application of ketonization to organic acids are discussed, including our own work, which employed the process to crosslink carboxylated polymers for possible technical application in coatings. Despite its relative obscurity, the reaction was used by Woodward et al. in the total synthesis of strychnine, reported in 1963, and this is discussed in detail at the end of the article. See Featured Molecules .

  1. Repeated nicotine exposure enhances reward-related learning in the rat.

    Science.gov (United States)

    Olausson, Peter; Jentsch, J David; Taylor, Jane R

    2003-07-01

    Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

  2. Biological effects of repeated exposure of beagle dogs to relatively insoluble aerosols of 144Ce. IV

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Hanika-Rebar, C.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1977-01-01

    This experiment is being conducted to study the behavior and long-term biological effects in Beagle dogs of 144 Ce inhaled in fused aluminosilicate particles in repeated inhalation exposures for comparison with similar data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every eight weeks for two years (13 exposures) to achieve specified exposure goals. The 144 Ce-exposed dogs received increasing or relatively constant beta radiation dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Exposures in the first and second groups were planned to yield a cumulative absorbed dose to lung of approximately equal to 35,000 rads and those in the third group approximately equal to 17,000 rads within two years after the first exposure. Singly exposed dogs that had died with pulmonary tumors when this experiment was initiated had cumulative doses to death of 29,000 to 61,000 rads. All 13 exposures have been completed. One dog in the 4.5-μCi 144 Ce/kg body weight group died at 771 days after first exposure with emaciation, adrenal cortical degeneration and bone marrow aplasia. One control dog died accidentally during anesthesia. During the past year, two additional dogs have died. One dog in the repeated 2.5-μCi 144 Ce/kg body weight group died at 1256 days after the first exposure with radiation pneumonitis and pulmonary fibrosis and a control dog died at 1052 days with autoimmune hemolytic anemia. The remaining 32 dogs appear to be in good physical condition except for a persistent lymphopenia at approximately equal to 4 years after the first exposure. They are being maintained for life span observations

  3. Impact of repeated exposure on toxicity of perchloroethylene in Swiss Webster mice

    International Nuclear Information System (INIS)

    Philip, Binu K.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M.

    2007-01-01

    The aim was to study the subchronic toxicity of perchloroethylene (Perc) by measuring injury and repair in liver and kidney in relation to disposition of Perc and its major metabolites. Male SW mice (25-29 g) were given three dose levels of Perc (150, 500, and 1000 mg/kg day) via aqueous gavage for 30 days. Tissue injury was measured during the dosing regimen (0, 1, 7, 14, and 30 days) and over a time course of 24-96 h after the last dose (30 days). Perc produced significant liver injury (ALT) after single day exposure to all three doses. Liver injury was mild to moderate and regressed following repeated exposure for 30 days. Subchronic Perc exposure induced neither kidney injury nor dysfunction during the entire time course as evidenced by normal renal histology and BUN. TCA was the major metabolite detected in blood, liver, and kidney. Traces of DCA were also detected in blood at initial time points after single day exposure. With single day exposure, metabolism of Perc to TCA was saturated with all three doses. AUC/dose ratio for TCA was significantly decreased with a concomitant increase in AUC/dose of Perc levels in liver and kidney after 30 days as compared to 1 day exposures, indicating inhibition of metabolism upon repeated exposure to Perc. Hepatic CYP2E1 expression and activity were unchanged indicating that CYP2E1 is not the critical enzyme inhibited. Hepatic CYP4A expression, measured as a marker of peroxisome proliferation was increased transiently only on day 7 with the high dose, but was unchanged at later time points. Liver tissue repair peaked at 7 days, with all three doses and was sustained after medium and high dose exposure for 14 days. These data indicate that subchronic Perc exposure via aqueous gavage does not induce nephrotoxicity and sustained hepatotoxicity suggesting adaptive hepatic repair mechanisms. Enzymes other than CYP2E1, involved in the metabolism of Perc may play a critical role in the metabolism of Perc upon subchronic exposure

  4. Effects of repeated exposure to either vegetables or fruits on infant's vegetable and fruit acceptance at the beginning of weaning

    NARCIS (Netherlands)

    Barends, C.; Vries, de J.; Mojet, J.; Graaf, de C.

    2013-01-01

    This study investigated the effects of repeated exposure to either vegetables or fruits on an infant's vegetable and fruit acceptance during the first 18 days of weaning. We hypothesized that repeated exposure to a type of vegetable or fruit, would increase its intake. Furthermore, we expected that

  5. A model of human nasal epithelial cells adapted for direct and repeated exposure to airborne pollutants.

    Science.gov (United States)

    Bardet, Gaëlle; Achard, Sophie; Loret, Thomas; Desauziers, Valérie; Momas, Isabelle; Seta, Nathalie

    2014-08-17

    Airway epithelium lining the nasal cavity plays a pivotal role in respiratory tract defense and protection mechanisms. Air pollution induces alterations linked to airway diseases such as asthma. Only very few in vitro studies to date have succeeded in reproducing physiological conditions relevant to cellular type and chronic atmospheric pollution exposure. We therefore, set up an in vitro model of human Airway Epithelial Cells of Nasal origin (hAECN) close to real human cell functionality, specifically adapted to study the biological effects of exposure to indoor gaseous pollution at the environmental level. hAECN were exposed under air-liquid interface, one, two, or three-times at 24 h intervals for 1 h, to air or formaldehyde (200 μg/m(3)), an indoor air gaseous pollutant. All experiments were ended at day 4, when both cellular viability and cytokine production were assessed. Optimal adherence and confluence of cells were obtained 96 h after cell seeding onto collagen IV-precoated insert. Direct and repeated exposure to formaldehyde did not produce any cellular damage or IL-6 production change, although weak lower IL-8 production was observed only after the third exposure. Our model is significantly better than previous ones due to cell type and the repeated exposure protocol. Copyright © 2014. Published by Elsevier Ireland Ltd.

  6. Eye lens radiation exposure and repeated head CT scans: A problem to keep in mind

    International Nuclear Information System (INIS)

    Michel, Morgane; Jacob, Sophie; Roger, Gilles; Pelosse, Béatrice; Laurier, Dominique; Le Pointe, Hubert Ducou; Bernier, Marie-Odile

    2012-01-01

    Objectives: The deterministic character of radiation-induced cataract is being called into question, raising the possibility of a risk in patients, especially children, exposed to ionizing radiation in case of repeated head CT-scans. This study aims to estimate the eye lens doses of a pediatric population exposed to repeated head CTs and to assess the feasibility of an epidemiological study. Methods: Children treated for a cholesteatoma, who had had at least one CT-scan of the middle ear before their tenth birthday, were included. Radiation exposure has been assessed from medical records and telephone interviews. Results: Out of the 39 subjects contacted, 32 accepted to participate. A total of 76 CT-scans were retrieved from medical records. At the time of the interview (mean age: 16 years), the mean number of CT per child was 3. Cumulative mean effective and eye lens doses were 1.7 mSv and 168 mGy, respectively. Conclusion: A relatively high lens radiation dose was observed in children exposed to repeated CT-scans. Due to that exposure and despite the difficulties met when trying to reach patients’ families, a large scale epidemiological study should be performed in order to assess the risk of radiation-induced cataracts associated with repeated head CT.

  7. Perturbations in different forms of cost/benefit decision making induced by repeated amphetamine exposure.

    Science.gov (United States)

    Floresco, Stan B; Whelan, Jennifer M

    2009-08-01

    Psychostimulant abuse has been linked to impairments in cost-benefit decision making. We assessed the effects of repeated amphetamine (AMPH) treatment in rodents on two distinct forms of decision making. Separate groups of rats were trained for 26 days on either a probabilistic (risk) or effort-discounting task, each consisting of four discrete blocks of ten choice trials. One lever always delivered a smaller reward (one or two pellets), whereas another lever delivered a four-pellet reward. For risk-discounting, the probability of receiving the larger reward decreased across trial blocks (100-12.5%), whereas on the effort task, four pellets could be obtained after a ratio of presses that increased across blocks (2-20). After training, rats received 15 saline or AMPH injections (escalating from 1 to 5 mg/kg) and were then retested during acute and long-term withdrawal. Repeated AMPH administration increased risky choice 2-3 weeks after drug exposure, whereas these treatments did not alter effort-based decision making in a separate group of animals. However, prior AMPH exposure sensitized the effects of acute AMPH on both forms of decision making, whereby lower doses were effective at inducing "risky" and "lazy" patterns of choice. Repeated AMPH exposure leads to relatively long-lasting increases in risky choice, as well as sensitization to the effects of acute AMPH on different forms of cost/benefit decision making. These findings suggest that maladaptive decision-making processes exhibited by psychostimulant abusers may be caused in part by repeated drug exposure.

  8. Enhancing consumer liking of low salt tomato soup over repeated exposure by herb and spice seasonings.

    Science.gov (United States)

    Ghawi, Sameer Khalil; Rowland, Ian; Methven, Lisa

    2014-10-01

    There is strong evidence for the link between high dietary sodium and increased risk of cardiovascular disease which drives the need to reduce salt content in foods. In this study, herb and spice blends were used to enhance consumer acceptability of a low salt tomato soup (0.26% w/w). Subjects (n = 148) scored their liking of tomato soup samples over 5 consecutive days. The first and last days were pre-and post-exposure visits where all participants rated three tomato soup samples; standard, low salt and low salt with added herbs and spices. The middle 3 days were the repeated exposure phase where participants were divided into three balanced groups; consuming the standard soup, the low salt soup, or the low salt soup with added herbs and spices. Reducing salt in the tomato soup led to a significant decline in consumer acceptability, and incorporating herbs and spices did not lead to an immediate enhancement in liking. However, inclusion of herbs and spices enhanced the perception of the salty taste of the low salt soup to the same level as the standard. Repeated exposure to the herbs and spice-modified soup led to a significant increase in the overall liking and liking of flavour, texture and aftertaste of the soup, whereas no changes in liking were observed for the standard and low salt tomato soups over repeated exposure. Moreover, a positive trend in increasing the post-exposure liking of the herbs and spices soup was observed. The findings suggest that the use of herbs and spices is a useful approach to reduce salt content in foods; however, herbs and spices should be chosen carefully to complement the food as large contrasts in flavour can polarise consumer liking. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Aberrant approach-avoidance conflict resolution following repeated cocaine pre-exposure.

    Science.gov (United States)

    Nguyen, David; Schumacher, Anett; Erb, Suzanne; Ito, Rutsuko

    2015-10-01

    Addiction is characterized by persistence to seek drug reinforcement despite negative consequences. Drug-induced aberrations in approach and avoidance processing likely facilitate the sustenance of addiction pathology. Currently, the effects of repeated drug exposure on the resolution of conflicting approach and avoidance motivational signals have yet to be thoroughly investigated. The present study sought to investigate the effects of cocaine pre-exposure on conflict resolution using novel approach-avoidance paradigms. We used a novel mixed-valence conditioning paradigm to condition cocaine-pre-exposed rats to associate visuo-tactile cues with either the delivery of sucrose reward or shock punishment in the arms in which the cues were presented. Following training, exploration of an arm containing a superimposition of the cues was assessed as a measure of conflict resolution behavior. We also used a mixed-valence runway paradigm wherein cocaine-pre-exposed rats traversed an alleyway toward a goal compartment to receive a pairing of sucrose reward and shock punishment. Latency to enter the goal compartment across trials was taken as a measure of motivational conflict. Our results reveal that cocaine pre-exposure attenuated learning for the aversive cue association in our conditioning paradigm and enhanced preference for mixed-valence stimuli in both paradigms. Repeated cocaine pre-exposure allows appetitive approach motivations to gain greater influence over behavioral output in the context of motivational conflict, due to aberrant positive and negative incentive motivational processing.

  10. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage

    International Nuclear Information System (INIS)

    Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J.; Rudich, Yinon

    2016-01-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. - Highlights: • Repeated exposure to urban PM cause systemic inflammation and oxidative damage to lung tissue lipids and proteins. • Repeated exposure to these PM extracts decreased transcription of Nrf2 protective genes. • Single as opposed to repeated exposure, induced confined lung response accompanied by activated defense mechanisms. • Metals, potentially from break and tire wear, drive the pulmonary response with exposure to urban PM. - Repeated exposures to urban PM water extracts

  11. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    Science.gov (United States)

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

  12. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats

    Directory of Open Access Journals (Sweden)

    Jessica Saalfield

    2015-12-01

    Full Text Available Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively would affect ethanol conditioned taste aversions 2 days (CTA1 and >3 weeks (CTA2 post-exposure using supersaccharin and saline as conditioning stimuli (CS, respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25% or water every 48 h from postnatal day (P 25–45 (early AIE or P45-65 (late AIE, or were left non-manipulated (NM. During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

  13. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

    Science.gov (United States)

    Saalfield, Jessica; Spear, Linda

    2015-12-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Dealing with consumer differences in liking during repeated exposure to food; typical dynamics in rating behavior.

    Science.gov (United States)

    Dalenberg, Jelle R; Nanetti, Luca; Renken, Remco J; de Wijk, René A; Ter Horst, Gert J

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in consumers; averaging will mix and hide possible subgroups of consumer behaviors, leading to a misinterpretation of the results. To deal with the variability in consumer liking, we propose to use clustering on data from consumer-product combinations to investigate the nature of the behavioral differences within the complete dataset. The resulting behavioral clusters can then be used to describe product acceptance. To test this approach we used two independent data sets in which young adults were repeatedly exposed to drinks and snacks, respectively. We found that five typical consumer behaviors existed in both datasets. These behaviors differed both in the average level of liking as well as its temporal dynamics. By investigating the distribution of a single product across typical consumer behaviors, we provide more precise insight in how consumers divide in subgroups based on their product liking (i.e. product modality). This work shows that taking into account and using interindividual differences can unveil information about product acceptance that would otherwise be ignored.

  15. Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Sun, J.D.; MacGregor, J.T.; Wehr, C.M.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

    1990-01-01

    Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased

  16. Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

    Directory of Open Access Journals (Sweden)

    Kimberly H LeBlanc

    Full Text Available There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT paradigm or habit formation (assayed using sensitivity to reward devaluation. After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

  17. Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

    Science.gov (United States)

    LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

    2013-01-01

    There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

  18. The effects of multiple UV exposures on HIV-LTR (long terminal repeat) expression

    International Nuclear Information System (INIS)

    Schreck, S.; Milton, J.; Panozzo, J.; Libertin, C.R.; Woloschak, G.E.; Loyola Univ., Maywood, IL

    1995-01-01

    Previous studies have shown that cellular stress agents such as UV radiation induce transcription from the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Using HeLa cells stably transfected with the HIV-LTR sequence, which transcriptionally drives the chloramphenicol acetyl transferase (CAT) reporter gene, we examined the effects of multiple exposures to UVC (254 nm) on HIV-LTR-CAT expression. Low doses (≤ 5 J m -2 ) had no effect on CAT expression, but up to 29-fold induction was observed with 10 J m -2 when cells were harvested 48 h after completion of the exposure. Little difference was noted in induction levels when cells were exposed to one 25 J m -2 dose, viable cells were harvested at 24 h, 48 h or 72 h, and cell lysates were assayed for CAT expression. Two sequential 12.5 J m -2 exposures, given 24 h apart, resulted in an additive effect on CAT expression; these two exposures produced CAT activity equivalent to that induced following a single 25 J m -2 dose. Our data suggest that HIV-LTR requires a specific threshold UV dose in order to elicit induction; a maximal induction dose is also evident; exposures higher than this maximal dose contribute no more to HIV-LTR induction in viable cells. (author)

  19. Anti-Inflammatory and Antioxidant Effects of Repeated Exposure to Cruciferous Allyl Nitrile in Sensitizer-Induced Ear Edema in Mice.

    Science.gov (United States)

    Tanii, Hideji; Sugitani, Kayo; Saijoh, Kiyofumi

    2016-02-29

    Skin sensitizers induce allergic reactions through the induction of reactive oxygen species. Allyl nitrile from cruciferous vegetables has been reported to induce antioxidants and phase II detoxification enzymes in various tissues. We assessed the effects of repeated exposure to allyl nitrile on sensitizer-induced allergic reactions. Mice were dosed with allyl nitrile (0-200 µmol/kg), and then received a dermal application of 1 of 3 sensitizers on the left ear or 1 of 2 vehicles on the right ear. Quantitative assessment of edema was carried out by measuring the difference in weight between the portions taken from the right and left ears. We tested enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) in ears. Repeated exposure to allyl nitrile reduced edemas induced by glutaraldehyde and by 2, 4-dinitrochlorobenzene (DNCB), but not by formaldehyde. The repeated exposure decreased levels of TBARS, a marker of oxidative stress, induced by glutaraldehyde and by DNCB, but not by formaldehyde. Allyl nitrile elevated SOD levels for the 3 sensitizers, and CAT levels for formaldehyde and DNCB. Allyl nitrile also increased GPx levels for formaldehyde and DNCB, but not for glutaraldehyde. The reduced edemas were associated with changes in oxidative stress levels and antioxidant enzymes. Repeated exposure to allyl nitrile reduced allergic reactions induced by glutaraldehyde and by DNCB, but not by formaldehyde. This reduction was associated with changes in ROS levels and antioxidant enzyme activities.

  20. Tetranucleotide repeat polymorphism at the human prostatic acid phosphatase (ACPP) gene

    Energy Technology Data Exchange (ETDEWEB)

    Polymeropoulos, M H; Xiao, Hong; Rath, D S; Merril, C R [National Inst. of Mental Health Neuroscience Center, Washington, DC (United States)

    1991-09-11

    The polymorphic (AAAT){sub n} repeat begins at base pair 2342 of the human prostatic acid phosphatase gene on chromosome 3q21-qter. The polymorphism can be typed using the polymerase chain reaction (PCR) as described previously. The predicted length of the amplified sequence was 275 bp. Co-dominant segregation was observed in two informative families. The human prostatic acid phosphatase gene has been assigned to chromosome 3q21-qter.

  1. Biological effects of repeated inhalation exposure of beagle dogs to relatively insoluble aerosols of 144Ce

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1980-01-01

    Beagle dogs were exposed repeatedly to a relatively insoluble form of 144 Ce (in fused aluminosilicate particles) to study the deposition, retention, and long-term biological effects for comparison with data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every 8 weeks for 2 years (13 exposures) to achieve specified exposure goals. These goals were: to increase the lung burden by 2.5 μCi 144 Ce/kg body weight with each exposure; to reestablish lung burdens of 9 or 4.5 μCi 144 Ce/kg body weight and to expose controls to fused aluminosilicate particles containing nonradioactive cerium. To date, 19 exposed dogs and 2 control dogs have died or were euthanized. The most prevalent findings to date have been pulmonary carcinomas (7 dogs) and hemangiosarcomas in the tracheobronchial lymph nodes (3 dogs). Observations are continuing on the surviving 8 144 Ce-exposed and 7 control dogs who are now at approximately 2500 days (6.8 years) after the first exposure

  2. The effects of repeated low-level blast exposure on hearing in marines

    Directory of Open Access Journals (Sweden)

    Lina R Kubli

    2017-01-01

    Full Text Available Background: The study evaluates a group of Military Service Members specialized in blast explosive training called “Breachers” who are routinely exposed to multiple low-level blasts while teaching breaching at the U.S. Marine Corps in Quantico Virginia. The objective of this study was to determine if there are any acute or long-term auditory changes due to repeated low-level blast exposures used in training. The performance of the instructor group “Breachers” was compared to a control group, “Engineers”. Methods: A total of 11 Breachers and four engineers were evaluated in the study. The participants received comprehensive auditory tests, including pure-tone testing, speech-in-noise (SIN measures, and central auditory behavioral and objective tests using early and late (P300 auditory evoked potentials over a period of 17 months. They also received shorter assessments immediately following the blast-exposure onsite at Quantico. Results: No acute or longitudinal effects were identified. However, there were some interesting baseline effects found in both groups. Contrary to the expected, the onsite hearing thresholds and distortion product otoacoustic emissions were slightly better at a few frequencies immediately after blast-exposure than measurements obtained with the same equipment weeks to months after each blast-exposure. Conclusions: To date, the current study is the most comprehensive study that evaluates the long-term effects of blast-exposure on hearing. Despite extensive testing to assess changes, the findings of this study suggest that the levels of current exposures used in this military training environment do not seem to have an obvious deleterious effect on hearing.

  3. Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

    Science.gov (United States)

    Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

    2018-01-01

    A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

  4. Physiological responses and manual performance in humans following repeated exposure to severe cold at night.

    Science.gov (United States)

    Ozaki, H; Nagai, Y; Tochihara, Y

    2001-04-01

    We evaluated human physiological responses and the performance of manual tasks during exposure to severe cold (-25 degrees C) at night (0300-0500 hours) and in the afternoon (1500-1700 hours). Thirteen male students wearing standard cold protective clothing occupied a severely cold room (-25 degrees C) for 20 min, and were then transferred to a cool room (10 degrees C) for 20 min. This pattern of exposure was repeated three times, for a total time of exposure to extreme cold of 60 min. The experiments were started either at 1500 hours or 0300 hours and measurements of rectal temperature, skin temperature, blood pressure, performance in a counting task, hand tremor, and subjective responses were made in each condition. At the end of the experiment at night the mean decrease in rectal temperature [0.68 (SEM 0.04) degree C] was significantly greater than that at the end of the experiment in the afternoon [0.55 (SEM 0.08) degree C, P second cold exposure at night the mean increase in diastolic blood pressure [90 (SEM 2.0) mmHg] was significantly greater than that at the end of the second cold exposure in the afternoon [82 (SEM 2.8) mmHg, P second cold exposure at night, mean finger skin temperature [11.8 (SEM 0.8) degrees C] was significantly higher than that at the comparable time in the afternoon [9.0 (SEM 0.7) degrees C, P second cold exposure at night [25.6 (SEM 1.5) degrees C] was significantly higher than in the afternoon [20.1 (SEM 0.8) degrees C, P < 0.01]. The increased skin temperatures in the periphery resulted in increased heat loss. Since peripheral skin temperatures were highest at night, the subjects noted diminished sensations of thermal cold and pain at that time. Manual dexterity at the end of the first cold exposure at night [mean 83.7 (SEM 3.6) times.min-1] had decreased significantly more than at the end of the first cold exposure in the afternoon [mean 89.4 (SEM 3.5) times.min-1, P < 0.01]. These findings of a lowered rectal temperature and

  5. The role of temporal delay and repeated prospective memory cue exposure on the deactivation of completed intentions.

    Science.gov (United States)

    Walser, Moritz; Plessow, Franziska; Goschke, Thomas; Fischer, Rico

    2014-07-01

    Previous studies have shown that completed prospective memory (PM) intentions entail aftereffects in terms of ongoing-task-performance decrements in trials containing repeated PM cues which previously served as PM cues triggering the intended action. Previous research reported that PM aftereffects decrease over time, thus revealing a specific time course of PM aftereffects. In the present study, we tested two accounts for this pattern, assuming either that the decline of aftereffects is related to the temporal distance to PM task completion or may be a result of the repeated exposure of repeated PM cues in the ongoing task. In three experiments, we manipulated both the temporal distance to PM task completion and the frequency of repeated PM cues and demonstrated that aftereffects of completed intentions declined with repeated exposure of formerly relevant PM cues. In addition, effects of repeated exposure were not only limited to the repetition of specific PM-cue exemplars but also generalized to other semantically related PM cues within the PM-cue category. Together, findings show that decreased aftereffects of completed intentions are not related to the temporal duration of the subsequent test block, but crucially depend on the repeated exposure of the previously relevant PM cues.

  6. Thermal responses from repeated exposures to severe cold with intermittent warmer temperatures.

    Science.gov (United States)

    Ozaki, H; Enomoto-Koshimizu, H; Tochihara, Y; Nakamura, K

    1998-09-01

    This study was conducted to evaluate physiological reaction and manual performance during exposure to warm (30 degrees C) and cool (10 degrees C) environments after exposure to very low temperatures (-25 degrees C). Furthermore, this experiment was conducted to study whether it is desirable to remove cold-protective jackets in warmer rooms after severe cold exposure. Eight male students remained in an extremely cold room for 20 min, after which they transferred into either the warm room or the cool room for 20 min. This pattern was repeated three times, and the total cold exposure time was 60 min. In the warm and cool rooms, the subjects either removed their cold-protective jackets (Condition A), or wore them continuously (Condition B). Rectal temperature, skin temperatures, manual performance, blood pressure, thermal, comfort and pain sensations were measured during the experiment. The effects of severe cold on almost all measurements in the cool (10 degrees C) environment were greater than those in the warm (30 degrees C) environment under both clothing conditions. The effects of severe cold on all measurements under Condition A except rectal temperature and toe skin temperature were significantly greater than those under Condition B in the cool environment but, not at all differences between Condition A and Condition B in the warm environments were significant. It was recognized that to remove cold-protective jackets in the cool room (10 degrees C) after severe cold exposure promoted the effects of severe cold. When rewarming in the warm resting room (30 degrees C), the physiological and psychological responses and manual performance were not influenced by the presence or absence of cold-protective clothing. These results suggest that it is necessary for workers to make sure to rewarm in the warm room outside of the cold storage and continue to wear cold-protective clothing in the cool room.

  7. Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Differential Microclimate Exposure: Comparison of Acute vs. Repeated Drug Exposure.

    Science.gov (United States)

    Morrison, Lucas M; Unger, Kirk A; Watterson, James H

    2017-07-01

    Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls. Skeletal elements (vertebrae, ribs, pelvic girdles, femora, tibiae, skulls and scapulae) were recovered, pulverized and underwent methanolic microwave assisted extraction (MAE). Extracts were analyzed by GC-MS following clean-up by solid-phase extraction (SPE). Drug levels, expressed as mass-normalized response ratios and the ratios of DXT and DXM levels (RRDXT/RRDXM) were compared between drug exposures, microclimate sites, and across skeletal elements. DXM levels differed significantly (P < 0.05) between corresponding bone elements across exposure groups (5/7-site A; 4/7-site B), but no significant differences in DXT levels were observed between corresponding elements. RRDXT/RRDXM differed significantly (P < 0.05) between corresponding bone elements across exposure groups (6/7-site A; 5/7-site B). No significant differences were observed in levels of DXM, DXT or RRDXT/RRDXM between corresponding elements from either group between sites. When data from all bone elements was pooled, levels of DXM and RRDXT/RRDXM differed significantly between exposure groups at each site, while those of DXT did not. For both exposure groups, comparison of pooled data between sites showed no significant differences in levels of DXM, DXT or RRDXT/RRDXM. Different decomposition microclimates did not impede the discrimination of DXM exposure patterns from the analyses of DXM, DXT and RRDXT/RRDXM in bone samples. © The Author 2017

  8. Adaptive Changes in Sensorimotor Coordination and Motion Sickness Following Repeated Exposures to Virtual Environments

    Science.gov (United States)

    Harm, D. L.; Taylor, L. C.; Bloomberg, J. J.

    2007-01-01

    Virtual environments offer unique training opportunities, particularly for training astronauts and preadapting them to the novel sensory conditions of microgravity. Two unresolved human factors issues in virtual reality (VR) systems are: 1) potential "cybersickness", and 2) maladaptive sensorimotor performance following exposure to VR systems. Interestingly, these aftereffects are often quite similar to adaptive sensorimotor responses observed in astronauts during and/or following space flight. Initial interpretation of novel sensory information may be inappropriate and result in perceptual errors. Active exploratory behavior in a new environment, with resulting feedback and the formation of new associations between sensory inputs and response outputs, promotes appropriate perception and motor control in the new environment. Thus, people adapt to consistent, sustained alterations of sensory input such as those produced by microgravity, unilateral labyrinthectomy and experimentally produced stimulus rearrangements. The purpose of this research was to compare disturbances in sensorimotor coordination produced by dome and head-mounted virtual environment displays and to examine the effects of exposure duration, and repeated exposures to VR systems. The first study examined disturbances in balance control, and the second study examined disturbances in eye-head-hand (EHH) and eye-head coordination.

  9. Repeated exposure to immobilization or two different footshock intensities reveals differential adaptation of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Rabasa, Cristina; Muñoz-Abellán, Cristina; Daviu, Núria; Nadal, Roser; Armario, Antonio

    2011-05-03

    Factors involved in adaptation to repeated stress are not well-characterized. For instance, acute footshock (FS) of high intensity appears to be less severe than immobilization (IMO) in light of the speed of post-stress recovery of the hypothalamic-pituitary-adrenal (HPA) axis and other physiological variables. However, repeated exposure to IMO consistently resulted in reduction of the HPA response to the same stressor (adaptation), whereas failure to adapt has been usually reported after FS. Thus, in the present work we directly compared the activation of HPA axis and other physiological changes in response to both acute and repeated exposure to IMO and two intensities of FS (medium and high) in adult male rats. Control rats were exposed to the FS boxes but they did not receive shocks. Daily repeated exposure to IMO resulted in significant adaptation of the overall ACTH and corticosterone responses to the stressor. Such a reduction was also observed with repeated exposure to FS boxes and FS-medium, whereas repeated exposure to FS-high only resulted in a small reduction of the corticosterone response during the post-stress period. This suggests that some properties of FS-high make adaptation to it difficult. Interestingly, overall changes in food intake and body weight gain throughout the week of exposure to the stressors reveal a greater impact of IMO than FS-high, indicating that factors other than the intensity of a stressor, at least when evaluated in function of the above physiological variables, can influence HPA adaptation. Since FS exposure is likely to cause more pain than IMO, activation of nociceptive signals above a certain level may negatively affect HPA adaptation to repeated stressors. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.

    Science.gov (United States)

    Gimenez-Rivera, Vladimir-Andrey; Siebenhaar, Frank; Zimmermann, Carolin; Siiskonen, Hanna; Metz, Martin; Maurer, Marcus

    2016-12-01

    Allergic contact dermatitis is a chronic T cell-driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient Kit W-sh/W-sh (Sash) and MCPT5-Cre + iDTR + mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-γ, IL-17α, and IL-23, as well as increased accumulation of Ag-specific IFN-γ-producing CD8 + tissue-resident memory T (T RM ) cells. The CD8 + T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous T RM cells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8 + T RM cells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

    Science.gov (United States)

    Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

    2017-02-01

    The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe 2 O 3 -NPs) could be toxic to mice testis. Fe 2 O 3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe 2 O 3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe 2 O 3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe 2 O 3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe 2 O 3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe 2 O 3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe 2 O 3 -NPs exposure may be associated with Fe 2 O 3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe 2 O 3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe 2 O 3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017. © 2016 Wiley Periodicals, Inc.

  12. The hidden price of repeated traumatic exposure: Different cognitive deficits in different first-responders

    Directory of Open Access Journals (Sweden)

    Einat eLevy-Gigi

    2014-08-01

    Full Text Available Studies on first responders who are repeatedly exposed to traumatic events report low levels of PTSD symptoms and diagnosis. However, neuroimaging and behavioral studies show that traumatic exposure is associated with brain and cognitive dysfunctions. Taking together it may suggest that traumatic exposure have a price, which is not sufficiently defined by the standard PTSD measures. In a recent study we revealed that similar to individuals with PTSD, non-PTSD highly exposed firefighters display a selective impairment in hippocampal related functions. In the current study we aimed to test whether different first responders display a similar impairment. We concentrated on unique populations of active duty firefighters and criminal scene-investigators (CSI police, who are frequently exposed to similar levels and types of traumatic events, and compared them to civilian matched-controls with no history of trauma-exposure. We used a hippocampal dependent cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context related information. We predicted and found that all participants were equally able to acquire and retain stimulus-outcome associations. However, there were significant differences in reversal learning between the groups. Performance among firefighters replicated our prior findings; they struggled to learn that a previously negative context is later associated with a positive outcome. CSI police on the other hand showed a selective impairment in reversing the outcome of a negative cue. Hence after learning that a specific cue is associated with a negative outcome, they could not learn that later it is associated with a positive outcome. Performance in both groups did not correlate with levels of PTSD, anxiety, depression or behavioral inhibition symptoms. The results provide further evidence of the hidden price of traumatic exposure, suggesting that this price may differ as a

  13. Effect of squatting on sprinting performance and repeated exposure to complex training in male rugby players.

    Science.gov (United States)

    Comyns, Thomas M; Harrison, Andrew J; Hennessy, Liam K

    2010-03-01

    This study was undertaken to examine the effect of a heavy weight training exercise on sprinting performance and on the effect of repeated exposure to a complex training protocol. Eleven male rugby union players (age 20.9 +/- 3.1 years) participated in the study, which involved 5 separate testing sessions. Back squat 3 repetition maximum (3RM) was established in session 1. Sessions 2-5 were identical and involved the subjects completing a 30-m sprint before and after a 3RM back squat protocol. Four minutes of rest was given between the back squatting and the posttest 30-m sprint. All sprint trials were measured with a laser measurement device (LAVEG, Jenoptik, Jena, Germany). Sprint time and instantaneous, average, and maximum velocity were the dependent variables. The criterion for significance was set at an alpha level of p > or = 0.05. No significant improvement was evident for any of the testing sessions (p > or = 0.05). In session 1, there was a significant increase in 30-m time and a significant reduction in average 30-m velocity and maximum velocity (p benefits in sprinting may not have been realized because of intra and intersubject variations in sprint technique. The session x phase interaction revealed a significant improvement in the pre to posttest changes in instantaneous velocity at 20 m (p = 0.035) and 30 m (p = 0.036) from session 1 to session 4. This indicates that the rugby players may be able to learn to apply the potentiation effects of complex training. From a practical perspective, players may need repeated exposure to this training modality to gain benefit from it, and this should be reflected in program planning.

  14. Constraints and consequences of the emergence of amino acid repeats in eukaryotic proteins.

    Science.gov (United States)

    Chavali, Sreenivas; Chavali, Pavithra L; Chalancon, Guilhem; de Groot, Natalia Sanchez; Gemayel, Rita; Latysheva, Natasha S; Ing-Simmons, Elizabeth; Verstrepen, Kevin J; Balaji, Santhanam; Babu, M Madan

    2017-09-01

    Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why, then, are homorepeats prevalent in eukaryotic proteomes? In yeast, homorepeats are enriched in proteins that are essential and pleiotropic and that buffer environmental insults. The presence of homorepeats increases the functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation. Their presence facilitates rapid protein divergence through accumulation of amino acid substitutions, which often affect linear motifs and post-translational-modification sites. These substitutions may result in rewiring protein interaction and signaling networks. Thus, homorepeats are distinct modules that are often retained in stringently regulated proteins. Their presence facilitates rapid exploration of the genotype-phenotype landscape of a population, thereby contributing to adaptation and fitness.

  15. Fatal cardiac arrhythmia after repeated exposure to 1,1-difluoroethane (DFE).

    Science.gov (United States)

    Avella, Joseph; Wilson, James C; Lehrer, Michael

    2006-03-01

    A 42-year-old man was found dead after repeated exposure to 1,1-difluoroethane (DFE, Freon 152a), a propellant found in CRC Duster, a product intended for the removal of dust and lint. Toxicologic analysis detected DFE in femoral blood 136.3 mg/L, brain 117.5 mg/kg, liver 87.6 mg/kg, lung 60.3 mg/kg, adipose 235.7 mg/kg, and vitreous fluid 25.1 mg/L. The cause of death was determined to be a fatal cardiac arrhythmia due to intoxication with 1,1-difluoroethane. After comparison to previously published cases involving DFE, we suggest that analysis of adipose tissue for DFE and similar compounds, along with blood and other tissues, may be useful in distinguishing between acute versus chronic exposure. Adipose may also be a valuable alternate specimen for detection in cases where loss or elimination from blood is likely to have occurred.

  16. Occupational hazards of traditional healers: repeated unprotected blood exposures risk infectious disease transmission.

    Science.gov (United States)

    Audet, Carolyn M; Salato, José; Blevins, Meridith; Silva, Wilson; González-Calvo, Lázaro; Vermund, Sten H; Gaspar, Felisbela

    2016-11-01

    Healers provide support for acute and chronic illnesses in rural Mozambique, such as socially acceptable traditional 'vaccinations' (subcutaneous cuts in the skin to rub herbs directly into the bloody lesion). We aimed to document the frequency of blood exposure by traditional practitioners in Mozambique. We conducted surveys with a simple random sample of 236 traditional healers in Zambézia province. Chi-square and Wilcoxon rank-sum tests were used to compare 'injection' behaviours across districts. Healers treated a median of eight patients in the past month (IQR: 4-15). About 75% conducted 'injections'. These healers 'injected' a median of four patients (IQR: 1-8), used a new razor a median of three times (IQR: 1-8), and almost never used gloves. Lifetime blood exposures among those who provided 'injections' during treatments were estimated to be 1758 over a healer's career. The majority of healers are exposed repeatedly to patient blood. Given the high prevalence of HIV, hepatitis B and C virus, and other blood-borne agents, specific healer practices are an occupational hazard and reuse of razors is risky for their clients. © 2016 John Wiley & Sons Ltd.

  17. Repeated Exposure to Dissection Does Not Influence Students' Attitudes towards Human Body Donation for Anatomy Teaching

    Science.gov (United States)

    Mwachaka, Philip Maseghe; Mandela, Pamela; Saidi, Hassan

    2016-01-01

    The use of unclaimed bodies for anatomical dissection has been the main method of instruction at our institution. There is however a shortage of cadavers for dissection given the increase in the number of medical schools as well as in the number of students enrolling in these schools. This shortage could be mitigated by having voluntary human body donation programs. This study aimed at assessing the attitudes of medical students and surgical residents towards body donation for anatomy learning. We conducted an online survey involving 72 first-year medical students and 41 surgical residents at University of Nairobi who had completed one year of anatomy dissection. For the medical students, this was their first dissection experience while it was the second exposure for the surgery trainees. Most of the surgical trainees (70.7%) and medical students (68.1%) were opposed to self-body donation. This was mainly due to cultural (37%) and religious (20%) barriers. Surprisingly, of those not willing to donate themselves, 67.9% (82.8% surgical trainees, 59.2% medical students) would recommend the practice to other people. Exposure to repeated dissection does not change the perceptions towards body donation. It is noteworthy that culture and religion rank high as clear barriers amongst this “highly informed” group of potential donors. PMID:27190650

  18. Repeated exposure to media violence is associated with diminished response in an inhibitory frontolimbic network.

    Directory of Open Access Journals (Sweden)

    Christopher R Kelly

    Full Text Available BACKGROUND: Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging (fMRI, we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. CONCLUSIONS: These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression.

  19. Repeated Exposure to Dissection Does Not Influence Students' Attitudes towards Human Body Donation for Anatomy Teaching.

    Science.gov (United States)

    Mwachaka, Philip Maseghe; Mandela, Pamela; Saidi, Hassan

    2016-01-01

    The use of unclaimed bodies for anatomical dissection has been the main method of instruction at our institution. There is however a shortage of cadavers for dissection given the increase in the number of medical schools as well as in the number of students enrolling in these schools. This shortage could be mitigated by having voluntary human body donation programs. This study aimed at assessing the attitudes of medical students and surgical residents towards body donation for anatomy learning. We conducted an online survey involving 72 first-year medical students and 41 surgical residents at University of Nairobi who had completed one year of anatomy dissection. For the medical students, this was their first dissection experience while it was the second exposure for the surgery trainees. Most of the surgical trainees (70.7%) and medical students (68.1%) were opposed to self-body donation. This was mainly due to cultural (37%) and religious (20%) barriers. Surprisingly, of those not willing to donate themselves, 67.9% (82.8% surgical trainees, 59.2% medical students) would recommend the practice to other people. Exposure to repeated dissection does not change the perceptions towards body donation. It is noteworthy that culture and religion rank high as clear barriers amongst this "highly informed" group of potential donors.

  20. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.

    Science.gov (United States)

    Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J; Rudich, Yinon

    2016-03-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-05-15

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

  2. Impact of product information and repeated exposure on consumer liking, sensory perception and concept associations of local apple juice

    DEFF Research Database (Denmark)

    Stolzenbach, Sandra; Bredie, Wender Laurentius Petrus; Christensen, Rune Haubo Bojesen

    2013-01-01

    The impact of product information and repeated exposure of local apple juice on consumer liking, sensory perception and concept associations was studied. Findings showed that consumers had high expectations towards the studied local apples juices. Consequently, the liking for the local apple juices...... did not fully determine consumer liking. Thus the sensory characteristics were also found to be of importance. Besides liking, the concept associations were also affected by product information. All local apple juices were associated as being more exclusive under informed tasting conditions....... No effects were found for liking of the apple juices over repeated exposure. Also, the consumers did not change their sensory perception over repeated consumption. However, the local apple juices were conceptualised as more familiar but remained exclusive after repeated consumption. When local producers have...

  3. Repeated exposures to cobalt or chromate on the hands of patients with hand eczema and contact allergy to that metal

    DEFF Research Database (Denmark)

    Nielsen, N H; Kristiansen, J; Borg, L

    2000-01-01

    The present study aimed at evaluating the effects of daily repeated exposures to low cobalt or chromate concentrations on the hands of patients with hand eczema and cobalt or chromate allergy. For 2 weeks, the patients immersed a finger for 10 min daily into the appropriate metal salt solution in...... of providing evidence-based medicine in the area of allergic contact dermatitis in the future.......-sensitive patients. During the exposure period, accumulation of cobalt or chromate in the nail was demonstrated. Standardization of chemical methods of quantification of skin exposure to allergens, combined with experimental exposure studies in patients with specific contact allergy, will increase the possibility...

  4. Deterioration of neurobehavioral performance in resident physicians during repeated exposure to extended duration work shifts.

    Science.gov (United States)

    Anderson, Clare; Sullivan, Jason P; Flynn-Evans, Erin E; Cade, Brian E; Czeisler, Charles A; Lockley, Steven W

    2012-08-01

    Although acute sleep loss during 24- to 30-h extended duration work shifts (EDWS) has been shown to impair the performance of resident physicians, little is known about the effects of cumulative sleep deficiency on performance during residency training. Chronic sleep restriction induces a gradual degradation of neurobehavioral performance and exacerbates the effects of acute sleep loss in the laboratory, yet the extent to which this occurs under real-world conditions is unknown. In this study, the authors quantify the time course of neurobehavioral deterioration due to repeated exposure to EDWS during a 3-week residency rotation. A prospective, repeated-measures, within-subject design. Medical and cardiac intensive care units, Brigham and Women's Hospital, Boston, MA. Thirty-four postgraduate year one resident physicians (23 males; age 28.0 ± 1.83 (standard deviation) years) Residents working a 3-week Q3 schedule (24- to 30-h work shift starts every 3(rd) day), consisting of alternating 24- to 30-h (EDWS) and approximately 8-h shifts, underwent psychomotor vigilance testing before, during, and after each work shift. Mean response time, number of lapses, and slowest 10% of responses were calculated for each test. Residents also maintained daily sleep/wake/work logs. EDWS resulted in cumulative sleep deficiency over the 21-day rotation (6.3 h sleep obtained per day; average 2.3 h sleep obtained per extended shift). Response times deteriorated over a single 24- to 30-h shift (P Performance on the fifth and sixth shift was significantly worse than on the first shift (P performance and exacerbated the effects of acute sleep loss inherent in the 24- to 30-h EDWS that are commonly used in resident schedules.

  5. Impact of repeated daily exposure to intermittent hypoxia and mild sustained hypercapnia on apnea severity.

    Science.gov (United States)

    Yokhana, Sanar S; Gerst, David G; Lee, Dorothy S; Badr, M Safwan; Qureshi, Tabarak; Mateika, Jason H

    2012-02-01

    We examined whether exposure to intermittent hypoxia (IH) during wakefulness impacted on the apnea/hypopnea index (AHI) during sleep in individuals with sleep apnea. Participants were exposed to twelve 4-min episodes of hypoxia in the presence of sustained mild hypercapnia each day for 10 days. A control group was exposed to sustained mild hypercapnia for a similar duration. The intermittent hypoxia protocol was completed in the evening on day 1 and 10 and was followed by a sleep study. During all sleep studies, the change in esophageal pressure (ΔPes) from the beginning to the end of an apnea and the tidal volume immediately following apneic events were used to measure respiratory drive. Following exposure to IH on day 1 and 10, the AHI increased above baseline measures (day 1: 1.95 ± 0.42 fraction of baseline, P ≤ 0.01, vs. day 10: 1.53 ± 0.24 fraction of baseline, P < 0.06). The indexes were correlated to the hypoxic ventilatory response (HVR) measured during the IH protocol but were not correlated to the magnitude of ventilatory long-term facilitation (vLTF). Likewise, ΔPes and tidal volume measures were greater on day 1 and 10 compared with baseline (ΔPes: -8.37 ± 0.84 vs. -5.90 ± 1.30 cmH(2)0, P ≤ 0.04; tidal volume: 1,193.36 ± 101.85 vs. 1,015.14 ± 119.83 ml, P ≤ 0.01). This was not the case in the control group. Interestingly, the AHI on day 10 (0.78 ± 0.13 fraction of baseline, P ≤ 0.01) was significantly less than measures obtained during baseline and day 1 in the mild hypercapnia control group. We conclude that enhancement of the HVR initiated by exposure to IH may lead to increases in the AHI during sleep and that initiation of vLTF did not appear to impact on breathing stability. Lastly, our results suggest that repeated daily exposure to mild sustained hypercapnia may lead to a decrease in breathing events.

  6. An observation of histological evidence on internal organ damages in mice caused by repeated exposures to motorcycle emissions

    Science.gov (United States)

    Wardoyo, Arinto Y. P.; Juswono, Unggul P.; Noor, Johan A. E.

    2017-05-01

    Motor vehicle emissions have been identified as a source of ultrafine particles, which have significant impacts on human health. Repeated and prolonged exposure to ultrafine particles may have a significant association with organ damage. Here, we evaluated the correlation between repeated exposure to ultrafine particles and organ damage in mice. Motorcycle emissions were injected into an exposure chamber with mice for a period of 20 seconds. This treatment was conducted over 10 days. The mice were sacrificed on the 2nd, 4th, 6th, 8th, and 10th days for organ preparations. Based on the results, motorcycle emission exposure caused organ damage in mice, with different severities depending on the organ. The highest damage was found for the lung, followed by the kidney, erythrocytes, and liver.

  7. Antidepressant-like effect of oleanolic acid in mice exposed to the repeated forced swimming test.

    Science.gov (United States)

    Yi, Li-Tao; Li, Jing; Liu, Qing; Geng, Di; Zhou, Ya-Fei; Ke, Xiao-Qing; Chen, Huan; Weng, Lian-Jin

    2013-05-01

    The study aimed to explore the antidepressant-like effect of oleanolic acid and its possible mechanism related to the monoaminergic system and neurotrophin in mice exposed to the repeated forced swimming test (FST). Both the duration and the latency of immobility affected by oleanolic acid (10, 20 and 40 mg/kg) were evaluated in the FST repeated at intervals on days 1, 7 and 14, followed by neurochemical and brain-derived neurotrophic factor (BDNF) analyses in the mouse brain regions of frontal cortex and whole hippocampus. A repeated analysis of variance (ANOVA) indicated that over retesting the immobility time increased, whereas latency to immobility tended to decrease. Minute-by-minute analysis showed that immobility time also increased during the 4-min course of the test. In addition, post-hoc Dunnett's test demonstrated that sub-chronic and chronic, but not acute, oleanolic acid treatment reduced the immobility time (sub-chronic: 20 mg/kg, 43.5%; chronic: 10 mg/kg, 19.3%; 20 mg/kg, 31.8%) and increased the latency to immobility (sub-chronic: 10 mg/kg, 60.6%; 20 mg/kg, 80.1%; chronic: 10 mg/kg, 121.8%; 20 mg/kg, 140.8%; 40 mg/kg, 80.0%). Furthermore, chronic administration of oleanolic acid significantly increased serotonin (5-HT) levels (frontal cortex: 44.5%, 41.9%, 27.5% for 10, 20, 40 mg/kg; hippocampus: 57.2%, 80.9% for 10, 20 mg/kg), decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio (frontal cortex: 31.6%, 30.1%, 23.5%; hippocampus: 40.6%, 47.7%, 29.2% for 10, 20, 40 mg/kg) and elevated norepinephrine (NE) levels (hippocampus: 20 mg/kg, 45.4%) but did not alter dopamine (DA) levels. Moreover, BDNF levels in the two brain regions were also elevated by chronic oleanolic acid treatment (frontal cortex: 20 mg/kg, 67.2%; hippocampus: 10 mg/kg, 36.4%; 20 mg/kg, 55.1%). Taken together, these findings imply that functions of 5-HT, NE and BDNF may be involved in the antidepressant-like effect of oleanolic acid.

  8. Adaptive Changes In Postural Equilibrium And Motion Sickness Following Repeated Exposures To Virtual Environments

    Science.gov (United States)

    Harm, D. L.; Taylor, L. C.

    2006-01-01

    Virtual environments offer unique training opportunities, particularly for training astronauts and preadapting them to the novel sensory conditions of microgravity. Two unresolved human factors issues in virtual reality (VR) systems are: 1) potential "cybersickness", and 2) maladaptive sensorimotor performance following exposure to VR systems. Interestingly, these aftereffects are often quite similar to adaptive sensorimotor responses observed in astronauts during and/or following space flight. Changes in the environmental sensory stimulus conditions and the way we interact with the new stimuli may result in motion sickness, and perceptual, spatial orientation and sensorimotor disturbances. Initial interpretation of novel sensory information may be inappropriate and result in perceptual errors. Active exploratory behavior in a new environment, with resulting feedback and the formation of new associations between sensory inputs and response outputs, promotes appropriate perception and motor control in the new environment. Thus, people adapt to consistent, sustained alterations of sensory input such as those produced by microgravity, unilateral labyrinthectomy and experimentally produced stimulus rearrangements. Adaptation is revealed by aftereffects including perceptual disturbances and sensorimotor control disturbances. The purpose of the current study was to compare disturbances in postural control produced by dome and head-mounted virtual environment displays, and to examine the effects of exposure duration, and repeated exposures to VR systems. Forty-one subjects (21 men, 20 women) participated in the study with an age range of 21-49 years old. One training session was completed in order to achieve stable performance on the posture and VR tasks before participating in the experimental sessions. Three experimental sessions were performed each separated by one day. The subjects performed a navigation and pick and place task in either a dome or head-mounted display

  9. Hearing loss associated with repeated MRI acquisition procedure-related acoustic noise exposure: an occupational cohort study

    NARCIS (Netherlands)

    Bongers, Suzan; Slottje, Pauline; Kromhout, Hans

    2017-01-01

    OBJECTIVE: To study the effects of repeated exposure to MRI-related acoustic noise during image acquisition procedures (scans) on hearing. METHODS: A retrospective occupational cohort study was performed among workers of an MRI manufacturing facility (n=474). Longitudinal audiometry data from the

  10. Damage of rat liver tissue caused by repeated and sustained +Gz exposure and the mechanism thereof

    Directory of Open Access Journals (Sweden)

    Wen-bing LI

    2014-03-01

    Full Text Available Objective  To explore the mechanisms of positive acceleration (+Gz on the damage of rat liver tissue and the effect of +Gz on the expression of JNK/c-Jun in liver cells. Methods  Twenty four male Wistar rats were randomly divided into 4 groups (n=6: control, +2Gz, +6Gz and +10Gz group. With prone position, the rats in control group were fixed to the turning arm of centrifuge with head towards the axis for 5 minutes. The fixation method in +2Gz, +6Gz and +10Gz group was the same as in the control group. The increase rate of acceleration was 1G/s with a peak-time of 3 minutes, and each +Gz exposure repeated 5 times with an interval of 30 minutes. HE staining was used to observe the morphological changes of liver tissue, fluorescence real-time quantitative PCR to detect the expression of hepatic c-Jun mRNA, and Western blotting to detect the hepatic protein expression of p-c-Jun, c-Jun, p-JNK and JNK. Plasma aspartate aminotransferase (AST and alanine aminotransferase (ALT were determined. Results  The levels of serum ALT and AST increased significantly in +6Gz and, especially, the +10Gz group than in control group and +2Gz group (P<0.05. The same situation also existed in the increase of c-Jun mRNA expression (P<0.05. Hepatic c-jun and p-c-Jun (c-Jun activated form protein expression increased with the increase of G value. Compared with control group, no change was found in JNK protein expression in the other three groups, but the expression of p-JNK (activated form of JNK increased in +6Gz and +10Gz groups (P<0.05. HE staining showed the disorganized liver cells with irregular shapes, the unclear cell gap and the vacuolar changes in +6Gz and +10Gz groups. Conclusions  Repeated and sustained +Gz may cause enhanced expression of c-Jun/ p-c-Jun and p-JNK in hepatic cells. JNK/c-Jun signaling pathway may play an important role in the process of hepatic stress injury. DOI: 10.11855/j.issn.0577-7402.2014.03.15

  11. Glucometabolic effects of single and repeated exposure to forced-swimming stressor in Sprague-Dawley rats.

    Science.gov (United States)

    Morakinyo, Ayodele Olufemi; Iranloye, Bolanle Olubusola; Ogunsola, Oluseyi Abimbola

    2018-04-01

    We aimed to evaluate the effects of a single (acute) and repeated (chronic) exposure to forced-swimming stressor on glucose tolerance, insulin sensitivity, lipid profile and glycogen content in male rats. Thirty adult male Sprague-Dawley rats (12 weeks old) were divided randomly into five groups: control group, single exposure (SE) to forced-swim stressor, repeated exposure to forced-swim stressor for 7 days (RE7), 14 days (RE14) and 28 days (RE28). Glucose tolerance test and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) were undertaken on fasting rats to obtain glucose and insulin profiles. ELISA was performed to assess plasma insulin and corticosterone levels. Total cholesterol, triglyceride, high- and low-density lipoproteins, hepatic and skeletal glycogen content were also determined. Repeated exposure to stressor induced glucose intolerance and insulin resistance in the experimental rats. Results showed that all RE groups exhibited a significantly higher area under the curve compared with others (p=0.0001); similarly, HOMA-IR increased (p=0.0001) in all RE groups compared with control. Prolonged exposure to stressor significantly increased the plasma insulin and corticosterone levels but decreased the glycogen content in the liver and skeletal muscle when compared with the control group. Additionally, chronic stressor significantly increased the total cholesterol and triglyceride levels, however, acute stressor produced significantly elevated high-density lipoproteins level. In conclusion, repeated exposure to forced-swimming stressor induced glucose intolerance and insulin resistance in rats by disrupting the insulin sensitivity as well as heightening the glycogenolysis in the liver and skeletal muscle. Acute stressor was unable to cause glucose intolerance and insulin resistance but it appears that may have a positive effect on the lipid metabolism.

  12. Effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections

    Directory of Open Access Journals (Sweden)

    Mustafa Ataş

    2014-10-01

    Full Text Available AIM:To evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections.METHODS:Seventy-two eyes of 36 patients [36 eyes in control group, 36 eyes in intravitreal injection (IVI group] were enrolled in the study. All the eyes had at least one IVI and had diabetic macular edema (DME or age-related macular degeneration (ARMD. Moxifloxacin was prescribed to all the patients four times a day for five days following injection. Conjunctival cultures were obtained from the lower fornix via standardized technique with every possible effort made to minimize contamination from the lids, lashes, or skin. Before the application of any ophthalmic medication, conjunctival cultures were obtained from both eyes using sterile cotton culture. An automated microbiology system was used to identify the growing bacteria and determine antibiotic sensitivity. RESULTS:The bacterial cultures were isolated from 72 eyes of 36 patients, sixteen of whom patients (44.4% were male and twenty (55.6% were female. Average age was 68.4±9.0 (range 50-86. The average number of injections before taking cultures was 3.1+1.0. Forty-eight (66.7% of 72 eyes had at least one significant organism. There was no bacterial growth in 8 (20.5% of IVI eyes and in 16 (44.4% of control eyes (P=0.03. Of the bacteria isolated from culture, 53.8% of coagulase negative staphylococci (CoNS in IVI eyes and 47.2% CoNS in control eyes. This difference between IVI eyes and control eyes about bacteria isolated from culture was not statistically significant (P=0.2. Eleven of 25 bacteria (44.0% isolated from IVI eyes and 11 (57.9% of 19 bacteria isolated from control eyes were resistant to oxacillin. The difference in frequency of moxifloxacine resistance between two groups was not statistically significant (12.0% in IVI eyes and 21.1% in control eyes (P=0.44. There were no cases of resistance to vancomycin, teicoplanin and

  13. Long-term health outcomes after exposure to repeated concussion in elite level: rugby union players.

    Science.gov (United States)

    McMillan, T M; McSkimming, P; Wainman-Lefley, J; Maclean, L M; Hay, J; McConnachie, A; Stewart, W

    2017-06-01

    There is continuing concern about effects of concussion in athletes, including risk of the neurodegenerative disease chronic traumatic encephalopathy. However, information on long-term health and wellbeing in former athletes is limited. Outcome after exposure to repeated brain injury was investigated in 52 retired male Scottish international rugby players (RIRP) and 29 male controls who were similar in age and social deprivation. Assessment included history of playing rugby and traumatic brain injury, general and mental health, life stress, concussion symptoms, cognitive function, disability and markers of chronic stress (allostatic load). The estimated number of concussions in RIRP averaged 14 (median=7; IQR 5-40). Performance was poorer in RIRP than controls on a test of verbal learning (p=0.022) and of fine co-ordination of the dominant hand (p=0.038) and not significantly different on other cognitive tests (p>0.05). There were no significant associations between number of concussions and performance on cognitive tests. Other than a higher incidence of cardiovascular disease in controls, no group differences were detected in general or mental health or estimates of allostatic load. In RIRP, persisting symptoms attributed to concussion were more common if reporting more than nine concussions (p=0.028), although these symptoms were not perceived to affect social or work functioning. Despite a high number of concussions in RIRP, differences in mental health, social or work functioning were not found late after injury. Subtle group differences were detected on two cognitive tests, the cause of which is uncertain. Prospective group comparison studies on representative cohorts are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    Directory of Open Access Journals (Sweden)

    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  15. Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin.

    Science.gov (United States)

    Wang, Frank; Smith, Noah R; Tran, Bao Anh Patrick; Kang, Sewon; Voorhees, John J; Fisher, Gary J

    2014-04-01

    Solar UV irradiation causes photoaging, characterized by fragmentation and reduced production of type I collagen fibrils that provide strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis. The role of UV-A irradiation (320-400 nm) in promoting similar molecular alterations is less clear yet important to consider because it is 10 to 100 times more abundant in natural sunlight than UV-B irradiation and penetrates deeper into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the primary component of tanning beds. To evaluate the effects of low levels of UV-A1 irradiation, as might be encountered in daily life, on expression of matrix metalloproteinase 1 and type I procollagen (the precursor of type I collagen). In vivo biochemical analyses were conducted after UV-A1 irradiation of normal human skin at an academic referral center. Participants included 22 healthy individuals without skin disease. Skin pigmentation was measured by a color meter (chromometer) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Gene expression in skin samples was assessed by real-time polymerase chain reaction. Lightly pigmented human skin (L* >65) was exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20 J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2 hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and did not alter matrix metalloproteinase 1 or type I procollagen gene expression. With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1 irradiation significantly induced matrix metalloproteinase 1 gene expression, which increased progressively with successive exposures. Repeated UV-A1

  16. Prenatal Earthquake Exposure and Midlife Uric Acid Levels Among Chinese Adults.

    Science.gov (United States)

    Ji, Chunpeng; Li, Yanping; Cui, Liufu; Cai, Jianfang; Shi, Jihong; Cheng, Feon W; Li, Yuqing; Curhan, Gary C; Wu, Shouling; Gao, Xiang

    2017-05-01

    To test whether prenatal exposure to earthquake (as a surrogate for acute prenatal stress) could have unfavorable effects on uric acid levels later in life. We included 536 individuals who had been prenatally exposed to the Tangshan earthquake in 1976, and 536 sex- and age-matched individuals without that exposure. Serum uric acid concentrations were measured based on fasting blood samples, which were repeatedly collected in 2006, 2008, and 2010. Mean uric acid concentrations in 2010 and the increasing rate from 2006 to 2010 were compared between the 2 groups, after adjustment for age, sex, body mass index, serum concentrations of glucose, triglycerides, C-reactive protein level, estimated glomerular filtration rate, and other potential confounders. We also used multiple logistic regression to estimate the risk of hyperuricemia (>416 μmole/liter in men or >357 μmole/liter in women) in 2010 by calculating the odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjustment for the previously mentioned covariates. Participants with prenatal exposure to the earthquake had higher concentrations of serum uric acid (adjusted means 315 μmole/liter versus 296 μmole/liter; P = 0.001) and a higher likelihood of having hyperuricemia (multivariate adjusted OR 1.70 [95% CI 1.09-2.66]) in 2010 relative to those without the exposure. Prenatal exposure to the earthquake was consistently significantly associated with a faster increase in uric acid concentration from 2006 to 2010 (P earthquake was associated with higher serum uric acid and higher odds of hyperuricemia in early adulthood. © 2016, American College of Rheumatology.

  17. 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.

    Science.gov (United States)

    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.

  18. Microprocessor-controlled inhalation system for repeated exposure of animals to aerosols

    International Nuclear Information System (INIS)

    Carpenter, R.L.; Barr, F.P.; Leydig, R.L.; Rajala, R.E.

    1979-01-01

    A microprocessor-controlled inhalation exposure system (MCIES) has been built to automate aerosol generation and sampling while controlling exposure time for animal toxicity studies. The system has a time resolution of 0.1 s and automatically sequences the exposure events from initiation to temination of the exposure. The operator is required to preset all airflows, read in a paper tape containing the time sequence of events, and initiate the automatic sequence by closing a switch

  19. Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

    Science.gov (United States)

    Pomponio, Giuliana; Zurich, Marie-Gabrielle; Schultz, Luise; Weiss, Dieter G; Romanelli, Luca; Gramowski-Voss, Alexandra; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24 h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14 days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Cumulative effects of repeated exposure to pO2 = 200 kPa (2 atm).

    Science.gov (United States)

    Shykoff, Barbara E

    2014-01-01

    Even asymptomatic exposures to elevated oxygen partial pressure (pO2) can influence subsequent exposures. Dry chamber dives of three hours' duration at pO2 of 200 kPa were conducted to examine cumulative effects. Experiments were single (n = 27), or paired exposures with surface intervals (SIs) 15 to 17 hours (n = 30), six hours (n = 33), or three hours (n = 36). Flow-volume loops, diffusing capacity, and symptoms were recorded before and after exposures. Immediately after surfacing from second exposures, some significant (p < 0.05) mean changes from baseline in pulmonary function indices occurred for all SIs and persisted for two days for three-hour SIs and for one day for 15-hour SIs. Incidences of symptoms were 15% immediately after one exposure and 28%, 38% and 31% immediately after a second exposure following 15-, six- , or three-hour SIs, respectively. Incidences of changes in pulmonary function indices (deltaPF) were 5%, 11%, 12% and 14% for single exposures or two with 15-, six-, or three-hour SIs, respectively. Two days following the second exposure, resolution of symptoms was incomplete after six- or 15-hour SIs, as was resolution of deltaPF after 15-hour SIs. The incidences indicate non-linear superposition of effects of a first and second exposure, and are not readily explained by delayed-onset injury.

  1. Hearing loss associated with repeated MRI acquisition procedure-related acoustic noise exposure: an occupational cohort study.

    Science.gov (United States)

    Bongers, Suzan; Slottje, Pauline; Kromhout, Hans

    2017-11-01

    To study the effects of repeated exposure to MRI-related acoustic noise during image acquisition procedures (scans) on hearing. A retrospective occupational cohort study was performed among workers of an MRI manufacturing facility (n=474). Longitudinal audiometry data from the facility's medical surveillance scheme collected from 1973 to 2010 were analysed by studying the association of cumulative exposure to MRI-related acoustic noise from voluntary (multiple) MRI scans and the hearing threshold of the volunteer. Repeated acoustic noise exposure during volunteer MRI scans was found to be associated with a small exposure-dependent increased rate change of hearing threshold level (dB/year), but the association was only found related to the number of voluntary MRI scans and not to modelled cumulative noise exposure (dB*hour) based on MRI-system type. The increased rate change of hearing threshold level was found to be statistically significant for the frequencies 500, 1000, 2000, 3000 and 4000 Hz in the right ear. From our longitudinal cohort study, it appeared that exposure to noise from voluntarily MRI scans may have resulted in a slight amount of hearing loss. Mandatory use of hearing protection might have prevented more severe hearing loss. Lack of consistency in findings between the left and right ears and between the two exposure measures prohibits definitive conclusions. Further research that addresses the study's methodological limitations is warranted to corroborate our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Orally administered conjugated linoleic acid ameliorates allergic dermatitis induced by repeated applications of oxazolone in mice.

    Science.gov (United States)

    Nakanishi, Tomonori; Tokunaga, Yuzo; Yamasaki, Masao; Erickson, Laurie; Kawahara, Satoshi

    2016-12-01

    Conjugated linoleic acid (CLA) is one of the constituents of animal products with possible health benefits such as anti-carcinogenic and anti-obesity effects. In this study, we investigated the immunomodulatory effects of CLA using a mouse model of allergic dermatitis. Mice were orally administered either a CLA mixture containing equal amounts of 9c, 11 t-CLA and 10 t, 12c-CLA, or high linoleic acid safflower oil, and allergic dermatitis was induced on the ear by repeated topical applications of oxazolone. Oral administration of the CLA mixture but not the high linoleic safflower oil attenuated the symptoms of allergic dermatitis in both ear weights and clinical scores. This effect was associated with decreased levels of ear interleukin-4 (IL-4) and plasma immunoglobulin E. The immunomodulatory effects of the CLA isomers were compared by an in vitro cytokine production assay. The results showed that 9c, 11 t-CLA, the most predominant isomer in animal products, significantly inhibited IL-4 and interferon-γ production from mouse splenocytes with similar potency to 10 t, 12c-CLA. These findings suggest that CLA, a constituent of animal products, has a potentially beneficial effect for amelioration of allergic dermatitis. © 2016 Japanese Society of Animal Science.

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

    Science.gov (United States)

    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.

  4. No impact of repeated extinction exposures on operant responding maintained by different reinforcer rates.

    Science.gov (United States)

    Bai, John Y H; Podlesnik, Christopher A

    2017-05-01

    Greater rates of intermittent reinforcement in the presence of discriminative stimuli generally produce greater resistance to extinction, consistent with predictions of behavioral momentum theory. Other studies reveal more rapid extinction with higher rates of reinforcers - the partial reinforcement extinction effect. Further, repeated extinction often produces more rapid decreases in operant responding due to learning a discrimination between training and extinction contingencies. The present study examined extinction repeatedly with training with different rates of intermittent reinforcement in a multiple schedule. We assessed whether repeated extinction would reverse the pattern of greater resistance to extinction with greater reinforcer rates. Counter to this prediction, resistance to extinction was consistently greater across twelve assessments of training followed by six successive sessions of extinction. Moreover, patterns of responding during extinction resembled those observed during satiation tests, which should not alter discrimination processes with repeated testing. These findings join others suggesting operant responding in extinction can be durable across repeated tests. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Perspectives on repeated low-level blast and the measurement of neurotrauma in humans as an occupational exposure risk

    Science.gov (United States)

    Carr, W.; Dell, K. C.; Yanagi, M. A.; Hassan, D. M.; LoPresti, M. L.

    2017-11-01

    A pressing question in military medical research is the nature and degree of effects on the human brain from occupational repeated exposure to low-level explosive blast, but reliable and effective means to objectively measure such effects remain elusive. In survey results, headache, difficulty sleeping, irritability, cognitive impairment, and a variety of other symptoms consistent with post-concussive syndrome have been reported by those exposed to blast and there was positive correlation between degree of blast exposure and degree of symptomology, but an important goal is to obtain more objective evidence of an effect than self-report alone. This review reflects recent efforts to measure and evaluate such hypothesized effects and current recommendations for ongoing study. Optimal measures are likely those with sensitivity and specificity to systemic effects in mild neurotrauma, that have minimal to no volitional component, and that can be sampled relatively quickly with minimal intrusion in prospective, observational field studies during routine training with explosives. An understanding of an association between parameters of exposure to repeated low-level blast and negative neurologic effects would support the evaluation of clinical implications and development of protective equipment and surveillance protocols where warranted. At present, low-level blast exposure surveillance measurements do not exist as a systematic record for any professional community.

  6. Effects of repeated exposure to malathion on growth, food consumption, and locomotor performance of the western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    Holem, Ryan R. [University of Georgia, Savannah River Ecology Laboratory, Aiken, SC 29801 (United States); ENTRIX, Inc., Okemos, MI 48864 (United States); Hopkins, William A. [University of Georgia, Savannah River Ecology Laboratory, Aiken, SC 29801 (United States); Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States)], E-mail: hopkinsw@vt.edu; Talent, Larry G. [Natural Resource Ecology and Management, Oklahoma State University, Stillwater, OK 74078 (United States)

    2008-03-15

    Effects of repeated pollutant exposure on growth, locomotor performance, and behavior have rarely been evaluated in reptiles. We administered three doses of malathion (2.0, 20, or 100 mg/kg body weight) to western fence lizards (Sceloporus occidentalis) over an 81 day period. Eight and 23% mortality occurred at 20 and 100 mg/kg (p = 0.079) and 85% of lizards in the 100 mg/kg group exhibited clinical symptoms of poisoning. Growth, food consumption, body condition index, and terrestrial locomotor performance were not significantly influenced by malathion. However, arboreal sprint velocity was significantly reduced in lizards receiving 100 mg/kg. Fifty percent of lizards in the 100 mg/kg group also refused to sprint in the arboreal setting (p = 0.085). Based on these results, arboreal locomotor performance was the most sensitive metric of exposure we evaluated. Further study of compounds such as malathion is warranted due to highly variable application rates and exposure scenarios. - Repeated exposure of western fence lizards to malathion caused reduced arboreal performance and some mortality but growth, food consumption, and terrestrial performance were not affected.

  7. Effects of repeated exposure to malathion on growth, food consumption, and locomotor performance of the western fence lizard (Sceloporus occidentalis)

    International Nuclear Information System (INIS)

    Holem, Ryan R.; Hopkins, William A.; Talent, Larry G.

    2008-01-01

    Effects of repeated pollutant exposure on growth, locomotor performance, and behavior have rarely been evaluated in reptiles. We administered three doses of malathion (2.0, 20, or 100 mg/kg body weight) to western fence lizards (Sceloporus occidentalis) over an 81 day period. Eight and 23% mortality occurred at 20 and 100 mg/kg (p = 0.079) and 85% of lizards in the 100 mg/kg group exhibited clinical symptoms of poisoning. Growth, food consumption, body condition index, and terrestrial locomotor performance were not significantly influenced by malathion. However, arboreal sprint velocity was significantly reduced in lizards receiving 100 mg/kg. Fifty percent of lizards in the 100 mg/kg group also refused to sprint in the arboreal setting (p = 0.085). Based on these results, arboreal locomotor performance was the most sensitive metric of exposure we evaluated. Further study of compounds such as malathion is warranted due to highly variable application rates and exposure scenarios. - Repeated exposure of western fence lizards to malathion caused reduced arboreal performance and some mortality but growth, food consumption, and terrestrial performance were not affected

  8. Secondhand tobacco smoke exposure and heart rate variability and inflammation among non-smoking construction workers: a repeated measures study.

    Science.gov (United States)

    Zhang, Jinming; Fang, Shona C; Mittleman, Murray A; Christiani, David C; Cavallari, Jennifer M

    2013-10-02

    Although it has been well recognized that exposure to secondhand tobacco smoke (SHS) is associated with cardiovascular mortality, the mechanisms and time course by which SHS exposure may lead to cardiovascular effects are still being explored. Non-smoking workers were recruited from a local union and monitored inside a union hall while exposed to SHS over approximately 6 hours. Participants were fitted with a continuous electrocardiographic monitor upon enrollment which was removed at the end of a 24-hr monitoring period. A repeated measures study design was used where resting ECGs and blood samples were taken from individuals before SHS exposure (baseline), immediately following SHS exposure (post) and the morning following SHS exposure (next-morning).Inflammatory markers, including high sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were analyzed. Heart rate variability (HRV) was analyzed from the ECG recordings in time (SDNN, rMSSD) and frequency (LF, HF) domain parameters over 5-minute periods. SHS exposure was quantified using a personal fine particulate matter (PM2.5) monitor.Linear mixed effects regression models were used to examine within-person changes in inflammatory and HRV parameters across the 3 time periods. Exposure-response relationships with PM2.5 were examined using mixed effects models. All models were adjusted for age, BMI and circadian variation. A total of 32 male non-smokers were monitored between June 2010 and June 2012. The mean PM2.5 from SHS exposure was 132 μg/m3. Immediately following SHS exposure, a 100 μg/m3 increase in PM2.5 was associated with declines in HRV (7.8% [standard error (SE) =3%] SDNN, 8.0% (SE = 3.9%) rMSSD, 17.2% (SE = 6.3%) LF, 29.0% (SE = 10.1%) HF) and increases in WBC count 0.42 (SE = 0.14) k/μl. Eighteen hours following SHS exposure, a 100 μg/m3 increase in PM2.5 was associated with 24.2% higher CRP levels. Our study suggest that short-term SHS exposure is associated

  9. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Ana ePalomino

    2014-03-01

    Full Text Available Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression (CB1 receptors and enzymes that produce (DAGLα/β and NAPE-PLD and degrade (MAGL and FAAH eCB were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system (glutamate synthesizing enzymes LGA and KGA, mGluR3/5 metabotropic receptors, and NR1/2A/2B/2C-NMDA and GluR1/2/3/4-AMPA ionotropic receptor subunits and the gene expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-AG production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that

  10. Radiation dose exposure in patients affected by lymphoma undergoing repeat CT examinations: how to manage the radiation dose variability.

    Science.gov (United States)

    Paolicchi, Fabio; Bastiani, Luca; Guido, Davide; Dore, Antonio; Aringhieri, Giacomo; Caramella, Davide

    2018-03-01

    To assess the variability of radiation dose exposure in patients affected by lymphoma undergoing repeat CT (computed tomography) examinations and to evaluate the influence of different scan parameters on the overall radiation dose. A series of 34 patients (12 men and 22 women with a median age of 34.4 years) with lymphoma, after the initial staging CT underwent repeat follow-up CT examinations. For each patient and each repeat examination, age, sex, use of AEC system (Automated Exposure Control, i.e. current modulation), scan length, kV value, number of acquired scans (i.e. number of phases), abdominal size diameter and dose length product (DLP) were recorded. The radiation dose of just one venous phase was singled out from the DLP of the entire examination. All scan data were retrieved by our PACS (Picture Archiving and Communication System) by means of a dose monitoring software. Among the variables we considered, no significant difference of radiation dose was observed among patients of different ages nor concerning tube voltage. On the contrary the dose delivered to the patients varied depending on sex, scan length and usage of AEC. No significant difference was observed depending on the behaviour of technologists, while radiologists' choices had indirectly an impact on the radiation dose due to the different number of scans requested by each of them. Our results demonstrate that patients affected by lymphoma who undergo repeat whole body CT scanning may receive unnecessary overexposure. We quantified and analyzed the most relevant variables in order to provide a useful tool to manage properly CT dose variability, estimating the amount of additional radiation dose for every single significant variable. Additional scans, incorrect scan length and incorrect usage of AEC system are the most relevant cause of patient radiation exposure.

  11. Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

    International Nuclear Information System (INIS)

    Hinzpeter, Ricarda; Sprengel, Kai; Wanner, Guido A.; Mildenberger, Peter; Alkadhi, Hatem

    2017-01-01

    Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

  12. Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

    Energy Technology Data Exchange (ETDEWEB)

    Hinzpeter, Ricarda, E-mail: Ricarda.Hinzpeter@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland); Sprengel, Kai, E-mail: Kai.Sprengel@usz.ch [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Wanner, Guido A., E-mail: Guido.Wanner@sbk-vs.de [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Department of General Surgery, Schwarzwald-Baar Klinikum, University of Freiburg, Klinikstr. 11, D-78052 Villingen-Schwenningen (Germany); Mildenberger, Peter, E-mail: peter.mildenberger@unimedizin-mainz.de [Department of Diagnostic and Interventional Radiology, University Hospital of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Alkadhi, Hatem, E-mail: hatem.alkadhi@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland)

    2017-03-15

    Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

  13. The value of repeating studies and multiple controls: replicated 28-day growth studies of rainbow trout exposed to clofibric acid.

    Science.gov (United States)

    Owen, Stewart F; Huggett, Duane B; Hutchinson, Thomas H; Hetheridge, Malcolm J; McCormack, Paul; Kinter, Lewis B; Ericson, Jon F; Constantine, Lisa A; Sumpter, John P

    2010-12-01

    Two studies to examine the effect of waterborne clofibric acid (CA) on growth-rate and condition of rainbow trout were conducted using accepted regulatory tests (Organisation for Economic Co-operation and Development [OECD] 215). The first study (in 2005) showed significant reductions after 21 d of exposure (21-d growth lowest-observed-effect concentration [LOEC] = 0.1 µg/L, 21-d condition LOEC = 0.1 µg/L) that continued to 28 d. Growth rate was reduced by approximately 50% (from 5.27 to 2.67% per day), while the condition of the fish reduced in a concentration-dependant manner. Additionally, in a concentration-dependent manner, significant changes in relative liver size were observed, such that increasing concentrations of CA resulted in smaller livers after 28-d exposure. A no-observed-effect concentration (NOEC) was not achieved in the 2005 study. An expanded second study (in 2006) that included a robust bridge to the 2005 study, with four replicate tanks of eight individual fish per concentration, did not repeat the 2005 findings. In the 2006 study, no significant effect on growth rate, condition, or liver biometry was observed after 21 or 28 d (28-d growth NOEC = 10 µg/L, 28-d condition NOEC = 10 µg/L), contrary to the 2005 findings. We do not dismiss either of these findings and suggest both are relevant and stand for comparison. However, the larger 2006 study carries more statistical power and multiple-tank replication, so probably produced the more robust findings. Despite sufficient statistical power in each study, interpretation of these and similar studies should be conducted with caution, because much significance is placed on the role of limited numbers of individual and tank replicates and the influence of control animals. Copyright © 2010 SETAC.

  14. Repeated exposure to the thin ideal and implications for the self : Two weight loss program studies

    NARCIS (Netherlands)

    Klesse, A.K.; Goukens, C.; Geyskens, K.; de Ruyter, K.

    2012-01-01

    Exposure to thin models results in self-esteem shifts that influence people's motivation to diet. This research study applies a goal perspective to explain the effect of exposure to thin models on dieters' motivation to lose weight. Two (one-week) weight loss program studies that included treatment

  15. Repeated exposures to blue light-activated eosin Y enhance inactivation of E. faecalis biofilms, in vitro.

    Science.gov (United States)

    Marinic, Karlo; Manoil, Daniel; Filieri, Anna; Wataha, John C; Schrenzel, Jacques; Lange, Norbert; Bouillaguet, Serge

    2015-09-01

    In dentistry, antibacterial photodynamic therapy (a-PDT) has shown promising results for inactivating bacterial biofilms causing carious, endodontic and periodontal diseases. In the current study, we assessed the ability of eosin Y exposed to 3 irradiation protocols at inactivating Enterococcus faecalis biofilms, in vitro. E. faecalis biofilms formed on hydroxyapatite disks were incubated with eosin Y (10-80μM), then activated with blue light using different irradiation protocols. Biofilms exposed to continuous exposure were incubated for 40min before being light-activated for 960 s. For the intermittent exposure, biofilms were exposed 4 times to the light/photosensitizer combination (960 s total) without renewing the photosensitizer. For repeated a-PDT, the same light dose was delivered in a series of 4 irradiation periods separated by dark periods; fresh photosensitizer was added between each light irradiation. After treatment, bacteria were immediately labeled with LIVE/DEAD BacLight Bacterial Viability kit and viability was assessed by flow cytometry (FCM). Results were statistically analyzed using one-way ANOVA and Tukey multiple comparison intervals (α=0.05). The viability of E. faecalis biofilms exposed to 10μM eosin Y, was significantly reduced compared to controls (light only-eosin Y only). After a second exposure to blue light-activated eosin Y, viability significantly decreased from 58% to 12% whereas 6.5% of the bacterial biofilm remained live after a third exposure (p<0.05). Only 3.5% of the bacterial population survived after the fourth exposure. The results of this study indicate that blue light-activated eosin Y can photoinactivate E. faecalis biofilms grown on hydroxyapatite disks. Also, repeated exposures to blue light-activated eosin Y were shown to significantly improve efficacy. Further studies seem warranted to optimize the antibacterial activity of blue light-activated eosin Y on major oral pathogens. Copyright © 2015 Elsevier B.V. All

  16. Repeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats

    NARCIS (Netherlands)

    Groblewski, Peter A.; Zietz, Chad; Willuhn, Ingo; Phillips, Paul E. M.; Chavkin, Charles

    2015-01-01

    Cocaine-experienced Wistar and Wistar Kyoto (WKY) rats received four daily repeated forced swim stress sessions (R-FSS), each of which preceded 4-hour cocaine self-administration sessions. Twenty-four hours after the last swim stress, cocaine valuation was assessed during a single-session threshold

  17. The root of the problem: increasing root vegetable intake in preschool children by repeated exposure and flavour flavour learning.

    Science.gov (United States)

    Ahern, Sara M; Caton, Samantha J; Blundell, Pam; Hetherington, Marion M

    2014-09-01

    Children's vegetable consumption falls below current recommendations, highlighting the need to identify strategies that can successfully promote intake. The current study aimed to investigate the effectiveness of flavour-flavour learning as one such strategy for increasing vegetable intake in preschool children. Children (N = 29) aged 15 to 56 months were recruited through participating nurseries. Each received a minimum of six and maximium eight exposures to a root vegetable puree with added apple puree (flavour-flavour learning) alternating with six to eight exposures to another with nothing added (repeated exposure). A third puree acted as a control. Pre- and post-intervention intake measures of the three purees with nothing added were taken to assess change in intake. Follow-up measures took place 1 month (n = 28) and 6 months (n = 10) post-intervention. Intake increased significantly from pre- to post-intervention for all purees (~36 g), with no effect of condition. Magnitude of change was smaller in the control condition. Analysis of follow-up data showed that intake remained significantly higher than baseline 1 month (p exposure increases intake of a novel vegetable in young children. Results also suggest that mere exposure (to the food, the experimenters, the procedure) can generalise to other, similar vegetables but the addition of a familiar flavour confers no added advantage above mere exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Changes of lead speciation and microbial toxicity in soil treated with repeated Pb exposure in the presence of BDE209.

    Science.gov (United States)

    Zhang, Rong; Zhang, Wei; Liu, Gao; Lin, Kuangfei; Fu, Rongbing

    2016-03-01

    Lead (Pb) and decabromodiphenyl ether (BDE209) are main pollutants at electric waste (e-waste) recycling sites (EWRSs), and their joint toxicological effects have received extensive attention. Frequently, soil pollution at EWRSs usually results from the occurrence of repeated single or multiple pollution events, with continuous impacts on soil microorganisms. Therefore, a laboratory incubation study was conducted to determine Pb bioavailability and microbial toxicity in repeated Pb-polluted soil in the presence of BDE209 for the first time. We evaluated the impacts of repetitive exposure trials on chemical fractions of Pb, and the results showed that repeated single Pb pollution event resulted in an increase of carbonates fraction of Pb, which was different from one-off single Pb exposure. Moreover, one-off Pb-treated groups exhibited higher I R (reduced partition index) values on day 30 and all treatments remained the same I R level at the end of incubation period. The parameters of microbial toxicity were well reflected by soil enzymes. During the entire incubation, the dehydrogenase and urease activities were significantly inhibited by Pb (P soil enzymes were clearly observed (P < 0.05 or 0.01). Such observations would provide useful information for ecological effects of Pb and BDE209 at EWRSs.

  19. Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure

    Directory of Open Access Journals (Sweden)

    Danny Bega

    2012-12-01

    Full Text Available Background: Hyperammonemia is known to cause neuronal injury, and can result from valproic acid exposure. Prompt reduction of elevated ammonia levels may prevent permanent neurological injury. We report a case of fatal hyperammonemic brain injury in a woman exposed to valproic acid. Case: A 38-year-old woman with schizoaffective disorder and recent increase in valproic acid dosage presented with somnolence and confusion and rapidly progressed to obtundation. Brain MRI showed diffuse bilateral restricted diffusion in nearly the entire cerebral cortex. She had normal liver function tests but serum ammonia level was severely elevated at 288 µmol/l. Genetic testing showed no mutation in urea cycle enzymes. Despite successful elimination of ammonia with hemodialysis she developed fatal cerebral edema. Conclusion: Cerebral edema secondary to hyperammonemia is potentially reversible if recognized early. Ammonia excretion can be facilitated by initiation of hemodialysis and administration of scavenging agents (sodium phenylacetate and sodium benzoate. Severe hyperammonemia can result from valproic acid exposure even in the absence of hepatotoxicity or inborn errors of metabolism. It is important to check serum ammonia in any patient with encephalopathy who has had recent valproic acid exposure.

  20. The effect of chronic exposure to fatty acids

    DEFF Research Database (Denmark)

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

    2001-01-01

    Fatty acids affect insulin secretion of pancreatic beta-cells. Investigating gene expression profiles may help to characterize the underlying mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 microM) for up to 44 d. Insulin secretion and expressions of 8740 genes were studied. We...... 44, respectively. Genes involved in fatty acid oxidation were up-regulated, whereas those involved in glycolysis were down-regulated with 200 microM palmitate. A suppression of insulin receptor and insulin receptor substate-2 gene expression was found on d 44 in cells cultured at 200 microM palmitate....... In conclusion, chronic exposure to low palmitate alters insulin secretion as well as gene expression. The number of genes that changed expression was palmitate dose and exposure time dependent. Randle's fatty acid-glucose cycle seems to be operative on the gene transcription level. A modification of expression...

  1. Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice.

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    Full Text Available Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15 µg/animal every 2(nd day for 6 days (a total of 4 exposures, and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α in the bronchoalveolar lavage (BAL fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP and TNF α concentrations, systolic blood pressure (SBP as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1. Pretreatment with curcumin by oral gavage (45 mg/kg 1 h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.

  2. Phasic Mesolimbic Dopamine Signaling Encodes the Facilitation of Incentive Motivation Produced by Repeated Cocaine Exposure

    OpenAIRE

    Ostlund, SB; LeBlanc, KH; Kosheleff, AR; Wassum, KM; Maidment, NT

    2014-01-01

    Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the curr...

  3. Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yayoi [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Negishi, Takayuki [Aoyama Gakuin University, Department of Chemistry and Biological Science, Tokyo (Japan); Mizumura, Ayano; Watanabe, Takayuki [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); Hirano, Seishiro [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); National Institute for Environmental Studies, Research Center for Environmental Risk, Tsukuba, Ibaraki (Japan)

    2008-08-15

    Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide. (orig.)

  4. Combined Study of Titanium Dioxide Nanoparticle Transport and Toxicity on Microbial Nitrifying Communities under Single and Repeated Exposures in Soil Columns.

    Science.gov (United States)

    Simonin, Marie; Martins, Jean M F; Uzu, Gaëlle; Vince, Erwann; Richaume, Agnès

    2016-10-04

    Soils are exposed to nanoparticles (NPs) as a result of their increasing use in many commercial products. Adverse effects of NPs on soil microorganisms have been reported in several ecotoxicological studies using microcosms. Although repeated exposures are more likely to occur in soils, most of these previous studies were performed as a single exposure to NPs. Contrary to single contamination, the study of multiple NP contaminations in soils requires the use of specialized setups. Using a soil column experiment, we compared the influence of single and repeated exposures (one, two, or three exposures that resulted in the same final concentration applied) on the transport of titanium dioxide (TiO 2 ) NPs through soil and the effect of these different exposure scenarios on the abundance and activity of soil nitrifying microbial communities after a 2 month incubation. The transport of TiO 2 NPs was very limited under both single and repeated exposures and was highest for the lowest concentration injected during the first application. Significant decreases in nitrification activity and ammonia-oxidizing archaea and bacteria populations were observed only for the repeated exposure scenario (three TiO 2 NP contaminations). These results suggest that, under repeated exposures, the transport of TiO 2 NPs to deep soil layers and groundwater is limited and that a chronic contamination is more harmful for the soil microbiological functioning than a single exposure.

  5. Continuous citric acid production in repeated-fed batch fermentation by Aspergillus niger immobilized on a new porous foam.

    Science.gov (United States)

    Yu, Bin; Zhang, Xin; Sun, Wenjun; Xi, Xun; Zhao, Nan; Huang, Zichun; Ying, Zhuojun; Liu, Li; Liu, Dong; Niu, Huanqing; Wu, Jinglan; Zhuang, Wei; Zhu, Chenjie; Chen, Yong; Ying, Hanjie

    2018-03-24

    The efficiency of current methods for industrial production of citric acid is limited. To achieve continuous citric acid production with enhanced yield and reduced cost, immobilized fermentation was employed in an Aspergillus niger 831 repeated fed-batch fermentation system. We developed a new type of material (PAF201), which was used as a carrier for the novel adsorption immobilization system. Hydrophobicity, pore size and concentration of carriers were researched in A. niger immobilization. The efficiency of the A. niger immobilization process was analyzed by scanning electron microscopy. Then eight-cycle repeated fed-batch cultures for citric acid production were carried out over 600 h, which showed stable production with maximum citric acid concentrations and productivity levels of 162.7 g/L and 2.26 g L -1  h -1 , respectively. Compared with some other literatures about citric acid yield, PAF201 immobilization system is 11.3% higher than previous results. These results indicated that use of the new adsorption immobilization system could greatly improve citric acid productivity in repeated fed-batch fermentation. Moreover, these results could provide a guideline for A.niger or other filamentous fungi immobilization in industry. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    International Nuclear Information System (INIS)

    Zhu, Changlian; Gao, Jianfeng; Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu; Kuhn, Hans-Georg; Blomgren, Klas

    2011-01-01

    Research highlights: → The effect of MRI on the developing brain is a matter of debate. → Repeated exposure to MRI did not affect neurogenesis. → Memory function was not affected by repeated MRI during development. → Neither late gestation nor young postnatal brains were affected by MRI. → Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 o C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  7. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A(®)) Following Acute Repeated Inhalation Exposure.

    Science.gov (United States)

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m(3), five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution by day 7. In summary, acute

  8. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A following Acute Repeated Inhalation Exposure

    Directory of Open Access Journals (Sweden)

    Jenny R. Roberts

    2014-01-01

    Full Text Available Introduction Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. Methods The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m 3 , five hours per day, over nine work days, or filtered air (control. At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. Results No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following metha-choline (MCh inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP responses to these agents; however, the baseline heart rate (HR and HR responses to isoproterenol (ISO were significantly elevated at one-day post exposure

  9. Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

    DEFF Research Database (Denmark)

    Lof, A.; Lam, Henrik Rye; Gullstrand, E.

    1999-01-01

    Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg....../l), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total white...... spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure...

  10. Beyond Extinction: Prolonged Conditioning and Repeated Threat Exposure Abolish Contextual Renewal of Fear-Potentiated Startle Discrimination but Leave Expectancy Ratings Intact.

    Science.gov (United States)

    Leer, Arne; Haesen, Kim; Vervliet, Bram

    2018-01-01

    Extinction treatments decrease fear via repeated exposures to the conditioned stimulus (CS) and are associated with a return of fear. Alternatively, fear can be reduced via reductions in the perceived intensity of the unconditioned stimulus (US), e.g., through repeated exposures to the US. Promisingly, the few available studies show that repeated US exposures outperform standard extinction. US exposure treatments can decrease fear via two routes: (1) by weakening the CS-US association (extinction-like mechanism), and/or (2) by weakening the subjective US aversiveness (habituation-like mechanism). The current study further investigated the conditions under which US exposure treatment may reduce renewal, by adding a group in which CS-US pairings continued following fear acquisition. During acquisition, participants learned that one of two visual stimuli (CS+/CS-) predicted the occurrence of an aversive electrocutaneous stimulus (US). Next, the background context changed and participants received one of three interventions: repeated CS exposures, (2) repeated US exposures, or (3) continued CS-US pairings. Following repeated CS exposures, test presentations of the CSs in the original conditioning context revealed intact CS+/CS- differentiation in the fear-potentiated startle reflex, while the differentiation was abolished in the other two groups. Differential US expectancy ratings, on the other hand, were intact in all groups. Skin conductance data were inconclusive because standard context renewal following CS exposures did not occur. Unexpectedly, there was no evidence for a habituation-like process having taken place during US exposures or continued CS-US pairings. The results provide further evidence that US exposures outperform the standard extinction treatment and show that effects are similar when US exposures are part of CS-US pairings.

  11. Photoprotection due to pigmentation and epidermal thickness after repeated exposure to ultraviolet light and psoralen plus ultraviolet A therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bech-Thomsen, N.; Wulf, H.C. [Rigshospitalet, The National Univ. Hospital, Dept. of Dermatology, Lab. of Photobiology, Copenhagen (Denmark)

    1995-10-01

    Tanning and thickening of the epidermis are cardinal defensive responses of human skin to ultraviolet (UV) radiation that lead to increased photoprotection. Earlier studies have shown that skin pigmentation can be used to predict minimal erythema dose and minimal phototoxic dose. In this study it was calculated how much of the increase in photoprotection after 4 weeks of repeated exposure to suberythemogenic doses of either UVA or UVB radiation sources or psoralen plus UVA (PUVA) therapy that was attributable to melanogenesis. The backs of 12 volunteers were exposed to 6 different UVA and UVB radiation sources 9 times during 4 weeks. Skin pigmentation was assessed by skin reflectance measuring. Photoprotection was determined from the minimal erythema dose. Melanogenesis accounted for 63-95% of the increase in photoprotection after 4 weeks of exposure to UVA radiation. Exposure to two UVB sources induced a significant increase in photoprotection but not in pigmentation. Melanogenesis accounted only for 6-11% of the increase in photoprotection after 4 weeks of UVB exposure. The pigmentary and photoprotective responses to PUVA therapy were followed in 14 patients. After 2 weeks of exposure, the increase in photoprotection was significantly higher than predicted form the increase in skin pigmentation. After 4 weeks, melanogenesis accounted for only 36% of the increase in photoprotection. This study shows that melanogenesis accounts for the increased photoprotection after 2 weeks of exposure to UVA radiation, but after 4 weeks other protective mechanisms occur during suberythemal UVB exposure and during PUVA therapy the importance of skin pigmentation in the overall photoprotection gradually decreases during a 4-week irradiation period. (au) 17 refs.

  12. Photoprotection due to pigmentation and epidermal thickness after repeated exposure to ultraviolet light and psoralen plus ultraviolet A therapy

    International Nuclear Information System (INIS)

    Bech-Thomsen, N.; Wulf, H.C.

    1995-01-01

    Tanning and thickening of the epidermis are cardinal defensive responses of human skin to ultraviolet (UV) radiation that lead to increased photoprotection. Earlier studies have shown that skin pigmentation can be used to predict minimal erythema dose and minimal phototoxic dose. In this study it was calculated how much of the increase in photoprotection after 4 weeks of repeated exposure to suberythemogenic doses of either UVA or UVB radiation sources or psoralen plus UVA (PUVA) therapy that was attributable to melanogenesis. The backs of 12 volunteers were exposed to 6 different UVA and UVB radiation sources 9 times during 4 weeks. Skin pigmentation was assessed by skin reflectance measuring. Photoprotection was determined from the minimal erythema dose. Melanogenesis accounted for 63-95% of the increase in photoprotection after 4 weeks of exposure to UVA radiation. Exposure to two UVB sources induced a significant increase in photoprotection but not in pigmentation. Melanogenesis accounted only for 6-11% of the increase in photoprotection after 4 weeks of UVB exposure. The pigmentary and photoprotective responses to PUVA therapy were followed in 14 patients. After 2 weeks of exposure, the increase in photoprotection was significantly higher than predicted form the increase in skin pigmentation. After 4 weeks, melanogenesis accounted for only 36% of the increase in photoprotection. This study shows that melanogenesis accounts for the increased photoprotection after 2 weeks of exposure to UVA radiation, but after 4 weeks other protective mechanisms occur during suberythemal UVB exposure and during PUVA therapy the importance of skin pigmentation in the overall photoprotection gradually decreases during a 4-week irradiation period. (au) 17 refs

  13. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Qvortrup, Klaus

    2011-01-01

    Background: The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food...... and food contact materials. Results: AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study...... in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of Ag...

  14. Surface antigens and potential virulence factors from parasites detected by comparative genomics of perfect amino acid repeats

    Directory of Open Access Journals (Sweden)

    Adler Joël

    2007-12-01

    Full Text Available Abstract Background Many parasitic organisms, eukaryotes as well as bacteria, possess surface antigens with amino acid repeats. Making up the interface between host and pathogen such repetitive proteins may be virulence factors involved in immune evasion or cytoadherence. They find immunological applications in serodiagnostics and vaccine development. Here we use proteins which contain perfect repeats as a basis for comparative genomics between parasitic and free-living organisms. Results We have developed Reptile http://reptile.unibe.ch, a program for proteome-wide probabilistic description of perfect repeats in proteins. Parasite proteomes exhibited a large variance regarding the proportion of repeat-containing proteins. Interestingly, there was a good correlation between the percentage of highly repetitive proteins and mean protein length in parasite proteomes, but not at all in the proteomes of free-living eukaryotes. Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites. Conclusion Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance. An on-line tool is available at http://genomics.unibe.ch/dora.

  15. Effect of Acute, Subacute, and Repeated Exposure to High Altitude (5050 m on Psychomotor Vigilance

    Directory of Open Access Journals (Sweden)

    Matiram Pun

    2018-06-01

    Full Text Available Aim: High altitude (HA hypoxia may affect cognitive performance and sleep quality. Further, vigilance is reduced following sleep deprivation. We investigated the effect on vigilance, actigraphic sleep indices, and their relationships with acute mountain sickness (AMS during very HA exposure, acclimatization, and re-exposure.Methods: A total of 21 healthy altitude-naive individuals (25 ± 4 years; 13 females completed 2 cycles of altitude exposure separated by 7 days at low altitude (LA, 520 m. Participants slept at 2900 m and spent the day at HA, (5050 m. We report acute altitude exposure on Day 1 (LA vs. HA1 and after 6 days of acclimatization (HA1 vs. HA6. Vigilance was quantified by reaction speed in the 10-min psychomotor vigilance test reaction speed (PVT-RS. AMS was evaluated using the Environmental Symptoms Questionnaire Cerebral Score (AMS-C score. Nocturnal rest/activity was recorded to estimate sleep duration using actigraphy.Results: In Cycle 1, PVT-RS was slower at HA1 compared to LA (4.1 ± 0.8 vs. 4.5 ± 0.6 s-1, respectively, p = 0.029, but not at HA6 (4.6 ± 0.7; p > 0.05. In Cycle 2, PVT-RS at HA1 (4.6 ± 0.7 and HA6 (4.8 ± 0.6 were not different from LA (4.8 ± 0.6, p > 0.05 and significantly greater than corresponding values in Cycle 1. In both cycles, AMS scores were higher at HA1 than at LA and HA6 (p < 0.05. Estimated sleep durations (TST at LA, 1st and 5th nights were 431.3 ± 28.7, 418.1 ± 48.6, and 379.7 ± 51.4 min, respectively, in Cycle 1 and they were significantly reduced during acclimatization exposures (LA vs. 1st night, p > 0.05; LA vs. 5th night, p = 0.012; and 1st vs. 5th night, p = 0.054. LA, 1st and 5th nights TST in Cycle 2 were 477.5 ± 96.9, 430.9 ± 34, and 341.4 ± 32.2, respectively, and we observed similar deteriorations in TST as in Cycle 1 (LA vs. 1st night, p > 0.05; LA vs. 5th night, p = 0.001; and 1st vs. 5th night, p < 0.0001. At HA1, subjects who reported higher AMS-C scores exhibited slower

  16. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Gloria A. Santa-Gonzalez

    2016-10-01

    Full Text Available Many environmental and physiological stresses are chronic. Thus, cells are constantly exposed to diverse types of genotoxic insults that challenge genome stability, including those that induce oxidative DNA damage. However, most in vitro studies that model cellular response to oxidative stressors employ short exposures and/or acute stress models. In this study, we tested the hypothesis that chronic and repeated exposure to a micromolar concentration of hydrogen peroxide (H2O2 could activate DNA damage responses, resulting in cellular adaptations. For this purpose, we developed an in vitro model in which we incubated mouse myoblast cells with a steady concentration of ~50 μM H2O2 for one hour daily for seven days, followed by a final challenge of a 10 or 20X higher dose of H2O2 (0.5 or 1 mM. We report that intermittent long-term exposure to this oxidative stimulus nearly eliminated cell toxicity and significantly decreased genotoxicity (in particular, a >5-fold decreased in double-strand breaks resulting from subsequent acute exposure to oxidative stress. This protection was associated with cell cycle arrest in G2/M and induction of expression of nine DNA repair genes. Together, this evidence supports an adaptive response to chronic, low-level oxidative stress that results in genomic protection and up-regulated maintenance of cellular homeostasis.

  17. An analysis of single amino acid repeats as use case for application specific background models

    Directory of Open Access Journals (Sweden)

    Sykacek Peter

    2011-05-01

    Full Text Available Abstract Background Sequence analysis aims to identify biologically relevant signals against a backdrop of functionally meaningless variation. Increasingly, it is recognized that the quality of the background model directly affects the performance of analyses. State-of-the-art approaches rely on classical sequence models that are adapted to the studied dataset. Although performing well in the analysis of globular protein domains, these models break down in regions of stronger compositional bias or low complexity. While these regions are typically filtered, there is increasing anecdotal evidence of functional roles. This motivates an exploration of more complex sequence models and application-specific approaches for the investigation of biased regions. Results Traditional Markov-chains and application-specific regression models are compared using the example of predicting runs of single amino acids, a particularly simple class of biased regions. Cross-fold validation experiments reveal that the alternative regression models capture the multi-variate trends well, despite their low dimensionality and in contrast even to higher-order Markov-predictors. We show how the significance of unusual observations can be computed for such empirical models. The power of a dedicated model in the detection of biologically interesting signals is then demonstrated in an analysis identifying the unexpected enrichment of contiguous leucine-repeats in signal-peptides. Considering different reference sets, we show how the question examined actually defines what constitutes the 'background'. Results can thus be highly sensitive to the choice of appropriate model training sets. Conversely, the choice of reference data determines the questions that can be investigated in an analysis. Conclusions Using a specific case of studying biased regions as an example, we have demonstrated that the construction of application-specific background models is both necessary and

  18. Repeated Exposure to Neurotoxic Levels of Chlorpyriphos Alters Hippocampal Expression of Neurotrophins and Neuropeptides

    Science.gov (United States)

    2016-01-13

    hormone bindi Bdnf BDNF Brain-derived neurotrophic factor Mdk MDK Midkine (neurite growth -promoting fa Rbp4 RBP4 Retinol binding protein 4, plasma...cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits ), but the biological mechanism(s...neurobehavioral deficits following subchronic exposure to CPF at a level that inhibits hippocampal cholinesterase to less than 20% of control. An equally

  19. Writing content predicts benefit from written expressive disclosure: Evidence for repeated exposure and self-affirmation.

    Science.gov (United States)

    Niles, Andrea N; Byrne Haltom, Kate E; Lieberman, Matthew D; Hur, Christopher; Stanton, Annette L

    2016-01-01

    Expressive disclosure regarding a stressful event improves psychological and physical health, yet predictors of these effects are not well established. The current study assessed exposure, narrative structure, affect word use, self-affirmation and discovery of meaning as predictors of anxiety, depressive and physical symptoms following expressive writing. Participants (N = 50) wrote on four occasions about a stressful event and completed self-report measures before writing and three months later. Essays were coded for stressor exposure (level of detail and whether participants remained on topic), narrative structure, self-affirmation and discovery of meaning. Linguistic Inquiry and Word Count software was used to quantify positive and negative affect word use. Controlling for baseline anxiety, more self-affirmation and detail about the event predicted lower anxiety symptoms, and more negative affect words (very high use) and more discovery of meaning predicted higher anxiety symptoms three months after writing. Findings highlight the importance of self-affirmation and exposure as predictors of benefit from expressive writing.

  20. Analgesia induced by repeated exposure to low dose X-rays in mice, and involvement of the accessory olfactory system in modulation of the radiation effects

    International Nuclear Information System (INIS)

    Miyachi, Yukihisa; Yamada, Takeshi

    1997-01-01

    The effects of low-dose X-rays on mouse nociceptive behavior were examined using a formalin injected test which rated the amount of time the animals spent licking the injected hind-paw. Male ICR White Swiss mice showed a marked suppression of licking behavior after repeated low-dose X-irradiation (5 cGy/day, 6 consecutive days). The most profound effect was observed on the day 30 after irradiation. The decline of licking behavior, however, was not observed at all following olfactory bulbectomy or vomeronasal tract cut. The analgesic effects could be observed in writhing animals administered acetic-acid intraperitoneally. Moreover, analgesia was totally blocked by the administration of N-nitro-L-arginine, a nitric oxide synthase inhibitor, to accessory olfactory bulbs prior to the exposure. The present results indicate that the olfactory system plays an important role in modulation of radiation-induced analgesia, and a possible involvement of nitric oxide in the formation of recognition memory subjected to repeated X-rays. Relatively higher doses (5 cGy x 9 days, 5 cGy x 12 days), however, did not induce such effects, namely, the decline of nociceptive response was limited to the animals irradiated with the smaller dose. (author)

  1. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study

    Directory of Open Access Journals (Sweden)

    Taro Yamaguchi

    2017-08-01

    Full Text Available We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h, hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days, there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin®, a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss.

  2. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study.

    Science.gov (United States)

    Yamaguchi, Taro; Yoneyama, Masanori; Onaka, Yusuke; Imaizumi, Atsushi; Ogita, Kiyokazu

    2017-08-01

    We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h), hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days), there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin ® , a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  4. Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen.

    Science.gov (United States)

    Thompson, Aaron M S; Zanobetti, Antonella; Silverman, Frances; Schwartz, Joel; Coull, Brent; Urch, Bruce; Speck, Mary; Brook, Jeffrey R; Manno, Michael; Gold, Diane R

    2010-01-01

    Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardio-vascular disease. We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.080.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.060.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

  5. Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

    Science.gov (United States)

    Helland, Arne; Lydersen, Stian; Lervåg, Lone-Eirin; Jenssen, Gunnar D; Mørland, Jørg; Slørdal, Lars

    2016-09-01

    Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure

    Directory of Open Access Journals (Sweden)

    Salvatrice Calabrò

    2015-08-01

    Full Text Available Background/Aims: The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+]i, energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS from 2′,7′-dichlorodihydrofuorescein diacetate (DCFDA fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit. Results: A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml significantly increased the percentage of annexin-V-binding cells (to 9.3 ±0.9 % and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca2+]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM and SB203580 (2 µM. Conclusions: Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.

  7. Hematological effects of four ethylene glycol monoalkyl ethers in short-term repeated exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Starek, Andrzej [Jagiellonian University, Department of Biochemical Toxicology, Medical College, Krakow (Poland); Szymczak, Wieslaw [University of Lodz, Institute of Psychology, Lodz (Poland); Zapor, Lidia [Central Institute for Labour Protection National Research Institute, Laboratory of Toxicology, Department of Chemical and Aerosol Hazards, Warsaw (Poland)

    2008-02-15

    This study was carried out to compare the hematological effects of 2-methoxyethanol (ME), 2-ethoxyethanol (EE), 2-isopropoxyethanol (IPE), and 2-butoxyethanol (BE) in short-term studies in rats. Male rats were subcutaneously treated with ME or EE at a dosage of 0, 1.25, 2.5 and 5.0 mM/kg in saline, 5 days per week, for 4 weeks. Other rats were exposed to IPE or BE at doses of 0, 0.25, 0.5, 0.75 and 1.25 mM/kg in the same manner. Administration of each chemical, except of ME, resulted in a time- and dose-dependent swelling of erythrocytes as evidenced by an increase in mean corpuscular volume (MCV). Subsequently, red blood cells (RBC), packed cell volumes (PCV), hemoglobin concentration (HGB), and mean cell hemoglobin concentration (MCHC) decreased. Furthermore, an increase in mean cell hemoglobin (MCH) and reticulocyte counts was observed. The onset of hemolysis induced by EE, IPE or BE was faster than after ME administration. While in rats exposed to ME hematological changes were strongly pronounced and progressively increased with exposure time beginning from the day 11, those in animals treated with EE were rather persisted at low constant level for all exposure period. In contrast, the rats exposed to IPE and BE demonstrated the dramatic hematological changes more pronounced in case of BE than IPE at the beginning of exposure (on day 4). Despite of exposure duration, these changes were regressed, although the decrease in RBC and MCHC and the increase in MCV and MCH in rats treated with highest doses of both compound (0.5, 0.75, and 1.25 mM/kg) were more persistent, probably due to selective hemolysis of the aged erythrocytes. In addition, significant leukopenia due to reduction of lymphocytes in rats exposed to ME was observed. In summary, this study demonstrated no tolerance to ME- and EE-induced intravascular hemolysis developed under these experimental conditions. On the contrary, tolerance to IPE- and BE-induced hemolysis in rats exposed to these compounds

  8. Arsenic induced apoptosis in rat liver following repeated 60 days exposure

    International Nuclear Information System (INIS)

    Bashir, Somia; Sharma, Yukti; Irshad, M.; Nag, T.C.; Tiwari, Monica; Kabra, M.; Dogra, T.D.

    2006-01-01

    Background: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 μM) concentration. Aim: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. Methods: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5 mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. Results: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. Conclusion: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis

  9. Eosinophilia and biotoxin exposure in bottlenose dolphins (Tursiops truncatus) from a coastal area impacted by repeated mortality events

    International Nuclear Information System (INIS)

    Schwacke, Lori H.; Twiner, Michael J.; De Guise, Sylvain; Balmer, Brian C.; Wells, Randall S.; Townsend, Forrest I.; Rotstein, David C.; Varela, Rene A.; Hansen, Larry J.; Zolman, Eric S.; Spradlin, Trevor R.

    2010-01-01

    Bottlenose dolphins (Tursiops truncatus) inhabiting coastal waters in the northern Gulf of Mexico have been impacted by recurrent unusual mortality events over the past few decades. Several of these mortality events along the Florida panhandle have been tentatively attributed to poisoning from brevetoxin produced by the dinoflagellate Karenia brevis. While dolphins in other regions of the Florida coast are often exposed to K. brevis blooms, large-scale dolphin mortality events are relatively rare and the frequency and magnitude of die-offs along the Panhandle raise concern for the apparent vulnerability of dolphins in this region. We report results from dolphin health assessments conducted near St. Joseph Bay, Florida, an area impacted by 3 unusual die-offs within a 7-year time span. An eosinophilia syndrome, manifested as an elevated blood eosinophil count without obvious cause, was observed in 23% of sampled dolphins. Elevated eosinophil counts were associated with decreased T-lymphocyte proliferation and increased neutrophil phagocytosis. In addition, indication of chronic low-level exposure to another algal toxin, domoic acid produced by the diatom Pseudo-nitzschia spp., was determined. Previous studies of other marine mammal populations exposed recurrently to Pseudo-nitzschia blooms have suggested a possible link between the eosinophilia and domoic acid exposure. While the chronic eosinophilia syndrome could over the long-term produce organ damage and alter immunological status and thereby increase vulnerability to other challenges, the significance of the high prevalence of the syndrome to the observed mortality events in the St. Joseph Bay area is unclear. Nonetheless, the unusual immunological findings and concurrent evidence of domoic acid exposure in this sentinel marine species suggest a need for further investigation to elucidate potential links between chronic, low-level exposure to algal toxins and immune health.

  10. Eosinophilia and biotoxin exposure in bottlenose dolphins (Tursiops truncatus) from a coastal area impacted by repeated mortality events

    Energy Technology Data Exchange (ETDEWEB)

    Schwacke, Lori H., E-mail: Lori.Schwacke@noaa.gov [National Oceanic and Atmospheric Administration, National Ocean Service, Center for Human Health Risks, 331 Fort Johnson Road, Charleston, SC 29412 (United States); Twiner, Michael J. [National Oceanic and Atmospheric Administration, National Ocean Service, Center for Coastal Environmental Health and Biomolecular Research, 219 Fort Johnson Road, Charleston, SC 29412 (United States); De Guise, Sylvain [University of Connecticut, Department of Pathobiology and Veterinary Science, 61 North Eagleville Road, U-89, Storrs, CT 06269 (United States); Balmer, Brian C.; Wells, Randall S. [Chicago Zoological Society, c/o Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Townsend, Forrest I. [Bayside Hospital for Animals, 251 N.E. Racetrack Road, Fort Walton Beach, FL 32547 (United States); Rotstein, David C. [National Oceanic and Atmospheric Administration, National Marine Fisheries Service, Office of Protected Resources, Marine Mammal Health and Stranding Response Program, 1315 East West Highway, Silver Spring, MD 20910 (United States); Varela, Rene A. [Ocean Embassy Inc, 6433 Pinecastle Blvd, Ste 2, Orlando, FL 32809 (United States); Hansen, Larry J. [National Oceanic and Atmospheric Administration, National Marine Fisheries Service Southeast Fisheries Science Center,101 Pivers Island Road, Beaufort, NC 28516 (United States); Zolman, Eric S. [National Oceanic and Atmospheric Administration, National Ocean Service, Center for Coastal Environmental Health and Biomolecular Research, 219 Fort Johnson Road, Charleston, SC 29412 (United States); Spradlin, Trevor R. [National Oceanic and Atmospheric Administration, National Marine Fisheries Service, Office of Protected Resources, Marine Mammal Health and Stranding Response Program, 1315 East West Highway, Silver Spring, MD 20910 (United States); and others

    2010-08-15

    Bottlenose dolphins (Tursiops truncatus) inhabiting coastal waters in the northern Gulf of Mexico have been impacted by recurrent unusual mortality events over the past few decades. Several of these mortality events along the Florida panhandle have been tentatively attributed to poisoning from brevetoxin produced by the dinoflagellate Karenia brevis. While dolphins in other regions of the Florida coast are often exposed to K. brevis blooms, large-scale dolphin mortality events are relatively rare and the frequency and magnitude of die-offs along the Panhandle raise concern for the apparent vulnerability of dolphins in this region. We report results from dolphin health assessments conducted near St. Joseph Bay, Florida, an area impacted by 3 unusual die-offs within a 7-year time span. An eosinophilia syndrome, manifested as an elevated blood eosinophil count without obvious cause, was observed in 23% of sampled dolphins. Elevated eosinophil counts were associated with decreased T-lymphocyte proliferation and increased neutrophil phagocytosis. In addition, indication of chronic low-level exposure to another algal toxin, domoic acid produced by the diatom Pseudo-nitzschia spp., was determined. Previous studies of other marine mammal populations exposed recurrently to Pseudo-nitzschia blooms have suggested a possible link between the eosinophilia and domoic acid exposure. While the chronic eosinophilia syndrome could over the long-term produce organ damage and alter immunological status and thereby increase vulnerability to other challenges, the significance of the high prevalence of the syndrome to the observed mortality events in the St. Joseph Bay area is unclear. Nonetheless, the unusual immunological findings and concurrent evidence of domoic acid exposure in this sentinel marine species suggest a need for further investigation to elucidate potential links between chronic, low-level exposure to algal toxins and immune health.

  11. Protective effect of SP600125 against liver cell injury in rats under repeated and sustained high +Gz exposure

    Directory of Open Access Journals (Sweden)

    Wen-bing LI

    2015-01-01

    Full Text Available Objective To explore the effect of JNK inhibitor SP600125 on expression of JNK/c-jun in liver cells of rats under repeated and sustained high +Gz exposure and its mechanism of the effect. Methods Eighteen inbred adult male Wistar rats were randomly divided into control group, +10Gz group and SP600125 group (n=6. The rats in +10Gz group and SP600125 group were fixed to the rotating arm of a centrifuge with head towards the axis. The increase rate of acceleration was 1G/s with a peak-time of 3 minutes, and the +Gz exposure was repeated 5 times with an interval of 30 minutes. SP600125 was given to rats of SP600125 group 30 minutes before the first centrifugation by intraperitoneal injection. All of the animals were sacrificed 30 minutes after centrifugation. Blood samples were collected from inferior vena cava to determine the plasma level of aspartate aminotransferase (AST and alanine aminotransferase (ALT. The expression of c-jun mRNA was determined by quantitative real-time RT-PCR (qRTPCR. The expressions of p-JNK, JNK, p-c-jun and c-jun protein were determined by Western blotting. The morphological change in the liver tissue was observed after HE staining. Results The plasma level of ALT and AST, expression level of c-jun mRNA and p-JNK, p-c-jun, c-jun protein in the liver tissue of SP600125 group were significantly higher than those of control group (P0.05. HE staining revealed disorganized hepatic cords, irregular liver cells, vacuolar changes, and marked edema of hepatocytes, and collapsed hepatic sinusoids in +10Gz group, but these changes were alleviated obviously in SP600125 group. Conclusion SP600125 could alleviate the liver cell injury in rats under repeated and sustained high +Gz exposure. DOI: 10.11855/j.issn.2577-7402.2014.11.02

  12. Previous Repeated Exposure to Food Limitation Enables Rats to Spare Lipid Stores during Prolonged Starvation.

    Science.gov (United States)

    McCue, Marshall D; Albach, Audrey; Salazar, Giovanni

    The risk of food limitation and, ultimately, starvation dates back to the dawn of heterotrophy in animals, yet starvation remains a major factor in the regulation of modern animal populations. Researchers studying starvation more than a century ago suggested that animals subjected to sublethal periods of food limitation are somehow more tolerant of subsequent starvation events. This possibility has received little attention over the past decades, yet it is highly relevant to modern science for two reasons. First, animals in natural populations are likely to be exposed to bouts of food limitation once or more before they face prolonged starvation, during which the risk of mortality becomes imminent. Second, our current approach to studying starvation physiology in the laboratory focuses on nourished animals with no previous exposure to nutritional stress. We examined the relationship between previous exposure to food limitation and potentially adaptive physiological responses to starvation in adult rats and found several significant differences. On two occasions, rats were fasted until they lost 20% of their body mass maintained lower body temperatures, and had presumably lower energy requirements when subjected to prolonged starvation than their naive cohort that never experienced food limitation. These rats that were trained in starvation also had lower plasma glucose set -points and reduced their reliance on endogenous lipid oxidation. These findings underscore (1) the need for biologists to revisit the classic hypothesis that animals can become habituated to starvation, using a modern set of research tools; and (2) the need to design controlled experiments of starvation physiology that more closely resemble the dynamic nature of food availability.

  13. Detection of local inflammation induced by repeated exposure to contact allergens by use of IVIS SpectrumCT analyses

    DEFF Research Database (Denmark)

    Nielsen, Morten M.; Schmidt, Jonas D.; Christensen, Jan P.

    2017-01-01

    Background: Contact allergy is characterized by local skin inflammation that, in some cases, can result in systemic immune activation. Objectives: To investigate whether IVIS SpectrumCT analyses can be used to detect the immune response induced by contact allergens. Methods: Mice were repeatedly...... exposed to vehicle or allergens on the ears. The local and systemic responses were analysed at different times with the ProSense 750 FAST probe in IVIS SpectrumCT measurements. In addition, changes in ear thickness, cytokine profile in the skin and immunological phenotype in the draining lymph nodes...... and spleen were determined. Results: Local inflammation was detected by ProSense 750 FAST and correlated with changes in ear thickness, cytokine profile and immunological phenotype following exposure to the strong contact allergen 2,4-dinitrofluorobenzene. Analysis of the systemic response with ProSense 750...

  14. Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort

    Directory of Open Access Journals (Sweden)

    Yuferov V

    2018-04-01

    Full Text Available Vadim Yuferov,* Eduardo R Butelman,* Mary Jeanne Kreek Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA *These authors contributed equally to this work Background: Cannabis use disorders (CUDs cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC, a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC. Methods: In this case-control study of adult African Americans (n=476; 206 females, 270 males, we examined the association of the functional prodynorphin 68 bp (PDYN 68 bp promoter repeats with categorical diagnoses of cannabis dependence (Diagnostic and Statistical Manual of Mental Disorders-IV criteria, as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek–McHugh–Schluger–Kellogg cannabis scale. Results: The PDYN 68 bp genotype (examined as short–short [SS], short–long [SL], or long–long [LL], based on the number of repeats was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the PDYN 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis (p<0.05 and earlier age of first cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; p<0.045. Males in the SS+SL group also had greater odds of high lifetime exposure to cannabis, compared to the LL group (p<0.045. Of interest, none of the aforementioned genetic associations were significant in females. Conclusion: This study provides the first data on how the PDYN 68 bp genotype is associated with gender-specific patterns of

  15. Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

    Directory of Open Access Journals (Sweden)

    Suk Peng Tang

    2017-01-01

    Full Text Available Paraquat (PQ is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day, Tualang honey (1.0 g/kg/day, or ubiquinol (0.2 g/kg/day throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week or PQ (10 mg/kg/week once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p<0.05. The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

  16. Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure.

    Science.gov (United States)

    Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah

    2017-01-01

    Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ ( p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

  17. Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

    Science.gov (United States)

    Sulaiman, Siti Amrah

    2017-01-01

    Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung. PMID:28127418

  18. Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort.

    Science.gov (United States)

    Yuferov, Vadim; Butelman, Eduardo R; Kreek, Mary Jeanne

    2018-01-01

    Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC. In this case-control study of adult African Americans (n=476; 206 females, 270 males), we examined the association of the functional prodynorphin 68 bp ( PDYN 68 bp) promoter repeats with categorical diagnoses of cannabis dependence ( Diagnostic and Statistical Manual of Mental Disorders-IV criteria), as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek-McHugh-Schluger-Kellogg cannabis scale). The PDYN 68 bp genotype (examined as short-short [SS], short-long [SL], or long-long [LL], based on the number of repeats) was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the PDYN 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis ( p cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; p cannabis, compared to the LL group ( p cannabis. Overall, this study shows that PDYN 68 bp polymorphisms affect behaviors involved in early stages of nonmedical cannabis use and potentially lead to increasing self-exposure. These data may eventually lead to improvements in personalized medicine for the prevention and treatment of highly prevalent CUDs and neuropsychiatric comorbidities.

  19. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone

    International Nuclear Information System (INIS)

    López-Arnau, Raúl; Martínez-Clemente, José; Rodrigo, Teresa; Pubill, David; Camarasa, Jorge; Escubedo, Elena

    2015-01-01

    Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3 × 25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26 ± 2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D 2 dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone. - Highlights: • We studied the dopaminergic and serotonergic neurotoxicity of mephedrone in rats. • Mephedrone induced a transient hypothermia following sustained hyperthermia. • In a weekend consumption pattern, mephedrone induced selective neurotoxicity. • Mephedrone generated oxidative stress. • Mephedrone induced an impairment in memory function

  20. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone

    Energy Technology Data Exchange (ETDEWEB)

    López-Arnau, Raúl; Martínez-Clemente, José [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Rodrigo, Teresa [Animal Experimentation Unit of Psychology and Pharmacy, University of Barcelona (Spain); Pubill, David [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Camarasa, Jorge, E-mail: jcamarasa@ub.edu [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Escubedo, Elena [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain)

    2015-07-01

    Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3 × 25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26 ± 2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D{sub 2} dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone. - Highlights: • We studied the dopaminergic and serotonergic neurotoxicity of mephedrone in rats. • Mephedrone induced a transient hypothermia following sustained hyperthermia. • In a weekend consumption pattern, mephedrone induced selective neurotoxicity. • Mephedrone generated oxidative stress. • Mephedrone induced an impairment in memory function.

  1. Simultaneous acid exposure and erosive particle wear of thermoset coatings

    DEFF Research Database (Denmark)

    Møller, Victor Buhl; Dam-Johansen, Kim; Frankær, Sarah Maria

    2018-01-01

    , similar to the erosion/corrosion-type phenomena found in metals. A vinyl ester-based coating was the most resistant to the simultaneous erosive/acidic exposure, with a maximum polishing rate of 3.24±0.61 μm/week, while novolac epoxy and polyurethane coatings showed high polishing rates of 11.7±1.50 and 13.4±0......Handling acidic chemicals is a challenge in the chemical industry, requiring a careful choice of contact material. Certain thermoset organic coatings are applicable in low pH environments, but when particulate erosion is also present the performance demand is increased. This is the case in, e...

  2. Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor.

    Science.gov (United States)

    Corona-González, Rosa Isela; Varela-Almanza, Karla María; Arriola-Guevara, Enrique; Martínez-Gómez, Álvaro de Jesús; Pelayo-Ortiz, Carlos; Toriz, Guillermo

    2016-04-01

    The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh. Copyright © 2016. Published by Elsevier Ltd.

  3. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    Science.gov (United States)

    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

  4. Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat.

    Science.gov (United States)

    Assier, E; Bouzinba-Segard, H; Stolzenberg, M C; Stephens, R; Bardos, J; Freemont, P; Charron, D; Trowsdale, J; Rich, T

    1999-04-16

    A novel human gene RED, and the murine homologue, MuRED, were cloned. These genes were named after the extensive stretch of alternating arginine (R) and glutamic acid (E) or aspartic acid (D) residues that they contain. We term this the 'RED' repeat. The genes of both species were expressed in a wide range of tissues and we have mapped the human gene to chromosome 5q22-24. MuRED and RED shared 98% sequence identity at the amino acid level. The open reading frame of both genes encodes a 557 amino acid protein. RED fused to a fluorescent tag was expressed in nuclei of transfected cells and localised to nuclear dots. Co-localisation studies showed that these nuclear dots did not contain either PML or Coilin, which are commonly found in the POD or coiled body nuclear compartments. Deletion of the amino terminal 265 amino acids resulted in a failure to sort efficiently to the nucleus, though nuclear dots were formed. Deletion of a further 50 amino acids from the amino terminus generates a protein that can sort to the nucleus but is unable to generate nuclear dots. Neither construct localised to the nucleolus. The characteristics of RED and its nuclear localisation implicate it as a regulatory protein, possibly involved in transcription.

  5. Effect of replacing sugar with non-caloric sweeteners in beverages on the reward value after repeated exposure.

    Directory of Open Access Journals (Sweden)

    Sanne Griffioen-Roose

    Full Text Available BACKGROUND: The reward value of food is partly dependent on learned associations. It is not yet known whether replacing sugar with non-caloric sweeteners in food is affecting long-term acceptance. OBJECTIVE: To determine the effect of replacing sugar with non-caloric sweeteners in a nutrient-empty drink (soft drink versus nutrient-rich drink (yoghurt drink on reward value after repeated exposure. DESIGN: We used a randomized crossover design whereby forty subjects (15 men, 25 women with a mean ± SD age of 21 ± 2 y and BMI of 21.5 ± 1.7 kg/m(2 consumed a fixed portion of a non-caloric sweetened (NS and sugar sweetened (SS versions of either a soft drink or a yoghurt drink (counterbalanced for breakfast which were distinguishable by means of colored labels. Each version of a drink was offered 10 times in semi-random order. Before and after conditioning the reward value of the drinks was assessed using behavioral tasks on wanting, liking, and expected satiety. In a subgroup (n=18 fMRI was performed to assess brain reward responses to the drinks. RESULTS: Outcomes of both the behavioral tasks and fMRI showed that conditioning did not affect the reward value of the NS and SS versions of the drinks significantly. Overall, subjects preferred the yoghurt drinks to the soft drinks and the ss drinks to the NS drinks. In addition, they expected the yoghurt drinks to be more satiating, they reduced hunger more, and delayed the first eating episode more. Conditioning did not influence these effects. CONCLUSION: Our study showed that repeated consumption of a non-caloric sweetened beverage, instead of a sugar sweetened version, appears not to result in changes in the reward value. It cannot be ruled out that learned associations between sensory attributes and food satiating capacity which developed preceding the conditioning period, during lifetime, affected the reward value of the drinks.

  6. Effect of replacing sugar with non-caloric sweeteners in beverages on the reward value after repeated exposure.

    Science.gov (United States)

    Griffioen-Roose, Sanne; Smeets, Paul A M; Weijzen, Pascalle L G; van Rijn, Inge; van den Bosch, Iris; de Graaf, Cees

    2013-01-01

    The reward value of food is partly dependent on learned associations. It is not yet known whether replacing sugar with non-caloric sweeteners in food is affecting long-term acceptance. To determine the effect of replacing sugar with non-caloric sweeteners in a nutrient-empty drink (soft drink) versus nutrient-rich drink (yoghurt drink) on reward value after repeated exposure. We used a randomized crossover design whereby forty subjects (15 men, 25 women) with a mean ± SD age of 21 ± 2 y and BMI of 21.5 ± 1.7 kg/m(2) consumed a fixed portion of a non-caloric sweetened (NS) and sugar sweetened (SS) versions of either a soft drink or a yoghurt drink (counterbalanced) for breakfast which were distinguishable by means of colored labels. Each version of a drink was offered 10 times in semi-random order. Before and after conditioning the reward value of the drinks was assessed using behavioral tasks on wanting, liking, and expected satiety. In a subgroup (n=18) fMRI was performed to assess brain reward responses to the drinks. Outcomes of both the behavioral tasks and fMRI showed that conditioning did not affect the reward value of the NS and SS versions of the drinks significantly. Overall, subjects preferred the yoghurt drinks to the soft drinks and the ss drinks to the NS drinks. In addition, they expected the yoghurt drinks to be more satiating, they reduced hunger more, and delayed the first eating episode more. Conditioning did not influence these effects. Our study showed that repeated consumption of a non-caloric sweetened beverage, instead of a sugar sweetened version, appears not to result in changes in the reward value. It cannot be ruled out that learned associations between sensory attributes and food satiating capacity which developed preceding the conditioning period, during lifetime, affected the reward value of the drinks.

  7. 17β-Estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the HPA axis during adolescence.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    Full Text Available Alcohol consumption during adolescence has long-term sexually dimorphic effects on anxiety behavior and mood disorders. We have previously shown that repeated binge-pattern alcohol exposure increased the expression of two critical central regulators of stress and anxiety, corticotrophin-releasing hormone (CRH and arginine vasopressin (AVP, in adolescent male rats. By contrast, there was no effect of alcohol on these same genes in adolescent females. Therefore, we tested the hypothesis that 17β-estradiol (E(2, the predominant sex steroid hormone in females, prevents alcohol-induced changes in CRH and AVP gene expression in the paraventricular nucleus (PVN of the hypothalamus. To test this hypothesis, postnatal day (PND 26 females were ovariectomized and given E(2 replacement or cholesterol as a control. Next, they were given an alcohol exposure paradigm of 1 saline alone, 2 acute (single dose or 3 a repeated binge-pattern. Our results showed that acute and repeated binge-pattern alcohol treatment increased plasma ACTH and CORT levels in both E(2- and Ch-treated groups, however habituation to repeated binge-pattern alcohol exposure was evident only in E(2-treated animals. Further, repeated binge-pattern alcohol exposure significantly decreased CRH and AVP mRNA in Ch-, but not E(2-treated animals, which was consistent with our previous observations in gonad intact females. We further tested the effects of E(2 and alcohol treatment on the activity of the wild type CRH promoter in a PVN-derived neuronal cell line. Alcohol increased CRH promoter activity in these cells and concomitant treatment with E(2 completely abolished the effect. Together our data suggest that E(2 regulates the reactivity of the HPA axis to a repeated stressor through modulation of the habituation response and further serves to maintain normal steady state mRNA levels of CRH and AVP in the PVN in response to a repeated alcohol stressor.

  8. Assessment of occupational exposure to gaseous peracetic acid.

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    1993-01-01

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

  10. Murine protein H is comprised of 20 repeating units, 61 amino acids in length

    DEFF Research Database (Denmark)

    Kristensen, Torsten; Tack, B F

    1986-01-01

    A cDNA library constructed from size-selected (greater than 28 S) poly(A)+ RNA isolated from the livers of C57B10. WR mice was screened by using a 249-base-pair (bp) cDNA fragment encoding 83 amino acid residues of human protein H as a probe. Of 120,000 transformants screened, 30 hybridized......, 448 bp of 3'-untranslated sequence, and a polyadenylylated tail of undetermined length. Murine pre-protein H was deduced to consist of an 18-amino acid signal peptide and 1216 residues of H-protein sequence. Murine H was composed of 20 repetitive units, each about 61 amino acid residues in length...

  11. The reinforcing value of vegetables does not increase with repeated exposure during a randomized controlled provided vegetable intervention among overweight and obese adults

    Science.gov (United States)

    Objective: The primary aim of this randomized controlled trial is to determine whether the relative reinforcing value (RRV) of vegetables compared to a snack food can be increased through repeated exposure (incentive sensitization) to amounts of vegetables recommended by the Dietary Guidelines for A...

  12. Is repeated exposure the holy grail for increasing children's vegetable intake? Lessons learned from a Dutch childcare intervention using various vegetable preparations

    NARCIS (Netherlands)

    Zeinstra, Gertrude G.; Vrijhof, Milou; Kremer, Stefanie

    2018-01-01

    Children's failure to eat enough vegetables highlights the need for effective interventions encouraging this behaviour. The aim of this study was to investigate the effect of repeated exposure to three a priori unfamiliar vegetables, each prepared in two ways, on children's vegetable acceptance in a

  13. Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment

    NARCIS (Netherlands)

    Chaudhari, U.; Nemade, H.; Wagh, V.; Ellis, J.K.; Srinivasan, S.; Louisse, J.

    2016-01-01

    The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the

  14. Amino acid repeats avert mRNA folding through conservative substitutions and synonymous codons, regardless of codon bias

    Directory of Open Access Journals (Sweden)

    Sailen Barik

    2017-12-01

    Full Text Available A significant number of proteins in all living species contains amino acid repeats (AARs of various lengths and compositions, many of which play important roles in protein structure and function. Here, I have surveyed select homopolymeric single [(An] and double [(ABn] AARs in the human proteome. A close examination of their codon pattern and analysis of RNA structure propensity led to the following set of empirical rules: (1 One class of amino acid repeats (Class I uses a mixture of synonymous codons, some of which approximate the codon bias ratio in the overall human proteome; (2 The second class (Class II disregards the codon bias ratio, and appears to have originated by simple repetition of the same codon (or just a few codons; and finally, (3 In all AARs (including Class I, Class II, and the in-betweens, the codons are chosen in a manner that precludes the formation of RNA secondary structure. It appears that the AAR genes have evolved by orchestrating a balance between codon usage and mRNA secondary structure. The insights gained here should provide a better understanding of AAR evolution and may assist in designing synthetic genes.

  15. Amino acid repeats avert mRNA folding through conservative substitutions and synonymous codons, regardless of codon bias.

    Science.gov (United States)

    Barik, Sailen

    2017-12-01

    A significant number of proteins in all living species contains amino acid repeats (AARs) of various lengths and compositions, many of which play important roles in protein structure and function. Here, I have surveyed select homopolymeric single [(A)n] and double [(AB)n] AARs in the human proteome. A close examination of their codon pattern and analysis of RNA structure propensity led to the following set of empirical rules: (1) One class of amino acid repeats (Class I) uses a mixture of synonymous codons, some of which approximate the codon bias ratio in the overall human proteome; (2) The second class (Class II) disregards the codon bias ratio, and appears to have originated by simple repetition of the same codon (or just a few codons); and finally, (3) In all AARs (including Class I, Class II, and the in-betweens), the codons are chosen in a manner that precludes the formation of RNA secondary structure. It appears that the AAR genes have evolved by orchestrating a balance between codon usage and mRNA secondary structure. The insights gained here should provide a better understanding of AAR evolution and may assist in designing synthetic genes.

  16. Effects of Diet and Genetics on Growth Performance of Pigs in Response to Repeated Exposure to Heat Stress

    Directory of Open Access Journals (Sweden)

    Wendy M. Rauw

    2017-10-01

    Full Text Available Heat stress (HS is one of the costliest issues in the U.S. pork industry. Aims of the present study were to determine the consequences of repeated exposure to HS on growth performance, and the effects of a high fiber diet, the genetic potential for high lean tissue accretion, and the genetic potential for residual feed intake (RFI on resilience to HS. Barrows (n = 97 from three genetic lines (commercial, high RFI, low RFI where subjected three times to a 4-day HS treatment (HS1, HS2, and HS3 which was preceded by a 9-day neutral (TN adaptation period (TN1 and alternated by 7-day periods of neutral temperatures (TN2, TN3, and TN4. Body weight gain (BWG, feed intake (FI, feed conversion efficiency (FCE, RFI, and the drop in BWG and FI between TN and HS were estimated for each period, and slaughter traits were measured at the end of TN4. Commercial pigs had lower FI when fed a high fiber diet compared to a regular diet (2.70 ± 0.08 vs. 2.96 ± 0.08 kg/d; P < 0.05, while no differences were found for BWG, RFI or FCE. HS reduced FI, BWG, and FCE, increased RFI, and resulted in leaner pigs that generate smaller carcasses at slaughter. In TN, commercial pigs grew faster than the low and high RFI pigs (1.22 ± 0.06 vs. 0.720 ± 0.05 and 0.657 ± 0.07; P < 0.001 but growth rates were not significantly different between the lines during HS. Growth rates for the low RFI and high RFI pigs were similar both during TN and during HS. Pigs of interest for genetic improvement are those that are able to maintain growth rates during HS. Our results show that response in growth to HS was repeatable over subsequent 4-d HS cycles, which suggests the potential for including this response in the breeding index. The best performing animals during HS are likely those that are not highly superior for growth in TN.

  17. Barrier function and natural moisturizing factor levels after cumulative exposure to a fruit-derived organic acid and a detergent: different outcomes in atopic and healthy skin and relevance for occupational contact dermatitis in the food industry.

    Science.gov (United States)

    Angelova-Fischer, Irena; Hoek, Anne-Karin; Dapic, Irena; Jakasa, Ivone; Kezic, Sanja; Fischer, Tobias W; Zillikens, Detlef

    2015-12-01

    Fruit-derived organic compounds and detergents are relevant exposure factors for occupational contact dermatitis in the food industry. Although individuals with atopic dermatitis (AD) are at risk for development of occupational contact dermatitis, there have been no controlled studies on the effects of repeated exposure to multiple irritants, relevant for the food industry, in atopic skin. The aim of the study was to investigate the outcomes of repeated exposure to a fruit-derived organic acid and a detergent in AD compared to healthy volunteers. The volunteers were exposed to 2.0% acetic acid (AcA) and/or 0.5% sodium lauryl sulfate (SLS) in controlled tandem repeated irritation test. The outcomes were assessed by measurements of erythema, transepidermal water loss (TEWL) and natural moisturizing factor (NMF) levels. In the AD volunteers, repeated AcA exposure led to barrier disruption and significant TEWL increase; no significant differences after the same exposure in the healthy controls were found. Repeated exposure to SLS and the irritant tandems enhanced the reactions and resulted in a significantly higher increase in TEWL in the AD compared to the control group. Cumulative irritant exposure reduced the NMF levels in both groups. Differences in the severity of irritant-induced barrier impairment in atopic individuals contribute to the risk for occupational contact dermatitis in result of multiple exposures to food-derived irritants and detergents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Is repeated exposure the holy grail for increasing children's vegetable intake? Lessons learned from a Dutch childcare intervention using various vegetable preparations.

    Science.gov (United States)

    Zeinstra, Gertrude G; Vrijhof, Milou; Kremer, Stefanie

    2018-02-01

    Children's failure to eat enough vegetables highlights the need for effective interventions encouraging this behaviour. The aim of this study was to investigate the effect of repeated exposure to three a priori unfamiliar vegetables, each prepared in two ways, on children's vegetable acceptance in a childcare setting. Two hundred fifty children (mean age 25 months; 57% boys) participated in a pre-test and a post-test, where they were offered pumpkin, courgette, and white radish. The intervention group (N = 125) participated in a 5-month exposure period, where they were exposed repeatedly (∼12x) to the vegetables: pumpkin blanched and as a cracker spread; courgette blanched and as soup; white radish raw and as a cracker spread. The control group (N = 125) maintained their normal routine. Mixed model analyses were used to analyse intake data and Chi-square analyses for willingness to taste. At pre-test, children ate about 20 g of pumpkin and courgette, whereas white radish intake was approximately 10 g. There was a significant positive effect of the intervention for pumpkin (+15 g; p < 0.001) and white radish (+16 g; p = 0.01). Results for willingness to taste were in the same direction. There was no repeated exposure effect for courgette (p = 0.54); this may have been due to its less distinct taste profile or familiarity with boiled courgette. From our findings, we conclude that repeated exposure to multiple unfamiliar vegetable tastes within the daily routine of a childcare setting is effective in improving children's willingness to taste and intake of some of these vegetables. However, repeated exposure may not be sufficient for more familiar or blander tasting vegetables. This implies that one size does not fit all and that additional strategies are needed to increase children's intake of these vegetables. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effects of short-term repeated exposure to different flooring surfaces on the behavior and physiology of dairy cattle.

    Science.gov (United States)

    Schütz, K E; Cox, N R

    2014-05-01

    during the stand-off period. We observed no major effect of the repeated stand-off exposure. In summary, adding rubber matting onto concrete surfaces for stand-off purposes is beneficial for animal welfare. A well-managed wood chip surface offered the best welfare for dairy cows removed from pasture, and the findings of this study confirm that a concrete surface decreases the welfare of cows removed from pasture. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Identification, characterization, and utilization of genome-wide simple sequence repeats to identify a QTL for acidity in apple

    Science.gov (United States)

    2012-01-01

    Background Apple is an economically important fruit crop worldwide. Developing a genetic linkage map is a critical step towards mapping and cloning of genes responsible for important horticultural traits in apple. To facilitate linkage map construction, we surveyed and characterized the distribution and frequency of perfect microsatellites in assembled contig sequences of the apple genome. Results A total of 28,538 SSRs have been identified in the apple genome, with an overall density of 40.8 SSRs per Mb. Di-nucleotide repeats are the most frequent microsatellites in the apple genome, accounting for 71.9% of all microsatellites. AT/TA repeats are the most frequent in genomic regions, accounting for 38.3% of all the G-SSRs, while AG/GA dimers prevail in transcribed sequences, and account for 59.4% of all EST-SSRs. A total set of 310 SSRs is selected to amplify eight apple genotypes. Of these, 245 (79.0%) are found to be polymorphic among cultivars and wild species tested. AG/GA motifs in genomic regions have detected more alleles and higher PIC values than AT/TA or AC/CA motifs. Moreover, AG/GA repeats are more variable than any other dimers in apple, and should be preferentially selected for studies, such as genetic diversity and linkage map construction. A total of 54 newly developed apple SSRs have been genetically mapped. Interestingly, clustering of markers with distorted segregation is observed on linkage groups 1, 2, 10, 15, and 16. A QTL responsible for malic acid content of apple fruits is detected on linkage group 8, and accounts for ~13.5% of the observed phenotypic variation. Conclusions This study demonstrates that di-nucleotide repeats are prevalent in the apple genome and that AT/TA and AG/GA repeats are the most frequent in genomic and transcribed sequences of apple, respectively. All SSR motifs identified in this study as well as those newly mapped SSRs will serve as valuable resources for pursuing apple genetic studies, aiding the apple breeding

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

    Science.gov (United States)

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

    2017-10-01

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

  2. Activation of cell division and nucleic acid synthesis in the corneal epithelium of albino rats by repeated stress

    International Nuclear Information System (INIS)

    Berezhnova, N.I.; Timoshin, S.S.

    1985-01-01

    Adaption to unfavorable factors is accompanied by activation of nucleic acid and protein synthesis in systems responsible for adaption. The authors investigate the possibility of similar changes taking place in structures not actively participating in adaptation. The corneas of the dead male albin rats were preincubated with tritium-uridine for 1.5 hours. The mitotic index, the index of tritium-thymidine-labeled nuclei and the intensity of thymidine labeling were determined. The results indicate that after a single exposure to hypoxia, hyperthermia, and immobilization, mitotic index in the corneal epithelium decreased and DNA synthesis under these circumstances remained stable

  3. Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun Oularbi

    2014-04-01

    Full Text Available Lambda-cyhalothrin (LCT is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administered orally over 28 days. The effects of the insecticide on various biochemical parameters were evaluated at 14 and 28 days. Histopathological studies were carried out in the kidneys and adrenal glands at the end of the experiment. Lambda-cyhalothrin, as a pyrethroid insecticide, induced significant increases (P≤0.05 in plasma urea, creatinine, uric acid and glucose concentrations, and alanine aminotransferase and aspartate aminotransferase activities after 14 and 28 days. In the rat plasma samples after 28 days, residual concentrations of LCT 1R, cis,

  4. Repeated exposure to two stressors in sequence demonstrates that corticosterone and paraventricular nucleus of the hypothalamus interleukin-1β responses habituate independently.

    Science.gov (United States)

    Lovelock, D F; Deak, T

    2017-09-01

    A wide range of stress-related pathologies such as post-traumatic stress disorder are considered to arise from aberrant or maladaptive forms of stress adaptation. The hypothalamic-pituitary-adrenal (HPA) axis readily adapts to repeated stressor exposure, yet little is known about adaptation in neuroimmune responses to repeated or sequential stress challenges. In Experiment 1, rats were exposed to 10 days of restraint alone (60 minutes daily), forced swim alone (30 minutes daily) or daily sequential exposure to restraint (60 minutes) followed immediately by forced swim (30 minutes), termed sequential stress exposure. Habituation of the corticosterone (CORT) response occurred to restraint by 5 days and swim at 10 days, whereas rats exposed to sequential stress exposure failed to display habituation to the combined challenge. Experiment 2 compared 1 or 5 days of forced swim with sequential stress exposure and examined how each affected expression of several neuroimmune and cellular activation genes in the paraventricular nucleus of the hypothalamus (PVN), prefrontal cortex (PFC) and hippocampus (HPC). Sequential exposure to restraint and swim increased interleukin (IL)-1β in the PVN, an effect that was attenuated after 5 days. Sequential stress exposure also elicited IL-6 and tumour necrosis factor-α responses in the HPC and PFC, respectively, which did not habituate after 5 days. Experiment 3 tested whether prior habituation to restraint (5 days) would alter the IL-1β response evoked by swim exposure imposed immediately after the sixth day of restraint. Surprisingly, a history of repeated exposure to restraint attenuated the PVN IL-1β response after swim in comparison to acutely-exposed subjects despite an equivalent CORT response. Overall, these findings suggest that habituation of neuroimmune responses to stress proceeds: (i) independent of HPA axis habituation; (ii) likely requires more daily sessions of stress to develop; and (iii) IL-1β displays

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

    Science.gov (United States)

    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.

  6. Repeated Exposure to the “Spice” Cannabinoid JWH-018 Induces Tolerance and Enhances Responsiveness to 5-HT1A Receptor Stimulation in Male Rats

    Directory of Open Access Journals (Sweden)

    Joshua S. Elmore

    2018-02-01

    Full Text Available Naphthalen-1-yl-(1-pentylindol-3-ylmethanone (JWH-018 is a synthetic compound found in psychoactive “spice” products that activates cannabinoid receptors. Preclinical evidence suggests that exposure to synthetic cannabinoids increases 5-HT2A/2C receptor function in the brain, an effect which might contribute to psychotic symptoms. Here, we hypothesized that repeated exposures to JWH-018 would enhance behavioral responsiveness to the 5-HT2A/2C receptor agonist DOI. Male Sprague-Dawley rats fitted with subcutaneously (sc temperature transponders received daily injections of JWH-018 (1.0 mg/kg, sc or its vehicle for seven consecutive days. Body temperature and catalepsy scores were determined at 1, 2, and 4 h post-injection each day. At 1 and 7 days after the final repeated treatment, rats received a challenge injection of either DOI (0.1 mg/kg, sc or the 5-HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg, sc, then temperature and behavioral responses were assessed. Behaviors induced by DOI included wet dog shakes and back muscle contractions (i.e., skin jerks, while behaviors induced by 8-OH-DPAT included ambulation, forepaw treading, and flat body posture. On the first day of repeated treatment, JWH-018 produced robust hypothermia and catalepsy which lasted up to 4 h, and these effects were significantly blunted by day 7 of treatment. Repeated exposure to JWH-018 did not affect behaviors induced by DOI, but behavioral and hypothermic responses induced by 8-OH-DPAT were significantly augmented 1 day after cessation of JWH-018 treatment. Collectively, our findings show that repeated treatment with JWH-018 produces tolerance to its hypothermic and cataleptic effects, which is accompanied by transient enhancement of 5-HT1A receptor sensitivity in vivo.

  7. 'Just a pinch of salt'. An experimental comparison of the effect of repeated exposure and flavor-flavor learning with salt or spice on vegetable acceptance in toddlers.

    Science.gov (United States)

    Bouhlal, Sofia; Issanchou, Sylvie; Chabanet, Claire; Nicklaus, Sophie

    2014-12-01

    Children's vegetable intake is below the recommended amounts. No studies to date have tested the relevance of using salt or spices to increase children's vegetable acceptance. Our objective was to compare the effect of repeated exposure (RE) and of flavor-flavor learning (FFL) on toddlers' acceptance of a non-familiar vegetable. Two unconditioned stimuli were used: salt and a salt-associated spice. Toddlers attending six nurseries were assigned to 3 groups in a between subject design. Groups were exposed 8 times to a basic salsify puree (0.2% salt w/w; RE group; n = 47), a salty salsify puree (0.5% salt w/w; FFL-Salt group; n = 54) or a spiced salsify puree (0.2% salt and 0.02% nutmeg w/w; FFL-Nutmeg group; n = 50). Acceptance (intake and liking) of the target vegetable (basic salsify puree) and of a control vegetable (carrot puree) was evaluated at pre-exposure, at each exposure of the learning period, at post-exposure, and at 1, 3 and 6 months after exposure. In all groups, intake of the target vegetable increased from pre- to post-exposure. This increase was significantly higher in the RE group (64 ± 11 g) than in the FFL-Salt group (23 ± 11 g) and marginally higher than in the FFL-Nutmeg group (36 ± 11 g). No difference between groups was observed on the increase in liking of the target vegetable from pre- to post-exposure. The increase of the target vegetable intake was still observed after 6 months for all groups. Thus, repeated exposure appears to be the simplest choice to increase vegetable intake on the short and long term in toddlers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Repeated exposure to high-frequency spanking and child externalizing behavior across the first decade: a moderating role for cumulative risk.

    Science.gov (United States)

    MacKenzie, Michael J; Nicklas, Eric; Brooks-Gunn, Jeanne; Waldfogel, Jane

    2014-12-01

    This study used the Fragile Families and Child Well-Being Study to examine the effects of repeated exposure to harsh parenting on child externalizing behavior across the first decade of life, and a moderating role for cumulative ecological risk. Maternal report of harsh parenting, defined as high frequency spanking, was assessed at age 1, 3, 5, and 9, along with child externalizing at age 9 (N=2,768). Controlling for gender, race, maternal nativity, and city of residence, we found a cumulative risk index to significantly moderate the effects of repeated harsh parenting on child behavior, with the effects of repeated high-frequency spanking being amplified for those experiencing greater levels of cumulative risk. Harsh parenting, in the form of high frequency spanking, remains a too common experience for children, and results demonstrate that the effects of repeated exposure to harsh parenting across the first decade are amplified for those children already facing the most burden. Copyright © 2014. Published by Elsevier Ltd.

  9. Development of short and highly potent self-assembling elastin-derived pentapeptide repeats containing aromatic amino acid residues.

    Science.gov (United States)

    Taniguchi, Suguru; Watanabe, Noriko; Nose, Takeru; Maeda, Iori

    2016-01-01

    Tropoelastin is the primary component of elastin, which forms the elastic fibers that make up connective tissues. The hydrophobic domains of tropoelastin are thought to mediate the self-assembly of elastin into fibers, and the temperature-mediated self-assembly (coacervation) of one such repetitive peptide sequence (VPGVG) has been utilized in various bio-applications. To elucidate a mechanism for coacervation activity enhancement and to develop more potent coacervatable elastin-derived peptides, we synthesized two series of peptide analogs containing an aromatic amino acid, Trp or Tyr, in addition to Phe-containing analogs and tested their functional characteristics. Thus, position 1 of the hydrophobic pentapeptide repeat of elastin (X(1)P(2)G(3)V(4)G(5)) was substituted by Trp or Tyr. Eventually, we acquired a novel, short Trp-containing elastin-derived peptide analog (WPGVG)3 with potent coacervation ability. From the results obtained during this process, we determined the importance of aromaticity and hydrophobicity for the coacervation potency of elastin-derived peptide analogs. Generally, however, the production of long-chain synthetic polypeptides in quantities sufficient for commercial use remain cost-prohibitive. Therefore, the identification of (WPGVG)3, which is a 15-mer short peptide consisting simply of five natural amino acids and shows temperature-dependent self-assembly activity, might serve as a foundation for the development of various kinds of biomaterials. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  10. Repeated exposure to cat urine induces complex behavioral, hormonal, and c-fos mRNA responses in Norway rats ( Rattus norvegicus)

    Science.gov (United States)

    Yin, Baofa; Gu, Chen; Lu, Yi; Hegab, Ibrahim M.; Yang, Shengmei; Wang, Aiqin; Wei, Wanhong

    2017-08-01

    Prey species show specific adaptations that allow recognition, avoidance, and defense against predators. This study was undertaken to investigate the processing of a chronic, life-threatening stimulus to Norway rats ( Rattus norvegicus). One hundred forty-four Norway rats were tested by repeated presentation of cat urine for 1 h at different days in a defensive withdrawal apparatus. Rats exposed to urine for short periods showed significantly larger defensive behavioral and medial hypothalamic c-fos messenger RNA (mRNA) responses than other groups. These defensive responses habituated shortly after the presentation of cat urine. Serum levels of adrenocorticotropic hormone and corticosterone increased significantly when animals were repeatedly exposed to cat urine. However, the hormonal responses took longer to habituate than the behavioral and molecular responses did. We conclude that the behavioral and c-fos mRNA responses are "primed" for habituation to repeated exposures to cat urine, while the hormonal responses show "resistance." The results support our hypothesis that the strongest anti-predator responses at three levels would occur during short-term exposure to cat urine and that these responses would subsequently disappear on prolonged exposure. This study assists understanding the way in which the different levels of defensive responses are integrated and react during chronic stress.

  11. Removal of 2,4,6-trichlorophenol from a solution by humic acids repeatedly extracted from a peat soil

    International Nuclear Information System (INIS)

    Tzou, Y.-M.; Wang, S.-L.; Liu, J.-C.; Huang, Y.-Y.; Chen, J.-H.

    2008-01-01

    Humic acid (HA) is one of the major components of soil organic matter. It strongly affects the sorption behavior of organic and inorganic contaminants in soils. To obtain a better understanding of the interactions of contaminants with HA, a repeated extraction technique has been applied to a peat soil to obtain HA fractions with varying aliphaticity and aromaticity, which were subsequently correlated to the sorption properties of 2,4,6-trichlorophenol (TCP). HA fractions were extracted repeatedly using an alkaline solution and each HA fraction was separated into two portions with an air-drying or re-suspending (denoted as RSHAs) process. Solid-state 13 C NMR and elemental analysis demonstrated that the aromaticity and polarity of HAs decreased with extractions. Kinetic results indicated that air-dried HAs exhibited two-step first order sorption behavior with a rapid stage followed by a slower stage. The slower sorption is attributed to the diffusion of 2,4,6-TCP in the condensed aromatic domains of HAs. Conversely, sorption of 2,4,6-TCP on RSHAs was extremely rapid and could not be fitted with any kinetic model. For air-dried HAs the sorption capacity (K oc ) was weakly correlated with the chemical compositions of HAs. However, a positive trend between K oc and aromaticity was observed for RSHAs. Compared with the results of air-dried HAs with their counterparts of RSHAs, it is therefore concluded that air-drying may alter the structure of HAs through artificially creating a more condensed domain in HAs. The structural alternation may result in an incorrect interpretation of the relationship between sorption capacity and chemical composition of HAs and a misjudgment of the transport behavior of 2,4,6-TCP in soils and sediments

  12. Effects of Single and Repeated Exposure to a 50-Hz 2-mT Electromagnetic Field on Primary Cultured Hippocampal Neurons.

    Science.gov (United States)

    Zeng, Ying; Shen, Yunyun; Hong, Ling; Chen, Yanfeng; Shi, Xiaofang; Zeng, Qunli; Yu, Peilin

    2017-06-01

    The prevalence of domestic and industrial electrical appliances has raised concerns about the health risk of extremely low-frequency magnetic fields (ELF-MFs). At present, the effects of ELF-MFs on the central nervous system are still highly controversial, and few studies have investigated its effects on cultured neurons. Here, we evaluated the biological effects of different patterns of ELF-MF exposure on primary cultured hippocampal neurons in terms of viability, apoptosis, genomic instability, and oxidative stress. The results showed that repeated exposure to 50-Hz 2-mT ELF-MF for 8 h per day after different times in culture decreased the viability and increased the production of intracellular reactive oxidative species in hippocampal neurons. The mechanism was potentially related to the up-regulation of Nox2 expression. Moreover, none of the repeated exposure patterns had significant effects on DNA damage, apoptosis, or autophagy, which suggested that ELF-MF exposure has no severe biological consequences in cultured hippocampal neurons.

  13. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

    Science.gov (United States)

    Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

    1999-04-01

    D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal

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

    Directory of Open Access Journals (Sweden)

    Arezoo Jahanbin

    2014-06-01

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

  15. Irritancy of antiseptics tested by repeated open exposures on the human skin, evaluated by non-invasive methods

    NARCIS (Netherlands)

    Tupker, RA; Schuur, J; Coenraads, PJ

    1997-01-01

    The aim of the study was to test the irritancy of 6 antiseptics in an open exposure model. The following agents were tested in their normal use concentrations using open exposures, 2x daily for 4 days in 20 subjects: chlorhexidine 4% (CH), chlorhexidine 0.5% in ethanol 70% (CE), ethanol 70% (ET),

  16. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of

  17. Effect of exposure to evening light on sleep initiation in the elderly: a longitudinal analysis for repeated measurements in home settings.

    Science.gov (United States)

    Obayashi, Kenji; Saeki, Keigo; Iwamoto, Junko; Okamoto, Nozomi; Tomioka, Kimiko; Nezu, Satoko; Ikada, Yoshito; Kurumatani, Norio

    2014-05-01

    Epidemiologic data have demonstrated associations of sleep-onset insomnia with a variety of diseases, including depression, dementia, diabetes and cardiovascular diseases. Sleep initiation is controlled by the suprachiasmatic nucleus of the hypothalamus and endogenous melatonin, both of which are influenced by environmental light. Exposure to evening light is hypothesized to cause circadian phase delay and melatonin suppression before bedtime, resulting in circadian misalignment and sleep-onset insomnia; however, whether exposure to evening light disturbs sleep initiation in home settings remains unclear. In this longitudinal analysis of 192 elderly individuals (mean age: 69.9 years), we measured evening light exposure and sleep-onset latency for 4 days using a wrist actigraph incorporating a light meter and an accelerometer. Mixed-effect linear regression analysis for repeated measurements was used to evaluate the effect of evening light exposure on subsequent sleep-onset latency. The median intensity of evening light exposure and the median sleep-onset latency were 27.3 lux (interquartile range, 17.9-43.4) and 17 min (interquartile range, 7-33), respectively. Univariate models showed significant associations between sleep-onset latency and age, gender, daytime physical activity, in-bed time, day length and average intensity of evening and nighttime light exposures. In a multivariate model, log-transformed average intensity of evening light exposure was significantly associated with log-transformed sleep-onset latency independent of the former potential confounding factors (regression coefficient, 0.133; 95% CI, 0.020-0.247; p = 0.021). Day length and nighttime light exposure were also significantly associated with log-transformed sleep-onset latency (p = 0.001 and p < 0.001, respectively). In conclusion, exposure to evening light in home setting prolongs subsequent sleep-onset latency in the elderly.

  18. The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

    Directory of Open Access Journals (Sweden)

    Benjamin Nnamdi Okolonkwo

    2014-11-01

    Full Text Available Paraquat (PQ is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, Avit.c, B, Bvit.c, C, Cvit.c, D and Dvit.c were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight of PQ respectively on biweekly (14 days intervals over a period of three months (84 days. Subsequently, the subgrouped animals (Avit.c, Bvit.c, Cvit.c and Dvit.c were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG, pH, protein and glucose], blood (urea, creatinine, total protein and glucose, and the histological studies on kidney slides. The dose and exposure- time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused marked elevation in serum urea and creatinine levels with reduction in serum protein and glucose levels and alterations in the cellular integrity of the renal architecture, especially the glomeruli and tubular tissues. Treatments on the PQ insulted animals with vitamin

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

    Science.gov (United States)

    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.

  20. Shrimp Tropomyosin Retains Antibody Reactivity after Exposure to Acidic Conditions

    Science.gov (United States)

    Although shrimp can be found in certain high acid food matrices, the allergenic capacity of shrimp tropomyosin exposed to low pH condition has not been fully clarified. Thus, a model marinade comprising white vinegar adjusted to different pH was used to determine the effects of acid-induced denatura...

  1. A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats.

    Science.gov (United States)

    Bushita, Hiroto; Ito, Yuichi; Saito, Tetsuji; Nukada, Yuko; Ikeda, Naohiro; Nakagiri, Hideaki; Saito, Kazutoshi; Morita, Osamu

    2018-05-31

    Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil-which mainly consists of oleic and linolenic, linoleic acids-have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential adverse effects, if any, of ALA-DAG oil in rats (10/sex/group) fed diets containing 1.375%, 2.75%, or 5.5% ALA-DAG oil for 90 days. Compared to control rats fed rapeseed oil or ALA-triacylglycerol oil (flaxseed oil), rats receiving ALA-DAG oil did not reveal any toxicologically significant treatment-related changes as evaluated by clinical signs, functional observational battery, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, organ weight, necropsy and histopathology. The no observed adverse effect levels for dietary exposure to ALA-DAG oil for male and female rats were 2916 and 3326 mg/kg body weight/day, respectively, the highest dose tested. The findings from this study suggest that consumption of ALA-DAG oil is unlikely to cause adverse effects. Copyright © 2018. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    Yongyue Wei

    Full Text Available 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.

  3. Repeated injections of piracetam improve spatial learning and increase the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in aged rats

    NARCIS (Netherlands)

    Canonico, P. L.; Aronica, E.; Aleppo, G.; Casabona, G.; Copani, A.; Favit, A.; Nicoletti, F.; Scapagnini, U.

    1991-01-01

    Repeated injections of piracetam (400 mg/kg, i.p. once a day for 15 days) to 16-month old rats led to an improved performance on an 8-arm radial maze, used as a test for spatial learning. This effect was accompanied by a greater ability of excitatory amino acids (ibotenate and glutamate) to

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

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

    International Nuclear Information System (INIS)

    Cunningham, Jessie L.; McGeer, James C.

    2016-01-01

    Highlights: • Exposure to 18 nM waterborne Cd induced plasma Ca loss that recovered by day 30 for lake whitefish but not brown trout. • Ucrit measured after an initial swim to 85% of Ucrit and a 30 min rest period was reduced in 18 nM Cd exposed fish compared to controls. • Swimming to 85% of Ucrit resulted in decreased muscle glycogen and increased lactate that was not recovered in the 30 min recovery period. • Second swim impairment is not related to metabolic processes in white muscle. - Abstract: This study investigates the effect of chronic Cd exposure on the ability to perform repeat swim challenges in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). Fish were exposed to waterborne Cd (18 nM) in moderately hard water (120 mg L"−"1 CaCO_3) for 30 days. This level of exposure has been shown to cause sublethal physiological disruption and acclimation responses but no impairment of sustained swimming capacity (U_c_r_i_t) in single swim challenges. Swim trials were done over the course of the exposure and each one consisted of an initial swim to 85% of the U_c_r_i_t of control fish, a 30 min recovery period and finally a second swim challenge to determine U_c_r_i_t. Plasma and tissue samples were collected before and after each of the swim periods. As expected from previous studies, Cd exposure resulted in significant accumulation of Cd in gills, liver and kidney but not in white muscle. Exposure also induced a loss of plasma Ca followed by subsequent recovery (in lake whitefish but not brown trout) with few mortalities (100% survival for lake whitefish and 93% for brown trout). Both control and exposed fish swam to 85% of the single swim U_c_r_i_t and no differences in performance were seen. The Ucrit of unexposed controls in the second swim challenges were not different from the single swim Ucrit. However, second swim performance was significantly reduced in Cd exposed fish, particularly after a week of exposure where 31% and 38

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

    Science.gov (United States)

    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...

  7. Short-term exposure to repeated chasing stress does not induce habituation in Senegalese sole, Solea senegalensis

    DEFF Research Database (Denmark)

    Conde-Sieira, Marta; Valente, Luisa M.P.; Hernandez-Perez, Juan

    2018-01-01

    Animals can habituate to certain repeated stressors and reduce the physiological response that such stressor evoked initially. Studies related to stress habituation in fish are scarce and the available data differ depending on the species and on the type, duration and severity of the stressor...... no significant changes in serotonergic activity. However, incremented serotonergic activity was detected in fish previously trained. Furthermore, dopaminergic activity decreased in diurnal trained and nocturnal trained groups with respect to ST/naïve fish. Crh expression in hypothalamus was higher in ST...... for the animals to habituate, indicating that repeated chasing within short periods should be avoided when manipulating fish in order to keep proper welfare conditions in this species....

  8. The effect of sensory-nutrient congruency on food intake after repeated exposure: do texture and/or energy density matter?

    Science.gov (United States)

    Hogenkamp, P S

    2014-09-01

    Sensory properties guide the amount that people eat. In particular, food texture plays an important role in a food's 'expected satiation', which in turn affects the food-related decision making process. One hypothesis is that incongruent pairing of a textural cue with a post-ingestive outcome compromises this process, leading to poor energy compensation. Several studies examined the effect of both energy density and sensory characteristics (i.e. increased creaminess and thickness) on expectations, subjective appetite and food intake. To add to this literature, a re-analysis of data assessed whether the effect of sensory-nutrient pairings on energy intake compensation persisted after repeated exposure to a food. In this cross-over design, 27 participants consumed two preloads with 'congruent' (low-energy/liquid; high-energy/semi-solid) and two preloads with 'incongruent' (low-energy/semi-solid; high-energy/liquid) texture-nutrient combinations for nine subsequent meals, during which ad libitum intake was measured. Intake at first exposure did not differ between the low-energy (280±150kcal) and high-energy preloads (292±183kcal) in the incongruent conditions. By contrast, it was greater after the low-energy (332±203kcal) than after the high-energy (236±132kcal) preload in the congruent conditions (energy∗incongruent/congruent, p=0.04). Post-exposure, this pattern changed: intake depended on the energy density of the preloads in all conditions, and was greater after low-energy preloads (day∗energy∗incongruent/congruent-interaction for breakfast: p=0.02). Thus, manipulating the sensory properties of a food influenced energy compensation and meal size, but only at initial exposure. Repeated exposure 'corrected' the initial lack of compensation observed in conditions with incongruent sensory-nutrient pairings. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design

    Directory of Open Access Journals (Sweden)

    Maria W. Mauritz

    2016-09-01

    Full Text Available Background: In the Netherlands, most patients with severe mental illness (SMI receive flexible assertive community treatment (FACT provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1 PTSD and dissociative symptoms changes and (2 changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25 with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results

  10. Mercapturic acids as biomarkers of exposure to electrophilic chemicals: applications to environmental and industrial chemicals.

    NARCIS (Netherlands)

    de Rooij, B.M.; Commandeur, J.N.M.; Vermeulen, N.P.E.

    1998-01-01

    The use of mercapturic acids (N-acetyl-L-cysteine S-conjugates, MAs) in the biological monitoring of human exposure to environmental and industrial chemicals is receiving more and more attention. Mercapturic acids (MAs) are formed from glutathione (GSH) S-conjugates via the MA-pathway. Although this

  11. Characteristics of gastroesophageal reflux in symptomatic patients with and without excessive esophageal acid exposure

    NARCIS (Netherlands)

    Bredenoord, Albert J.; Weusten, Bas L. A. M.; Timmer, Robin; Smout, Andŕe J. P. M.

    2006-01-01

    OBJECTIVE: In some patients with a physiological esophageal acid exposure, an association between reflux episodes and symptoms can be demonstrated. Besides acidity, other factors such as proximal extent may determine whether a reflux episode is perceived or not. We aimed to investigate the reflux

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

    Science.gov (United States)

    Cunningham, Jessie L; McGeer, James C

    2016-04-01

    This study investigates the effect of chronic Cd exposure on the ability to perform repeat swim challenges in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). Fish were exposed to waterborne Cd (18nM) in moderately hard water (120mgL(-1) CaCO3) for 30 days. This level of exposure has been shown to cause sublethal physiological disruption and acclimation responses but no impairment of sustained swimming capacity (Ucrit) in single swim challenges. Swim trials were done over the course of the exposure and each one consisted of an initial swim to 85% of the Ucrit of control fish, a 30min recovery period and finally a second swim challenge to determine Ucrit. Plasma and tissue samples were collected before and after each of the swim periods. As expected from previous studies, Cd exposure resulted in significant accumulation of Cd in gills, liver and kidney but not in white muscle. Exposure also induced a loss of plasma Ca followed by subsequent recovery (in lake whitefish but not brown trout) with few mortalities (100% survival for lake whitefish and 93% for brown trout). Both control and exposed fish swam to 85% of the single swim Ucrit and no differences in performance were seen. The Ucrit of unexposed controls in the second swim challenges were not different from the single swim Ucrit. However, second swim performance was significantly reduced in Cd exposed fish, particularly after a week of exposure where 31% and 38% reductions were observed for brown trout and lake whitefish respectively. Swimming to 85% Ucrit resulted in metabolic expenditure with little recovery after 30min. Few differences were observed between control and Cd exposed fish with the exception of a reduction in resting white muscle ATP stores of Cd exposed fish after 1 week of exposure. The results show that chronic sublethal Cd exposure results in an impairment of swimming ability in repeat swim challenges but this impairment is generally not related to metabolic processes

  13. Repeated sublethal exposures to the sea lice pesticide Salmosan® (azamethiphos) on adult male lobsters (Homarus americanus) causes neuromuscular dysfunction, hypoxia, metabolic disturbances and mortality.

    Science.gov (United States)

    Dounia, Daoud; Andrea, Battison; Lefort, Natalie; Van Geest, Jordana Lynne

    2016-12-01

    In Atlantic Canada and other salmon-growing regions, treatment of sea lice infestations in salmon aquaculture is necessary to protect fish health. The product Salmosan®, which contains the organophosphate azamethiphos as the active ingredient, is a pesticide presently used for treatment against sea lice. It is applied as a bath treatment and then released into the surrounding seawater. The potential for lethality to non-target species following acute and chronic exposures to Salmosan® has been studied over the past decade, however, the potential for sublethal effects on lobsters remains a concern. Adult male lobsters were exposed to 0.06, 0.5, and 5µgL -1 azamethiphos for one hour, repeated five times, over 48h. Lobsters were assessed immediately after exposure and over six days of recovery. Inhibition of muscle cholinesterase activity was detected in lobsters exposed to 0.5 and 5µgL -1 azamethiphos. The 5µgL -1 dose was considered lethal (93% cumulative mortality). Significant changes in hemolymph plasma biochemistry were most apparent in the 5µgL -1 exposure group in the immediate post-exposure samples. Citrate synthase activity was significantly lower in muscles of the 0.5µgL -1 exposure group compared to control lobsters. Mean electron transport system and standard metabolic rates tended to be lower in muscle tissue of the 0.5µgL -1 exposure group than control group lobsters. These results suggest that sublethal effects on lobster energetics may occur under laboratory exposure conditions (i.e., concentrations and duration) considered environmentally relevant, which could result in impairment under natural conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Experimental investigation of coating degradation during simultaneous acid and erosive particle exposure

    DEFF Research Database (Denmark)

    Møller, Victor Buhl; Dam-Johansen, Kim; Frankær, Sarah Maria

    When used in industrial processes, such as stirred acid leaching in the mineral industry, thermoset coatings are exposed to a combination of aggressive chemicals and erosive particlewear. While each exposure condition has been studied separately, no research has been presented on the effects...... of a simultaneous exposure. To investigate this, a pilot-scale stirred acid leaching tank, containing erosive particles and acidic solutions, has been designed and constructed. Resin types considered are amine-cured novolac epoxy and vinyl ester. Transient coating degradation is mapped through visual inspection...

  15. The Effects of Exposure to Repeated Minor Pain During the Neonatal Period on Formalin Pain Behavior and Thermal Withdrawal Latencies

    Directory of Open Access Journals (Sweden)

    C Celeste Johnston

    2003-01-01

    Full Text Available Preterm infants undergoing untreated, repeated painful procedures as part of their early experience are more likely to behave differently to pain as they mature than infants who were born at term and did not experience excessive exogenous pain. The neonatal rat model was used to investigate the short- and long-term effects of repeated pain in infancy on later development of pain responses. Newborn rat pups were randomly assigned by litter to be left unhandled (UH, handled by being removed from the dam for 15 min four times daily (H, and being handled and receiving pain from a paw prick with a 26G needle four times daily (Pon postnatal days (PD 2 through 8 (PD2-PD8. Maternal behaviour and grooming of pups on their return to the nest were recorded at PD6 for H and P pups. At PD15, PD36 and PD65, animals were first tested for latency to thermal stimulation threshold using the Hargreaves test and then for inflammatory pain using the formalin test. Pups in the HP group received significantly more grooming from their mothers (359 s than pups in the H group (295 s, P<0.0001. When accounting for differences in maternal grooming, a decreased thermal threshold in the P group compared with the H group (6.04 s versus 5.3 s, P<0.05 was found, although the correlations were not significant between maternal grooming and thermal thresholds. No group differences were seen with the formalin test. Interestingly, age was a significant factor in both tests, with younger animals showing fewer pain behaviours regardless of group or maternal grooming of the pup. Sex was significant at one age only in latency to thermal stimulation testing. The results suggest that changes in maternal care may be an important factor mediating the long-term effects of repeated neonatal experiences of pain.

  16. Effects of acute and repeated oral exposure to the organophosphate insecticide chlorpyrifos on open-field activity in chicks.

    Science.gov (United States)

    Al-Badrany, Y M A; Mohammad, F K

    2007-11-01

    The effects of the organophosphate insecticide chlorpyrifos on 5min open-field activity were examined in a 7-15 days old chick model. Chlorpyrifos was acutely administered taking into account cholinesterase inhibition and determination of the acute (24h) median lethal dose (LD50). The oral LD50 value of chlorpyrifos in chicks was 18.14mg/kg, with cholinergic toxicosis observed on intoxicated chicks. Chlorpyrifos at the dose rates of 5,10 and 20mg/kg orally produced within 2h signs of cholinergic toxicosis in the chicks and significantly inhibited plasma (40-70%), whole brain (43-69%) and liver (31-46%) cholinesterase activities in a dose-dependent manner. Chlorpyrifos at 2 and 4mg/kg, orally did not produce overt signs of cholinergic toxicosis, but decreased (30, 60 and 90min after dosing) the general locomotor activity of the chicks as seen by a significant increase in the latency to move from the central square of the open-field arena, decreases in the numbers of lines crossed and vocalization score. Repeated daily chlorpyrifos treatments (2 and 4mg/kg, orally) for seven consecutive days also caused hypoactivity in chicks in the open-field behavioral paradigm. Only the high dose of chlorpyrifos (4mg/kg, orally) given repeatedly for 7 days caused significant cholinesterase inhibition in the whole brain (37%) and the liver (22%). In conclusion, chlorpyrifos at single or short-term repeated doses-induced behavioral changes in 7-15 days old chicks, in a model that could be used for further neurobehavioral studies involving subtle effects of organophosphates on chicks.

  17. Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment.

    Science.gov (United States)

    Chaudhari, Umesh; Nemade, Harshal; Wagh, Vilas; Gaspar, John Antonydas; Ellis, James K; Srinivasan, Sureshkumar Perumal; Spitkovski, Dimitry; Nguemo, Filomain; Louisse, Jochem; Bremer, Susanne; Hescheler, Jürgen; Keun, Hector C; Hengstler, Jan G; Sachinidis, Agapios

    2016-11-01

    The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the identification of predictive genomics biomarkers of functional relevance for drug-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The hiPSC-CMs were incubated with 156 nM doxorubicin, which is a well-characterized cardiotoxicant, for 2 or 6 days followed by washout of the test compound and further incubation in compound-free culture medium until day 14 after the onset of exposure. An xCELLigence Real-Time Cell Analyser was used to monitor doxorubicin-induced cytotoxicity while also monitoring functional alterations of cardiomyocytes by counting of the beating frequency of cardiomyocytes. Unlike single exposure, repeated doxorubicin exposure resulted in long-term arrhythmic beating in hiPSC-CMs accompanied by significant cytotoxicity. Global gene expression changes were studied using microarrays and bioinformatics tools. Analysis of the transcriptomic data revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety

  18. The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure

    NARCIS (Netherlands)

    Broeders, Jessica J W; Hermens, Joop L M; Blaauboer, Bas J; Zurich, Marie-Gabrielle

    2015-01-01

    Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the biokinetics of the test compound into account. In addition, the exposure in vivo

  19. Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs.

    Science.gov (United States)

    Gisslen, Tate; Hillman, Noah H; Musk, Gabrielle C; Kemp, Matthew W; Kramer, Boris W; Senthamaraikannan, Paranthaman; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

    2014-02-01

    Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30  min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.

  20. Intake during repeated exposure to low- and high-energy-dense yogurts by different means of consumption

    NARCIS (Netherlands)

    Hogenkamp, P.S.; Mars, M.; Stafleu, A.; Graaf, C.de

    2010-01-01

    Background: An important question in the regulation of energy intake is whether dietary learning of energy content depends on the food's characteristics, such as texture. Texture might affect the duration of sensory exposure and eating rate. Objective: The objective was to investigate whether a long

  1. Androgen receptor gene CAG repeat length as modifier of the association between Persistent Organohalogen Pollutant exposure markers and semen characteristics

    DEFF Research Database (Denmark)

    Giwercman, Aleksander; Rylander, Lars; Rignell-Hydbom, Anna

    2007-01-01

    OBJECTIVES: Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to inves...

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

    Science.gov (United States)

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

  3. A broad-spectrum sunscreen prevents cumulative damage from repeated exposure to sub-erythemal solar ultraviolet radiation representative of temperate latitudes.

    Science.gov (United States)

    Seité, S; Christiaens, F; Bredoux, C; Compan, D; Zucchi, H; Lombard, D; Fourtanier, A; Young, A R

    2010-02-01

    We have previously shown the detrimental effects of 19 sub-erythemal exposures to daily ultraviolet radiation (DUVR, which mimics non-extreme exposure conditions), delivered over 4 weeks to volunteers. This source had UVA (320-400 nm) to UVB (290-320 nm) irradiance ratio of 25, instead of that close to 10 that is typically the case with solar-simulated radiation (SSR) that represents summer global sunlight with a clear sky and quasi-zenith solar irradiance. Here, we report on an extension of this previous study, in which we evaluated the photoprotection afforded by a broad-spectrum daily-care product with a low-sun protection factor (SPF 8, UVA-PF 7 and 3* rated UVA protection). We assessed cellular and molecular markers of photodamage that are relevant to skin cancer and photoageing. This study shows that biological effects of repeated exposure to DUVR can be prevented by a broad-spectrum daily-care product and that the level of protection afforded varies with the studied endpoint. Efficient daily UVR protection, as provided by a broad-spectrum daily-care product, is necessary to prevent the 'silent' sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

  4. Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

    International Nuclear Information System (INIS)

    Nakashima, Ryosuke; Hayashi, Yumi; Khalequzzaman, Md.; Jia, Xiaofang; Wang, Dong; Naito, Hisao; Ito, Yuki; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

    2013-01-01

    Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

  5. Association between secondhand smoke exposure at home and cigarette gifting and sharing in Zhejiang, China: a repeat cross-sectional study.

    Science.gov (United States)

    Xu, Yue; Xu, ShuiYang; Wu, QingQing; Guo, YuJie

    2016-03-03

    The aims of the current study were to assess the prevalence of household cigarette gifting and sharing, and to evaluate the relationship between secondhand smoke (SHS) exposure, and cigarette gifting and sharing, in Zhejiang, China. A repeat cross-sectional design. 10 sites in 5 cities in Zhejiang, China. Two surveys were conducted with adults in Zhejiang, China, in 2010 (N=2112) and 2012 (N=2279), respectively. At both waves, the same questionnaire was used; respondents were asked questions on residence, number of family smokers, indoor smoking rules, household income and cigarette gifting and sharing. The findings revealed that more than half of respondents' families (54.50% in 2010, 52.79% in 2012) reported exposure to SHS. Many families (54.73% in 2010, 47.04% in 2012) shared cigarettes with others, and a minority (14.91% in 2010, 14.17% in 2012) reported their family giving cigarettes as a gift. There was a significant decrease in cigarette sharing from 2010 to 2012, irrespective of household with SHS exposure status; and the cigarette gifting was significantly decreased in household without SHS exposure. Compared to households without SHS exposure, the prevalence of cigarette gifting and sharing in households with SHS exposure was more obvious. Encouraging and promoting a smoke-free household environment is necessary to change public smoking customs in Zhejiang, China. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Mood and autonomic responses to repeated exposure to the Trier Social Stress Test for Groups (TSST-G).

    Science.gov (United States)

    Boesch, Maria; Sefidan, Sandra; Ehlert, Ulrike; Annen, Hubert; Wyss, Thomas; Steptoe, Andrew; La Marca, Roberto

    2014-05-01

    A group version of the Trier Social Stress Test (TSST-G) was introduced as a standardized, economic and efficient tool to induce a psychobiological stress response simultaneously in a group of subjects. The aim of the present study was to examine the efficacy of the TSST-G to repeatedly induce an affective and autonomic stress response while comparing two alternative protocols for the second examination. Healthy young male recruits participated twice in the TSST-G 10 weeks apart. In the first examination, the TSST-G consisted of a combination of mental arithmetic and a fake job interview (TSST-G-1st; n=294). For the second examination, mental arithmetic was combined with either (a) a defensive speech in response to a false shoplifting accusation (TSST-G-2nd-defence; n=105), or (b) a speech on a more neutral topic selected by the investigators (TSST-G-2nd-presentation; n=100). Affect ratings and salivary alpha-amylase (sAA) were determined immediately before and after the stress test, while heart rate (HR) and heart rate variability (HRV) were measured continuously. TSST-G-1st resulted in a significant increase of negative affect, HR, and sAA, and a significant decrease in positive affect and HRV. TSST-G-2nd, overall, resulted in a significant increase of HR and sAA (the latter only in response to TSST-G-2nd-defence) and a decrease in HRV, while no significant affect alterations were found. When comparing both, TSST-G-2nd-defence and -2nd-presentation, the former resulted in a stronger stress response with regard to HR and HRV. The findings reveal that the TSST-G is a useful protocol to repeatedly evoke an affective and autonomic stress response, while repetition leads to affective but not necessarily autonomic habituation. When interested in examining repeated psychosocial stress reactivity, a task that requires an ego-involving effort, such as a defensive speech, seems to be significantly superior to a task using an impersonal speech. Copyright © 2014 Elsevier

  7. In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra

    2013-01-01

    Inhalation of particles has been shown to induce mutations in the male germline in mice following both prenatal and adult exposures in several experiments. In contrast, the effects of particles on female germ cell mutagenesis are not well established. Germline mutations are induced during active...... cell division, which occurs during fetal development in females. We investigated the effects of prenatal exposure to carbon black nanoparticles (CB) on induction of mutations in the female mouse germline during fetal development, spanning the critical developmental stages of oogenesis. Pregnant C57BL/6...... mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring....

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

    Science.gov (United States)

    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

  9. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    Directory of Open Access Journals (Sweden)

    Boyd R Rorabaugh

    Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  10. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    Science.gov (United States)

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  11. Potential for the development of tolerance by Aspergillus amstelodami, A. repens and A. ruber after repeated exposure to potassium sorbate.

    Science.gov (United States)

    Viñas, I; Morlans, I; Sanchis, V

    1990-01-01

    Three strains of A. amstelodami, A. repens and A. ruber were exposed to various levels of potassium sorbate, and the MICs were determined. Selected strains of the molds were then repeatedly exposed to subinhibitory levels of the compound to determine whether increased tolerance might develop. The MIC of sorbate (pH 5.5 or 6.5) for 3 species of Aspergillus was 0.07%. Increasing levels of sorbate resulted in increasing growth suppression of the molds. The 3 Aspergillus species were tested for increased tolerance to potassium sorbate, and none was found. They developed a slight increase in tolerance dependent upon pH and the mold strain by subculturing at low levels of sorbate.

  12. Comparative study of the pharmacokinetics of carbon tetrachloride in the rat following repeated inhalation exposures of 8 and 11.5 hr/day

    International Nuclear Information System (INIS)

    Paustenbach, D.J.; Carlson, G.P.; Christian, J.E.; Born, G.S.

    1986-01-01

    To evaluate whether exposure to inhaled vapors for periods longer than 8 hr/day could affect the rates and routes of elimination, male Sprague-Dawley rats were repeatedly exposed to 100 ppm of radiolabeled carbon tetrachloride ( 14 CCl 4 ) in a closed-loop chamber. One group was exposed for 8 hr/day for 5 days and another group for 11.5 hr/day for 4 days. Two other groups were exposed for either 8 hr/day for 10 of 12 consecutive days or 11.5 hr/day for 7 of 10 days. The elimination of 14 C activity was measured in the expired air, urine, and feces for up to 100 hr following exposure and the pharmacokinetic parameters were determined. Following 2 weeks of exposure to the 8-hr/day schedule, 14 CCl 4 in the breath and 14 C activity in the feces comprised 45 and 48% of the total 14 C excreted, respectively. Following 2 weeks of exposure to the 11.5-hr/day schedule, the values were 32 and 62%, respectively, indicating that repeated exposure to the longer schedule altered the route of elimination of CCl 4 . Regardless of the period of exposure, less than 8% of the inhaled 14 CCl 4 was excreted in the urine and less than 2% was exhaled in the breath as the 14 CO 2 metabolite. Approximately 97-98% of the 14 C activity in the expired air was 14 CCl 4 . The quantities of 14 C noted in the feces and urine suggest that more than 60% of the inhaled CCl 4 was metabolized. Elimination of 14 CCl 4 and 14 CO 2 in the breath followed a two-compartment, first-order pharmacokinetic model (r2 = 0.98). For rats exposed 8 hr/day and 11.5 hr/day for 2 weeks, the average half-lives for elimination of 14 CCl 4 in the breath for the fast (alpha) and slow (beta) phases averaged 96 and 455 min, and 89 and 568 min, respectively. The average alpha and beta half-lives for elimination of 14 CO 2 in the breath

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

    Science.gov (United States)

    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 reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH acid reflux episodes [42 vs 34 % (p 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 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.

  14. Performance of bias-correction methods for exposure measurement error using repeated measurements with and without missing data.

    Science.gov (United States)

    Batistatou, Evridiki; McNamee, Roseanne

    2012-12-10

    It is known that measurement error leads to bias in assessing exposure effects, which can however, be corrected if independent replicates are available. For expensive replicates, two-stage (2S) studies that produce data 'missing by design', may be preferred over a single-stage (1S) study, because in the second stage, measurement of replicates is restricted to a sample of first-stage subjects. Motivated by an occupational study on the acute effect of carbon black exposure on respiratory morbidity, we compare the performance of several bias-correction methods for both designs in a simulation study: an instrumental variable method (EVROS IV) based on grouping strategies, which had been recommended especially when measurement error is large, the regression calibration and the simulation extrapolation methods. For the 2S design, either the problem of 'missing' data was ignored or the 'missing' data were imputed using multiple imputations. Both in 1S and 2S designs, in the case of small or moderate measurement error, regression calibration was shown to be the preferred approach in terms of root mean square error. For 2S designs, regression calibration as implemented by Stata software is not recommended in contrast to our implementation of this method; the 'problematic' implementation of regression calibration although substantially improved with use of multiple imputations. The EVROS IV method, under a good/fairly good grouping, outperforms the regression calibration approach in both design scenarios when exposure mismeasurement is severe. Both in 1S and 2S designs with moderate or large measurement error, simulation extrapolation severely failed to correct for bias. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Decreased extracellular adenosine levels lead to loss of hypoxia-induced neuroprotection after repeated episodes of exposure to hypoxia.

    Directory of Open Access Journals (Sweden)

    Mei Cui

    Full Text Available Achieving a prolonged neuroprotective state following transient ischemic attacks (TIAs is likely to effectively reduce the brain damage and neurological dysfunction associated with recurrent stroke. HPC is a phenomenon in which advanced exposure to mild hypoxia reduces the stroke volume produced by a subsequent TIA. However, this neuroprotection is not long-lasting, with the effects reaching a peak after 3 days. Therefore, in this study, we investigated the use of multiple episodes of hypoxic exposure at different time intervals to induce longer-term protection in a mouse stroke model. C57BL/6 mice were subjected to different hypoxic preconditioning protocols: a single episode of HPC or five identical episodes at intervals of 3 days (E3d HPC or 6 days (E6d HPC. Three days after the last hypoxic exposure, temporary middle cerebral artery occlusion (MCAO was induced. The effects of these HPC protocols on hypoxia-inducible factor (HIF regulated gene mRNA expression were measured by quantitative PCR. Changes in extracellular adenosine concentrations, known to exert neuroprotective effects, were also measured using in vivo microdialysis and high pressure liquid chromatography (HPLC. Neuroprotection was provided by E6d HPC but not E3d HPC. HIF-regulated target gene expression increased significantly following all HPC protocols. However, E3d HPC significantly decreased extracellular adenosine and reduced cerebral blood flow in the ischemic region with upregulated expression of the adenosine transporter, equilibrative nucleoside transporter 1 (ENT1. An ENT1 inhibitor, propentofylline increased the cerebral blood flow and re-established neuroprotection in E3d HPC. Adenosine receptor specific antagonists showed that adenosine mainly through A1 receptor mediates HPC induced neuroprotection. Our data indicate that cooperation of HIF-regulated genes and extracellular adenosine is necessary for HPC-induced neuroprotection.

  16. Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

    OpenAIRE

    Hassina Khaldoun Oularbi

    2014-01-01

    Lambda-cyhalothrin (LCT) is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administ...

  17. Prevention of diabetes in NOD mice by repeated exposures to a contact allergen inducing a sub-clinical dermatitis

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Buschard, Karsten; Hansen, Axel Jacob Kornerup

    2010-01-01

    Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect...... of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two...

  18. Acid production in dental plaque after exposure to probiotic bacteria

    Directory of Open Access Journals (Sweden)

    Keller Mette K

    2012-10-01

    Full Text Available Abstract Background The increasing interest in probiotic lactobacilli in health maintenance has raised the question of potential risks. One possible side effect could be an increased acidogenicity in dental plaque. The aim of this study was to investigate the effect of probiotic lactobacilli on plaque lactic acid (LA production in vitro and in vivo. Methods In the first part (A, suspensions of two lactobacilli strains (L. reuteri DSM 17938, L. plantarum 299v were added to suspensions of supragingival dental plaque collected from healthy young adults (n=25. LA production after fermentation with either xylitol or fructose was analyzed. In the second part (B, subjects (n=18 were given lozenges with probiotic lactobacilli (L. reuteri DSM 17938 and ATCC PTA 5289 or placebo for two weeks in a double-blinded, randomized cross-over trial. The concentration of LA in supragingival plaque samples was determined at baseline and after 2 weeks. Salivary counts of mutans streptococci (MS and lactobacilli were estimated with chair-side methods. Results Plaque suspensions with L. reuteri DSM 17938 produced significantly less LA compared with L. plantarum 299v or controls (p Conclusion Lactic acid production in suspensions of plaque and probiotic lactobacilli was strain-dependant and the present study provides no evidence of an increase in plaque acidity by the supply of selected probiotic lactobacilli when challenged by fructose or xylitol. The study protocol was approved by The Danish National Committee on Biomedical Research Ethics (protocol no H-2-2010-112. Trial registration NCT01700712

  19. Repeated exposure to media messages encouraging parent-child communication about sex: differential trajectories for mothers and fathers.

    Science.gov (United States)

    Blitstein, Jonathan L; Evans, W Douglas; Davis, Kevin C; Kamyab, Kian

    2012-01-01

    To examine changes in parent-child communication related to sexual behavior after exposure to public health messages. Randomized, controlled trial that was part of precampaign message testing. Exposure occurred online or through DVDs mailed to participants and viewed on their personal computers. Data collection occurred via a secure Web site. Participants included parents (n  =  1969) living with a child age 10 to 14 years drawn from a nationally representative sample of U.S. households. Treatment participants were exposed to video, audio, and print advertisements that promoted the benefits of speaking to their children early and often about delaying initiation of sexual activity; messages also directed parents to an informational Web site. The dependent variable assessed frequency of parent-child communication related to sexual behavior. The primary independent variable was treatment assignment. Longitudinal growth modeling that included five waves of data. The trajectory of growth over time differed between fathers in the treatment group and fathers in the control group (F[1, 2357]  =  4.15; p groups. This study demonstrates that father-child and mother-child communication patterns differ over time in response to public health messages. Findings have implication for researchers developing health marketing campaigns.

  20. Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure.

    Science.gov (United States)

    Qin, Guangqiu; Tang, Song; Li, Shibin; Lu, Haoliang; Wang, Yanwu; Zhao, Peng; Li, Bin; Zhang, Jiehong; Peng, Liang

    2017-02-01

    The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO 3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg -1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO 3 up to 1 mg kg -1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO 3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO 3 treated rats. However, the comparisons between AgNPs and AgNO 3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017. © 2016 Wiley Periodicals, Inc.

  1. Comparison of personal air benzene and urine t,t-muconic acid as a benzene exposure surrogate during turnaround maintenance in petrochemical plants.

    Science.gov (United States)

    Koh, Dong-Hee; Lee, Mi-Young; Chung, Eun-Kyo; Jang, Jae-Kil; Park, Dong-Uk

    2018-04-12

    Previous studies have shown that biomarkers of chemicals with long half-lives may be better surrogates of exposure for epidemiological analyses, leading to less attenuation of the exposure-disease association, than personal air samples. However, chemicals with short half-lives have shown inconsistent results. In the present study, we compared pairs of personal air benzene and its short-half-life urinary metabolite trans,trans-muconic acid (t,t-MA), and predicted attenuation bias of theoretical exposure-disease association. Total 669 pairs of personal air benzene and urine t,t-MA samples were taken from 474 male workers during turnaround maintenance operations held in seven petrochemical plants. Maintenance jobs were classified into 13 groups. Variance components were calculated for personal air benzene and urine t, t-MA separately to estimate the attenuation of the theoretical exposure-disease association. Personal air benzene and urine t, t-MA showed similar attenuation of the theoretical exposure-disease association. Analyses for repeated measurements showed similar results, while in analyses for values above the limits of detection (LODs), urine t, t-MA showed less attenuation of the theoretical exposure-disease association than personal air benzene. Our findings suggest that there may be no significant difference in attenuation bias when personal air benzene or urine t,t-MA is used as a surrogate for benzene exposure.

  2. Development of immunity against viral and bacterial antigens after repeated exposures to suberythemal doses of ultraviolet light

    Directory of Open Access Journals (Sweden)

    S. A. Snopov

    2012-01-01

    Full Text Available The effects of ultraviolet (UV radiation on human infectious immunity are not well studied. On the one hand, solar and artificial UU sources have been shown to change cytokine levels in human skin, lymphocyte subpopulation counts in parepheral blood, lymphocyte DNA synthesis and prolifarative response to mitogens. On the other hand, there are just only one or two observations suggesting an influence of UV radiation on human infection course. For instance, UV irradiations have been reported to induce a reccurence of orofacial vesicular lesions caused by herpes siplex virus. Moreover, there is a lack of data concerning immune effects of suberythtemal doses of UV in spite of a long history of using them by Russian prophylactic medicine. In this work we questioned whether such suberythemal UV exposures can affect the immune responses of children to infectious conjunctivitis, to simultaneous measles and polio vaccinations and to simultaneous polio and diphtheria-tetanus vaccinations. In peripheral blood of vaccinated children we examined leukocyte counts (monocytes, neutrophils, eosinophils, lymphocytes, percentages of lymphocyte subpopulations (CD3+, CD20+, CD4+, CD8+, CD25+, HLADR+, concentrations of cytokines (IL-1 beta, TNF-alpha, IFN- amma и IL-10, DNA-synthetic activity of lymphocytes and titres of antibodies against measles and diphtheria toxin. We observed no local or systemic reactions to the vaccines in the UV-group while a moderate rise in body temperature occured in several children from unexposed group. In the blood of childeren from UV-group we found increases in CD25+ и HLADR+ cell percentages, IL- 1 beta and IL-10 concentrations, PWMinduced DNA synthesis in mononuclears, and no decreases in formation of antibodies against measles and diphreria. We concluded that suberythemal UV exposures of children modulated their further responses to imminisations perhaps through the activation of a T helper 2-like

  3. The rate of repeating X-rays in the medical centers of Jenin District/Palestine and how to reduce patient exposure to radiation

    Science.gov (United States)

    Assi, Abed Al Nasser

    2018-03-01

    Reduction of the patient's received radiation dose to as low as reasonably achievable (ALARA) is based on recommendations of radiation protection organizations such as the International Commission on Radiological Protection (ICRP) and the National Radiological Protection Board (NRPB). The aim of this study was to explore the frequency and characteristics of rejected / repeated radiographic films in governmental and private centers in Jenin city. The radiological centers were chosen based on their high volume of radiographic studies. The evaluation was carried out over a period of four months. The collected data were compiled at the end of each week and entered into a computer for analysis at the end of study. Overall 5000 films (images) were performed in four months, The average repeat rate of radiographic images was 10% (500 films). Repetition rate was the same for both thoracic and abdominal images (42%). The main reason for repeating imaging was inadequate imaging quality (58.2%) and poor film processing (38%). Human error was the most likely reason necessitating the repetition of the radiographs (48 %). Infant and children groups comprised 85% of the patient population that required repetition of the radiographic studies. In conclusion, we have a higher repetition rate of imaging studies compared to the international standards (10% vs. 4-6%, respectively). This is especially noticeable in infants and children, and mainly attributed to human error in obtaining and processing images. This is an important issue that needs to be addressed on a national level due to the ill effects associated with excessive exposure to radiation especially in children, and to reduce cost of the care delivered.

  4. Disposition of Lead (Pb) in Saliva and Blood of Sprague-Dawley Rats Following a Single or Repeated Oral Exposure to Pb-Acetate

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Lin, Yuehe; Weitz, Karl K.; Wu, Hong; Gies, Richard A.; Moore, Dean A.; Yantasee, Wassana

    2006-05-01

    Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100 mg Pb-acetate/kg body weight in rats or {approx}1-week after 5 sequential daily oral gavage doses of 1, 10, or 100 mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and ?-amylase activity were also determined. At specified times post-dosing groups of animals were anethetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to PB-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r2=0.922) between the average Pb concentrations in these biological matrices which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24 hr post-dosing and a decrease in ?-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These

  5. Response of Chlamydomonas reinhardtii to naphthenic acid exposure

    Energy Technology Data Exchange (ETDEWEB)

    Goff, K.; Wilson, K. [Saskatchewan Univ., Saskatoon, SK (Canada); Headley, J. [Environment Canada, Ottawa, ON (Canada)

    2010-07-01

    This study examined the feasibility of using a model organism for the algal bioremediation of oil sands process water (OSPW), a highly toxic mixture of sediments, bitumen, ions, and organic and inorganic compounds. Naphthenic acids (NAs) are a contaminant class of particular concern. Bioremediation techniques may mitigate toxicity of OSPW in general, and NAs in particular. Although most studies on the biodegradation of NAs focus on the role of bacteria, fungi, and emergent macrophytes, studies have indicated that algae may also play a key role through direct degradation, biosequestration, or photosynthetic aeration of waters to promote other biological reactions. Chlamydomonas frigida is of particular interest, but no cultures are currently available. Therefore, this study used C. reinhardtii, a well-characterized model organism, to begin analysis of potential algal bioremediation of OSPW. Cultures of C. reinhardtii were grown heterotrophically in nutrient media spiked with a dilution series of NAs. Culture densities were measured to compile growth curves over time, changes in rate of growth, and survivability. Negative ion electrospray mass spectrometry was used to determine the concentration of NAs in solution in relation to growth rate and culture density. The study determined the tolerance of C. reinhardtii to NAs. A mechanism for this tolerance was then proposed.

  6. Comparative electrophysiological evaluation of hippocampal function following repeated inhalation exposures to JP-8, Jet A, JP-5, and the synthetic Fischer Tropsch fuel.

    Science.gov (United States)

    Rohan, Joyce G; McInturf, Shawn M; Miklasevich, Molly K; Gut, Chester P; Grimm, Michael D; Reboulet, James E; Howard, William R; Mumy, Karen L

    2018-01-01

    Exposure to fuels continues to be a concern in both military and general populations. The aim of this study was to examine effects of in vivo rat repeated exposures to different types of jet fuel utilizing microelectrode arrays for comparative electrophysiological (EP) measurements in hippocampal slices. Animals were exposed to increasing concentrations of four jet fuels, Jet Propellant (JP)-8, Jet A, JP-5, or synthetic Fischer Tropsch (FT) fuel via whole-body inhalation for 20 d (6 hr/d, 5 d/week for 28 d) and synaptic transmission as well as behavioral performance were assessed. Our behavioral studies indicated no significant changes in behavioral performance in animals exposed to JP-8, Jet A, or JP-5. A significant deviation in learning pattern during the Morris water maze task was observed in rats exposed to the highest concentration of FT (2000 mg/m 3 ). There were also significant differences in the EP profile of hippocampal neurons from animals exposed to JP-8, Jet A, JP-5, or FT compared to control air. However, these differences were not consistent across fuels or dose dependent. As expected, patterns of EP alterations in brain slices from JP-8 and Jet A exposures were more similar compared to those from JP-5 and FT. Further longitudinal investigations are needed to determine if these EP effects are transient or persistent. Such studies may dictate if and how one may use EP measurements to indicate potential susceptibility to neurological impairments, particularly those that result from inhalation exposure to chemicals or mixtures.

  7. Corrigendum to "Acute and repeated exposure to social stress reduces gut microbiota diversity in Syrian hamsters" [Behav. Brain Res. 345 (2018) 39-48].

    Science.gov (United States)

    Partrick, Katherine A; Chassaing, Benoit; Beach, Linda Q; McCann, Katharine E; Gewirtz, Andrew T; Huhman, Kim L

    2018-08-01

    Social stress can promote a variety of neuropsychiatric illnesses, many of which have a high co-morbidity with gastrointestinal disorders. Recent data indicate that gastrointestinal microbiota can affect their host's brain and behavior. Syrian hamsters are ideal subjects for social stress research because they are territorial, aggressive, and rapidly form dominant/subordinate relationships. The purpose of this study was to determine if exposure to social stress in hamsters alters gut microbiota in dominants and subordinates after an agonistic encounter and if pre-stress gut microbiota composition is correlated with the outcome of such a conflict. Microbiota composition was assessed via 16S mRNA Illumina sequencing on fecal samples. One agonistic encounter caused a decrease in alpha diversity in both dominant and subordinate animals with a more pronounced decrease after repeated encounters. PERMANOVA analysis of the unweighted unifrac distance revealed a distinct change in beta diversity after one and nine encounters in both dominants and subordinates. Linear discriminant analysis (LEfSE) showed bacteria from the order Lactobacillales were significantly reduced following social stress in both dominants and subordinates, and both groups exhibited increases in phyla Bacteroidetes and decreases in phyla Firmicutes following repeated encounters. LEfSE analysis on samples collected prior to social interaction revealed that some microbial taxa were correlated with a hamster achieving dominant or subordinate status. These data suggest that even an acute exposure to social stress can impact gastrointestinal microbiota and that the state of the microbial community before social stress may predict dominant/subordinate status following a subsequent agonistic encounter. Copyright © 2018.

  8. Twenty-three generations of mice bidirectionally selected for open-field thigmotaxis: selection response and repeated exposure to the open field.

    Science.gov (United States)

    Leppänen, Pia K; Ravaja, N; Ewalds-Kvist, S B M

    2006-03-01

    We examined: (a) the response to bidirectional selection for open-field (OF) thigmotaxis in mice for 23 generations and (b) the effects of repeated exposure (during 5 days) on different OF behaviors in the selectively bred high OF thigmotaxis (HOFT) and low OF thigmotaxis (LOFT) mice. A total of 2049 mice were used in the study. Prior to the testing in the selection experiment, the mice were exposed to the OF apparatus for approximately 2 min on each of 4 consecutive days. Thus, the selection was based on the scores registered on the 5th day after the four habituation periods. The HOFT mice were more thigmotactic than the LOFT mice in almost each generation. The HOFT mice also tended to rear less than the LOFT mice, which was explained by the inverse relationship between emotionality and exploratory tendencies. The lines did not generally differ in ambulation. Sex differences were found in thigmotaxis, ambulation, and rearing. In the repeated exposure experiment, the development of nine different OF behaviors across the 5 days of testing was addressed. Both lines ambulated, explored, and reared most on the 1st, 4th, and 5th days. Grooming and radial latency decreased and thigmotaxis increased linearly across the testing days. Line differences were found in ambulation, exploration, grooming, and rearing, while sex differences were manifested in ambulation and exploration. The line difference in thigmotaxis was evident only on the 5th day. Temporal changes were partially at variance with the general assumptions. OF thigmotaxis was found to be a powerful characteristic for producing two diverging lines of mice.

  9. Repeated exposure to Lutzomyia intermedia sand fly saliva induces local expression of interferon-inducible genes both at the site of injection in mice and in human blood.

    Science.gov (United States)

    Weinkopff, Tiffany; de Oliveira, Camila I; de Carvalho, Augusto M; Hauyon-La Torre, Yazmin; Muniz, Aline C; Miranda, Jose Carlos; Barral, Aldina; Tacchini-Cottier, Fabienne

    2014-01-01

    During a blood meal, Lutzomyia intermedia sand flies transmit Leishmania braziliensis, a parasite causing tegumentary leishmaniasis. In experimental leishmaniasis, pre-exposure to saliva of most blood-feeding sand flies results in parasite establishment in absence of any skin damages in mice challenged with dermotropic Leishmania species together with saliva. In contrast, pre-immunization with Lu. intermedia salivary gland sonicate (SGS) results in enhanced skin inflammatory exacerbation upon co-inoculation of Lu. intermedia SGS and L. braziliensis. These data highlight potential unique features of both L. braziliensis and Lu. intermedia. In this study, we investigated the genes modulated by Lu. intermedia SGS immunization to understand their potential impact on the subsequent cutaneous immune response following inoculation of both SGS and L. braziliensis. The cellular recruitment and global gene expression profile was analyzed in mice repeatedly inoculated or not with Lu. intermedia. Microarray gene analysis revealed the upregulation of a distinct set of IFN-inducible genes, an immune signature not seen to the same extent in control animals. Of note this INF-inducible gene set was not induced in SGS pre-immunized mice subsequently co-inoculated with SGS and L. braziliensis. These data suggest the parasite prevented the upregulation of this Lu. intermedia saliva-related immune signature. The presence of these IFN-inducible genes was further analyzed in peripheral blood mononuclear cells (PBMCs) sampled from uninfected human individuals living in a L. braziliensis-endemic region of Brazil thus regularly exposed to Lu. intermedia bites. PBMCs were cultured in presence or absence of Lu. intermedia SGS. Using qRT-PCR we established that the IFN-inducible genes induced in the skin of SGS pre-immunized mice, were also upregulated by SGS in PBMCs from human individuals regularly exposed to Lu. intermedia bites, but not in PBMCs of control subjects. These data demonstrate

  10. Repeated stressor exposure enhances contextual fear memory in a beta-adrenergic receptor-dependent process and increases impulsivity in a non-beta receptor-dependent fashion.

    Science.gov (United States)

    Camp, Robert M; Johnson, John D

    2015-10-15

    Memory formation is promoted by stress via the release of norepinephrine and stimulation of beta-adrenergic receptors (β-ARs). Previous data demonstrate that repeated stressor exposure increases norepinephrine turnover and β-AR signaling within the amygdala, which led to the hypothesis that some stress-induced behavioral changes are likely due to facilitated associative learning. To test this, Fischer rats were exposed to chronic mild stress for four days. On day 5, subjects (including non-stressed controls) were injected with the beta-blocker propranolol or vehicle prior to conditioning in an operant box (animals receive two mild foot shocks) or passive avoidance apparatus (animals received a foot shock upon entry into the dark chamber). Twenty-four hours later, subjects were returned to the operant box for measurement of freezing or returned to the passive avoidance apparatus for measurement of latency to enter the dark chamber. Subjects were also tested in an open field to assess context-independent anxiety-like behavior. Animals exposed to chronic stress showed significantly more freezing behavior in the operant box than did controls, and this exaggerated freezing was blocked by propranolol during the conditioning trial. There was no effect of stress on behavior in the open field. Unexpectedly, retention latency was significantly reduced in subjects exposed to chronic stress. These results indicate that chronic exposure to stress results in complex behavioral changes. While repeated stress appears to enhance the formation of fearful memories, it also results in behavioral responses that resemble impulsive behaviors that result in poor decision-making. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  12. Improving lactic acid productivity from wheat straw hydrolysates by membrane integrated repeated batch fermentation under non-sterilized conditions

    DEFF Research Database (Denmark)

    Zhang, Yuming; Chen, Xiangrong; Qi, Benkun

    2014-01-01

    to eliminate the sequential utilization of mixed sugar and feedback inhibition during batch fermentation, membrane integrated repeated batch fermentation (MIRB) was used to improve LA productivity. With MIRB, a high cell density was obtained and the simultaneous fermentation of glucose, xylose and arabinose...

  13. Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Nielsen, Olav W; Lund, Allan M

    2013-01-01

    Several episodes of sudden death among young Faroese individuals have been associated with primary carnitine deficiency (PCD). Patients suffering from PCD have low carnitine levels and can present with metabolic and/or cardiac complications. Pivalic acid exposure decreases carnitine levels...

  14. [Nickel exposure to A549 cell damage and L-ascorbic acid interference effect].

    Science.gov (United States)

    Fu, Yao; Wang, Yue; Dan, Han; Zhang, Lin; Ma, Wenhan; Pan, Yulin; Wu, Yonghui

    2015-05-01

    Studying different concentrations of nickel smelting smoke subjects of human lung adenocarcinoma cells (A549) carcinogenic effects, discusses the influence of L-ascorbic acid protection. The A549 cells were divided into experimental and L-ascorbic acid in the intervention group. Plus exposure group concentration of nickel refining dusts were formulated 0.00, 6.25, 12.50, 25.00, 50.00, 100.00 µg/ml suspension, the intervention group on the basis of the added exposure group containing L-ascorbic acid (100 mmol/L), contact 24 h. Detection of cell viability by MTT assay. When the test substance concentration select 0.00, 25.00, 50.00, 100.00 µg/ml experiment for internal Flou-3 fluorescent probe to detect cell Ca²⁺ concentration, within DCFH-DA detect intracellular reactive oxygen (ROS) content, real-time quantitative PCR (real time, in the RT-PCR) was used to detect cell HIF-1α gene expression. With the increase of concentration, subjects increased cell growth inhibition rate, intracellular Ca²⁺ concentration increases, ROS content increased, HIF-1α gene expression increased, differences were statistically significant (P nickel exposure damage to cells. With subjects following exposure to nickel concentration increased, its effect on A549 cell damage increases, L-ascorbic acid cell damage caused by nickel has certain protective effect.

  15. Food acceptability in field studies with US army men and women: relationship with food intake and food choice after repeated exposures.

    Science.gov (United States)

    de Graaf, Cees; Kramer, F Matthew; Meiselman, Herbert L; Lesher, Larry L; Baker-Fulco, Carol; Hirsch, Edward S; Warber, John

    2005-02-01

    Laboratory data with single exposures showed that palatability has a positive relationship with food intake. The question addressed in this study is whether this relationship also holds over repeated exposures in non-laboratory contexts in more natural environments. The data were collected in four field studies, lasting 4-11 days with 307 US Army men and 119 Army women, and comprised 5791 main meals and 8831 snacks in total. Acceptability was rated on the nine point hedonic scale, and intake was registered in units of 1/4, 1/2, 3/4, or 1 or more times of the provided portion size. Correlation coefficients between individual acceptability ratings and intakes varied from 0.22 to 0.62 for the main meals (n=193-2267), and between 0.13 and 0.56 for the snacks (n=304-2967). The likelihood of choosing a meal for the second time was positively related to the acceptability rating of the meal when it was consumed for the first time. The results reinforce the importance of liking in food choice and food intake/choice behavior. However, the magnitude of the correlation coefficients between acceptability ratings and food intake suggest that environmental factors also have an important role in determining intake and choice.

  16. INFLUENCE OF MORINGA OLEIFERA (DRUM-STICK FRUIT EXTRACT ON HAEMATOLOGICAL PROFILE FOLLOWING REPEATED EXPOSURE TO LOW LEVELS OF ARSENIC THROUGH FEED ON RATS

    Directory of Open Access Journals (Sweden)

    Vaibhav R. Pachade

    2012-01-01

    Full Text Available Effect of Moringa oleifera fruits hot methanolic extract (MFE, if any, in minimizing the adverse reactions of repeated exposure to arsenic trioxide (AT in feed was investigated in Wistar rats with reference to haematological profile. Three groups of rats each containing 10 (5male+5female were used. The group I served as negative control. Rats of group II were fed arsenic trioxide (AT alone @ 100 ppm in feed while those of group III simultaneously received AT (@100 ppm and MFE (50 mg/kg/day for 28 days. Blood samples were collected from retroorbital plexus for estimation of hematological parameters (haemoglobin, PCV, TEC, MCH, MCHC, MCV of different groups on 0 day, 15th day and 29th day respectively. Exposure to AT through feed in group II resulted in significant (P<0.05 decrease in haemoglobin, TEC and MCHC, accompanied by increased MCV, with no significant alteration of PCV or MCH of the rats. While rats of group III treated with AT (@100 ppm and MFE (50 mg/kg/day also resulted in same consequences as it was in group II but it was slightly less than that of group II suggesting of mild non significant protective effect.

  17. Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide

    International Nuclear Information System (INIS)

    Schlesinger, R.B.; Driscoll, K.E.; Gunnison, A.F.; Zelikoff, J.T.

    1990-01-01

    Ozone (O 3 ) and nitrogen dioxide (NO 2 ) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O 3 at 0.1, 0.3, or 1 ppm; NO 2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O 3 and 3 ppm NO 2 . Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O 3 . Exposure to 10 ppm NO 2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO 2 and depressed following 3 and 10 ppm. The O 3 /NO 2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O 3 . This study has demonstrated that acute exposure to either O 3 or NO 2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively

  18. Stress responses in juvenile pacu (Piaractus mesopotamicus submitted to repeated air exposure - DOI: 10.4025/actascianimsci.v30i1.3618 Stress responses in juvenile pacu (Piaractus mesopotamicus submitted to repeated air exposure - DOI: 10.4025/actascianimsci.v30i1.3618

    Directory of Open Access Journals (Sweden)

    Leonardo Susumu Takahashi

    2008-06-01

    Full Text Available Juvenis de pacu (5,2 Pacu juveniles (5.2 ± 1.5 g were submitted to two one-minute air exposures in a 24 h interval, and sampled before the exposure (control and 5, 15, 30 and 60 min, 24 and 48 h afterwards for whole-body cortisol, sodium, potassium and calcium ion concentrations. For the first air exposure, there was a trend of increased cortisol concentration after 15 min, whereas in the second air exposure, the cortisol concentration increased significantly within 5 min after stress was induced. Sodium ion concentration increased significantly 24 h after both air exposures. Potassium concentration presented fluctuations over the experimental period. Calcium ion concentration increased progressively from 5 to 30 min, in both air exposures. The repeated air exposures exacerbated the cortisol response, but they did not affect the recovery ability of pacu over the experimental period. Additionally, the whole-body cortisol measurement might be a reliable indicator of stress, when sampled fish are smaller and blood volumes are very low, making samples inadequate for analysis1,5 g foram submetidos a duas exposições aéreas de um minuto, em intervalo de 24 horas, e amostrados antes da exposição (controle e 5, 15, 30 e 60 min, 24 e 48 horas depois para análise da concentração corporal de cortisol e dos íons sódio, potássio e cálcio. Na primeira exposição, os peixes apresentaram concentrações de cortisol aumentadas a partir de 15 min, embora não diferissem estatisticamente do controle. Na segunda exposição, a concentração de cortisol aumentou significativamente aos 5 min, retornando às concentrações equivalentes às dos peixes-controle em 30 min. A concentração do íon sódio aumentou significativamente 24 horas depois das duas exposições aéreas. A concentração do íon potássio apresentou flutuações durante o experimento, enquanto a do cálcio apresentou-se reduzida aos 5 min, aumentando gradativamente até os 30 min

  19. Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

    Science.gov (United States)

    Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

    2014-02-07

    Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

  20. Estimating human exposure to perfluoroalkyl acids via solid food and drinks : Implementation and comparison of different dietary assessment methods

    NARCIS (Netherlands)

    Papadopoulou, Eleni; Poothong, Somrutai; Koekkoek, Jacco; Lucattini, Luisa; Padilla-Sánchez, Juan Antonio; Haugen, Margaretha; Herzke, Dorte; Valdersnes, Stig; Maage, Amund; Cousins, Ian T.; Leonards, Pim E.G.; Småstuen Haug, Line

    2017-01-01

    Background Diet is a major source of human exposure to hazardous environmental chemicals, including many perfluoroalkyl acids (PFAAs). Several assessment methods of dietary exposure to PFAAs have been used previously, but there is a lack of comparisons between methods. Aim To assess human exposure

  1. Behavioural responses of Acroneuria lycoria (Ins. Plecopt. ) Larvae to acute and chronic acid exposure

    Energy Technology Data Exchange (ETDEWEB)

    McNichol, R.E.; Scherer, E.

    1987-01-01

    This study was designed to investigate the responses of a perlid stonefly, Acroneuria lycorias (Newman), to acute and chronic acid exposure. Larvae of this species are common in streams and rivers impacted by acidic precipitation. It is also a suggested standard toxicity test species, which in previous studies has proven to be very sensitive to some toxicants. The effects of acute and chronic acid exposure on the locomotor activity, microdistribution, and drift behaviour of the stonefly larvae were studied in laboratory streams. When subjected to a reduction in pH from 8.1 to 2.5 over an 8-h period, larvae showed little behavioural response down to pH 4.2. As the pH fell to 3.0, head-rubbing activity appeared and increased in frequency. At pH 3.0 and below, larvae showed increased gill-ventilatory movements and locomotor activity. Most larvae died within 14 h of exposure to pH 2.5; however, they did not abandon their preferred refuges before death. Larvae exposed to 5 pH levels between 4.5 and 8.2 for 30-50 d displayed no significant changes in locomotor activity, drift behaviour or microdistribution when compared to control animals. Results indicate that later instar larvae of this species are relatively acid tolerant. 29 refs 4 figs 1 tab

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

    Science.gov (United States)

    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.

  3. The Effects of a Single Whole-Body Cryotherapy Exposure on Physiological, Performance, and Perceptual Responses of Professional Academy Soccer Players After Repeated Sprint Exercise.

    Science.gov (United States)

    Russell, Mark; Birch, Jack; Love, Thomas; Cook, Christian J; Bracken, Richard M; Taylor, Tom; Swift, Eamon; Cockburn, Emma; Finn, Charlie; Cunningham, Daniel; Wilson, Laura; Kilduff, Liam P

    2017-02-01

    Russell, M, Birch, J, Love, T, Cook, CJ, Bracken, RM, Taylor, T, Swift, E, Cockburn, E, Finn, C, Cunningham, D, Wilson, L, and Kilduff, LP. The effects of a single whole-body cryotherapy exposure on physiological, performance, and perceptual responses of professional academy soccer players after repeated sprint exercise. J Strength Cond Res 31(2): 415-421, 2017-In professional youth soccer players, the physiological, performance, and perceptual effects of a single whole-body cryotherapy (WBC) session performed shortly after repeated sprint exercise were investigated. In a randomized, counterbalanced, and crossover design, 14 habituated English Premier League academy soccer players performed 15 × 30 m sprints (each followed by a 10 m forced deceleration) on 2 occasions. Within 20 minutes of exercise cessation, players entered a WBC chamber (Cryo: 30 seconds at -60° C, 120 seconds at -135° C) or remained seated (Con) indoors in temperate conditions (∼25° C). Blood and saliva samples, peak power output (countermovement jump), and perceptual indices of recovery and soreness were assessed pre-exercise and immediately, 2-hour and 24-hour postexercise. When compared with Con, a greater testosterone response was observed at 2-hour (+32.5 ± 32.3 pg·ml, +21%) and 24-hour (+50.4 ± 48.9 pg·ml, +28%) postexercise (both P = 0.002) in Cryo (trial × treatment interaction: P = 0.001). No between-trial differences were observed for other salivary (cortisol and testosterone/cortisol ratio), blood (lactate and creatine kinase), performance (peak power output), or perceptual (recovery or soreness) markers (all trial × treatment interactions: P > 0.05); all of which were influenced by exercise (time effects: all P ≤ 0.05). A single session of WBC performed within 20 minutes of repeated sprint exercise elevated testosterone concentrations for 24 hours but did not affect any other performance, physiological, or perceptual measurements taken. Although unclear, WBC may be

  4. Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

    Science.gov (United States)

    Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

    2014-01-01

    Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

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

    Science.gov (United States)

    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

  6. Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P.

    2004-01-01

    The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

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

    Science.gov (United States)

    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.

  8. Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Triggered Isothermal Amplification for Site-Specific Nucleic Acid Detection.

    Science.gov (United States)

    Huang, Mengqi; Zhou, Xiaoming; Wang, Huiying; Xing, Da

    2018-02-06

    A novel CRISPR/Cas9 triggered isothermal exponential amplification reaction (CAS-EXPAR) strategy based on CRISPR/Cas9 cleavage and nicking endonuclease (NEase) mediated nucleic acids amplification was developed for rapid and site-specific nucleic acid detection. CAS-EXPAR was primed by the target DNA fragment produced by cleavage of CRISPR/Cas9, and the amplification reaction performed cyclically to generate a large number of DNA replicates which were detected using a real-time fluorescence monitoring method. This strategy that combines the advantages of CRISPR/Cas9 and exponential amplification showed high specificity as well as rapid amplification kinetics. Unlike conventional nucleic acids amplification reactions, CAS-EXPAR does not require exogenous primers, which often cause target-independent amplification. Instead, primers are first generated by Cas9/sgRNA directed site-specific cleavage of target and accumulated during the reaction. It was demonstrated this strategy gave a detection limit of 0.82 amol and showed excellent specificity in discriminating single-base mismatch. Moreover, the applicability of this method to detect DNA methylation and L. monocytogenes total RNA was also verified. Therefore, CAS-EXPAR may provide a new paradigm for efficient nucleic acid amplification and hold the potential for molecular diagnostic applications.

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

    Science.gov (United States)

    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

  10. Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

    Science.gov (United States)

    Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela

    2014-06-01

    A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. © The Author(s) 2014.

  11. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  12. Comparative analysis of transcriptomic responses to repeated-dose exposure to 2-MCPD and 3-MCPD in rat kidney, liver and testis.

    Science.gov (United States)

    Buhrke, Thorsten; Schultrich, Katharina; Braeuning, Albert; Lampen, Alfonso

    2017-08-01

    3-Chloro-1,2-propanediol (3-MCPD) and its isomer 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants present in oil- and fat-containing foodstuff. Kidney and testes are among the main target organs of 3-MCPD. Almost no data on 2-MCPD toxicity are available. Here, transcriptomic responses following repeated-dose exposure of rats to non-toxic doses of 10 mg/kg body weight per day 2-MCPD or 3-MCPD for 28 days were characterized by microarray analysis of kidney, liver, and testes. 3-MCPD exerted more pronounced effects than 2-MCPD in all organs. The limited overlap between the datasets indicates that 2-MCPD and 3-MCPD do not share the same molecular mechanisms of toxicity. By combining transcriptomic data with datasets on proteomic regulation by 3-MCPD, a comprehensive view on 3-MCPD-induced regulation of glucose utilization and oxidative stress response was developed. Bioinformatic analyses revealed that Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling is likely to be involved in mediating the oxidative stress response to 3-MCPD. In summary, this study for the first time presents data on alterations in global gene expression by two important food contaminants, 2-MCPD and 3-MCPD. Data demonstrate profound differences between the effects of the two compounds and substantially broaden our knowledge on molecular details of 3-MCPD-induced disturbance of glucose utilization and redox balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The Queensland study of Melanoma: Environmental and Genetic Associations (Q-MEGA). Study design, baseline characteristics, and repeatability of phenotype and sun exposure measures

    Science.gov (United States)

    Baxter, Amanda J.; Hughes, Maria Celia; Kvaskoff, Marina; Siskind, Victor; Shekar, Sri; Aitken, Joanne F.; Green, Adele C.; Duffy, David L.; Hayward, Nicholas K.; Martin, Nicholas G.; Whiteman, David C.

    2013-01-01

    Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia which has the world’s highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland study of Melanoma: Environmental and Genetic Associations, which followed-up four population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. 3,471 participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002–2005. Updated data on environmental and phenotypic risk factors, and 2,777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from six to 17 years later, are also described. PMID:18361720

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

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Silberberg, Gilad; Markram, Henry

    2008-01-01

    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...

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

    Science.gov (United States)

    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

  16. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men.

    Science.gov (United States)

    McGinley, Cian; Bishop, David J

    2016-12-01

    McGinley C, Bishop DJ. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men. J Appl Physiol 121: 1290-1305, 2016. First published October 14, 2016; doi:10.1152/japplphysiol.00630.2016-This study measured the adaptive response to exercise training for each of the acid-base transport protein families, including providing isoform-specific evidence for the monocarboxylate transporter (MCT)1/4 chaperone protein basigin and for the electrogenic sodium-bicarbonate cotransporter (NBCe)1. We investigated whether 4 wk of work-matched, high-intensity interval training (HIIT), performed either just above the lactate threshold (HIITΔ20; n = 8), or close to peak aerobic power (HIITΔ90; n = 8), influenced adaptations in acid-base transport protein abundance, nonbicarbonate muscle buffer capacity (βm in vitro ), and exercise capacity in active men. Training intensity did not discriminate between adaptations for most proteins measured, with abundance of MCT1, sodium/hydrogen exchanger (NHE) 1, NBCe1, carbonic anhydrase (CA) II, and CAXIV increasing after 4 wk, whereas there was little change in CAIII and CAIV abundance. βm in vitro also did not change. However, MCT4 protein content only increased for HIITΔ20 [effect size (ES): 1.06, 90% confidence limits × / ÷ 0.77], whereas basigin protein content only increased for HIITΔ90 (ES: 1.49, × / ÷ 1.42). Repeated-sprint ability (5 × 6-s sprints; 24 s passive rest) improved similarly for both groups. Power at the lactate threshold only improved for HIITΔ20 (ES: 0.49; 90% confidence limits ± 0.38), whereas peak O 2 uptake did not change for either group. Detraining was characterized by the loss of adaptations for all of the proteins measured and for repeated-sprint ability 6 wk after removing the stimulus of HIIT. In conclusion, 4 wk of HIIT induced improvements in each of the acid-base transport protein families, but, remarkably, a 40

  17. Deterioration of autoimmune condition associated with repeated injection of dextranomer/hyaluronic acid copolymer: A case report

    Directory of Open Access Journals (Sweden)

    Kazuto Suda

    2016-01-01

    Full Text Available A 6-year-old girl underwent ureterocystoneostomy (UCN because of left flank pain due to delayed onset of ureteral stenosis one and a half years after endoscopic dextranomer/hyaluronic acid copolymer (Deflux injection for the treatment of vesicoureteral reflux (VUR. Histopathological examination indicated chronic inflammation with abundant eosinophils characteristic of a reaction to Deflux. Several autoimmune diseases developed during the treatment for ureteral stenosis. First, 2 weeks prior to the onset of left flank pain, she was diagnosed as having systemic lupus erythematosus. Finally, she died of pulmonary hemorrhage due to thrombotic thrombocytopenic purpura 4 months after UCN. The fatal outcome in this case was suspected to be caused by autoimmune syndrome induced by adjuvants, which in this case was the hyaluronic acid polymer injected into the ureteric orifice for the treatment of VUR.

  18. The effect of humic acids on biodegradation of polycyclic aromatic hydrocarbons depends on the exposure regime

    International Nuclear Information System (INIS)

    Tejeda-Agredano, Maria-Carmen; Mayer, Philipp; Ortega-Calvo, Jose-Julio

    2014-01-01

    Binding of polycyclic aromatic hydrocarbons (PAHs) to dissolved organic matter (DOM) can reduce the freely dissolved concentration, increase apparent solubility or enhance diffusive mass transfer. To study the effects of DOM on biodegradation, we used phenanthrene and pyrene as model PAHs, soil humic acids as model DOM and a soil Mycobacterium strain as a representative degrader organism. Humic acids enhanced the biodegradation of pyrene when present as solid crystals but not when initially dissolved or provided by partitioning from a polymer. Synchronous fluorescence spectrophotometry, scintillation counting and a microscale diffusion technique were applied in order to determine the kinetics of dissolution and diffusive mass transfer of pyrene. We suggest that humic acids can enhance or inhibit biodegradation as a result of the balance of two opposite effects, namely, solubilization of the chemicals on the one hand and inhibition of cell adhesion to the pollutant source on the other. Highlights: • Humic acids can enhance the biodegradation of PAHs. • The enhancement depends on how the bacteria are exposed to PAHs. • Humic acids stimulate if PAHs are provided by dissolution form crystals. • An inhibition occurs if PAHs are provided by partitioning from a silicone. • The balance between enhanced dissolution and decreased adhesion is the cause. -- Humic acids cause opposite effects on biodegradation of PAHs depending on the exposure regime

  19. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

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

    Science.gov (United States)

    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.

  1. Assessing the survival of MRC5 and a549 cell lines upon exposure to pyruvic Acid, sodium citrate and sodium bicarbonate - biomed 2013.

    Science.gov (United States)

    Farah, Ibrahim O; Lewis, Veshell L; Ayensu, Wellington K; Cameron, Joseph A

    2013-01-01

    Lung cancer is among the most prevalent and deadly cancers in United States. In general, cancer cells are known to exhibit higher rates of glycolysis in comparison to normal cells. In attempting to exploit this unique cancer-dependent ATP generation phenomenon, it was our hypothesis that upon exposure to organic inhibitors of glycolysis, cancer cells would not survive normally and that their growth and viability would be vastly decreased; essential glycolytic ATP production will be exhausted to the point of collapsing energy utilization. Furthermore, we hypothesize that no negative effect would be seen with exposures to organic inhibitors for normal lung cells. The human lung fibroblast MRC-5 and the human A549 alveolar epithelial cell lines were used as in vitro models of normal lung and lung cancers respectively. Using standard methods, both cell lines were maintained and exposed to pyruvic acid, sodium citrate and sodium bicarbonate reagents at concentration levels ranging from 31.3-2,000 µg/ml in 96 well plates in quadruplets and experiments repeated at least three times using MTT, and cell counting (T4 Cellometer) assays as well as phase-contrast photo-imaging for parallel morphological displays of any changes in the course of their vitality and metabolic activities. Our results indicate that exposure of both cell lines to these organics resulted in concentration dependent cell destruction/cell survival depending on the cell line exposed. Pyruvic acid, sodium citrate and sodium bicarbonate showed statistically significant (pcancer biotherapeutics.

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

    Science.gov (United States)

    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 - 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 (Pmotor disorders in patients with SSBE and LSSBE. Acid reflux in upright and supine positions was more intense in LSBE.

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

    Science.gov (United States)

    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 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 pesticide exposures and ASD

  4. Prospective study of leptospirosis transmission in an urban slum community: role of poor environment in repeated exposures to the Leptospira agent.

    Science.gov (United States)

    Felzemburgh, Ridalva D M; Ribeiro, Guilherme S; Costa, Federico; Reis, Renato B; Hagan, José E; Melendez, Astrid X T O; Fraga, Deborah; Santana, Francisco S; Mohr, Sharif; dos Santos, Balbino L; Silva, Adriano Q; Santos, Andréia C; Ravines, Romy R; Tassinari, Wagner S; Carvalho, Marília S; Reis, Mitermayer G; Ko, Albert I

    2014-01-01

    Leptospirosis has emerged as an urban health problem as slum settlements have rapidly spread worldwide and created conditions for rat-borne transmission. Prospective studies have not been performed to determine the disease burden, identify risk factors for infection and provide information needed to guide interventions in these marginalized communities. We enrolled and followed a cohort of 2,003 residents from a slum community in the city of Salvador, Brazil. Baseline and one-year serosurveys were performed to identify primary and secondary Leptospira infections, defined as respectively, seroconversion and four-fold rise in microscopic agglutination titers. We used multinomial logistic regression models to evaluate risk exposures for acquiring primary and secondary infection. A total of 51 Leptospira infections were identified among 1,585 (79%) participants who completed the one-year follow-up protocol. The crude infection rate was 37.8 per 1,000 person-years. The secondary infection rate was 2.3 times higher than that of primary infection rate (71.7 and 31.1 infections per 1,000 person-years, respectively). Male gender (OR 2.88; 95% CI 1.40-5.91) and lower per capita household income (OR 0.54; 95% CI, 0.30-0.98 for an increase of $1 per person per day) were independent risk factors for primary infection. In contrast, the 15-34 year age group (OR 10.82, 95% CI 1.38-85.08), and proximity of residence to an open sewer (OR 0.95; 0.91-0.99 for an increase of 1 m distance) were significant risk factors for secondary infection. This study found that slum residents had high risk (>3% per year) for acquiring a Leptospira infection. Re-infection is a frequent event and occurs in regions of slum settlements that are in proximity to open sewers. Effective prevention of leptospirosis will therefore require interventions that address the infrastructure deficiencies that contribute to repeated exposures among slum inhabitants.

  5. Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines

    International Nuclear Information System (INIS)

    Dumont, Julie; Josse, Rozenn; Lambert, Carine; Antherieu, Sebastien; Laurent, Veronique; Loyer, Pascal; Robin, Marie-Anne; Guillouzo, Andre

    2010-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 μM PhIP or MeIQx. The most responsive genes to both HAA were downstream targets of the arylhydrocarbon receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1 after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was prevented by chemical inhibition or small interference RNA-mediated down-regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter, which contains a consensus AhR-related xenobiotic-responsive element (XRE). In addition, several other genes exhibited both time-dependent and compound-specific expression changes with, however, a smaller magnitude than previously reported for the prototypical AhR target genes. These changes concerned genes mainly related to cell growth and proliferation, apoptosis, and cancer. In conclusion, these results identify the AhR gene battery as the preferential target of PhIP and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA in diet might increase human cancer risk.

  6. Repeated in vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin/orexin-producing neurons in the lateral hypothalamus in mice.

    Science.gov (United States)

    Rao, Yan; Mineur, Yann S; Gan, Geliang; Wang, Alex Hanxiang; Liu, Zhong-Wu; Wu, Xinyuan; Suyama, Shigetomo; de Lecea, Luis; Horvath, Tamas L; Picciotto, Marina R; Gao, Xiao-Bing

    2013-04-01

    Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin-producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long-lasting, experience-dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine-conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up-regulation of AMPA-type glutamate receptors on hypocretin neurons. Phosphorylation of cAMP response element-binding protein (CREB) is also significantly increased in hypocretin neurons in cocaine-treated animals, suggesting that CREB-mediated pathways may contribute to synaptic potentiation in these cells. Furthermore, the potentiation of synaptic efficacy in hypocretin neurons persists during cocaine withdrawal, but reverses to baseline levels after prolonged abstinence. Finally, the induction of long-term potentiation (LTP) triggered by a high-frequency stimulation is facilitated in hypocretin neurons in cocaine-treated mice, suggesting that long-lasting changes in synapses onto hypocretin neurons would probably be further potentiated by other stimuli (such as concurrent environmental cues) paired with the drug. In summary, we show here that hypocretin neurons undergo experience-dependent synaptic potentiation that is distinct from that reported in other reward systems, such as the ventral tegmental area, following exposure to cocaine. These findings support the idea that the hypocretin system is important for behavioural changes associated with cocaine administration in animals and humans.

  7. Evaluation of Toluene Exposure in Workers at Industrial Area of Sidoarjo, Indonesia by Measurement of Urinary Hippuric Acid

    Directory of Open Access Journals (Sweden)

    Moch Sahri

    2013-12-01

    How to cite this article: Sahri M, Widajati N. Evaluation of Toluene Exposure in Workers at Industrial Area of Sidoarjo, Indonesia by Measurement of Urinary Hippuric Acid. Asia Pac J Med Toxicol 2013;2:145-9.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    1994-10-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. Simple intake and pharmacokinetic modeling to characterize exposure of Americans to perfluoroctanoic acid, PFOA.

    Science.gov (United States)

    Lorber, Matthew; Egeghy, Peter P

    2011-10-01

    Models for assessing intakes of perfluorooctanoic acid, PFOA, are described and applied. One model is based on exposure media concentrations and contact rates. This model is applied to general population exposures for adults and 2-year old children. The other model is a simple one-compartment, first-order pharmacokinetic (PK) model. Parameters for this model include a rate of elimination of PFOA and a blood volume of distribution. The model was applied to data from the National Health and Nutritional Examination Survey, NHANES, to backcalculate intakes. The central tendency intake estimate for adults and children based on exposure media concentrations and contact rates were 70 and 26 ng/day, respectively. The central tendency adult intake derived from NHANES data was 56 and 37 ng/day for males and females, respectively. Variability and uncertainty discussions regarding the intake modeling focus on lack of data on direct exposure to PFOA used in consumer products, precursor compounds, and food. Discussions regarding PK modeling focus on the range of blood measurements in NHANES, the appropriateness of the simple PK model, and the uncertainties associated with model parameters. Using the PK model, the 10th and 95th percentile long-term average adult intakes of PFOA are 15 and 130 ng/day.

  15. Effect of repeat unit structure and molecular mass of lactic acid bacteria hetero-exopolysaccharides on binding to milk proteins

    DEFF Research Database (Denmark)

    Birch, Johnny; HarÐarson, HörÐur Kári; Khan, Sanaullah

    2017-01-01

    -exopolysaccharides (HePSs) of 0.14–4.9 MDa from lactic acid bacteria to different milk proteins (β-casein, κ-casein, native and heat-treated β-lactoglobulin) at pH 4.0–5.0. Maximum binding capacity (RUmax) and apparent affinity (KA,app) were HePS- and protein-dependent and varied for example 10- and 600-fold......, respectively, in the complexation with native β-lactoglobulin at pH 4.0. Highest RUmax and KA,app were obtained with heat-treated β-lactoglobulin and β-casein, respectively. Overall, RUmax and KA,app decreased 6- and 20-fold, respectively, with increasing pH from 4.0 to 5.0. KA,app was influenced by ionic......Interactions of exopolysaccharides and proteins are of great importance in food science, but complicated to analyze and quantify at the molecular level. A surface plasmon resonance procedure was established to characterize binding of seven structure-determined, branched hetero...

  16. Trends in Pinus ponderosa foliar pigment concentration due to chronic exposure of ozone and acid rain

    International Nuclear Information System (INIS)

    Neuman, L.; Houpis, J.; Anderson, P.

    1991-01-01

    To determine the effects of ozone and acid rain on mature Ponderosa pine trees, Lawrence Livermore National Lab. has collaborated with University of California Berkeley, University of California Davis, California State University Chico, and the US Forest Service at the latter's Chico Tree Improvement Center. Foliar tissue from mature grafted scions of Pinus ponderosa were exposed to two times ambient ozone for ten months and to acid rain (3.0 pH) weekly for 10 weeks using branch exposure chambers. Pigment extracts were analyzed spectrophotometrically for concentrations of chlorophylls a and b, and carotenoid pigments, at 662 nm, 644 nm, and 470 nm, respectively. Pigment concentrations were expressed on a surface area basis. Preliminary results revealed that chlorophyll a showed a downward trend due to the ozone treatment. Acid rain caused no effects on these three pigments, however, chlorophyll b showed an upward trend due to the interaction of ozone and acid rain. The carotenoid pigments showed no changes due to the treatments either singly, or in combination

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

    Science.gov (United States)

    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.

  18. Repeating Marx

    DEFF Research Database (Denmark)

    Fuchs, Christian; Monticelli, Lara

    2018-01-01

    This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

  19. The Pentapeptide Repeat Proteins

    OpenAIRE

    Vetting, Matthew W.; Hegde, Subray S.; Fajardo, J. Eduardo; Fiser, Andras; Roderick, Steven L.; Takiff, Howard E.; Blanchard, John S.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S,T,A,V][D,N][L,F]-[S,T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Myc...

  20. Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Chidiebere Uchendu

    2014-01-01

    Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

  1. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

  2. Characterization of the Genetic Diversity of Acid Lime (Citrus aurantifolia (Christm.) Swingle) Cultivars of Eastern Nepal Using Inter-Simple Sequence Repeat Markers.

    Science.gov (United States)

    Munankarmi, Nabin Narayan; Rana, Neesha; Bhattarai, Tribikram; Shrestha, Ram Lal; Joshi, Bal Krishna; Baral, Bikash; Shrestha, Sangita

    2018-06-12

    Acid lime ( Citrus aurantifolia (Christm.) Swingle) is an important fruit crop, which has high commercial value and is cultivated in 60 out of the 77 districts representing all geographical landscapes of Nepal. A lack of improved high-yielding varieties, infestation with various diseases, and pests, as well as poor management practices might have contributed to its extremely reduced productivity, which necessitates a reliable understanding of genetic diversity in existing cultivars. Hereby, we aim to characterize the genetic diversity of acid lime cultivars cultivated at three different agro-ecological gradients of eastern Nepal, employing PCR-based inter-simple sequence repeat (ISSR) markers. Altogether, 21 polymorphic ISSR markers were used to assess the genetic diversity in 60 acid lime cultivars sampled from different geographical locations. Analysis of binary data matrix was performed on the basis of bands obtained, and principal coordinate analysis and phenogram construction were performed using different computer algorithms. ISSR profiling yielded 234 amplicons, of which 87.18% were polymorphic. The number of amplified fragments ranged from 7⁻18, with amplicon size ranging from ca. 250⁻3200 bp. The Numerical Taxonomy and Multivariate System (NTSYS)-based cluster analysis using the unweighted pair group method of arithmetic averages (UPGMA) algorithm and Dice similarity coefficient separated 60 cultivars into two major and three minor clusters. Genetic diversity analysis using Popgene ver. 1.32 revealed the highest percentage of polymorphic bands (PPB), Nei’s genetic diversity (H), and Shannon’s information index (I) for the Terai zone (PPB = 69.66%; H = 0.215; I = 0.325), and the lowest of all three for the high hill zone (PPB = 55.13%; H = 0.173; I = 0.262). Thus, our data indicate that the ISSR marker has been successfully employed for evaluating the genetic diversity of Nepalese acid lime cultivars and has furnished valuable information on

  3. Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Towards a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast

    Directory of Open Access Journals (Sweden)

    Stephen Thomas Ahlers

    2012-03-01

    Full Text Available Mild traumatic brain injury (mTBI resulting from exposure to improvised explosive devices (IEDs has fueled a requirement to develop animals models that mirror this condition using exposure to blast overpressure (BOP. En route to developing a model of repeated exposure to BOP we sought to initially characterize the effects of acute BOP exposure in rodents, focusing specifically on the levels of BOP exposure that produced clinical mTBI symptoms. We first measured BOP effects on gross motor function on a balance beam. Separate groups of unanesthetized rats were exposed (in different orientations to 40 kPa, 75 kPa and 120 kPa BOP exposure inside a pneumatically driven shock tube. Results demonstrated that rats exposed to 120 kPa demonstrated transient alterations or loss of consciousness indicated by a transient loss of righting and by increased latencies on the balance beam. The 120 kPa exposure was the threshold for overt pathology for acute BOP exposure with approximately 30% of rats presenting with evidence of subdural hemorrhage and cortical contusions. All animals exposed to 120 kPa BOP manifested evidence of significant pulmonary hemorrhage. Anterograde memory deficits were observed in rats exposed to 75 kPa facing the BOP wave and rats exposed to 120 kPa in the lateral (side orientation. We next assessed repeated exposure to either lateral or frontal 40 kPa BOP in anesthetized rats, once per day for 12 days. Results showed that repeated exposure in the frontal, but not side, orientation to the BOP wave produced a transitory learning deficit on a Morris water maze (MWM task as shown by significantly longer latencies to reach the submerged platform in the second and third blocks of a four block session. Implications of these data are discussed in relation to the manifestation of mTBI in military personnel exposed to IEDs. Finally, we suggest that there are multiple types of brain injury from blast.

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

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    Laura Helman

    2012-03-01

    Full Text Available CONTEXT: Barrett's esophagus (BE is characterized by intestinal metaplasia in the distal esophagus and is classified as short-segment (3 cm - LSSBE. It is suggested that LSSBE is associated with more severe esophageal motor abnormalities and increased acid exposure time than SSBE. OBJECTIVE: To evaluate the prevalence of esophageal manometriy abnormalities and acid exposure times in patients with SSBE and LSSBE. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

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    Milton Levin

    2008-12-01

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

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

    Science.gov (United States)

    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 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, Bartell SM

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  8. Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure

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    Sahbaie Peyman

    2007-06-01

    Full Text Available Abstract Background Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation. Methods Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment. Results The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure. Conclusion Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.

  9. Repeated ketamine administration alters N-methyl-d-aspartic acid receptor subunit gene expression: Implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans

    Science.gov (United States)

    Lipsky, Robert H

    2015-01-01

    For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. PMID:25245072

  10. Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system

    International Nuclear Information System (INIS)

    Tsai, Jean C.; Groot, Linda de; Pinon, Josefina D.; Iacono, Kathryn T.; Phillips, Joanna J.; Seo, Suhun; Lavi, Ehud; Weiss, Susan R.

    2003-01-01

    Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype

  11. Repeated ketamine administration alters N-methyl-D-aspartic acid receptor subunit gene expression: implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans.

    Science.gov (United States)

    Xu, Ke; Lipsky, Robert H

    2015-02-01

    For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. © 2014 by the Society for Experimental Biology and Medicine.

  12. Youth exposure to in-vehicle second-hand smoke and their smoking behaviours: trends and associations in repeated national surveys (2006-2012).

    Science.gov (United States)

    Healey, Benjamin; Hoek, Janet; Wilson, Nick; Thomson, George; Taylor, Steve; Edwards, Richard

    2015-03-01

    To extend the limited international evidence on youth in-vehicle second-hand smoke (SHS) exposure by examining trends in New Zealand, a country with a national smoke-free goal and indoors smoke-free environment legislation. We tracked exposure rates and explored the associations between in-vehicle SHS exposure and smoking behaviours. In-home exposure was also examined for comparative purposes. Data were collected in annual surveys of over 25 000 year 10 school students (14-15-year olds) for a 7-year period (2006-2012). Questions covered smoking behaviour, exposure to smoking and demographics. Youth SHS exposure rates in-vehicle and in-home trended down slightly over time (pvehicle in the previous week in 2012. However, marked inequalities in exposure between ethnic groups, and by school-based socioeconomic position, persisted. The strongest association with SHS exposure was parental smoking (eg, for both parents versus neither smoking in 2012: in-vehicle SHS exposure adjusted OR: 7.4; 95% CI: 6.5 to 8.4). After adjusting for seven other factors associated with initiation, logistic regression analyses revealed statistically significant associations of in-vehicle SHS exposure with susceptibility to initiation and smoking. The slow decline in SHS exposure in vehicles and the lack of progress in reducing relative inequalities is problematic. To accelerate progress, the New Zealand Government could follow the example of other jurisdictions and prohibit smoking in cars carrying children. Other major policy interventions, beside enhanced smoke-free environments, will also likely be required if New Zealand is to achieve its 2025 smoke-free nation goal. 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.

  13. Repeat exposure to ciguatoxin leads to enhanced and sustained thermoregulatory, pain threshold and motor activity responses in mice: relationship to blood ciguatoxin concentrations.

    Science.gov (United States)

    Bottein Dechraoui, Marie-Yasmine; Rezvani, Amir H; Gordon, Christopher J; Levin, Edward D; Ramsdell, John S

    2008-04-03

    Ciguatera is a common illness in tropical and subtropical regions that manifests in complex and long-lived symptoms which are more severe in subsequent exposures. This study measures central and peripheral neurologic signs, in parallel with blood toxin levels, in mice exposed once or twice (at 3 days interval) to a sublethal dose of ciguatoxin P-CTX-1 (0.26ng/g via i.p.). Mice were implanted with radiotransmitters to monitor motor activity and core temperature. A single exposure to ciguatoxin elicited an immediate and transient decrease in motor activity and temperature, and subsequent long-lasting thermoregulatory dysfunction resulting in stabilized body temperature around 36.0 degrees C with no observable circadian rhythm. The hypothermic response and the reduced activity were enhanced with a second exposure with 30% of the mice dying within 7h. Measurement of the peripheral nervous system by the tail flick assay revealed increased latency with a single ciguatoxin exposure, and a greater effect following the second exposure. Toxin was measurable in blood up to 3 days following the first exposure; at the 1h time point the concentrations were significantly elevated after a second exposure. These findings indicate an early response to ciguatoxin manifest in a central response to lower body temperature and reduce motor activity and a more persistent effect on the peripheral system leading to spinal heat antinociception and delayed fever-like response. The greater neurological response to a second ciguatoxin exposure was associated with elevated concentrations of ciguatoxin in the blood solely over the first hour of exposure. In conclusion, a single exposure to toxin exerts a significant neurological response which may be enhanced with subsequent exposure.

  14. Lexical-Semantic Organization in Bilingually Developing Deaf Children with ASL-Dominant Language Exposure: Evidence from a Repeated Meaning Association Task

    Science.gov (United States)

    Mann, Wolfgang; Sheng, Li; Morgan, Gary

    2016-01-01

    This study compared the lexical-semantic organization skills of bilingually developing deaf children in American Sign Language (ASL) and English with those of a monolingual hearing group. A repeated meaning-association paradigm was used to assess retrieval of semantic relations in deaf 6-10-year-olds exposed to ASL from birth by their deaf…

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

    Science.gov (United States)

    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.

  16. A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 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.

  20. Proteomic analysis revealed alterations of the Plasmodium falciparum metabolism following salicylhydroxamic acid exposure

    Directory of Open Access Journals (Sweden)

    Torrentino-Madamet M

    2011-09-01

    Full Text Available Marylin Torrentino-Madamet1, Lionel Almeras2, Christelle Travaillé1, Véronique Sinou1, Matthieu Pophillat3, Maya Belghazi4, Patrick Fourquet3, Yves Jammes5, Daniel Parzy11UMR-MD3, Université de la Méditerranée, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 2Unité de Recherche en Biologie et Epidémiologie Parasitaires, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 3Centre d'Immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée, 4Centre d'Analyse Protéomique de Marseille, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, 5UMR-MD2, Physiologie et Physiopathologie en Conditions d'Oxygénations Extrêmes, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, Marseille, FranceObjectives: Although human respiratory metabolism is characterized by the mitochondrial electron transport chain, some organisms present a “branched respiratory chain.” This branched pathway includes both a classical and an alternative respiratory chain. The latter involves an alternative oxidase. Though the Plasmodium falciparum alternative oxidase is not yet identified, a specific inhibitor of this enzyme, salicylhydroxamic acid (SHAM, showed a drug effect on P. falciparum respiratory function using oxygen consumption measurements. The present study aimed to highlight the metabolic pathways that are affected in P. falciparum following SHAM exposure.Design: A proteomic approach was used to analyze the P. falciparum proteome and determine the metabolic pathways altered following SHAM treatment. To evaluate the SHAM effect on parasite growth, the phenotypic alterations of P. falciparum after SHAM or/and hyperoxia exposure were observed.Results: After SHAM exposure, 26 proteins were significantly deregulated using a fluorescent two dimensional-differential gel electrophoresis. Among these deregulated proteins

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

    Science.gov (United States)

    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.

  2. Optimization of SPE for Analysis of Mandelic Acid as a Biomarker of Exposure to Ethyl Benzene

    Directory of Open Access Journals (Sweden)

    SJ Shahtaheri, M Abdollahi, F Golbabaei, A Rahimi-Froushani, F Ghamari

    2004-10-01

    Full Text Available Ethyl benzene is an important constituent of widely used solvents in industries and laboratories, causing widespread environmental and industrial pollutions. For evaluation of occupational exposure to such pollutants, biological monitoring is an essential process, in which, preparation of environmental and biological samples is one of the most time-consuming and error-prone aspects prior to chromatographic techniques. The use of solid-phase extraction (SPE has been grown and is a fertile technique of sample preparation as it provides better results than those of liquid-liquid extraction (LLE. In this study, SPE using bonded silica has been optimized with regard to sample pH, sample concentration, elution solvent, elution volume, sorbent type, and sorbent mass. Through experimental evaluation, a strong anion exchange silica cartridge (SAX has been found successful in simplifying sample preparation. The present approach proved that, mandelic acid could be retained on SAX sorbent based on specific interaction. Further study was employed using 10% acetic acid to extract the analyte from spiked urine and gave a clean sample for HPLC-UV system. In this study, a high performance liquid chromatography, using reverse-phase column was used. The isocratic run was done at a constant flow rate of 0.85 ml/min, the mobile phase was water/methanol/acetic acid and a UV detector was used, setting at 225 nm. At the developed conditions the extraction recovery was exceeded 98%. The factors were evaluated statically and also validated with three different pools of spiked urine samples and showed a good reproducibility over six consecutive days as well as six within-day experiments.

  3. Effect of restrictions on television food advertising to children on exposure to advertisements for 'less healthy' foods: repeat cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Jean Adams

    Full Text Available In 2007, new scheduling restrictions on television food advertising to children in the UK were announced. The aim of the restrictions was to "reduce significantly the exposure of children under 16 to high fat, salt or sugar (HFSS advertising". We explored the impact of the restrictions on relative exposure to HFSS food advertising among all viewers and among child television viewers, as well as adherence to the restrictions.We conducted two cross-sectional studies of all advertisements broadcast in one region of the UK over one week periods--the first (week 1 six months before the restrictions were introduced, and the second (week 2 six months after. Data on what products were advertised were linked to data on how many people watched each advertisement. Nutritional content of foods advertised was added to the dataset and used to calculate HFSS status. Relative exposure was calculated as the proportion of all advertising person-minute-views (PMVs that were for HFSS foods.1,672,417 advertising PMV were included. 14.6% of advertising PMV were for food and 51.1% of these were for HFSS food. Relative exposure of all viewers to HFSS food advertising increased between study weeks 1 and 2 (odds ratio (99% confidence intervals = 1·54 (1·51 to 1·57. Exposure of children to HFSS food advertising did not change between study weeks 1 and 2 (odds ratio (99% confidence intervals = 1·05 (0·99 to 1·12. There was almost universal adherence to the restrictions.Despite good adherence to the restrictions, they did not change relative exposure of children to HFSS advertising and were associated with an increase in relative exposure of all viewers to HFSS advertising. Stronger restrictions targeting a wider range of advertisements are necessary to reduce exposure of children to marketing of less healthful foods.

  4. Effect of restrictions on television food advertising to children on exposure to advertisements for 'less healthy' foods: repeat cross-sectional study.

    Science.gov (United States)

    Adams, Jean; Tyrrell, Rachel; Adamson, Ashley J; White, Martin

    2012-01-01

    In 2007, new scheduling restrictions on television food advertising to children in the UK were announced. The aim of the restrictions was to "reduce significantly the exposure of children under 16 to high fat, salt or sugar (HFSS) advertising". We explored the impact of the restrictions on relative exposure to HFSS food advertising among all viewers and among child television viewers, as well as adherence to the restrictions. We conducted two cross-sectional studies of all advertisements broadcast in one region of the UK over one week periods--the first (week 1) six months before the restrictions were introduced, and the second (week 2) six months after. Data on what products were advertised were linked to data on how many people watched each advertisement. Nutritional content of foods advertised was added to the dataset and used to calculate HFSS status. Relative exposure was calculated as the proportion of all advertising person-minute-views (PMVs) that were for HFSS foods. 1,672,417 advertising PMV were included. 14.6% of advertising PMV were for food and 51.1% of these were for HFSS food. Relative exposure of all viewers to HFSS food advertising increased between study weeks 1 and 2 (odds ratio (99% confidence intervals) = 1·54 (1·51 to 1·57)). Exposure of children to HFSS food advertising did not change between study weeks 1 and 2 (odds ratio (99% confidence intervals) = 1·05 (0·99 to 1·12)). There was almost universal adherence to the restrictions. Despite good adherence to the restrictions, they did not change relative exposure of children to HFSS advertising and were associated with an increase in relative exposure of all viewers to HFSS advertising. Stronger restrictions targeting a wider range of advertisements are necessary to reduce exposure of children to marketing of less healthful foods.

  5. Effect of Restrictions on Television Food Advertising to Children on Exposure to Advertisements for ‘Less Healthy’ Foods: Repeat Cross-Sectional Study

    Science.gov (United States)

    Adams, Jean; Tyrrell, Rachel; Adamson, Ashley J.; White, Martin

    2012-01-01

    Background In 2007, new scheduling restrictions on television food advertising to children in the UK were announced. The aim of the restrictions was to “reduce significantly the exposure of children under 16 to high fat, salt or sugar (HFSS) advertising”. We explored the impact of the restrictions on relative exposure to HFSS food advertising among all viewers and among child television viewers, as well as adherence to the restrictions. Methods We conducted two cross-sectional studies of all advertisements broadcast in one region of the UK over one week periods – the first (week 1) six months before the restrictions were introduced, and the second (week 2) six months after. Data on what products were advertised were linked to data on how many people watched each advertisement. Nutritional content of foods advertised was added to the dataset and used to calculate HFSS status. Relative exposure was calculated as the proportion of all advertising person-minute-views (PMVs) that were for HFSS foods. Results 1,672,417 advertising PMV were included. 14.6% of advertising PMV were for food and 51.1% of these were for HFSS food. Relative exposure of all viewers to HFSS food advertising increased between study weeks 1 and 2 (odds ratio (99% confidence intervals) = 1·54 (1·51 to 1·57)). Exposure of children to HFSS food advertising did not change between study weeks 1 and 2 (odds ratio (99% confidence intervals) = 1·05 (0·99 to 1·12)). There was almost universal adherence to the restrictions. Conclusions Despite good adherence to the restrictions, they did not change relative exposure of children to HFSS advertising and were associated with an increase in relative exposure of all viewers to HFSS advertising. Stronger restrictions targeting a wider range of advertisements are necessary to reduce exposure of children to marketing of less healthful foods. PMID:22355376

  6. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

    Science.gov (United States)

    Diaz, Marvin R; Vollmer, Cyndel C; Zamudio-Bulcock, Paula A; Vollmer, William; Blomquist, Samantha L; Morton, Russell A; Everett, Julie C; Zurek, Agnieszka A; Yu, Jieying; Orser, Beverley A; Valenzuela, C Fernando

    2014-04-01

    Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ∼60 mM (∼0.28 g/dl) during the 4 h of exposure. EtOH levels gradually decreased to baseline 8 h after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABA(A) receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The effects of a single whole body cryotherapy exposure on physiological, performance and perceptual responses of professional academy soccer players following repeated sprint exercise

    OpenAIRE

    Russell, Mark; Birch, Jack; Love, Thomas; Cook, Christian; Bracken, Richard M.; Taylor, Tom; Swift, Eamon; Cockburn, Emma; Finn, Charlie; Cunningham, Daniel; Wilson, Laura; Kilduff, Liam P.

    2017-01-01

    In professional youth soccer players, the physiological, performance and perceptual effects of a single whole body cryotherapy (WBC) session performed shortly after repeated sprint exercise were investigated. In a randomized, counter-balanced and crossover design, 14 habituated English Premier League academy soccer players performed 15 x 30 m sprints (each followed by a 10 m forced deceleration) on two occasions. Within 20 min of exercise cessation, players entered a WBC chamber (Cryo: 30 s a...

  8. Does folic acid use decrease the risk for spina bifida after in utero exposure to valproic acid?

    NARCIS (Netherlands)

    Jentink, J.; Bakker, M.K.; Nijenhuis, C.M.; Wilffert, B.; de Jong-van den Berg, L.T.W.

    Purpose Women with child wish are advised to take folic acid supplements to reduce the risk for spina bifida. However, there is less evidence for this protective effect in women using valproic acid (VPA). We investigated the effect of folic acid in women exposed to VPA in the first trimester of

  9. Changes in child exposure to secondhand smoke after implementation of smoke-free legislation in Wales: a repeated cross-sectional study

    Directory of Open Access Journals (Sweden)

    Holliday Jo

    2009-01-01

    Full Text Available Abstract Background Smoke-free legislation was introduced in Wales in April 2007. In response to concerns regarding potential displacement of smoking into the home following legislation, this study assessed changes in secondhand smoke (SHS exposure amongst non-smoking children. Methods Approximately 1,750 year 6 (aged 10-11 children from 75 Welsh primary schools were included in cross-sectional surveys immediately pre-legislation and one year later. Participants completed self-report questionnaires and provided saliva samples for cotinine assay. Regression analyses assessed the impact of legislation on children's SHS exposure at the population level, and amongst subgroups defined by parental figures who smoke within the home. Results Geometric mean salivary cotinine concentrations were 0.17 ng/ml (95% CI 0.15,0.20 pre-legislation and 0.15 ng/ml (95% CI 0.13,0.17, post-legislation, although this change was not statistically significant. Significant movement was however observed from the middle (0.10-0.50 ng/ml to lower tertile, though not from the higher end (>0.51 ng/ml to the middle. Reported exposure to SHS was greatest within the home. Home-based exposure did not change significantly post-legislation. Reported exposure in cafés or restaurants, buses and trains, and indoor leisure facilities fell significantly. The proportion of children reporting that parent figures smoked in the home declined (P = 0.03, with children with no parent figures who smoke in the home significantly more likely to provide saliva with cotinine concentrations of <0.10 ng/ml post-legislation. Amongst children with no parent figures who smoke in the home, the likelihood of 'not knowing' or 'never' being in a place where people were smoking increased post-legislation. Conclusion Smoke-free legislation in Wales did not increase SHS exposure in homes of children aged 10-11. Reported SHS exposure in public places fell significantly. The home remained the main source of

  10. Members of a novel protein family containing microneme adhesive repeat domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites.

    Science.gov (United States)

    Friedrich, Nikolas; Santos, Joana M; Liu, Yan; Palma, Angelina S; Leon, Ester; Saouros, Savvas; Kiso, Makoto; Blackman, Michael J; Matthews, Stephen; Feizi, Ten; Soldati-Favre, Dominique

    2010-01-15

    Numerous intracellular pathogens exploit cell surface glycoconjugates for host cell recognition and entry. Unlike bacteria and viruses, Toxoplasma gondii and other parasites of the phylum Apicomplexa actively invade host cells, and this process critically depends on adhesins (microneme proteins) released onto the parasite surface from intracellular organelles called micronemes (MIC). The microneme adhesive repeat (MAR) domain of T. gondii MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant on the host cell surface for invasion by this pathogen. By complementation and invasion assays, we demonstrate that TgMIC1 is one important player in Sia-dependent invasion and that another novel Sia-binding lectin, designated TgMIC13, is also involved. Using BLAST searches, we identify a family of MAR-containing proteins in enteroparasitic coccidians, a subclass of apicomplexans, including T. gondii, suggesting that all these parasites exploit sialylated glycoconjugates on host cells as determinants for enteric invasion. Furthermore, this protein family might provide a basis for the broad host cell range observed for coccidians that form tissue cysts during chronic infection. Carbohydrate microarray analyses, corroborated by structural considerations, show that TgMIC13, TgMIC1, and its homologue Neospora caninum MIC1 (NcMIC1) share a preference for alpha2-3- over alpha2-6-linked sialyl-N-acetyllactosamine sequences. However, the three lectins also display differences in binding preferences. Intense binding of TgMIC13 to alpha2-9-linked disialyl sequence reported on embryonal cells and relatively strong binding to 4-O-acetylated-Sia found on gut epithelium and binding of NcMIC1 to 6'sulfo-sialyl Lewis(x) might have implications for tissue tropism.

  11. Stability of fatty acids in grass and maize silages after exposure to air during the feed out period

    NARCIS (Netherlands)

    Khan, N.A.; Cone, J.W.; Hendriks, W.H.

    2009-01-01

    Lipids in forages are extensively hydrolysed in the silo with a concomitant increase in the level of free fatty acids (FFA). After opening of the silo, exposure of the FFA to air and light with, a concomitant increase in pH and microbial growth, could induce oxidization. The present study

  12. Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease

    NARCIS (Netherlands)

    Scheffer, R. C. H.; Wassenaar, E. B.; Herwaarden, M. A.; Holloway, R. H.; Samsom, M.; Smout, A. J. P. M.; Akkermans, L. M. A.

    2005-01-01

    This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour

  13. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. A step-by-step introduction to vegetables at the beginning of complementary feeding. The effects of early and repeated exposure.

    Science.gov (United States)

    Hetherington, Marion M; Schwartz, C; Madrelle, J; Croden, F; Nekitsing, C; Vereijken, C M J L; Weenen, H

    2015-01-01

    Breastfeeding (BF) is associated with willingness to accept vegetables. This may be due to the variety of flavours delivered via breast milk. Some mothers add vegetables to milk during complementary feeding (CF) to enhance acceptance. The present study tested a step-by-step exposure to vegetables in milk then rice during CF, on intake and liking of vegetables. Just before CF, enrolled mothers were randomised to an intervention (IG, n = 18; 6 BF) or control group (CG, n = 18; 6 BF). IG infants received 12 daily exposures to vegetable puree added to milk (days 1-12), then 12 × 2 daily exposures to vegetable puree added to rice at home (days 13-24). Plain milk and rice were given to CG. Then both received 11 daily exposures to vegetable puree. Intake was weighed and liking rated on days 25-26 and 33-35 after the start of CF in the laboratory, supplemented by the same data recorded at home. Vegetables were rotated daily (carrots, green beans, spinach, broccoli). Intake, liking and pace of eating were greater for IG than CG infants. Intake and liking of carrots were greater than green beans. However, at 6m then 18m follow up, vegetable (carrot > green beans) but not group differences were observed. Mothers reported appreciation of the structure and guidance of this systematic approach. Early exposure to vegetables in a step-by-step method could be included in CF guidelines and longer term benefits assessed by extending the exposure period. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Effects of ammonia exposure on carcass traits and fatty acid composition of broiler meat

    Directory of Open Access Journals (Sweden)

    Huan Xing

    2016-12-01

    Full Text Available We aimed to study the effects of ammonia on carcass traits, organ indices and fatty acid composition of broilers. Four hundred 21-d-old male Arbor Acres broilers with initial weight 563.52 ± 2.82 g were randomly allotted to 1 of 4 groups treated with ammonia at <3 mg/kg (control, 25 ± 3, 50 ± 3, and 75 ± 3 mg/kg concentrations. Each group consisted of 4 replicates of 25 birds. Broilers from 21 to 42 d were reared on the net floor in the respiration-metabolism chambers where similar environmental conditions were maintained. At 32 and 42 d of age, carcass traits and organ indices were determined for 4 birds per pen. At 42 d of age, fatty acid composition in the breast and thigh muscle of broilers was measured. Results showed as follows: 1 At 32 d, the dressing percentage of broilers exposed to 25 and 75 mg/kg ammonia were lower than those in the control group (P < 0.05; eviscerated yield percentage of broilers in the 25 mg/kg ammonia group was also lower (P < 0.05. At 42 d, the dressing percentage of broilers in the ammonia treatments and the thigh muscle percentage of broilers in the 50 and 75 mg/kg ammonia groups were lower (P < 0.05 than those in the control. Breast muscle percentage of broilers exposed to 25 and 50 mg/kg ammonia and eviscerated yield percentage exposed to 50 mg/kg ammonia were lower than those in the control (P < 0.05. 2 The kidney index of broilers (d 32 exposed to ammonia was greater (P < 0.05 than that of the control. At 42 d, hepatic index of broilers exposed to ammonia was increased (P < 0.05, and spleen index was decreased (P < 0.05. 3 At 42 d, stearic (C18:0 and saturated fatty acids (SFA in the thigh muscle of broilers were higher, while the unsaturated fatty acid:saturated fatty acid (U:F ratio and unsaturated fatty acid (UFA were lower in the 50 mg/kg ammonia treatment than in the control group (P < 0.05. In conclusion, ammonia over 25 mg/kg could decline carcass traits

  16. Repeated short-term stress synergizes the ROS signalling through up regulation of NFkB and iNOS expression induced due to combined exposure of trichloroethylene and UVB rays.

    Science.gov (United States)

    Ali, Farrah; Sultana, Sarwat

    2012-01-01

    Restraint stress is known to catalyse the pathogenesis of the variety of chronic inflammatory disorders. The present study was designed to evaluate the effect of repeated short-term stress (RRS) on cellular transduction apart from oxidative burden and early tumour promotional biomarkers induced due to combined exposure of trichloroethylene (TCE) and Ultra-violet radiation (UVB). RRS leads to the increase in the expression of the stress responsive cellular transduction elements NFkB-p65 and activity of iNOS in the epidermal tissues of mice after toxicant exposure. RRS augments the steep depletion of the cellular antioxidant machinery which was evidenced by the marked depletion in GSH (Glutathione and GSH dependant enzymes), superoxide dismutase and catalase activity that were observed at significance level of P stressed animals and down regulation of DT-diaphorase activity (P short-term stress in the toxic response of TCE and UVB radiation.

  17. Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections?

    Science.gov (United States)

    Arvonen, Miika; Virta, Lauri J; Pokka, Tytti; Kröger, Liisa; Vähäsalo, Paula

    2015-03-01

    Previous exposure to antibiotics has been associated with the pathogenesis of several autoimmune diseases. Our objective was to explore whether childhood exposure to antibiotics would be associated with the risk of developing juvenile idiopathic arthritis (JIA). The material was collected from national registers containing all children born in 2000-2010 in Finland and diagnosed with JIA by the end of December 2012 (n = 1298) and appropriate controls (n = 5179) matched for age, sex, and place of birth. All purchases of antibiotics were collected from birth until the index date (i.e., the date of special reimbursement for JIA medications). A conditional logistic regression was performed to evaluate the association between the exposure to antibiotics and the risk of JIA. The risk of JIA increased with the number of antibiotic purchases from birth to the index date: for ≥ 1 purchases versus none, OR 1.6, 95% CI 1.3-1.9 with an upward trend in OR (p Antibiotic groups lincosamides and cephalosporins showed the strongest association with JIA (OR 6.6, 95% CI 3.7-11.7, and OR 1.6, 95% CI 1.4-1.8, respectively). Overall exposure to antibiotics before 2 years of age was associated with an increased risk of JIA (OR 1.4, 95% CI 1.2-1.6), with the trend test of OR (p antibiotics may predispose individuals to develop JIA. Alternatively, the apparent association may reflect shared susceptibility to infections and JIA.

  18. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  19. Repeated exposure to enhanced UV-B radiation in successive generations increases developmental instability (leaf fluctuating asymmetry) in a desert annual

    International Nuclear Information System (INIS)

    Midgley, G.F.; Wand, S.J.E.; Musil, C.F.

    1998-01-01

    Populations of the desert annual Dimorphotheca sinuata, derived from a common seed stock, were exposed concurrently over four successive generations to either ambient (representing no stratospheric ozone depletion) or elevated (representing 20% stratospheric ozone depletion) UV-B levels during their complete life cycle. Leaf fluctuating asymmetry (FA) was measured in populations of plants grown from seeds of selected generations which had experienced different UV-B exposure histories, and from seeds collected from a wild population of this species which grows in a naturally enhanced UV-B environment. These measured plants had been grown in a greenhouse under essentially UV-B-free conditions. Leaf FA was significantly increased by greater numbers of enhanced UV-B exposures in the parentage of the seed. There was a linear to exponential dose–response relationship between number of UV-B exposure iterations in seed parentage and leaf FA, suggesting that damage to DNA caused by UV-B exposure during plant development may not be fully repaired, and thus be inherited by offspring and accumulated over successive generations in this species. Leaf FA of plants grown from seed from the wild population was not significantly greater than that of control plants whose parentage experienced only ambient UV-B exposures, although this negative result may have been due to low sampling intensity and measurement resolution, and the relatively low UV-B enhancement experienced by the wild population. We conclude that leaf FA may constitute a relatively sensitive yet inexpensive means of quantifying UV-B damage to plants. (author)

  20. Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength.

    Science.gov (United States)

    Marks, Wendie; Fournier, Neil M; Kalynchuk, Lisa E

    2009-08-04

    We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength. Separate groups of rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once per day for 21 consecutive days. Then, half the rats from each group were exposed to the traditional two-day forced swim test and the other half were exposed to our one-day forced swim test. After the forced swim testing, all the rats were tested in an open field and in a wire suspension grip strength test. The CORT injections significantly increased the time spent immobile and decreased the time spent swimming in both versions of the forced swim test. However, they had no significant effect on activity in the open field or grip strength in the wire suspension test. These results show that repeated CORT injections increase depression-like behavior regardless of the specific parameters of forced swim testing, and that these effects are independent of changes in locomotor activity or muscle strength.

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

    International Nuclear Information System (INIS)

    Noble, E.P.; Ritchie, T.

    1989-01-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

    A significant emerging environmental problem is the disturbance and oxidation of soils with high levels of iron sulphide minerals resulting in acidification and causing the mobilization of metals into groundwater. This process is occurring in many parts of the world. In Western Australia, impacted groundwater is extracted by residents for domestic use. We sought to establish domestic use patterns of bore water and the concentration of metals. Sixty-seven domestic bore water samples clearly indicated oxidation of sulphidic materials with heavy metal concentrations ranging for aluminium (< DL-37.0 mg/L), arsenic (< DL-6.6 mg/L), iron (< DL-1200 mg/L), cadmium (< DL-0.021 mg/L), lead (< DL-0.040 mg/L), selenium (< DL-0.006 mg/L). A high proportion of residents used bore water on home grown produce. The study suggests that there is potential for human exposure to heavy metals via the consumption of home grown produce. This warrants further investigation in light of increasing acid sulphate soil disturbance in many locations. - Acidified bore water may introduce metals into produce for home consumption

  3. Effects of naphthenic acid exposure on development and liver metabolic processes in anuran tadpoles

    International Nuclear Information System (INIS)

    Melvin, Steven D.; Lanctôt, Chantal M.; Craig, Paul M.; Moon, Thomas W.; Peru, Kerry M.; Headley, John V.; Trudeau, Vance L.

    2013-01-01

    Naphthenic acids (NA) are used in a variety of commercial and industrial applications, and are primary toxic components of oil sands wastewater. We investigated developmental and metabolic responses of tadpoles exposed to sub-lethal concentrations of a commercial NA blend throughout development. We exposed Lithobates pipiens tadpoles to 1 and 2 mg/L NA for 75 days and monitored growth and development, condition factor, gonad and liver sizes, and levels of liver glucose, glycogen, lipids and cholesterol following exposure. NA decreased growth and development, significantly reduced glycogen stores and increased triglycerides, indicating disruption to processes associated with energy metabolism and hepatic glycolysis. Effects on liver function may explain reduced growth and delayed development observed in this and previous studies. Our data highlight the need for greater understanding of the mechanisms leading to hepatotoxicity in NA-exposed organisms, and indicate that strict guidelines may be needed for the release of NA into aquatic environments. -- Highlights: ► We exposed Lithobates pipiens tadpoles to 1–2 mg/L NA in the laboratory. ► We monitored survival, growth and development for 75 days. ► We measured liver glycogen, glucose, triglycerides, and cholesterol levels. ► NA significantly reduced growth and development compared to controls. ► NA significantly reduced glycogen levels and increased triglycerides. -- Leopard frog (Lithobates pipiens) tadpoles chronically exposed to sub-lethal NA concentrations (1–2 mg/L) suffered decreased growth and development and disruption to liver metabolic processes

  4. Repeated Exposure of Epithelial Cells to Apoptotic Cells Induces the Specific Selection of an Adaptive Phenotype: Implications for Tumorigenesis.

    Science.gov (United States)

    Feng, Lanfei; Vujicic, Snezana; Dietrich, Michael E; Litbarg, Natalia; Setty, Suman; Antoni, Angelika; Rauch, Joyce; Levine, Jerrold S

    2018-05-16

    The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU.MPT SEL ) resistant to apoptotic target-induced death. Resistance is exquisitely specific. Not only are BU.MPT SEL responders fully resistant to apoptotic target-induced death (~85% survival versus exposure in selected versus non-selected responders indicated that the acquired resistance of BU.MPT SEL cells lies in a regulatory step affecting the generation of the pro-apoptotic protein, truncated BH3 interacting-domain death agonist (tBID), most likely at the level of BID cleavage by caspase-8. This specific adaptation has especial relevance for cancer, in which the prominence and persistence of cell death entail magnification of the post-mortem effects of apoptotic cells. Just as cancer cells acquire specific resistance to chemotherapeutic agents, we propose that cancer cells may also adapt to their ongoing exposure to apoptotic targets. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

    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.

  6. Acid-base and ionic fluxes in rainbow trout (Oncorhynchus mykiss) during exposure to chloramine-T

    Energy Technology Data Exchange (ETDEWEB)

    Powell, M.D.; Perry, S.F. [Department of Biology, University of Ottawa, 30 Marie Curie Ottawa, Ontario, K1N 6N5 (Canada)

    1998-09-01

    The effects of chloramine-T and its degradation products, sodium hypochlorite (NaOCl) and para-toluenesulphonamide (pTSA), on whole body acid-base and branchial and renal ion (Na{sup +}and Cl{sup -}) fluxes were examined in rainbow trout (Oncorhynchus mykiss). Exposure to chloramine-T (3.5 h, 18 mg l{sup -1}) resulted in increases in plasma total CO{sub 2} but no coincident rise in P{sub a}CO{sub 2} or reduction in blood pH. Exposure of fish to 2, 9 or 18 mg l{sup -1} chloramine-T (3.5 h duration) resulted in a reduction in net acid uptake suggesting the development of a metabolic alkalosis. Exposure to the chloramine-T breakdown product pTSA (dissolved in DMSO) resulted in increased net acid uptake (decreased acid excretion) suggesting a metabolic acidosis. Whole body ion fluxes demonstrated increases in the losses of both Na{sup +}and Cl{sup -} with chloramine-T, NaOCl and pTSA. However, the effect of DMSO alone could not be isolated. Confirmatory studies using fish in which the urinary bladder (to allow collection of urine) and dorsal aorta (to allow injection of [{sup 14}C]polyethylene glycol 4000 ([{sup 14}C]PEG), an extracellular fluid marker) were catheterised, revealed that changes in whole body ion fluxes during chloramine-T exposure could not be explained by increased renal efflux through urine flow, glomerular filtration or renal clearance. Branchial effluxes of [{sup 14}C]PEG were not significantly affected by chloramine-T exposure suggesting that the changes in whole body ionic fluxes were caused by transcellular rather than paracellular processes. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  7. Acid-base and ionic fluxes in rainbow trout (Oncorhynchus mykiss) during exposure to chloramine-T

    International Nuclear Information System (INIS)

    Powell, M.D.; Perry, S.F.

    1998-01-01

    The effects of chloramine-T and its degradation products, sodium hypochlorite (NaOCl) and para-toluenesulphonamide (pTSA), on whole body acid-base and branchial and renal ion (Na + and Cl - ) fluxes were examined in rainbow trout (Oncorhynchus mykiss). Exposure to chloramine-T (3.5 h, 18 mg l -1 ) resulted in increases in plasma total CO 2 but no coincident rise in P a CO 2 or reduction in blood pH. Exposure of fish to 2, 9 or 18 mg l -1 chloramine-T (3.5 h duration) resulted in a reduction in net acid uptake suggesting the development of a metabolic alkalosis. Exposure to the chloramine-T breakdown product pTSA (dissolved in DMSO) resulted in increased net acid uptake (decreased acid excretion) suggesting a metabolic acidosis. Whole body ion fluxes demonstrated increases in the losses of both Na + and Cl - with chloramine-T, NaOCl and pTSA. However, the effect of DMSO alone could not be isolated. Confirmatory studies using fish in which the urinary bladder (to allow collection of urine) and dorsal aorta (to allow injection of [ 14 C]polyethylene glycol 4000 ([ 14 C]PEG), an extracellular fluid marker) were catheterised, revealed that changes in whole body ion fluxes during chloramine-T exposure could not be explained by increased renal efflux through urine flow, glomerular filtration or renal clearance. Branchial effluxes of [ 14 C]PEG were not significantly affected by chloramine-T exposure suggesting that the changes in whole body ionic fluxes were caused by transcellular rather than paracellular processes. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  8. Early Effect of High Dose of Ionizing Radiation Exposure on Plasma Lipids Profile and Liver Fatty Acids Composition in Rats

    International Nuclear Information System (INIS)

    Noaman, E.; Mansour, S.Z.; Ibrahim, N.K.

    2005-01-01

    The present study was conducted to analyze the effect of acute gamma-irradiation on rats at supralethal doses of 20 Gy to determine the synthesis and amounts of free fatty acids, neutral lipids and phospholipids of plasma and liver after 24 and 48 h of gamma-irradiation. Male Wistar rats weighing 120+- 20 g were exposed to 20 Gy of gamma radiation (dose rate of 0.59 Gy/min). Exposure of rats to ionizing radiation resulted in significant alterations in the assayed parameters indicating lipid metabolism disturbance. Plasma cholesterol and phospholipid levels increased up to 71.3 and 71.5 %, respectively, after 24 h from radiation exposure and then returned to 28 and 27 % change in-compare with control values after 48 h post-irradiation. Plasma triacylglycerol concentrations increased concomitantly with irradiation, but their values are less high than cholesterol and phospholipid levels recording significant changes at 19 and 9 % comparing with control rats. Lipid peroxidation measured as MDA recorded significant elevation after 24 and 48 h post irradiation. It was shown that the synthesis of free fatty acids, cholesterol, cholesterol ethers and phospholipids was activated 48 h after irradiation at 20 Gy. The amount of free fatty acids of the rat liver decreased at 20 Gy exposures. This is assumed to be a result of the radioresistance to some degree in the system of free fatty acid synthesis of the rat to the gamma-irradiation in the lethal doses

  9. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations.

    Science.gov (United States)

    Worley, Rachel Rogers; Yang, Xiaoxia; Fisher, Jeffrey

    2017-09-01

    Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. Published by Elsevier Inc.

  10. Film repeats in radiology department

    International Nuclear Information System (INIS)

    Suwan, A. Z.; Al-Shakharah, A. I

    1997-01-01

    During a one year period, 4910 radiographs of 55780 films were repeated. The objective of our study was to analyse and to classify the causes in order to minimize the repeats, cut the expenses and to provide optimal radiographs for accurate diagnosis. Analysis of the different factors revealed that, 43.6% of film repeats in our service were due to faults in exposure factors, centering comprises 15.9% of the repeats, while too much collimation was responsible for 7.6% of these repeats. All of which can be decreased by awareness and programmed training of technicians. Film blurring caused by patient motion was also responsible for 4.9% for radiographs reexamination, which can be minimized by detailed explanation to the patient and providing the necessary privacy. Fogging of X-Ray films by improper storage or inadequate handling or processing faults were responsible for 14.5% in repeats in our study. Methods and criteria for proper storage and handling of films were discussed. Recommendation for using modern day-light and laser processor has been high lighted. Artefacts are noticeably high in our cases, due to spinal dresses and frequent usage of precious metals for c osmotic purposes in this part of the world. The repeated films comprise 8.8% of all films We conclude that, the main factor responsible for repeats of up to 81.6% of cases was the technologists, thus emphasizing the importance of adequate training of the technologists. (authors). 15 refs., 9 figs., 1 table

  11. Immunomodulatory effects of exposure to polychlorinated biphenyls and perfluoroalkyl acids in East Greenland ringed seals (Pusa hispida)

    International Nuclear Information System (INIS)

    Levin, Milton; Gebhard, Erika; Jasperse, Lindsay; Desforges, Jean-Pierre; Dietz, Rune; Sonne, Christian; Eulaers, Igor; Covaci, Adrian; Bossi, Rossana; De Guise, Sylvain

    2016-01-01

    To better elucidate the potential immune-related health effects of exposure to environmentally persistent organic pollutants (POP), such as polychlorinated biphenyls (PCBs) and perfluoroalkyl substances (PFASs), in ringed seals (Pusa hispida), a sentinel Arctic species, we assessed 1) associations between mitogen-induced lymphocyte proliferation and in vivo tissue contaminant burdens, and 2) the concentration-response effects of in vitro exposure to PFASs and PCB congeners on mitogen-induced lymphocyte proliferation. Upon in vitro contaminant exposure, the non-coplanar PCB congeners CB 138, 153, and 180, but not the coplanar CB 169, significantly reduced lymphocyte proliferation between 10 and 20 µg g −1 ww. The respective in vitro EC 50 values for these congeners were 13.3, 20.7, 20.8, and 54.6 µg g −1 ww. No modulation of lymphocyte proliferation was observed upon in vitro exposure to two individual PFASs, perfluorooctane sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA), at concentrations up to 1000 ng g-1. In addition, no significant correlations were found between lymphocyte proliferation and any blood or blubber contaminant measured. Taken together, these data suggest this population of ringed seals is not currently at high risk of altered lymphocyte proliferation from exposure to the POPs or PFASs in this study. - Highlights: • Assess relationships between tissue contaminants and changes in immune function. • Risk for contaminant-induced immunotoxicity in East Greenland ringed seal is low. • Weight of evidence suggest non-coplanar PCBs are immunotoxic at high concentrations.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. The use of docosahexaenoic acid supplementation to ameliorate the hyperactivity of rat pups induced by in utero ethanol exposure

    OpenAIRE

    Furuya, Hiroyuki; Aikawa, Hiroyuki; Yoshida, Takahiko; Okazaki, Isao

    2000-01-01

    It has been demonstrated thatin utero ethanol (EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid (DHA) on these neurobehavioral dysfunctions of rat pups induced byin utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a) 5% safflower oil with tap water (TW/n-6), (b) 3% safflower oil and 2% DHA...

  15. Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

    DEFF Research Database (Denmark)

    Li, Ying; Han, Meihua; Liu, Tingting

    2017-01-01

    The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA...... to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum...

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  17. Deletion of intragenic tandem repeats in unit C of FLO1 of Saccharomyces cerevisiae increases the conformational stability of flocculin under acidic and alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Ee Li

    Full Text Available Flocculation is an attractive property for Saccaromyces cerevisiae, which plays important roles in fermentation industry and environmental remediation. The process of flocculation is mediated by a family of cell surface flocculins. As one member of flocculins, Flo1 is characterized by four families of repeats (designated as repeat units A, B, C and D in the central domain. It is generally accepted that variation of repeat unit A in length in Flo1 influences the degree of flocculation or specificity for sugar recognization. However, no reports were observed for other repeat units. Here, we compared the flocculation ability and its sensitivity to environmental factors between yeast strain YSF1 carrying the intact FLO1 gene and yeast strains carrying the derived forms of FLO1 with partial or complete deletion of repeats in unit C. No obvious differences in flocculation ability and specificity of carbohydrate recognition were observed among these yeast strains, which indicates the truncated flocculins can stride across the cell wall and cluster the N-terminal domain on the surface of yeast cells as the intact Flo1 thereby improving intercellular binding. However, yeast strains with the truncated flocculins required more mannose to inhibit completely the flocculation, displayed broad tolerance of flocculation to pH fluctuation, and the fewer the repeats in unit C, the stronger adaptability of flocculation to pH change, which was not relevant to the position of deletion. This suggests that more stable active conformation is obtained for flocculin by deletion the repeat unit C in the central domain of Flo1, which was validated further by the higher hydrophobicity on the surface of cells of YSF1c with complete deletion of unit C under neutral and alkaline conditions and the stabilization of GFP conformation by fusion with flocculin with complete deletion of unit C in the central domain.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 enamel microhardness between different durations of exposure to theobromine gel and immersion in citric acid (p 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.

  1. Early life exposure to polyunsaturated fatty acids and psychomotor development in children from the EDEN mother-child cohort

    OpenAIRE

    Bernard Jonathan Y.; Armand Martine; Forhan Anne; De Agostini Maria; Charles Marie-Aline; Heude Barbara

    2016-01-01

    Epidemiological studies have reported that breastfed children have improved psychomotor development compared to never breastfed children. Human studies suggest that polyunsaturated fatty acids (PUFA), especially long chain PUFA (LC-PUFA) which are highly contained in breast milk, could explain this link, since they are needed for pre- and postnatal brain development. Our aim was to study the relationships between several measures of pre- and postnatal exposures to PUFA and child’s psychomotor...

  2. Opioid gene expression changes and post-translational histone modifications at promoter regions in the rat nucleus accumbens after acute and repeated 3,4-methylenedioxy-methamphetamine (MDMA) exposure.

    Science.gov (United States)

    Caputi, Francesca Felicia; Palmisano, Martina; Carboni, Lucia; Candeletti, Sanzio; Romualdi, Patrizia

    2016-12-01

    The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been shown to produce neurotoxic damage and long-lasting changes in several brain areas. In addition to the involvement of serotoninergic and dopaminergic systems, little information exists about the contribution of nociceptin/orphaninFQ (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by MDMA. Here we investigated the behavioral and molecular effects induced by acute (8mg/kg) or repeated (8mg/kg twice daily for seven days) MDMA exposure. MDMA exposure affected body weight gain and induced hyperlocomotion; this latter effect progressively decreased after repeated administration. Gene expression analysis indicated a down-regulation of the N/OFQ system and an up-regulation of the DYN system in the nucleus accumbens (NAc), highlighting an opposite systems regulation in response to MDMA exposure. Since histone modifications have been strongly associated to the addiction-related maladaptive changes, we examined two permissive (acH3K9 and me3H3K4) and two repressive transcription marks (me3H3K27 and me2H3K9) at the pertinent opioid gene promoter regions. Chromatin immunoprecipitation assays revealed that acute MDMA increased me3H3K4 at the pN/OFQ, pDYN and NOP promoters. Following acute and repeated treatment a significant decrease of acH3K9 at the pN/OFQ promoter was observed, which correlated with gene expression results. Acute treatment caused an acH3K9 increase and a me2H3K9 decrease at the pDYN promoter which matched its mRNA up-regulation. Our data indicate that the activation of the DYNergic stress system together with the inactivation of the N/OFQergic anti-stress system contribute to the neuroadaptive actions of MDMA and offer novel epigenetic information associated with MDMA abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

    International Nuclear Information System (INIS)

    Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

    1983-01-01

    Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

  4. Chronic copper exposure and fatty acid composition of the amphipod Dikerogammarus villosus: Results from a field study

    Energy Technology Data Exchange (ETDEWEB)

    Maazouzi, Chafik [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: maazouzi@univ-metz.fr; Masson, Gerard [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: masson1@univ-metz.fr; Izquierdo, Maria Soledad [Grupo de Investigacion en Acuicultura, ULPGC and ICCM, P.O. Box 56, 35200 Telde, Las Palmas de Gran Canaria (Spain)], E-mail: mizquierdo@dbio.ulpgc.es; Pihan, Jean-Claude [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: pihan@univ-metz.fr

    2008-11-15

    Field study allows assessment of long-term effects on fatty acid (FA) composition of organisms under chronic exposure to metals. One expected effect of copper is peroxidation of lipids and essentially polyunsaturated fatty acids (PUFA). FA analysis was established for the amphipod Dikerogammarus villosus subjected to different degrees of copper exposure (4-40 {mu}g Cu L{sup -1}). A previous study in our team showed that this species regulates its body Cu concentration (106-135 mg Cu kg{sup -1} dry weight). Despite the high capacity of bioaccumulation, the absence of a correlation between copper concentration in D. villosus and water prevents its use as bioindicator of copper pollution. Both sexes from the most polluted site showed the lowest total FA content, but the highest PUFA percent, mainly of the long-chained variety (C20-C22). Mechanisms leading to the prevention of lipid peroxidation in this species were discussed (metallothioneins and intracellular granules) and proposed with support from literature data. - Under chronic copper exposure, Dikerogammarus villosus loses in total fatty acids content but increases its essential {omega}3 and {omega}6 PUFA percent.

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

    Science.gov (United States)

    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. Dietary exposure of Hong Kong adults to fatty acid esters of 3-monochloropropane-1,2-diol.

    Science.gov (United States)

    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.

  7. Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

    Science.gov (United States)

    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 acid reflux episodes (pH 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 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.

  8. Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

    Directory of Open Access Journals (Sweden)

    Ana Laura Nicoletti Carvalho

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  10. SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, C-H; Lim, S-I [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ({sup 1}H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo {sup 1}H MRS. Methods: We used high-field {sup 1}H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

  11. SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

    International Nuclear Information System (INIS)

    Yoo, C-H; Lim, S-I; Song, K-H; Choe, B-Y; Woo, D-C

    2016-01-01

    Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ("1H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo "1H MRS. Methods: We used high-field "1H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

  12. [Secondary traumatization/trauma among employees in palliative care units--the products of prolonged repeated exposure to suffering and death].

    Science.gov (United States)

    Samson, Tali; Shvartzman, Pesach

    2012-11-01

    The palliative care philosophy accepts the dying process as a natural phase in the life cycle and provides quality end of life care for terminal patients and their family members. Prolonged exposure to the physical symptoms and pain, as well as the psychological, spiritual, and existential suffering of the dying patient, may be fertile ground for the development of post-traumatic stress symptoms among palliative care teams. Work-related positive outcomes (such as compassion, satisfaction and meaning) and work-related negative outcomes (such as compassion fatigue, secondary traumatization and burnout) can exist side by side, and the unique balance between them will determine the quality of life of the worker. This review presents the current knowledge about the prevalence and causes of work-related stress outcomes among palliative care teams and measurement tools that are available. The literature review discusses secondary traumatization in palliative care teams and relevant messages for the development of treatment options, burnout prevention programs and support interventions for professionals who lead the care for terminal patients in Israel.

  13. Repeated exposure of human fibroblasts to ionizing radiation reveals an adaptive response that is not mediated by interleukin-6 or TGF-β

    International Nuclear Information System (INIS)

    Dieriks, Birger; De Vos, Winnok; Baatout, Sarah; Van Oostveldt, Patrick

    2011-01-01

    Exposing cells to a low dose can protect them against a subsequent higher exposure. This phenomenon is known as adaptive response and is frequently observed in a variety of cells. Even though similarities are suspected with other non-targeted effects, such as bystander effects, the exact mechanism behind adaptive response is not fully clarified. In this study human primary fibroblasts were tested for their response to ionizing radiation (IR) after administrating a low priming dose (0.1-0.5 Gy). Both the abundance of γH2AX as a marker for double-stranded breaks and the levels of cytokines, secreted in the medium, were monitored in time. Upon challenge, IR-primed cells showed modified γH2AX spot size distributions and altered repair kinetics, consistent with an adaptive response. In addition, 24 h after priming with IR, four cytokines were significantly upregulated in the medium - GM-CSF (1.33x); IL6 (4.24x); IL8 (1.33x); TGF-β (1.46x). In order to mimick the protective effect of IR priming, we primed the cells with either IL6 or TGF-β. This did not elicit an altered γH2AX response as observed in IR-primed cells, indicating that the adaptive response in these primary fibroblasts is regulated in an IL-6 and TGF-β independent manner.

  14. School-based intervention with children. Peer-modeling, reward and repeated exposure reduce food neophobia and increase liking of fruits and vegetables.

    Science.gov (United States)

    Laureati, Monica; Bergamaschi, Valentina; Pagliarini, Ella

    2014-12-01

    This study investigated the effectiveness of the 'Food Dudes' school-based intervention consisting of rewards, peer-modeling and food exposure on food neophobia and the liking of fruits and vegetables (FV) in a large cohort of children. Five-hundred sixty children recruited from three schools were assigned to the experimental or control group. For 16 days, children in the experimental group watched motivational videos, were read letters to encourage them to eat FV and received a small reward for eating one portion of both a fruit and a vegetable. The control group was only provided with FV for the same time period. Food neophobia and liking were measured in both groups of children before and after the intervention, and a follow-up measurement was carried out 6 months later. The intervention was effective in reducing food neophobia and, most importantly, a persistent effect was observed 6 months after the intervention as children of the experimental group showed significantly lower neophobia scores than the control group. Additionally, the program was effective in increasing liking for both FV; however, this effect was maintained only for fruit after 6 months. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Koskela, A., E-mail: antti.koskela@oulu.fi [Institute of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, Faculty of Medicine, University of Oulu, Oulu (Finland); Finnilä, M.A. [Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu (Finland); Korkalainen, M. [National Institute for Health and Welfare, Department of Health Protection, Kuopio (Finland); Spulber, S. [Department of Neuroscience, Karolinska Institutet, Stockholm (Sweden); Koponen, J. [National Institute for Health and Welfare, Department of Health Protection, Kuopio (Finland); Håkansson, H. [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Tuukkanen, J. [Institute of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, Faculty of Medicine, University of Oulu, Oulu (Finland); Viluksela, M. [National Institute for Health and Welfare, Department of Health Protection, Kuopio (Finland); Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio (Finland)

    2016-06-15

    Perfluorooctanoic acid (PFOA) is a ubiquitous and persistent environmental chemical, which has been used extensively due to its stability and surface tension-lowering properties. Toxicological effects include induction of neonatal mortality and reproductive toxicity. In this study, pregnant C57BL/6 mice were exposed orally to 0.3 mg PFOA/kg/day throughout pregnancy, and female offspring were studied at the age of 13 or 17 months. Morphometrical and biomechanical properties of femurs and tibias were analyzed with micro-computed tomography and 3-point bending, and bone PFOA concentrations were determined by mass spectrometry. The effects of PFOA on bone cell differentiation were studied in osteoclasts from C57BL/6 mice and in the MC3T3 pre-osteoblast cell line. PFOA exposed mice showed increased femoral periosteal area as well as decreased mineral density of tibias. Biomechanical properties of these bones were not affected. Bone PFOA concentrations were clearly elevated even at the age of 17 months. In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100 μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1–1.0 μM, but decreased at higher concentrations. The results show that PFOA accumulates in bone and is present in bones until the old age. PFOA has the potential to influence bone turnover over a long period of time. Therefore bone is a target tissue for PFOA, and altered bone geometry and mineral density seem to persist throughout the life of the animal. - Highlights: • Bone is a target tissue for PFOA both in vivo and in vitro. • Maternal exposure during pregnancy results in PFOA accumulation in bone of the offspring. • PFOA is present in bones until the old age. • PFOA causes mild alterations in bone morphometry

  16. Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation

    International Nuclear Information System (INIS)

    Koskela, A.; Finnilä, M.A.; Korkalainen, M.; Spulber, S.; Koponen, J.; Håkansson, H.; Tuukkanen, J.; Viluksela, M.

    2016-01-01

    Perfluorooctanoic acid (PFOA) is a ubiquitous and persistent environmental chemical, which has been used extensively due to its stability and surface tension-lowering properties. Toxicological effects include induction of neonatal mortality and reproductive toxicity. In this study, pregnant C57BL/6 mice were exposed orally to 0.3 mg PFOA/kg/day throughout pregnancy, and female offspring were studied at the age of 13 or 17 months. Morphometrical and biomechanical properties of femurs and tibias were analyzed with micro-computed tomography and 3-point bending, and bone PFOA concentrations were determined by mass spectrometry. The effects of PFOA on bone cell differentiation were studied in osteoclasts from C57BL/6 mice and in the MC3T3 pre-osteoblast cell line. PFOA exposed mice showed increased femoral periosteal area as well as decreased mineral density of tibias. Biomechanical properties of these bones were not affected. Bone PFOA concentrations were clearly elevated even at the age of 17 months. In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100 μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1–1.0 μM, but decreased at higher concentrations. The results show that PFOA accumulates in bone and is present in bones until the old age. PFOA has the potential to influence bone turnover over a long period of time. Therefore bone is a target tissue for PFOA, and altered bone geometry and mineral density seem to persist throughout the life of the animal. - Highlights: • Bone is a target tissue for PFOA both in vivo and in vitro. • Maternal exposure during pregnancy results in PFOA accumulation in bone of the offspring. • PFOA is present in bones until the old age. • PFOA causes mild alterations in bone morphometry

  17. The impact of long term exposure to phthalic acid esters on reproduction in Chinese rare minnow (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Guo, Yongyong; Yang, Yuanjin; Gao, Yong; Wang, Xianfeng; Zhou, Bingsheng

    2015-01-01

    The environmental risk of phthalic acid esters (PAEs) is of great concern. We investigated the reproductive impairment of di-(2-ethylhexyl)-phthalate (DEHP) on Chinese rare minnow, an endemic fish inhabiting the upper streams of the Yangtze River. Chinese rare minnow larvae were exposed to environmentally relevant concentrations of DEHP (0, 4.2, 13.3, and 40.8 μg/L) for 6 months. Plasma testosterone and 17β-estradiol levels decreased in females, accompanied by downregulation of cyp19a and cyp17 gene transcription in ovary. Increases in plasma testosterone concentration were observed in males, accompanied by downregulation of cyp19a gene transcription in testes. Hepatic VTG gene transcription was upregulated in males and females. Exposure to DEHP reduced egg production and inhibited oocyte maturation in females and retarded spermiation in males. Decreased egg protein content was measured in F1 embryos. These results indicate that long-term exposure to low concentrations of DEHP (13.3 μg/L) causes endocrine disruption and impairs fish reproduction. - Highlights: • PAEs in the aquatic environment may pose risk to endemic fish species. • Long-term exposure to DEHP affected sex hormone levels in rare minnow. • DEHP affected gonad development. • Long-term exposure caused reduction of fecundity, but not sex ratio. • Environmentally relevant concentrations of DEHP impair fish reproduction. - Long-term exposure to low concentrations of DEHP adversely impact Chinese rare minnow reproduction

  18. 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.

    Science.gov (United States)

    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.

  19. In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures.

    Science.gov (United States)

    Schlage, Walter K; Iskandar, Anita R; Kostadinova, Radina; Xiang, Yang; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Talikka, Marja; Geertz, Marcel; Mathis, Carole; Ivanov, Nikolai; Hoeng, Julia; Peitsch, Manuel C

    2014-10-01

    Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air-liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products.

  20. Immunomodulatory effects of exposure to polychlorinated biphenyls and perfluoroalkyl acids in East Greenland ringed seals (Pusa hispida)

    Energy Technology Data Exchange (ETDEWEB)

    Levin, Milton, E-mail: Milton.levin@uconn.edu [Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089 (United States); Gebhard, Erika; Jasperse, Lindsay [Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089 (United States); Desforges, Jean-Pierre; Dietz, Rune; Sonne, Christian; Eulaers, Igor [Department of Bioscience, Arctic Research Centre (ARC), Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde (Denmark); Covaci, Adrian [Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, BE-2610 Wilrijk (Belgium); Bossi, Rossana [Department of Environmental Science, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde (Denmark); De Guise, Sylvain [Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089 (United States)

    2016-11-15

    To better elucidate the potential immune-related health effects of exposure to environmentally persistent organic pollutants (POP), such as polychlorinated biphenyls (PCBs) and perfluoroalkyl substances (PFASs), in ringed seals (Pusa hispida), a sentinel Arctic species, we assessed 1) associations between mitogen-induced lymphocyte proliferation and in vivo tissue contaminant burdens, and 2) the concentration-response effects of in vitro exposure to PFASs and PCB congeners on mitogen-induced lymphocyte proliferation. Upon in vitro contaminant exposure, the non-coplanar PCB congeners CB 138, 153, and 180, but not the coplanar CB 169, significantly reduced lymphocyte proliferation between 10 and 20 µg g{sup −1} ww. The respective in vitro EC{sub 50} values for these congeners were 13.3, 20.7, 20.8, and 54.6 µg g{sup −1} ww. No modulation of lymphocyte proliferation was observed upon in vitro exposure to two individual PFASs, perfluorooctane sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA), at concentrations up to 1000 ng g-1. In addition, no significant correlations were found between lymphocyte proliferation and any blood or blubber contaminant measured. Taken together, these data suggest this population of ringed seals is not currently at high risk of altered lymphocyte proliferation from exposure to the POPs or PFASs in this study. - Highlights: • Assess relationships between tissue contaminants and changes in immune function. • Risk for contaminant-induced immunotoxicity in East Greenland ringed seal is low. • Weight of evidence suggest non-coplanar PCBs are immunotoxic at high concentrations.

  1. Effects of chronic fly ash exposure on golden hamsters: changes in lung phospholipids and their fatty acid composition as a result of inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, I; Negishi, T; Kamihira, M

    1986-01-01

    Changes in lung phospholipids of golden hamsters exposed to 2 mg/mT coal fly ash for 180 days, 7 days/week, 20 hours/day were examined. In the exposed group the amount of phospholipids in lavaged lung organ increased significantly compared with the control group, but in pulmonary surfactant did not. As regards lipid composition of phospholipids in lavaged lung organ, phosphatidylcholine was slightly increased but sphingomyelin was decreased by exposure. Some significant changes in fatty acid composition of phospholipids were observed between exposed and control group. In pulmonary surfactant, palmitic acid showed no change but myristic acid and oleic acid decreased. On the other hand, in lavaged lung organ, palmitic acid increased but stearic acid and decosatetraenoic acid decreased. Arachidonic acid composition increased in both parts of lung. An increase in the proportion of polyunsaturated fatty acid in whole fatty acid of phospholipids was found in pulmonary surfactant of exposed hamsters. 24 refs., 2 figs., 3 tabs.

  2. A four-year field program investigating long-term effects of repeated exposure of honey bee colonies to flowering crops treated with thiamethoxam.

    Directory of Open Access Journals (Sweden)

    Edward Pilling

    Full Text Available Neonicotinoid residues in nectar and pollen from crop plants have been implicated as one of the potential factors causing the declines of honey bee populations. Median residues of thiamethoxam in pollen collected from honey bees after foraging on flowering seed treated maize were found to be between 1 and 7 µg/kg, median residues of the metabolite CGA322704 (clothianidin in the pollen were between 1 and 4 µg/kg. In oilseed rape, median residues of thiamethoxam found in pollen collected from bees were between <1 and 3.5 µg/kg and in nectar from foraging bees were between 0.65 and 2.4 µg/kg. Median residues of CGA322704 in pollen and nectar in the oilseed rape trials were all below the limit of quantification (1 µg/kg. Residues in the hive were even lower in both the maize and oilseed rape trials, being at or below the level of detection of 1 µg/kg for bee bread in the hive and at or below the level of detection of 0.5 µg/kg for hive nectar, honey and royal jelly samples. The long-term risk to honey bee colonies in the field was also investigated, including the sensitive overwintering stage, from four years consecutive single treatment crop exposures to flowering maize and oilseed rape grown from thiamethoxam treated seeds at rates recommended for insect control. Throughout the study, mortality, foraging behavior, colony strength, colony weight, brood development and food storage levels were similar between treatment and control colonies. Detailed examination of brood development throughout the year demonstrated that colonies exposed to the treated crop were able to successfully overwinter and had a similar health status to the control colonies in the following spring. We conclude that these data demonstrate there is a low risk to honey bees from systemic residues in nectar and pollen following the use of thiamethoxam as a seed treatment on oilseed rape and maize.

  3. A Four-Year Field Program Investigating Long-Term Effects of Repeated Exposure of Honey Bee Colonies to Flowering Crops Treated with Thiamethoxam

    Science.gov (United States)

    Pilling, Edward; Campbell, Peter; Coulson, Mike; Ruddle, Natalie; Tornier, Ingo

    2013-01-01

    Neonicotinoid residues in nectar and pollen from crop plants have been implicated as one of the potential factors causing the declines of honey bee populations. Median residues of thiamethoxam in pollen collected from honey bees after foraging on flowering seed treated maize were found to be between 1 and 7 µg/kg, median residues of the metabolite CGA322704 (clothianidin) in the pollen were between 1 and 4 µg/kg. In oilseed rape, median residues of thiamethoxam found in pollen collected from bees were between <1 and 3.5 µg/kg and in nectar from foraging bees were between 0.65 and 2.4 µg/kg. Median residues of CGA322704 in pollen and nectar in the oilseed rape trials were all below the limit of quantification (1 µg/kg). Residues in the hive were even lower in both the maize and oilseed rape trials, being at or below the level of detection of 1 µg/kg for bee bread in the hive and at or below the level of detection of 0.5 µg/kg for hive nectar, honey and royal jelly samples. The long-term risk to honey bee colonies in the field was also investigated, including the sensitive overwintering stage, from four years consecutive single treatment crop exposures to flowering maize and oilseed rape grown from thiamethoxam treated seeds at rates recommended for insect control. Throughout the study, mortality, foraging behavior, colony strength, colony weight, brood development and food storage levels were similar between treatment and control colonies. Detailed examination of brood development throughout the year demonstrated that colonies exposed to the treated crop were able to successfully overwinter and had a similar health status to the control colonies in the following spring. We conclude that these data demonstrate there is a low risk to honey bees from systemic residues in nectar and pollen following the use of thiamethoxam as a seed treatment on oilseed rape and maize. PMID:24194871

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

    International Nuclear Information System (INIS)

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

    1989-01-01

    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 in 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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 in 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.

  6. Microtensile strength of spruce pine after exposure to acids and bases

    Science.gov (United States)

    Floyd G. Manwiller; Paul R. Godfrey

    1972-01-01

    Earlywood and latewood microtensile specimens from 12 trees of Pinus glabra Wal. were subjected to 10-percent solution of 5 acids and 3 bases at 90oC for up to 3 hours. Hydrochloric and sulfuric acids were the most damaging, lowering maximum tensile strength 27 and 17 percent in earlywood and 36 and 39 percent in latewood; they...

  7. Identification of dynamic changes in proteins associated with the cellular cytoskeleton after exposure to okadaic acid

    DEFF Research Database (Denmark)

    Opsahl, Jill A; Ljostveit, Sonja; Solstad, Therese

    2013-01-01

    be combined with control cells before the isolation of lipid rafts. Protein phosphorylation events and translocations induced by okadaic acid were identified by mass spectrometry. Okadaic acid was shown to regulate the phosphorylation status and location of proteins associated with the actin cytoskeleton...... of the cortical actin cytoskeleton and cell detachment....

  8. Microtensile strength of spruce pine after exposure to acids and bases

    Science.gov (United States)

    F.G. Manwiller; P.R. Godfrey

    1973-01-01

    Earlywood and latewood microtensile specimens from 12 trees of Pinus glabra Walt. were subjected to 10-percent solution of 5 acids and 3 bases at good for up to 3 hours. Hydrochloric and sulfuric acids were the most damaging, lowering maximum tensile strength 27 and 17 percent in earlywood and 36 and 39 percent in latewood; they reduced work to maximum load 40 percent...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. - Highlights: • Three PFOS precursors and six diPAPs were detected in food pools. • Precursor concentrations were highest in 1999 and 2005 food pools, and lowest in 2010. • The relative importance of precursors to total PFOS dietary intake was <4%. • The relative importance of diPAPs as an indirect dietary source of PFCAs was chain length dependent. - The relative contribution of precursors to PFOS dietary intakes is small, whereas the contribution of diPAPs to PFCA dietary intakes varies with the PFCA chain length

  10. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Ruben, E-mail: Ruben.Strecker@cos.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Weigt, Stefan, E-mail: stefan.weigt@merckgroup.com [Institute of Toxicology, Merck KGaA, 64293 Darmstadt (Germany); Braunbeck, Thomas, E-mail: braunbeck@uni-hd.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany)

    2013-04-15

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head.

  11. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    International Nuclear Information System (INIS)

    Strecker, Ruben; Weigt, Stefan; Braunbeck, Thomas

    2013-01-01

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head

  12. Effects of cadmium exposure on phytochelatin and the synthesis of abscisic acid in funalia trogii

    Energy Technology Data Exchange (ETDEWEB)

    Yuerekli, F.; Porgali, Z.B. [Inonu University, Arts and Science Faculty, Department of Biology, 44069 Malatya (Turkey); Uenyayar, A.; Mazmanci, M.A. [Mersin University, Engineering Faculty, Engineering Faculty, 33000 Mersin (Turkey)

    2004-08-01

    Heavy metal toxicity poses major environmental and health problems as heavy metals are more difficult to remediate than chemical contaminants, which can be degraded by microorganisms. Phytochelatins are formed in plants and some fungi upon exposure to a range of different heavy metals. Fungi show sensitivity to many environmental factors, including nutrient limitation, changes in carbon sources and heavy metal exposure. (Abstract Copyright [2004], Wiley Periodicals, Inc.)

  13. Resistance of an enamel-bonding agent to saliva and acid exposure in vitro assessed by liquid scintillation.

    Science.gov (United States)

    Schmidlin, P R; Göhring, T N; Sener, B; Lutz, F

    2002-06-01

    To determine the leakage and resistance of a bonding agent and a light-curing fine hybrid composite when exposed to saliva or lactic acid (pH 4) in vitro. Twenty discs in each of four groups of selected irradiated bovine lower central incisors were treated with one of three sealing options: an enamel bond (Heliobond, Vivadent, Schaan, Liechenstein) in a single-step application; Heliobond in a two-step application; and Tetric Flow (Vivadent) as the negative control. One group served as the positive control and remained unsealed. Loss of apatite was determined using the radiochemical method of liquid scintillation. The Cherenkov radiation was assessed in order to evaluate the acid resistance and leakage of smooth surface enamel bonding after exposure to saliva and lactic acid. In addition, replicas were made for SEM analysis of micromorphologic surface changes. A mean loss of 416.5 g (s.d. 57.0) apatite was observed over the unsealed sites following 14 days of exposure to lactic acid. The application of Heliobond in a one- and two-step application still revealed a remarkable degree of leakage, and substance losses of 196.5 g (s.d. 38.9) and 161.8 g (s.d. 39.7), but a protective potential was evident. In saliva, untreated, as well as sealed teeth, showed a modest leakage that was less than 20 g. When Tetric Flow was used (negative control) leakage was reduced to a minimum of 2.4 g (s.d. 1.0) in saliva and 12.8 g (s.d. 19.6) in lactic acid. These results were confirmed by SEM analysis. The method of liquid scintillation was revealed to be of considerable value in evaluating leakage and acid resistance of potential smooth enamel sealing options. Sealing with an unfilled resin still demonstrated remarkable levels of acid dissolution, although a protection tendency could be observed. This leads to the conclusion that there is a need for further investigation to establish more acid-resistant enamel sealing agents.

  14. The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: IV. Vascular effects of repeated inhalation exposure to a mixture of five inorganic gases.

    Science.gov (United States)

    Mauderly, J L; Kracko, D; Brower, J; Doyle-Eisele, M; McDonald, J D; Lund, A K; Seilkop, S K

    2014-09-01

    An experiment was conducted to test the hypothesis that a mixture of five inorganic gases could reproduce certain central vascular effects of repeated inhalation exposure of apolipoprotein E-deficient mice to diesel or gasoline engine exhaust. The hypothesis resulted from preceding multiple additive regression tree (MART) analysis of a composition-concentration-response database of mice exposed by inhalation to the exhausts and other complex mixtures. The five gases were the predictors most important to MART models best fitting the vascular responses. Mice on high-fat diet were exposed 6 h/d, 7 d/week for 50 d to clean air or a mixture containing 30.6 ppm CO, 20.5 ppm NO, 1.4 ppm NO₂, 0.5 ppm SO₂, and 2.0 ppm NH₃ in air. The gas concentrations were below the maxima in the preceding studies but in the range of those in exhaust exposure levels that caused significant effects. Five indicators of stress and pro-atherosclerotic responses were measured in aortic tissue. The exposure increased all five response indicators, with the magnitude of effect and statistical significance varying among the indicators and depending on inclusion or exclusion of an apparent outlying control. With the outlier excluded, three responses approximated predicted values and two fell below predictions. The results generally supported evidence that the five gases drove the effects of exhaust, and thus supported the potential of the MART approach for identifying putative causal components of complex mixtures.

  15. Element uptake and physiological responses of Lactuca sativa upon co-exposures to tourmaline and dissolved humic acids.

    Science.gov (United States)

    Jia, Weili; Wang, Cuiping; Ma, Chuanxin; Wang, Jicheng; Sun, Hongwen

    2018-03-27

    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.

  16. Minimal health impacts but detectable tissue residues after exposure of northern leopard frogs (Lithobates pipiens) to commercial naphthenic acids

    International Nuclear Information System (INIS)

    Hersikorn, B.; Young, R.; Fedorak, P.; Smits, J.

    2010-01-01

    This presentation reported on a study that examined whether naphthenic acids (NAs) are a toxic component in oil sands process-affected materials (OSPM). The study investigated the toxicity of commercial (Refined Merichem) NAs to native amphibians (northern leopard frogs) exposed to saline conditions comparable to those of reclaimed wetlands on oil sand leases. Gas chromatography-mass spectroscopy analysis showed that the exposure of frogs to NAs solutions for 28 days resulted in proportional NA concentrations in extracts of frog muscle tissue. Biological assays were performed to determine if the increasing exposure to NAs caused a proportional compromise in the health of test animals. The innate immune function, thyroid hormones, and hepatic detoxification enzyme induction did not differ in response to increased tissue concentrations of NAs. The commercial NAs were absorbed and deposited in muscle tissue. It was concluded that NAs play only a small, if any, role in the toxicity of OSPM to frogs.

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

    OpenAIRE

    Leduc, Dimitri; Fally, Sophie; De Vuyst, Paul; Wollast, Roland; Yernault, Jean Claude

    1995-01-01

    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 fog...

  18. Analysis of three variable number terminal repeat loci is sufficient to characterize the deoxyribonucleic acid fingerprints of a panel of human tumor cell lines.

    Science.gov (United States)

    Anding, Allyson L; Reiss, Tanika; Germain, Glen S

    2003-01-01

    Using primers for the MCT118, YNZ22, and COL2A1 loci in polymerase chain reaction analysis we could distinguish among the approximately 20 cell lines routinely maintained in our laboratory. We also demonstrated that the cell line NB-1691 (a neuroblastoma) and its xenograft had an identical number of repeats at two loci. Rh30 (a rhabdomyosarcoma) made resistant to rapamycin was identical to its parent line and to a subline that had reverted to sensitivity after it was cultured without rapamycin in the medium.

  19. Early life exposure to polyunsaturated fatty acids and psychomotor development in children from the EDEN mother-child cohort

    Directory of Open Access Journals (Sweden)

    Bernard Jonathan Y.

    2016-01-01

    Full Text Available Epidemiological studies have reported that breastfed children have improved psychomotor development compared to never breastfed children. Human studies suggest that polyunsaturated fatty acids (PUFA, especially long chain PUFA (LC-PUFA which are highly contained in breast milk, could explain this link, since they are needed for pre- and postnatal brain development. Our aim was to study the relationships between several measures of pre- and postnatal exposures to PUFA and child’s psychomotor development at 2 and 3 years in the EDEN cohort. We evaluated breastfeeding duration, colostrum PUFA levels and maternal dietary PUFA intake during pregnancy, that we related with three scores of psychomotor development, after taking into account potential confounders. Breastfeeding duration was positively associated with psychomotor development. No relationship was found with both pre- and postnatal exposure to LC-PUFA. However, the maternal dietary omega-6/omega-3 ratio was negatively associated with psychomotor development, mainly driven by intake in linoleic acid (LA. Among breastfed children, linoleic acid levels were negatively associated with psychomotor development. Furthermore, children exposed to the highest colostrum LA levels tended to score closer to never breastfed children than to children exposed to the lowest colostrums LA levels. Taken together, these results do not provide evidence in favour of a positive role of pre- and postnatal exposure to LC-PUFA on later psychomotor development, but highlight a potential negative role of being exposed in early life to high LA levels. From a public health perspective, this work reiterates the need to promote breastfeeding duration, and to monitor the balance of PUFA intake during pregnancy and lactation periods.

  20. Association of Lead Exposure, Serum Uric Acid and Parameters of Renal Function in Nigerian Lead-Exposed Workers

    Directory of Open Access Journals (Sweden)

    DD Alasia

    2010-09-01

    Full Text Available Background: 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. Objective: To determine the relationship between serum uric acid and renal function indices in lead-exposed workers. Methods: 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. Results: 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. Conclusion: People with occupational lead exposure are at risk of developing hyperuricemia and renal impairment.

  1. Laser confers less embryo exposure than acid tyrode for embryo biopsy in preimplantation genetic diagnosis cycles: a randomized study.

    Science.gov (United States)

    Geber, Selmo; Bossi, Renata; Lisboa, Cintia B; Valle, Marcelo; Sampaio, Marcos

    2011-04-28

    We compared two methods of zona pellucida drilling. 213 embryos were biopsied with acid Tyrode. Each biopsy took 3 minutes and the entire procedure ~29 minutes. 5% of blastomeres lysed, 49% of embryos became blastocyst and 36% of patients became pregnant. 229 embryos were biopsied with laser. Each biopsy took 30 seconds and the entire procedure ~7 minutes. 2.5% of blastomeres lysed, 50.6% of embryos became blastocyst and 47% of patients became pregnant. We can conclude that laser can be used for embryo biopsy. Reduction of embryo exposure and of removed blastomeres is associated with increased blastocysts available for transfer and a better clinical outcome.

  2. Laser confers less embryo exposure than acid tyrode for embryo biopsy in preimplantation genetic diagnosis cycles: a randomized study

    Directory of Open Access Journals (Sweden)

    Valle Marcelo

    2011-04-01

    Full Text Available Abstract We compared two methods of zona pellucida drilling. 213 embryos were biopsied with acid Tyrode. Each biopsy took 3 minutes and the entire procedure ~29 minutes. 5% of blastomeres lysed, 49% of embryos became blastocyst and 36% of patients became pregnant. 229 embryos were biopsied with laser. Each biopsy took 30 seconds and the entire procedure ~7 minutes. 2.5% of blastomeres lysed, 50.6% of embryos became blastocyst and 47% of patients became pregnant. We can conclude that laser can be used for embryo biopsy. Reduction of embryo exposure and of removed blastomeres is associated with increased blastocysts available for transfer and a better clinical outcome.

  3. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

    2007-01-01

    as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

  4. Oleic acid exposure of cultured endothelial cells alters lipid mediator production

    Science.gov (United States)

    Diesel, biodiesel, and other combustion sources contain free fatty acid (FFA) components capable of entering the body through particulate inhalation. FFA can also be endogenously released into circulation in response to stress. When in circulation, bioactive FFA may interact with...

  5. Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption

    DEFF Research Database (Denmark)

    Mahaffey, K. R.; Sunderland, E. M.; Chan, H. M.

    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. (C) 2011...

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

    Science.gov (United States)

    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

  7. Molecular characterization of long direct repeat (LDR) sequences expressing a stable mRNA encoding for a 35-amino-acid cell-killing peptide and a cis-encoded small antisense RNA in Escherichia coli.

    Science.gov (United States)

    Kawano, Mitsuoki; Oshima, Taku; Kasai, Hiroaki; Mori, Hirotada

    2002-07-01

    Genome sequence analyses of Escherichia coli K-12 revealed four copies of long repetitive elements. These sequences are designated as long direct repeat (LDR) sequences. Three of the repeats (LDR-A, -B, -C), each approximately 500 bp in length, are located as tandem repeats at 27.4 min on the genetic map. Another copy (LDR-D), 450 bp in length and nearly identical to LDR-A, -B and -C, is located at 79.7 min, a position that is directly opposite the position of LDR-A, -B and -C. In this study, we demonstrate that LDR-D encodes a 35-amino-acid peptide, LdrD, the overexpression of which causes rapid cell killing and nucleoid condensation of the host cell. Northern blot and primer extension analysis showed constitutive transcription of a stable mRNA (approximately 370 nucleotides) encoding LdrD and an unstable cis-encoded antisense RNA (approximately 60 nucleotides), which functions as a trans-acting regulator of ldrD translation. We propose that LDR encodes a toxin-antitoxin module. LDR-homologous sequences are not pre-sent on any known plasmids but are conserved in Salmonella and other enterobacterial species.

  8. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

    Science.gov (United States)

    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

  9. Risk assessment of plant food supplements and other herbal products containing aristolochic acids using the margin of exposure (MOE) approach.

    Science.gov (United States)

    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.

  10. Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice

    DEFF Research Database (Denmark)

    Ordóñez-Gutiérrez, Lara; Re, Francesca; Bereczki, Erika

    2015-01-01

    , it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid...... Aβ may be therapeutically relevant in AD. FROM THE CLINICAL EDITOR: Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected...

  11. What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

    Science.gov (United States)

    Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

    2013-11-01

    Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients

  12. The leucine-rich repeat structure.

    Science.gov (United States)

    Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

    2008-08-01

    The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

  13. Calculation of chemical elimination half-life from blood with an ongoing exposure source: the example of perfluorooctanoic acid (PFOA).

    Science.gov (United States)

    Russell, Mark H; Waterland, Robert L; Wong, Fiona

    2015-06-01

    Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.

    Science.gov (United States)

    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.

  15. Fish-friendly prophylaxis/disinfection in aquaculture: Low concentration of peracetic acid is stress-free to the carp (Cyprinus carpio) after repeated applications

    Science.gov (United States)

    Application of peracetic acid (PAA) at low concentrations has been proved to be a broad functional and eco-friendly prophylaxis/disinfection method against various fish pathogens. Therefore, regular applications of low concentration PAA is sufficient to control (potential) pathogens in recirculatin...

  16. Dietary exposure to selected Perfluoroalkyl acids (PFAAs) in four European regions

    NARCIS (Netherlands)

    Klenow, S.; Heinemeyer, G.; Brambilla, G.; Dellatte, E.; Herzke, D.; de Voogt, P.

    2013-01-01

    The dietary exposure to selected PFAAs was estimated in four selected European states (Belgium, the Czech Republic, Italy and Norway) representing Western, Southern, Eastern and Northern Europe. The harmonised sampling programme designed in the European Union project PERFOOD was targeted at

  17. Stress responses in juvenile pacu (Piaractus mesopotamicus submitted to repeated air exposure = Respostas de estresse em juvenis de pacu (Piaractus mesopotamicus submetidos à exposição aérea repetitiva

    Directory of Open Access Journals (Sweden)

    Jaqueline Dalbello Biller

    2008-01-01

    Full Text Available Pacu juveniles (5.2 ± 1.5 g were submitted to two one-minute air exposures in a 24h interval, and sampled before the exposure (control and 5, 15, 30 and 60 min., 24 and 48h afterwards for whole-body cortisol, sodium, potassium and calcium ion concentrations. For the first air exposure, there was a trend of increased cortisol concentration after 15 min., whereas in the second air exposure, the cortisol concentration increased significantly within 5 min. after stress was induced. Sodium ion concentrationincreased significantly 24h after both air exposures. Potassium concentration presented fluctuations over the experimental period. Calcium ion concentration increased progressively from 5 to 30 min., in both air exposures. The repeated air exposures exacerbated the cortisol response, but they did not affect the recovery ability of pacu over the experimental period. Additionally, the whole-body cortisol measurement might be a reliable indicator of stress, when sampled fish are smaller and blood volumes are very low, making samples inadequate for analysis.Juvenis de pacu (5,2 ± 1,5 g foram submetidos a duas exposições aéreas de um minuto, em intervalo de 24 horas, e amostradosantes da exposição (controle e 5, 15, 30 e 60 min., 24 e 48 horas depois para análise da concentração corporal de cortisol e dos íons sódio, potássio e cálcio. Na primeira exposição, os peixes apresentaram concentrações de cortisol aumentadas a partir de 15 min., embora não diferissem estatisticamente do controle. Na segunda exposição, a concentração de cortisol aumentou significativamente aos 5 min., retornando às concentrações equivalentes às dos peixes-controle em 30 min.. A concentração do íon sódio aumentousignificativamente 24 horas depois das duas exposições aéreas. A concentração do íon potássio apresentou flutuações durante o experimento, enquanto a do cálcio apresentou-se reduzida aos 5 min, aumentando gradativamente até os 30

  18. Gene Transcription and Virulence Potential of Listeria monocytogenes Strains After Exposure to Acidic and NaCl Stress

    DEFF Research Database (Denmark)

    Olesen, Inger; Vogensen, Finn Kvist; Jespersen, Lene

    2009-01-01

    transcription were observed both after exposure to shock (six genes) and after long-term adaptation to stress (18 genes). In the shock experiments, a transient induction of clpC and clpE was seen for both strains, while transient induction of sigB, inlA, and inlB was observed for strain 4140 only; actA was only...... induced in EGD-e after NaCl shock. The longterm stress experiments were included to imitate the stress conditions encountered by L. monocytogenes when present in food products. Long-term adaptation of EGD-e to acidic stress induced transcription of iap and repressed flaA, while genes related to stress......Gene transcription and virulence potential of two strains of Listeria monocytogenes, EGD-e and 4140, were compared by quantitative real-time polymerase chain reaction and in a Caco-2 in vitro model after exposure to acidic (pH 5.5) and NaCl (4.5% w=v) stress. Strain-dependent differences in gene...

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

    Science.gov (United States)

    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

  20. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lamparter, Christina L. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L 3N6 (Canada)

    2016-09-01

    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 h 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 activity

  1. Human exposure assessment of silver and copper migrating from an antimicrobial nanocoated packaging material into an acidic food simulant.

    Science.gov (United States)

    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.

  2. Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

    International Nuclear Information System (INIS)

    Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech; Turski, Waldemar A.; Dekundy, Andrzej

    2009-01-01

    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 α7 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-β-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 μg/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.

  3. Efficacy of repeated trickle applications of oxalic acid in syrup for varroosis control in Apis mellifera: influence of meteorological conditions and presence of brood.

    Science.gov (United States)

    Bacandritsos, Nicolaos; Papanastasiou, Iosif; Saitanis, Costas; Nanetti, Antonio; Roinioti, Erifylli

    2007-09-01

    Oxalic acid field trails for the control of varroosis (Varroa destructor) were carried out in an apiary located on the Mt. Imittos (Attica, Greece). The colonies received four successive applications (approximately one every 16 days) with 4.2% oxalic acid (OA) and 60% sugar solution by trickling method with two alternative types of syringes (an automatic self-filling dosing and a single-use) from the broodright to broodless period. The results indicate that the first three applications (from 6th October to 25th November-broodright period) resulted in 65.3% cumulative mite mortality, while only the last application (after the 26th November-broodless period) resulted in 77.3% mite mortality. Very low outern temperatures reduce to the minimum the bee movability, which may result into a slower development of the OA efficacy. No poor colony growth or queen loss were observed even if the bee colonies were received the four successive OA applications with the last one taken place at a very low outern temperature (6.2 degrees C). The trickling method using an automatic-filling syringe seems to be a very quick way for applying oxalic acid in large apiaries (approximately 150hives/h).

  4. Resistance of biofilm-covered mortars to microbiologically influenced deterioration simulated by sulfuric acid exposure

    Energy Technology Data Exchange (ETDEWEB)

    Soleimani, Sahar, E-mail: ssoleima@connect.carleton.ca; Isgor, O. Burkan, E-mail: burkan_isgor@carleton.ca; Ormeci, Banu, E-mail: banu_ormeci@carleton.ca

    2013-11-15

    Following the reported success of biofilm applications on metal surfaces to inhibit microbiologically influenced corrosion, effectiveness and sustainability of E. coli DH5α biofilm on mortar surface to prevent microbiologically influenced concrete deterioration (MICD) are investigated. Experiments simulating microbial attack were carried out by exposing incrementally biofilm-covered mortar specimens to sulfuric acid solutions with pH ranging from 3 to 6. Results showed that calcium concentration in control reactors without biofilm was 23–47% higher than the reactors with biofilm-covered mortar. Formation of amorphous silica gel as an indication of early stages of acid attack was observed only on the control mortar specimens without biofilm. During acidification, the biofilm continued to grow and its thickness almost doubled from ∼ 30 μm before acidification to ∼ 60 μm after acidification. These results demonstrated that E. coli DH5α biofilm was able to provide a protective and sustainable barrier on mortar surfaces against medium to strong sulfuric acid attack. -- Highlights: •Effectiveness of E.coli DH5α biofilm to prevent MICD was studied. •Conditions that lead to MICD were simulated by chemical acidification. •Biofilm-covered mortar specimens were exposed to sulfuric acid solutions. •The presence of biofilm helped reduce the chemically-induced mortar deterioration. •Biofilm remained alive and continued to grow during the acidification process.

  5. Resistance of biofilm-covered mortars to microbiologically influenced deterioration simulated by sulfuric acid exposure

    International Nuclear Information System (INIS)

    Soleimani, Sahar; Isgor, O. Burkan; Ormeci, Banu

    2013-01-01

    Following the reported success of biofilm applications on metal surfaces to inhibit microbiologically influenced corrosion, effectiveness and sustainability of E. coli DH5α biofilm on mortar surface to prevent microbiologically influenced concrete deterioration (MICD) are investigated. Experiments simulating microbial attack were carried out by exposing incrementally biofilm-covered mortar specimens to sulfuric acid solutions with pH ranging from 3 to 6. Results showed that calcium concentration in control reactors without biofilm was 23–47% higher than the reactors with biofilm-covered mortar. Formation of amorphous silica gel as an indication of early stages of acid attack was observed only on the control mortar specimens without biofilm. During acidification, the biofilm continued to grow and its thickness almost doubled from ∼ 30 μm before acidification to ∼ 60 μm after acidification. These results demonstrated that E. coli DH5α biofilm was able to provide a protective and sustainable barrier on mortar surfaces against medium to strong sulfuric acid attack. -- Highlights: •Effectiveness of E.coli DH5α biofilm to prevent MICD was studied. •Conditions that lead to MICD were simulated by chemical acidification. •Biofilm-covered mortar specimens were exposed to sulfuric acid solutions. •The presence of biofilm helped reduce the chemically-induced mortar deterioration. •Biofilm remained alive and continued to grow during the acidification process

  6. Liquid chromatographic determination of urinary 2-thiothiazolidine-4-carboxylic acid, a biomarker of carbon disulphide exposure.

    Science.gov (United States)

    Lee, B L; Yang, X F; New, A L; Ong, C N

    1995-06-23

    An effective gradient high-performance liquid chromatographic method for baseline separation of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA), with photodiode array detection at 271 nm was described. o-Methylhippuric acid was used as an internal standard (I.S.). A 1-ml urine sample was saturated with 300 mg of sodium sulphate, acidified with 100 microliters of 6 M hydrochloric acid, extracted twice with 2 ml of diethyl ether, and after evaporation, the residue was taken up in 1 ml of 0.1% (v/v) phosphoric acid. The two mobile phases used for gradient elution were: (A) 10 mM ammonium dihydrogenphosphate (pH 3.5) and (B) same concentration of buffer but containing 20% (v/v) of methanol (pH 4.8). The flow-rate was set at 1.0 ml/min. TTCA and I.S. were detected at 2.2 and 9.1 min, respectively. The method was validated with urine samples collected from normal subjects and workers occupationally exposed to carbon disulphide. The present method enables the detection of urinary TTCA at a concentration of 0.025 mg/l. Analytical recovery and reproducibility generally exceeded 90%. The proposed method is considered more sensitive, specific and reliable than other existing methods.

  7. Preliminary Transcriptome Analysis of Mature Biofilm and Planktonic Cells of Salmonella Enteritidis Exposure to Acid Stress

    Directory of Open Access Journals (Sweden)

    Kun Jia

    2017-09-01

    Full Text Available Salmonella has emerged as a well-recognized food-borne pathogen, with many strains able to form biofilms and thus cause cross-contamination in food processing environments where acid-based disinfectants are widely encountered. In the present study, RNA sequencing was employed to establish complete transcriptome profiles of Salmonella Enteritidis in the forms of planktonic and biofilm-associated cells cultured in Tryptic Soytone Broth (TSB and acidic TSB (aTSB. The gene expression patterns of S. Enteritidis significantly differed between biofilm-associated and planktonic cells cultivated under the same conditions. The assembled transcriptome of S. Enteritidis in this study contained 5,442 assembled transcripts, including 3,877 differentially expressed genes (DEGs identified in biofilm and planktonic cells. These DEGs were enriched in terms such as regulation of biological process, metabolic process, macromolecular complex, binding and transferase activity, which may play crucial roles in the biofilm formation of S. Enteritidis cultivated in aTSB. Three significant pathways were observed to be enriched under acidic conditions: bacterial chemotaxis, porphyrin-chlorophyll metabolism and sulfur metabolism. In addition, 15 differentially expressed novel non-coding small RNAs (sRNAs were identified, and only one was found to be up-regulated in mature biofilms. This preliminary study of the S. Enteritidis transcriptome serves as a basis for future investigations examining the complex network systems that regulate Salmonella biofilm in acidic environments, which provide information on biofilm formation and acid stress interaction that may facilitate the development of novel disinfection procedures in the food processing industry.

  8. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    Science.gov (United States)

    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

  9. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    International Nuclear Information System (INIS)

    Monette, Michelle Y.; Yada, Takashi; Matey, Victoria; McCormick, Stephen 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 μg l -1 Al), acid and low Al (LAl: pH 5.4, 11 μg l -1 Al), acid and moderate Al (MAl: pH 5.3, 42 μg l -1 Al), and acid and high Al (HAl: pH 5.4, 56 μg l -1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h 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

  10. 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.

    Science.gov (United States)

    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 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 (PAcid exposure time was 51.2 (4.5) min for control versus 23.6 (3.8) min for lesogaberan (Pacid reflux in dogs, with comparable efficacy to baclofen. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Existence of life-time stable proteins in mature rats-Dating of proteins' age by repeated short-term exposure to labeled amino acids throughout age

    DEFF Research Database (Denmark)

    Bechshøft, Cecilie Leidesdorff; Schjerling, Peter; Bornø, Andreas

    2017-01-01

    In vivo turnover rates of proteins covering the processes of protein synthesis and breakdown rates have been measured in many tissues and protein pools using various techniques. Connective tissue and collagen protein turnover is of specific interest since existing results are rather diverging. Th...... living days, indicating very slow turnover. The data support the hypothesis that some proteins synthesized during the early development and growth still exist much later in life of animals and hence has a very slow turnover rate.......In vivo turnover rates of proteins covering the processes of protein synthesis and breakdown rates have been measured in many tissues and protein pools using various techniques. Connective tissue and collagen protein turnover is of specific interest since existing results are rather diverging....... The aim of this study is to investigate whether we can verify the presence of protein pools within the same tissue with very distinct turnover rates over the life-span of rats with special focus on connective tissue. Male and female Lewis rats (n = 35) were injected with five different isotopically...

  12. Combined effects of dietary polyunsaturated fatty acids and parasite exposure on eicosanoid-related gene expression in an invertebrate model.

    Science.gov (United States)

    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.

  13. Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Abdoljalal Marjani

    2010-10-01

    Full Text Available 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.

  15. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Maryam Goudarzi

    2016-05-01

    Full Text Available With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR of 3.0 mGy/min and a high dose rate (HDR of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs and Strontium-90 (90Sr. The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation.

  16. Exposure to perfluoroundecanoic acid (PFUnDA accelerates insulitis development in a mouse model of type 1 diabetes

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    Johanna Bodin

    Full Text Available Perfluoralkylated substances (PFAS are classified as persistent, bioaccumulative and toxic substances and are widespread environmental contaminants. Humans are exposed through food, drinking water and air. We have previously reported that bisphenol A accelerates spontaneous diabetes development in non-obese diabetic (NOD mice and observed in the present study that perfluoroundecanoic acid, PFUnDA, increased insulitis development, a prerequisite for diabetes development in NOD mice. We exposed NOD mice to PFUnDA in drinking water (3, 30 and 300 μg/l at mating, during gestation and lactation and until 30 weeks of age. After 300 μg/l PFUnDA exposure, we report (i increased pancreatic insulitis, (ii increased number of apoptotic cells in pancreatic islets prior to insulitis and (iii decreased phagocytosis in peritoneal macrophages. There was also a trend of decreased number of tissue resident macrophages in pancreatic islets prior to insulitis after exposure to 300 μg/l, and altered cytokine secretion in activated splenocytes after exposure to 3 μg/l PFUnDA. Although insulitis is a prerequisite for autoimmune diabetes, the accelerated insulitis was not associated with accelerated diabetes development. Instead, the incidence of diabetes tended to be reduced in the animals exposed to 3 and 30 μg/l PFUnDA, suggesting a non-monotonic dose response. The effects of PFUnDA exposure on increased apoptosis in pancreas and reduced macrophage function as well as accelerated insulitis development in NOD mice, may also be relevant for human insulitis. Further observational autoimmune diabetes clinical cohort studies and animal experiments for PFUnDA as well as other PFASs are therefore encouraged. Keywords: Perfluoralkylated substances, PFUnDA, T1DM, Diabetes, NOD mice, Insulitis

  17. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation.

    Science.gov (United States)

    Goudarzi, Maryam; Chauthe, Siddheshwar; Strawn, Steven J; Weber, Waylon M; Brenner, David J; Fornace, Albert J

    2016-05-20

    With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; external γ irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 ((137)Cs) and Strontium-90 ((90)Sr). The multiple reaction monitoring analy