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Sample records for acute phenobarbital exposure

  1. An integrated functional genomic study of acute phenobarbital exposure in the rat

    Science.gov (United States)

    2010-01-01

    Background Non-genotoxic carcinogens are notoriously difficult to identify as they do not damage DNA directly and have diverse modes of action, necessitating long term in vivo studies. The early effects of the classic rodent non-genotoxic hepatocarcinogen phenobarbital have been investigated in the Fisher rat using a combination of metabolomics and transcriptomics, to investige early stage mechanistic changes that are predictive of longer term pathology. Results Liver and blood plasma were profiled across 14 days, and multivariate statistics used to identify perturbed pathways. Both metabolomics and transcriptomics detected changes in the liver which were dose dependent, even after one day of exposure. Integration of the two datasets associated perturbations with specific pathways. Hepatic glycogen was decreased due to a decrease in synthesis, and plasma triglycerides were decreased due to an increase in fatty acid uptake by the liver. Hepatic succinate was increased and this was associated with increased heme biosynthesis. Glutathione synthesis was also increased, presumably in response to oxidative stress. Liquid Chromatography Mass Spectrometry demonstrated a remodeling of lipid species, possibly resulting from proliferation of the smooth endoplasmic reticulum. Conclusions The data fusion of metabolomic and transcriptomic changes proved to be a highly sensitive approach for monitoring early stage changes in altered hepatic metabolism, oxidative stress and cytochrome P450 induction simultaneously. This approach is particularly useful in interpreting changes in metabolites such as succinate which are hubs of metabolism. PMID:20053287

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

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

    2012-06-01

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

  3. Transient leucopenia, thrombocytopenia and anaemia associated with severe acute phenobarbital intoxication in a dog.

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    Khoutorsky, A; Bruchim, Y

    2008-07-01

    A nine-year-old Labrador retriever dog was admitted to the emergency unit of the Hebrew University Veterinary Teaching Hospital with acute-onset tremors and coma. It had recently ingested a large quantity of phenobarbital and had a high serum phenobarbital concentration. On this basis, a diagnosis of acute phenobarbital intoxication was made. Significant leucopenia, thrombocytopenia and mild anaemia developed on the third day after admission. The leucopenia resolved on day 6 and the thrombocytopenia on day 13. The red blood cell count remained low for the next month. The dog was discharged on day 13 at which time it was ambulatory but weak. It was completely recovered clinically eight days later. In summary, high levels of serum phenobarbital as a result of acute intoxication induced pancytopenia, which improved when the serum phenobarbital level was normalised.

  4. Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos

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    Yu Yan

    2016-09-01

    Full Text Available Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in both in vivo and in vitro long bone models. Next, we established that phenobarbital treatment delayed blood vessel invasion in a cartilage template, and this finding was supported by the down-regulation of vascular endothelial growth factor in the hypertrophic zone following phenobarbital treatment. Phenobarbital treatment inhibited tube formation and the migration of human umbilical vein endothelial cells. In addition, it impaired angiogenesis in chick yolk sac membrane model and chorioallantoic membrane model. In summary, phenobarbital exposure led to shortened lengths of long bones during embryogenesis, which might result from inhibiting mesenchyme differentiation, chondrocyte proliferation, and delaying mineralization by impairing vascular invasion.

  5. Exposure to Excess Phenobarbital Negatively Influences the Osteogenesis of Chick Embryos

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    Yan, Yu; Cheng, Xin; Yang, Ren-Hao; Li, He; Chen, Jian-Long; Ma, Zheng-Lai; Wang, Guang; Chuai, Manli; Yang, Xuesong

    2016-01-01

    Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in both in vivo and in vitro long bone models. Next, we established that phenobarbital treatment delayed blood vessel invasion in a cartilage template, and this finding was supported by the down-regulation of vascular endothelial growth factor in the hypertrophic zone following phenobarbital treatment. Phenobarbital treatment inhibited tube formation and the migration of human umbilical vein endothelial cells. In addition, it impaired angiogenesis in chick yolk sac membrane model and chorioallantoic membrane model. In summary, phenobarbital exposure led to shortened lengths of long bones during embryogenesis, which might result from inhibiting mesenchyme differentiation, chondrocyte proliferation, and delaying mineralization by impairing vascular invasion. PMID:27746734

  6. Brief postnatal exposure to phenobarbital impairs passive-avoidance learning and sensorimotor gating in rats

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    Gutherz, Samuel B.; Kulick, Catherine V.; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A.

    2014-01-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference to cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition as compared to vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention as compared to matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. PMID:25112558

  7. Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.

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    Gutherz, Samuel B; Kulick, Catherine V; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A

    2014-08-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

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    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Comparison of the long-term behavioral effects of neonatal exposure to retigabine or phenobarbital in rats.

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    Frankel, Sari; Medvedeva, Natalia; Gutherz, Samuel; Kulick, Catherine; Kondratyev, Alexei; Forcelli, Patrick A

    2016-04-01

    Anticonvulsant drugs, when given during vulnerable periods of brain development, can have long-lasting consequences on nervous system function. In rats, the second postnatal week approximately corresponds to the late third trimester of gestation/early infancy in humans. Exposure to phenobarbital during this period has been associated with deficits in learning and memory, anxiety-like behavior, and social behavior, among other domains. Phenobarbital is the most common anticonvulsant drug used in neonatology. Several other drugs, such as lamotrigine, phenytoin, and clonazepam, have also been reported to trigger behavioral changes. A new generation anticonvulsant drug, retigabine, has not previously been evaluated for long-term effects on behavior. Retigabine acts as an activator of KCNQ channels, a mechanism that is unique among anticonvulsants. Here, we examined the effects retigabine exposure from postnatal day (P)7 to P14 on behavior in adult rats. We compared these effects with those produced by phenobarbital (as a positive control) and saline (as a negative control). Motor behavior was assessed by using the open field and rotarod, anxiety-like behavior by the open field, elevated plus maze, and light-dark transition task, and learning/memory by the passive avoidance task; social interactions were assessed in same-treatment pairs, and nociceptive sensitivity was assessed via the tail-flick assay. Motor behavior was unaltered by exposure to either drug. We found that retigabine exposure and phenobarbital exposure both induced increased anxiety-like behavior in adult animals. Phenobarbital, but not retigabine, exposure impaired learning and memory. These drugs also differed in their effects on social behavior, with retigabine-exposed animals displaying greater social interaction than phenobarbital-exposed animals. These results indicate that neonatal retigabine induces a subset of behavioral alterations previously described for other anticonvulsant drugs and extend

  10. Exposure to Excess Phenobarbital Negatively Influences the Osteogenesis of Chick Embryos

    OpenAIRE

    Yu Yan; Xin Cheng; Ren-hao Yang; He Li; Jian-long Chen; Zheng-lai Ma; Guang Wang; Manli Chuai; Xuesong Yang

    2016-01-01

    Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phe...

  11. Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors

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    C.M. Yokoro

    2001-03-01

    Full Text Available The aim of the present study was to determine if phenobarbital affects the nociception threshold. Systemic (1-20 mg/kg phenobarbital administration dose dependently induced hyperalgesia in the tail-flick, hot-plate and formalin tests in rats and in the abdominal constriction test in mice. Formalin and abdominal constriction tests were the most sensitive procedures for the detection of hyperalgesia in response to phenobarbital compared with the tail-flick and hot-plate tests. The hyperalgesia induced by systemic phenobarbital was blocked by previous administration of 1 mg/kg ip picrotoxin or either 1-2 mg/kg sc or 10 ng icv bicuculline. Intracerebroventricular phenobarbital administration (5 µg induced hyperalgesia in the tail-flick test. In contrast, intrathecal phenobarbital administration (5 µg induced antinociception and blocked systemic-induced hyperalgesia in this test. We suggest that phenobarbital may mediate hyperalgesia through GABA-A receptors at supraspinal levels and antinociception through the same kind of receptors at spinal levels.

  12. Phenobarbital Augments Hypothermic Neuroprotection

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    Barks, John D.; Liu, Yi-Qing; Shangguan, Yu; Silverstein, Faye S.

    2010-01-01

    Seizures are associated with adverse outcome in infants with hypoxic-ischemic encephalopathy. We hypothesized that early administration of the anticonvulsant phenobarbital after cerebral hypoxia-ischemia could enhance the neuroprotective efficacy of delayed-onset hypothermia. We tested this hypothesis in a neonatal rodent model. Seven-day-old rats (n=104) underwent right carotid ligation, followed by 90 min 8%O2 exposure; 15 min later, they received injections of phenobarbital (40 mg/kg) or saline. One or 3h later, all were treated with hypothermia (30°C, 3h). Function and neuropathology were evaluated after 7 days (“early outcomes”) or 1 month (“late outcomes”). Early outcome assessment demonstrated better sensorimotor performance and less cortical damage in phenobarbital-treated groups; there were no differences between groups in which the hypothermia delay was shortened from 3h to 1h. Late outcome assessment confirmed sustained benefits of phenobarbital+hypothermia treatment; sensorimotor performance was better (persistent attenuation of contralateral forepaw placing deficits and absence of contralateral forepaw neglect); neuropathology scores were lower (medians, phenobarbital 2, saline 8.5, pphenobarbital may augment the neuroprotective efficacy of therapeutic hypothermia. PMID:20098339

  13. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial.

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    Malamiri, Reza Azizi; Ghaempanah, Mahdieh; Khosroshahi, Nahid; Nikkhah, Ali; Bavarian, Behrouz; Ashrafi, Mahmoud Reza

    2012-09-01

    Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children. Copyright

  14. High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

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    Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

    2016-08-01

    Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.

  15. Repeated inhalation exposure to octamethylcyclotetrasiloxane produces hepatomegaly, transient hepatic hyperplasia, and sustained hypertrophy in female Fischer 344 rats in a manner similar to phenobarbital.

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    McKim, J M; Kolesar, G B; Jean, P A; Meeker, L S; Wilga, P C; Schoonhoven, R; Swenberg, J A; Goodman, J I; Gallavan, R H; Meeks, R G

    2001-04-15

    Octamethylcyclotetrasiloxane (D4) has been described as a phenobarbital-like inducer of hepatic enzymes. Phenobarbital (PB) and phenobarbital-like chemicals induce transient hepatic and thyroid hyperplasia and sustained hypertrophy in rats and mice. The extent to which these processes are involved with D4-induced hepatomegaly is not known. The present study has evaluated the effects of repeated inhalation exposure to D4 vapors on hepatic and thyroid cell proliferation and hypertrophy with respect to time and exposure concentration. Female Fischer 344 rats were exposed via whole body inhalation to 0 ppm D4, 700 ppm D4 vapors (6 h/day; 5 days/week), or 0.05% PB in drinking water over a 4-week period. Incorporation of 5'-bromo-2-deoxyuridine (BrdU) and the abundance of proliferating cell nuclear antigen were used as indicators of cell proliferation. Designated animals from each treatment group were euthanized on study days 6, 13, and 27. The effect of D4 exposure concentration on hepatic cell proliferation was evaluated at 0, 7, 30, 70, 150, 300, or 700 ppm. Liver-to-body weight ratios in animals exposed to 700 ppm D4 were increased 18, 20, and 22% over controls while PB-treated animals showed increases of 33, 27, and 27% over controls on days 6, 13, and 27 respectively. Hepatic incorporation of BrdU following exposure to D4 was highest on day 6 (labeling index = 15-22%) and was at or below control values by day 27. This pattern of transient hyperplasia was observed in all hepatic lobes examined and was similar to the pattern observed following treatment with PB.

  16. DIETARY EXPOSURE OF PHENOBARBITAL TO MALE AND FEMALE CD1 MICE FOR 2 OR 7 DAYS: EXAMINATION OF IN-LIFE, HEPATOCELLULAR ENZYME, PROLIFERATION, AND GENE EXPRESSION RESPONSES.

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    Phenobarbital (PB) is a barbiturate used to relieve anxiety and control epilepsy. PB is also an archetypical inducer of the constitutive androstane receptor (CAR), resulting in liver hypertrophy in humans and both liver hypertrophy and hyperplasia in rodents. In this study, male ...

  17. DIETARY EXPOSURE OF PHENOBARBITAL TO MALE AND FEMALE CD1 MICE FOR 2 OR 7 DAYS: EXAMINATION OF IN-LIFE, HEPATOCELLULAR ENZYME, PROLIFERATION, AND GENE EXPRESSION RESPONSES.

    Science.gov (United States)

    Phenobarbital (PB) is a barbiturate used to relieve anxiety and control epilepsy. PB is also an archetypical inducer of the constitutive androstane receptor (CAR), resulting in liver hypertrophy in humans and both liver hypertrophy and hyperplasia in rodents. In this study, male ...

  18. Spatial distribution of CYP2B1/2 messenger RNA within the rat liver acinus following exposure to the inducers phenobarbital and dieldrin.

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    Dail, Mary B; Burgess, Shane C; Meek, Edward C; Wagner, Jennifer; Baravik, Jeffrey; Chambers, Janice E

    2007-09-01

    Traditionally, the liver has been considered a homogeneous organ, but literature suggests that the cytochromes P450 are differentially distributed among the hepatocytes and that the pattern of this distribution is altered by various xenobiotics. In this study, the CYP2B1/2 messenger RNA (mRNA) in the hepatocytes was compared following treatment of rats with either of two inducers, phenobarbital (PB), or dieldrin. Adult male Sprague-Dawley-derived rats were treated with either ip PB in saline at 80 mg/kg/day for 5 days or dieldrin in corn oil by oral gavage at 2.5 mg/kg/day for 13 days. Control rats received ip saline or po corn oil for the same time. Laser capture microdissection (LCM) followed by duplex quantitative real-time reverse transcriptase PCR was used to measure the CYP2B1/2 mRNA produced in bands of hepatocytes isolated from three locations along the sinusoidal path. The amounts of mRNA present in whole liver subsamples were also analyzed. CYP2B1/2 enzyme activity was determined by assaying 16beta-hydroxytestosterone formation. Whole liver mRNA samples exhibited significant induction in CYP2B1/2 transcript levels: sixfold for PB and 2200-fold for dieldrin. All the LCM band samples also showed significant fold induction in CYP2B1/2 mRNA compared to controls. Dieldrin caused marked increases in CYP2B1/2 mRNA levels in the direction of blood flow through the acinus: periportal, 300-fold; midzonal, 600-fold; and centrilobular, 1700-fold. A different pattern of induction was observed in the PB-treated rats: periportal, 1800-fold; midzonal, 8800-fold; and centrilobular, 1600-fold. The present study indicates the differences in spatial responses that can be exhibited within the liver following exposure to various xenobiotics. It also indicates the importance of examining xenobiotic metabolism in the liver in light of its nonhomogeneous, zoned microenvironment.

  19. In Vivo Nanodetoxication for Acute Uranium Exposure

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    Luis Guzmán

    2015-06-01

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

  20. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

    DEFF Research Database (Denmark)

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders

    2016-01-01

    Background: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option......, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. Methods: The study was a register-based cohort study of patients admitted for alcohol...... withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. Results: A total...

  1. DILI (drug induced liver injury in a 9-month-old infant: a rare case of phenobarbital-induced hepatotoxicity

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    Anna Paola Pinna

    2013-04-01

    Full Text Available Phenobarbital is one of the most commonly prescribed antiepileptic drugs in childhood, but it can rarely cause serious adverse effects, such as hepatotoxicity that includes a broad clinical spectrum (from isolate hypertransaminasemia to acute liver failure. We describe a case of DILI in a 9-month-old infant caused by chronic therapy with phenobarbital.

  2. Phenobarbital for Neonatal Seizures: Response Rate and Predictors of Refractoriness.

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    Spagnoli, Carlotta; Seri, Stefano; Pavlidis, Elena; Mazzotta, Silvia; Pelosi, Annalisa; Pisani, Francesco

    2016-10-01

    Background Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p  ≤  0.005) correlated with response to phenobarbital. However, EEG (p  ≤  0.02) and seizure type (p  ≤  0.001) were the only independent predictors. Conclusion Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns. Georg Thieme Verlag KG Stuttgart · New York.

  3. Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

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    Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

    2010-01-01

    Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

  4. Effect of pregnancy on plasma phenobarbital concentrations in rats.

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    Moriyama,Masahiro; Domoto, Haruyo; Yamashita, Syoichi; Furuno,Katsushi; Oishi, Ryozo; Kawasaki,Hiromu; Gomita, Yutaka

    1995-01-01

    We examined the pharmacokinetics of phenobarbital before and during pregnancy in rats. Animals were divided into four groups: (a) control, (b) pregnant, (c) phenobarbital-treated, and (d) phenobarbital-treated pregnant groups. The increase in body weight of nonpregnant or pregnant rats was not influenced by long-term phenobarbital treatment. Plasma phenobarbital concentrations during the period of long-term phenobarbital treatment with a fixed dosage by body weight were not significantly affe...

  5. High Phenobarbital Clearance During Continuous Renal Replacement Therapy

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    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-01-01

    Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

  6. A patch test confirmed phenobarbital-induced fixed drug eruption in a child.

    Science.gov (United States)

    Chadly, Zohra; Aouam, Karim; Chaabane, Amel; Belhadjali, Hichem; Abderrazzak Boughattas, Naceur; Zili, Jamel Eddine

    2014-06-01

    A-10-year-old girl was referred to our department for multiple hyperpigmented plaques. One week previously, she had been given one suppository of acetylsalicylic acid - phenobarbital for fever. Twelve hours after the drug intake the child developed pruritic red plaques on the left thigh. Six weeks after resolution of the acute reaction, patch tests were performed separately, with phenobarbital and acetylsalicylic acid. On 48-hour reading, only the phenobarbital patch test on residual pigmented lesion was positive. Because of possible cross-reactions between aromatic anticonvulsants, subsequent patch tests using carbamazepine and phenytoin on residual pigmented lesions were performed. They were all negative at 48-hour reading. To our knowledge, only two isolated pediatric cases of Phenobarbital-induced FDE have been reported in the literature. In this case report, as it was difficult to determine whether phenobarbital or acetylsalicylic acid was responsible for this reaction, subsequent patch tests allowed the identification of the culprit component since it was positive to phenobarbital.

  7. Clinical pharmacokinetics of phenobarbital in neonates

    NARCIS (Netherlands)

    Touw, D J; Graafland, O; Cranendonk, A; Vermeulen, R J; van Weissenbruch, M M

    2000-01-01

    Demographic and clinical pharmacokinetic data collected from term and preterm neonates who were treated with intravenous phenobarbital have been analysed to evaluate the role of patient characteristics in pharmacokinetic parameters. Significant relationships between total body weight (TBW) or body

  8. Compound list: phenobarbital [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available phenobarbital PB 00004 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/phenobar...bital.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/phenobar...bital.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...dbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/phenobarbital.Rat.in_vivo.Liver.Repeat.zip ...

  9. Biochemical Characterization of Porphobilinogen Deaminase–Deficient Mice During Phenobarbital Induction of Heme Synthesis and the Effect of Enzyme Replacement

    Science.gov (United States)

    Johansson, Annika; Möller, Christer; Fogh, Jens; Harper, Pauline

    2003-01-01

    Acute intermittent porphyria (AIP) is a genetic disorder caused by a deficiency of porphobilinogen deaminase (PBGD), the 3rd enzyme in heme synthesis. It is clinically characterized by acute attacks of neuropsychiatric symptoms and biochemically by increased urinary excretion of the porphyrin precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA). A mouse model that is partially deficient in PBGD and biochemically mimics AIP after induction of the hepatic ALA synthase by phenobarbital was used in this study to identify the site of formation of the presumably toxic porphyrin precursors and study the effect of enzyme-replacement therapy by using recombinant human PBGD (rhPBGD). After 4 d of phenobarbital administration, high levels of PBG and ALA were found in liver, kidney, plasma, and urine of the PBGD-deficient mice. The administration of rhPBGD intravenously or subcutaneously after a 4-d phenobarbital induction was shown to lower the PBG level in plasma in a dose-dependent manner with maximal effect seen after 30 min and 2 h, respectively. Injection of rhPBGD subcutaneously twice daily during a 4-d phenobarbital induction reduced urinary PBG excretion to 25% of the levels found in PBGD-deficient mice administered with only phenobarbital. This study points to the liver as the main producer of PBG and ALA in the phenobarbital-induced PBGD-deficient mice and demonstrates efficient removal of accumulated PBG in plasma and urine by enzyme-replacement therapy. PMID:15208740

  10. Pulmonary Inflammatory Responses to Acute Meteorite Dust Exposures - to Acute Meteorite Dust Exposures - Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    New initiatives to begin lunar and martian colonization within the next few decades are illustrative of the resurgence of interest in space travel. One of NASA's major concerns with extended human space exploration is the inadvertent and repeated exposure to unknown dust. This highly interdisciplinary study evaluates both the geochemical reactivity (e.g. iron solubility and acellular reactive oxygen species (ROS) generation) and the relative toxicity (e.g. in vitro and in vivo pulmonary inflammation) of six meteorite samples representing either basalt or regolith breccia on the surface of the Moon, Mars, and Asteroid 4Vesta. Terrestrial mid-ocean ridge basalt (MORB) is also used for comparison. The MORB demonstrated higher geochemical reactivity than most of the meteorite samples but caused the lowest acute pulmonary inflammation (API). Notably, the two martian meteorites generated some of the highest API but only the basaltic sample is significantly reactive geochemically. Furthermore, while there is a correlation between a meteorite's soluble iron content and its ability to generate acellular ROS, there is no direct correlation between a particle's ability to generate ROS acellularly and its ability to generate API. However, assorted in vivo API markers did demonstrate strong positive correlations with increasing bulk Fenton metal content. In summary, this comprehensive dataset allows for not only the toxicological evaluation of astromaterials but also clarifies important correlations between geochemistry and health.

  11. EFFECTS OF ACUTE PYRETHROID EXPOSURE ON THERMOREGULATION IN RATS.

    Science.gov (United States)

    Pyrethroid insecticides produce acute neurotoxicity in mammals. According to the FQPA mandate, the USEPA is required to consider the risk of cumulative toxicity posed to humans through exposure to pyrethroid mixtures. Thermoregulatory response (TR) is being used to determine if t...

  12. Occupational exposure to solvents and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Talibov, Madar; Lehtinen-Jacks, Susanna; Martinsen, Jan Ivar;

    2014-01-01

    OBJECTIVE: The aim of the current study was to assess the relation between occupational exposure to solvents and the risk of acute myeloid leukemia (AML). METHODS: Altogether, this study comprises 15 332 incident cases of AML diagnosed in Finland, Norway, Sweden and Iceland from 1961-2005 and 76...

  13. Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1991-01-01

    exposed to mixtures of solvents experience an increased frequency of work related irritative and neurological symptoms although the exposure has been far below the occupational exposure limits. A series of controlled human exposure studies was carried out. Different groups of persons were exposed...... to the most frequent solvent, toluene. Toluene in alveolar air and the urinary excretion of the metabolites were measured and the acute effects of toluene were assessed by the performance in a series of test of the perceptual and psychomotor functions as well as a standardized registration of annoyance...

  14. Health Impacts from Acute Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2003-09-30

    Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above this is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.

  15. Mode of Action and Human Relevance Analysis for Nuclear Receptor-Mediated Liver Toxicity: A Case Study with Phenobarbital as a Model Constitutive Androstane Receptor (CAR) Activator

    Science.gov (United States)

    The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are key nuclear receptors involved in the regulation of cellular responses. to exposure to many xenobiotics and various physiological processes. Phenobarbital (PB) is a non­ genotoxic i...

  16. Acute inhalation exposure of azodicarbonamide in the guinea pig.

    Science.gov (United States)

    Shopp, G M; Cheng, Y S; Gillett, N A; Bechtold, W E; Medinsky, M A; Hobbs, C H; Birnbaum, L S; Mauderly, J L

    1987-02-01

    Humans have been exposed to azodicarbonamide (ADA) by inhalation where bulk quantities of ADA are handled in the workplace. Responses of some workers have led to concern for the potential irritant and sensitizing properties of inhaled ADA. This study examined the effects of inhaling ADA on lung structure and function of guinea pigs during and after an acute exposure. Groups of 20 guinea pigs were exposed to each of 3 concentrations of ADA (19, 58, and 97 mg/m3), plus air as a control, for 1 hr. Pulmonary function was measured before exposure (baseline), during exposure, immediately after exposure and 24 hr after exposure. Dynamic compliance (Cdyn), total pulmonary resistance (RL), tidal volume (VT), respiratory frequency and minute volume were measured. In addition, gross necropsies and histological examinations of respiratory tract tissues were done either immediately following the exposure or 24 hr after exposure. There were no effects of ADA exposure on gross necropsy, histology, Cdyn, or RL. Some significant, concentration-related decreases in VT, respiratory frequency and minute volume were seen. The magnitudes of these changes were small: the largest change was seen in minute volume, amounting to a 24% decrease in the high concentration group. Inhalation exposure of guinea pigs to ADA at concentrations of up to 97 mg/m3 resulted in minor changes in pulmonary function without any changes in lung histology.

  17. 21 CFR 862.3660 - Phenobarbital test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Phenobarbital test system. 862.3660 Section 862....3660 Phenobarbital test system. (a) Identification. A phenobarbitol test system is a device intended to measure phenobarbital, an antiepileptic and sedative-hypnotic drug, in human specimens. Measurements...

  18. Phenobarbital induced Stevens–Johnson syndrome in a child

    OpenAIRE

    Sumit Gaur; Rupali Agnihotri

    2012-01-01

    Phenobarbital, an antiepileptic agent has numerous adverse reactions including Stevens- Johnson syndrome (SJS), a rare medical emergency. A 12-year-old male epileptic child with phenobarbital-induced SJS was referred for the management of severe pain in relation to extensively decayed molar tooth and oral mucosal ulcerations. The patient was managed by withdrawal of phenobarbital and palliative treatment of the lesions.

  19. Phenobarbital induced Stevens-Johnson syndrome in a child.

    Science.gov (United States)

    Gaur, Sumit; Agnihotri, Rupali

    2012-01-01

    Phenobarbital, an antiepileptic agent has numerous adverse reactions including Stevens- Johnson syndrome (SJS), a rare medical emergency. A 12-year-old male epileptic child with phenobarbital-induced SJS was referred for the management of severe pain in relation to extensively decayed molar tooth and oral mucosal ulcerations. The patient was managed by withdrawal of phenobarbital and palliative treatment of the lesions.

  20. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    Science.gov (United States)

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration.

  1. Acute liver failure associated with occupational exposure to tetrachloroethylene.

    Science.gov (United States)

    Shen, Chuan; Zhao, Cai-Yan; Liu, Fang; Wang, Ya-Dong; Wang, Wei

    2011-01-01

    Tetrachloroethylene is a chlorinated solvent that is primarily used in dry cleaning and degreasing operations. Although the hepatotoxicity caused by tetrachloroethylene has been well documented in literature, it is rarely considered as a cause of acute liver failure. We report a case of a 39-yr-old man who was admitted to our hospital for acute liver failure due to tetrachloroethylene exposure. Histological examination of the liver revealed massive hepatic necrosis, prominently, in zone 3 of the hepatic lobules. The patient underwent supportive treatment along with 3 sessions of plasmapheresis, and consequently, he presented a favorable outcome. Repeat liver biopsy performed 6 months after the patient's discharge showed architectural distortion with postnecrotic cirrhosis. Physicians should be aware of the possibility of acute liver failure induced by tetrachloroethylene. Early plasmapheresis can be effective for individuals with sufficient capacity for hepatocyte regeneration.

  2. Evaluation of Subcutaneous Phenobarbital Administration in Hospice Patients.

    Science.gov (United States)

    Hosgood, Jessica Richards; Kimbrel, Jason M; McCrate Protus, Bridget; Grauer, Phyllis A

    2016-04-01

    Phenobarbital is used in hospice and palliative care to treat refractory symptoms. In end-of-life care, Food and Drug Administration approved routes of administration may be unreasonable based on patients' status. In these cases, phenobarbital may be administered subcutaneously for symptom management. However, according to the American Hospital Formulary Service, subcutaneous administration of commercially available injectable phenobarbital is cautioned due to possible skin reactions. This study evaluates the tolerability of phenobarbital administered subcutaneously. Of 69 patients and 774 distinct subcutaneous phenobarbital injections, 2 site reactions were recorded (2.9% of patients; 0.3% of injections). Both were mild, grade 1 reactions. Each patient continued to receive subcutaneous phenobarbital via newly placed ports with no additional reactions. Based on these findings, phenobarbital appears to be well tolerated when administered subcutaneously. © The Author(s) 2014.

  3. High-Dose Phenobarbital for Ohtahara Syndrome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-05-01

    Full Text Available Oral high-dose phenobarbital therapy was effective in the control of tonic spasms in a 1 month-old-infant with early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome treated at Tokyo Metropolitan Hachioji Children’s Hospital, Tokyo, Japan.

  4. Acute versus repeated chocolate exposure: effects on intake and cravings in restrained and unrestrained eaters.

    Science.gov (United States)

    Coelho, Jennifer S; Nederkoorn, Chantal; Jansen, Anita

    2014-04-01

    The cue-reactivity model, which is based on conditioning processes, posits that repeated food exposure (in the absence of consumption) should decrease cue reactivity. To examine whether repeated chocolate exposure attenuates cravings and intake, relative to those exposed to an acute cue, a 2 (repeated vs acute cue) × 2 (restrained vs unrestrained eaters) design was employed. Fifty female participants were recruited. Repeated exposure reduced cravings in unrestrained eaters (relative to acute exposure), but increased cravings in restrained eaters. An interaction between restraint and exposure emerged on intake, such that restrained eaters ate less after acute exposure than did unrestrained eaters.

  5. Endocrine responses in the rhesus monkey during acute cold exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lotz, W.G.; Saxton, J.L. (Naval Aerospace Medical Research Lab., Pensacola, FL (United States))

    1991-03-11

    The authors studied five young male rhesus monkeys (Macaca mulatta), 3.4 to 6.7 kg, to determine the relationship between fluid balance hormones and urine production during acute, dry cold exposure. Each monkey served as its own control in duplicate experimental sessions at 6C or 26C. A 6-h experimental session consisted of 120 min equilibration at 26C, 120 min experimental exposure, and 120 min recovery at 26C. Urinary and venous catheters were inserted on the morning of a session. Rectal (Tre) and skin temperatures were monitored continuously. Blood samples were taken at 0, 30, 60 and 120 min of exposure, and at 60 min postexposure. Plasma was analyzed for arginine vasopressin (AVP), atrial natriuretic factor (ANF), plasma renin activity (PRA), plasma aldosterone (PA), and osmolality. Urine samples were analyzed for osmolality, electrolytes, and creatinine. Mean Tre was 1.6C lower after 120 min at 6C than at 26C. Urine volume and osmolality were not altered by cold exposure, as they are in humans and rats. Vasopressin and PA increased sharply, with mean plasma levels in monkeys exposed to cold more than threefold and tenfold, respectively, the levels in monkeys exposed at 26C. In contrast, ANF, PRA, and plasma osmolality were not significantly changed by cold exposure. The absence of a cold-induced diuresis in the monkey may be related to the marked increase in plasma AVP level.

  6. Bumetanide augments the neuroprotective efficacy of phenobarbital plus hypothermia in a neonatal hypoxia-ischemia model

    Science.gov (United States)

    Liu, YiQing; Shangguan, Yu; Barks, John D.E.; Silverstein, Faye S.

    2014-01-01

    The NaKCl cotransporter NKCC1 facilitates intraneuronal chloride accumulation in the developing brain. Bumetanide, a clinically available diuretic, inhibits this chloride transporter, and augments the antiepileptic effects of phenobarbital in neonatal rodents. In a neonatal cerebral hypoxia-ischemia (HI) model, elicited by right carotid ligation, followed by 90 min 8% O2 exposure in 7-day-old(P7) rats, phenobarbital(PB) increases the neuroprotective efficacy of hypothermia. We evaluated whether bumetanide influenced the neuroprotective efficacy of combination treatment with PB and hypothermia(HT). P7 rats underwent HI lesioning; 15 min later, all received PB (30 mg/kg). 10 min later, half received bumetanide (10 mg/kg, PB-HT+BUM) and half received saline (PB-HT+SAL). One hour after HI, all were cooled (30°C, 3h). Contralateral forepaw sensorimotor function and brain damage were evaluated 1 to 4 weeks later. Forepaw functional measures were close to normal in the PB-HT+BUM group, while deficits persisted in PB-HT+SAL controls; there were corresponding reductions in right cerebral hemisphere damage (at P35, % damage: PB-HT+BUM, 21±16 versus 38±20 in controls). These results provide evidence that NKCC1 inhibition amplifies phenobarbital bioactivity in the immature brain, and suggest that co-administration of phenobarbital and bumetanide may represent a clinically feasible therapy to augment the neuroprotective efficacy of therapeutic hypothermia in asphyxiated neonates. PMID:22398701

  7. Acute radiation syndrome caused by accidental radiation exposure - therapeutic principles

    Directory of Open Access Journals (Sweden)

    Dörr Harald

    2011-11-01

    Full Text Available Abstract Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.

  8. Effects of asphalt fume condensate exposure on acute pulmonary responses

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.Y.C.; Barger, M.W.; Castranova, V. [Health Effects Lab. Div., National Inst. for Occupational Safety and Health, Morgantown, WV (United States); Kriech, A.J. [Heritage Research Group, Indianapolis, IN (United States)

    2000-10-01

    The present study was carried out to characterize the effects of in vitro exposure to paving asphalt fume condensate (AFC) on alveolar macrophage (AM) functions and to monitor acute pulmonary responses to in vivo AFC exposure in rats. Methods: For in vitro studies, rat primary AM cultures were incubated with various concentrations of AFC for 24 h at 37 C. AM-conditioned medium was collected and assayed for lactate dehydrogenase (LDH) as a marker of cytotoxicity. Tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1 (IL-1) production were assayed in AM-conditioned medium to monitor AM function. The effect of AFC on chemiluminescence (CL) generated by resting AM or AM in response to zymosan or PMA stimulation was also determined as a marker of AM activity. For in vivo studies, rats received either (1) a single intratracheal (IT) instillation of saline, or 0.1 mg or 0.5 mg AFC and were killed 1 or 3 days later; or (2) IT instillation of saline, or 0.1, 0.5, or 2 mg AFC for three consecutive days and were killed the following day. Differential counts of cells harvested by bronchoalveolar lavage were measured to monitor inflammation. Acellular LDH and protein content in the first lavage fluid were measured to monitor damage. CL generation, TNF-{alpha} and IL-1 production by AM were assayed to monitor AM function. Results: In vitro AFC exposure at <200 {mu}g/ml did not induce cytotoxicity, oxidant generation, or IL-1 production by AM, but it did cause a small but significant increase in TNF-{alpha} release from AM. In vitro exposure of AM to AFC resulted in a significant decline of CL in response to zymosan or PMA stimulation. The in vivo studies showed that AFC exposure did not induce significant neutrophil infiltration or alter LDH or protein content in acellular lavage samples. Macrophages obtained from AFC-exposed rats did not show significant differences in oxidant production or cytokine secretion at rest or in response to LPS in comparison with control

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

  11. Effects of Acute Exposures to Carbon Dioxide upon Cognitive Functions

    Science.gov (United States)

    Ryder, V. E.; Scully, R. R.; Alexander, D. J.; Lam, C. W.; Young, M.; Satish, U.; Basner, M.

    2017-01-01

    Carbon dioxide (CO2) originates from human metabolism and typically remains about 10-fold higher in concentration on the International Space Station (ISS) than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the ISS that associates CO2 levels with reports of headaches by crewmembers. Consequently, flight rules have been employed to control CO2 below 3 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached, and there is evidence that CO2 has effects at levels below the threshold for headaches. This concern appears to be substantiated in reports that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. Therefore, we set out to determine if decision-making under volatile, uncertain, confusing and ambiguous circumstances, where feedback is delayed or absent, is correlated with low levels of CO2 during acute exposures (several hours) in crew-like subjects and to determine if additional cognitive domains are sensitive to concentrations of CO2 at, or below, current ISS levels by using a test battery that is currently available onboard ISS. We enrolled 22 volunteers (8 females, 14 males) between the ages of 30-55 (38.8 +/- 7.0) years whose training and professional experience reflect that of the astronaut corps. Subjects were divided among 4 study

  12. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

    Science.gov (United States)

    Adkins, B; O'Connor, R W; Dement, J M

    1987-06-01

    Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

  13. High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

    Science.gov (United States)

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-08-01

    Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

  14. Depression of contraction and the calcium transient in single cardiomyocytes with acute ethanol exposure

    Energy Technology Data Exchange (ETDEWEB)

    Rozanski, D.J.; Delaville, F.J.; Thomas, A.P. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1992-01-01

    The mechanism by which acute ethanol (ET) exposure causes reversible myocardial dysfunction is unknown. The purpose of this study was to examine the effects of ET exposure on contraction and cytosolic free Ca[sup 2+] ([Ca[sup 2+

  15. Self-reported acute health symptoms and exposure to companion animals

    Science.gov (United States)

    Background: In order to understand the etiological burden of disease associated with acute health symptoms (e.g. gastrointestinal [GI], respiratory, dermatological), it is important to understand how common exposures influence these symptoms. Exposures to familiar and unfamiliar ...

  16. Acute symptoms during non-inhalation exposure to combinations of toluene, trichloroethylene, and n-hexane

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1999-01-01

    To study the acute effect of exposure to a mixture of three commonly used solvents in humans using a route of exposure not involving the nose and lungs, in this case a gastrointestinal application....

  17. Infant acute leukemia and maternal exposures during pregnancy.

    Science.gov (United States)

    Pombo-de-Oliveira, Maria S; Koifman, Sergio

    2006-12-01

    Infant acute leukemia (IAL) has a unique profile characterized by the high incidence of translocations involving the MLL gene located at the 11q23 region. To test the potential role of intrauterine and perinatal factors linked to the risk of IAL development, a hospital-based case-control study was conducted in different cities of Brazil. A total of 202 children (ages 0-21 months) with newly diagnosed IAL was enrolled (1999-2005), and 440 age-matched controls were selected from the same hospitals wherein IAL cases were treated. A statistically significant association between maternal use of hormones during pregnancy and IAL was observed [odds ratio (OR), 8.76; 95% confidence interval (95% CI), 2.85-26.93] in a multivariable analysis. The association of certain exposures during pregnancy (hormones, dipyrone, metronidazole, and misoprostol) and MLL gene rearrangements was tested using a case-case approach. Despite the lack of statistical significance, the magnitude of the OR for maternal exposure to dipyrone (OR, 1.45; 95% CI, 0.75-2.86), metronidazole (OR, 1.72; 95% CI, 0.64-4.58), quinolones (OR, 2.25; 95% CI, 0.70-25.70), and hormones (OR, 1.88; 95% CI, 0.50-7.01) may suggest the occurrence of interactions between such maternal exposures during pregnancy and MLL rearrangements, yielding into IAL development. The strong and statistically significant association between IAL and estrogen exposure during pregnancy observed in this study deserves further investigation to investigate its role in intrauterine leukemogenesis.

  18. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality.

    Science.gov (United States)

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders; Molander, Anna Camilla; Madsen, Kenneth Grønkjær; Pottegård, Anton

    2016-04-01

    Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. The study was a register-based cohort study of patients admitted for alcohol withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. A total of 1063 patients treated with chlordiazepoxide and 1365 patients treated with phenobarbital were included. After one year, the outcome rates per 100 person-years in the phenobarbital versus the chlordiazepoxide cohort were 9.20 vs. 5.13 for use of benzodiazepine, 37.9 vs. 37.9 for alcohol recidivism and 29 vs. 59 for mortality. Comparing phenobarbital to chlordiazepoxide treated, the HR of subsequent use of benzodiazepines was 1.56 (95%CI 1.05-2.30). Similarly, the HR for alcohol recidivism was 0.99 (95%CI 0.84-1.16). Lastly, the HR for 30-days and 1 year mortality was 0.25 (95%CI 0.08-0.78) and 0.51 (95%CI 0.31-0.86). There was no decreased risk of subsequent benzodiazepine use or alcohol recidivism in patients treated with phenobarbital compared to chlordiazepoxide. Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics.

    Science.gov (United States)

    Pacifici, Gian M

    2016-01-01

    Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. Its mechanism of action is the synaptic inhibition through an action on GABAA. The loading dose of phenobarbital is 20 mg/kg intravenously and the maintenance dose is 3 to 4 mg/kg by mouth. The serum concentration of phenobarbital is up to 40 µg/ml. Nonresponders should receive additional doses of 5 to 10 mg/kg until seizures stop. Infants with refractory seizures may have a serum concentration of phenobarbital of 100 µg/ml. Phenobarbital is metabolized in the liver by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1. A quarter of the dose of phenobarbital is excreted unchanged in the urine. In adults, the half-life of phenobarbital is 100 hours and in term and preterm infants is 103 and 141 hours, respectively. The half-life of phenobarbital decreases 4.6 hours per day and it is 67 hours in infants 4 week old.

  20. Acute acid exposure increases rabbit esophageal cell proliferation.

    Science.gov (United States)

    Carpizo, D R; Reaka, A J; Glaws, W R; Pooley, N; Schmidt, L; Halline, A G; Goldstein, J L; Layden, T J

    1998-02-01

    In the present study we examined whether an acute infusion of HCl into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCl or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division. Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H+ infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H+ infusion (31%+/-6%) as compared with that in control animals infused with NSS (15%+/-4%). This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H+ infusion. Rete pegs were infrequent in control tissues (4+/-4 rete pegs per 100 microm of esophageal length) or in animals examined 24 hours after acid exposure (4+/-2 rete pegs per 100 microm). However, rete pegs were very prominent 48 hours after acid infusion (22+/-6 rete pegs per 100 microm). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.

  1. Sildenafil does not Improve Exercise Capacity under Acute Hypoxia Exposure.

    Science.gov (United States)

    Toro-Salinas, A H; Fort, N; Torrella, J R; Pagès, T; Javierre, C; Viscor, G

    2016-09-01

    The increase in pulmonary arterial pressure (PAP) due to hypoxic pulmonary vasoconstriction (HPV) could be a limiting factor for physical performance during hypoxic exposure. Sildenafil has been shown to reduce PAP in situations of moderate or severe hypoxia, and consequently its role as an ergogenic aid and even a possible doping substance must be considered. We performed a double-blind crossover study to determine the effects of sildenafil on cardiovascular, respiratory and metabolic parameters in normoxia and during acute exposure to hypobaric hypoxia (4 000 m) at rest and during maximal and submaximal (60% VO2 max) exercise tests. One hour before testing started, sildenafil (100 mg) or a placebo was orally administered to 11 volunteers. In normoxic conditions, sildenafil did not affect performance. Similarly, no significant differences were found in cardiovascular and respiratory parameters in hypoxic conditions at rest or during exercise. The use of sildenafil to improve physical performance in non-acclimatized subjects is not supported by our data. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Continuous phenobarbital treatment leads to recurrent plantar fibromatosis.

    Science.gov (United States)

    Strzelczyk, Adam; Vogt, Heinrich; Hamer, Hajo M; Krämer, Günter

    2008-11-01

    Despite contrary recommendations by expert opinion and international guidelines phenobarbital remains the most widely prescribed anticonvulsant worldwide. Although associated connective tissue disorders were described in a timely way after its introduction, the association between plantar fibromatosis--also called Ledderhose syndrome--and phenobarbital seems not to be well known in general. Our case series uniquely demonstrates that continuous phenobarbital treatment leads to recurrent plantar fibromatosis and may result in long-term disability and numerous unnecessary operations. In general, the association between connective tissue disorders and phenobarbital most prominently appears in adult patients of northern European descent. However, our case series and data from the literature suggest that patient groups less susceptible to connective tissue disorders may as well develop Ledderhose syndrome or other associated syndromes as Dupuytren's contractures, frozen shoulder, Peyronie's disease or complex regional pain syndrome in the course of phenobarbital treatment.

  3. Changes in Cardiac Autonomic Regulation after Acute Lung Exposure to Carbon Nanotubes: Implications for Occupational Exposure

    Directory of Open Access Journals (Sweden)

    Jacopo M. Legramante

    2012-01-01

    Full Text Available Carbon nanotubes (CNTs are among the most relevant engineered nanomaterials (ENMs. Given the expected rise of exposure to ENMs, there is concern that they may adversely affect health of exposed people. Aim of the study was to test the hypothesis that single wall carbon nanotubes (SWCNTs pulmonary exposure acutely affect the autonomic cardiovascular regulation in conscious rats. We studied Wistar-Kyoto rats in which a telemetry transmitter for continuous arterial pressure (AP and heart rate (HR recordings was surgically implanted. SWCNTs dispersed in phosphate buffer saline (PBS or PBS alone were randomly administered intratracheally. Immediately before, and 24 hours after each instillation a 30 min AP recording was performed. The sequence analysis was performed to evaluate the baroreflex function. In the control group, PBS instillation did not induce any significant changes. At variance the SWCNT exposure induced a significant reduction of baroreflex system (BRS (3.5±0.6 versus 2.6±0.40 msec/mmHg without significant changes in the occurrence of baroreflex sequences (7.5±0.47% versus 7.4±0.38%. Our results show that SWCNT pulmonary exposure might affect the cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events.

  4. Side effects of phenobarbital in epilepsy: a systematic review.

    Science.gov (United States)

    Zhang, Ling-Li; Zeng, Li-Nan; Li, You-Ping

    2011-12-01

    In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. Despite the development of better tolerated new generation AEDs, phenobarbital is still widely used particularly in developing countries because of its low cost. The purpose of this review was to: (i) investigate whether phenobarbital can be safely used as an antiepileptic drug and (ii) determine the questions which need to be addressed in order to comprehensively and adequately evaluate the safety of phenobarbital for the treatment of epilepsy. The literature was searched using the Cochrane Central Register of randomised controlled trials (1800-2009), Medline (1966-2009), Embase (1966-2009) and three Chinese databases. Twenty studies were finally included in this systematic review. The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection. These factors may also have been responsible for the heterogeneity present in the meta-analysis. The data did not demonstrate any evidence of association between phenobarbital and a higher risk of adverse events. However, phenobarbital appeared to be associated with a higher rate of adverse drug reaction related withdrawal (ADR-related withdraw), compared to carbamazepine, valproic acid and phenytoin. This may have been due to a concern for possible adverse effects of phenobarbital. Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin. However, in the case of pregnant women, it is important for clinicians to evaluate the benefits and risks of phenobarbital administration before making a final recommendation. Furthermore, unified scales for

  5. 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.

  6. Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure

    Science.gov (United States)

    Moshiri, Mohammad; Moallem, Seyed Adel; Attaranzadeh, Armin; Saberi, Zahra; Etemad, Leila

    2017-01-01

    Objective(s): Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. Materials and Methods: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. Results: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. Conclusion: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations. PMID:28392896

  7. Phenobarbital Meets Phosphorylation of Nuclear Receptors.

    Science.gov (United States)

    Negishi, Masahiko

    2017-05-01

    Phenobarbital was the first therapeutic drug to be characterized for its induction of hepatic drug metabolism. Essentially at the same time, cytochrome P450, an enzyme that metabolizes drugs, was discovered. After nearly 50 years of investigation, the molecular target of phenobarbital induction has now been delineated to phosphorylation at threonine 38 of the constitutive androstane receptor (NR1I3), a member of the nuclear receptor superfamily. Determining this mechanism has provided us with the molecular basis to understand drug induction of drug metabolism and disposition. Threonine 38 is conserved as a phosphorylation motif in the majority of both mouse and human nuclear receptors, providing us with an opportunity to integrate diverse functions of nuclear receptors. Here, I review the works and accomplishments of my laboratory at the National Institutes of Health National Institute of Environmental Health Sciences and the future research directions of where our study of the constitutive androstane receptor might take us. U.S. Government work not protected by U.S. copyright.

  8. Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice

    Science.gov (United States)

    Markowitz, Geoffrey J.; Kadam, Shilpa D.; Smith, Dani R.; Johnston, Michael V.; Comi, Anne M.

    2011-01-01

    Neonatal stroke presents with seizures that are usually treated with phenobarbital. We hypothesized that anticonvulsants would attenuate ischemic injury, but that the dose-dependent effects of standard anticonvulsants would impact important age-dependent and injury-dependent consequences. In this study, ischemia induced by unilateral carotid ligation in postnatal day 12 (P12) CD1 mice was immediately followed by an i.p. dose of vehicle, low-dose or high-dose phenobarbital. Severity of acute behavioral seizures was scored. 5-bromo-2’-deoxyuridine (BrdU) was administered from P18-P20, behavioral testing performed, and mice perfused at P40. Atrophy quantification and counts of BrdU/NeuN-labeled cells in the dentate gyrus were performed. Blood phenobarbital concentrations were measured. 30 mg/kg phenobarbital reduced acute seizures and chronic brain injury, and restored normal weight gain and exploratory behavior. By comparison, 60 mg/kg was a less efficacious anticonvulsant, was not neuroprotective, did not restore normal weight gain, and impaired behavioral and cognitive recovery. Hippocampal neurogenesis was not different between treatment groups. These results suggest a protective effect of lower-dose phenobarbital, but a lack of this effect at higher concentrations after stroke in P12 mice. PMID:21481568

  9. Current position of phenobarbital in epilepsy and its future.

    Science.gov (United States)

    Brodie, Martin J; Kwan, Patrick

    2012-12-01

    This article reviews the current position of phenobarbital using articles published since 2000 and speculates on its likely future contribution to epilepsy care. Over the last decade there have been no major double-blind randomized placebo-controlled or comparative trials with phenobarbital. Previous studies have suggested that phenobarbital is as effective in monotherapy as phenytoin and carbamazepine. Several observational studies undertaken in developing countries over the last decade have confirmed its efficacy and safety for the common epilepsies. This was particularly so in the substantial demonstration project undertaken in rural China under the auspices of the World Health Organization in partnership with the International League Against Epilepsy and International Bureau for Epilepsy. Phenobarbital is still widely used for neonatal and childhood seizures and for drug-resistant convulsive and nonconvulsive status epilepticus. Recent data have confirmed in a prospective cohort of women taking phenobarbital as monotherapy that the drug can be associated with a range of congenital defects in exposed infants. Much effort has gone into exploring the apparent contradiction of higher withdrawal rates due to cognitive and behavioral side effects in studies undertaken in developed countries but not in those sited in the developing world. A raft of data over the last 10 years, including a systematic review, showed no important differences between the tolerability of phenobarbital compared to that with other antiepileptic drugs. Finally, cognitive test scores and mood ratings in 136 people with epilepsy receiving phenobarbital for a year were similar to those in 137 age-, sex-, and education-matched controls in a number of Chinese villages. Indeed, there were some cognitive gains in the patients possibly due to improved seizure control. Phenobarbital is still the most cost-effective pharmacologic treatment for epilepsy. All these data predict a healthy future for

  10. Successful use of haemodialysis to treat phenobarbital overdose.

    Science.gov (United States)

    Hoyland, Kimberley; Hoy, Michael; Austin, Richard; Wildman, Martyn

    2013-11-21

    A 50-year-old woman presented with coma caused by a phenobarbital overdose, requiring intubation and admission to critical care. She was an international visitor and had been prescribed the drug for night-sedation. Phenobarbital is a long-acting barbiturate, which in an overdose can cause central nervous system depression, respiratory failure and haemodynamic instability; these patients can remain obtunded for many days. After initial supportive therapy, she was dialysed to help in the elimination of the drug. Haemodialysis resulted in a markedly reduced plasma level of phenobarbital, which decreased the length of intubation and stay in the critical care unit and aided full recovery.

  11. Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

    Science.gov (United States)

    Stabile, F; Barnett, C R; De Risio, L

    2017-02-18

    Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands. British Veterinary Association.

  12. Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure

    Directory of Open Access Journals (Sweden)

    Mohammad Moshiri

    2017-03-01

    Full Text Available Objective(s: Pregabalin (PGB is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. Materials and Methods: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP. Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. Results: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. Conclusion: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations.

  13. [Efficacy of intravenous phenobarbital treatment for status epilepticus].

    Science.gov (United States)

    Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

    2013-08-01

    Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

  14. Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes

    Science.gov (United States)

    Hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations in rodents. PB induction of hepatic xenobiotic metabolizing enzymes increases thyroid hormones catabolism and biliary elimination. This study examines the catabolism and cl...

  15. Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes

    Science.gov (United States)

    Hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations in rodents. PB induction of hepatic xenobiotic metabolizing enzymes increases thyroid hormones catabolism and biliary elimination. This study examines the catabolism and cl...

  16. Pharmacokinetics of Phenobarbital in Microenema Via Macy Catheter Versus Suppository

    National Research Council Canada - National Science Library

    Lam, Y W Francis; Lam, Ansom; Macy, Brad

    2016-01-01

    .... the same dose given via suppository. This was a randomized, open-label, crossover study comparing the early absorption profile of equal doses of phenobarbital administered rectally in three treatment phases...

  17. ESTIMATED RATE OF FATAL AUTOMOBILE ACCIDENTS ATTRIBUTABLE TO ACUTE SOLVENT EXPOSURE AT LOW INHALED CONCENTRATIONS

    Science.gov (United States)

    Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mecha...

  18. Long term exposure to ambient air pollution and incidence of acute coronary events

    DEFF Research Database (Denmark)

    Cesaroni, Giulia; Forastiere, Francesco; Stafoggia, Massimo

    2014-01-01

    To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE).......To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE)....

  19. Estrogen Effects after a Crush Muscle Injury and Acute Exposure to Hypobaric Hypoxia

    Science.gov (United States)

    2015-03-01

    et al. Intermittent hypobaric hypoxia increases the ability of neutrophils to generate superoxide anion in humans. Clin Exp Pharmacol Physiol. 2003...AFRL-SA-WP-TR-2015-0007 Estrogen Effects after a Crush Muscle Injury and Acute Exposure to Hypobaric Hypoxia Dr. Barbara St...after a Crush Muscle Injury and Acute Exposure to Hypobaric Hypoxia 5a. CONTRACT NUMBER FA7014-10-2-0001 5b. GRANT NUMBER 5c. PROGRAM

  20. Association of HLA genotypes with phenobarbital hypersensitivity in children.

    Science.gov (United States)

    Manuyakorn, Wiparat; Mahasirimongkol, Surakameth; Likkasittipan, Plernpit; Kamchaisatian, Wasu; Wattanapokayakit, Sukanya; Inunchot, Wimala; Visudtibhan, Anannit; Wichukchinda, Nuanjun; Benjaponpitak, Suwat

    2016-10-01

    Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children

  1. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  2. In vitro and in vivo models of acute alcohol exposure

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc; Gyongyi Szabo

    2009-01-01

    Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse,and identifies their suitability for biomedical research.

  3. Effects of acute electromagnetic fields exposure on the interhemispheric homotopic functional connectivity during resting state.

    Science.gov (United States)

    Lv, Bin; Shao, Qing; Chen, Zhiye; Ma, Lin; Wu, Tongning

    2015-08-01

    In this paper, we aimed to investigate the possible effects of acute radiofrequency electromagnetic fields (EMF) on the interhemispheric homotopic functional connectivity with resting state functional magnetic resonance imaging (fMRI) technique. We designed a controllable LTE-related EMF exposure environment at 2.573 GHz and performed the 30 min real/sham exposure experiments on human brain under the safety limits. The resting state fMRI signals were collected before and after EMF exposure. Then voxel-mirrored homotopic connectivity method was utilized to evaluate the acute effects of LTE EMF exposure on the homotopic functional connectivity between two human hemispheres. Based on our previous research, we further demonstrated that the 30 min short-term LTE EMF exposure would modulate the interhemispheric homotopic functional connectivity in resting state around the medial frontal gyrus and the paracentral lobule during the real exposure.

  4. Calcium-dependent behavioural responses to acute copper exposure in Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Poulsen, S.B.; Svendsen, Jon Christian; Aarestrup, Kim;

    2014-01-01

    Using rainbow trout Oncorhynchus mykiss, the present study demonstrated that: (1) calcium (Ca) increased the range of copper (Cu) concentrations that O. mykiss avoided; (2) Ca conserved the maintenance of pre-exposure swimming activity during inescapable acute (10 min) Cu exposure. Data showed...... their spontaneous swimming speed, whereas no response was observed in O. mykiss acclimated and tested at high Ca concentration. Collectively, the data support the conclusion that in O. mykiss the behavioural responses to acute Cu exposure are Ca-dependent....

  5. Genome-wide Gene Expression Profiling of Acute Metal Exposures in Male Zebrafish

    Science.gov (United States)

    2014-10-23

    and methods Experimental overview Fig. 1 shows the design scheme. Fish exposures Briefly, adult,male zebrafishwere exposed to concentrations of each...before and after exposures. Initially 25 adult (6–9 months) presumptive male zebrafish were selected per condition to ensure that 20 male fish were...evaluated in whole adult male zebra ???sh following acute 24 h high dose exposure to three metals with known human health risks. Male adult zebra ???sh

  6. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Nielsen, M. Gissel

    1978-01-01

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

  7. Pharmacokinetics of Phenobarbital in Microenema Via Macy Catheter Versus Suppository.

    Science.gov (United States)

    Lam, Y W Francis; Lam, Ansom; Macy, Brad

    2016-06-01

    The oral route is compromised for nearly all patients approaching death. When agitation, seizures, or other intractable symptoms occur, a quick, discreet, comfortable, and effective alternate route for medication delivery that is easy to administer in the home setting is highly desirable. To characterize the early absorption profile, variability, and comfort of phenobarbital given in microenema suspensions delivered via the Macy Catheter(®) (MC) vs. the same dose given via suppository. This was a randomized, open-label, crossover study comparing the early absorption profile of equal doses of phenobarbital administered rectally in three treatment phases: phenobarbital suppository and two different microenemas with phenobarbital tablets crushed and suspended in 6 mL (MC-6) or 20 mL (MC-20) of tap water. Mean plasma phenobarbital concentrations at 10 minutes were 12× higher for MC-20 and 8× higher for MC-6 compared to suppository. Concentrations achieved in 30 minutes via MC-20 took almost three hours to achieve with suppository. Mean AUC values were higher for MC-20 and MC-6 (82% and 46%, respectively) vs. suppository (P suppository. MC administrations were reported as "not uncomfortable" compared to suppositories, which were reported as "mildly uncomfortable" (P suppository in delivering the medication reliably and rapidly. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Acute expanded perlite exposure with persistent reactive airway dysfunction syndrome.

    Science.gov (United States)

    Du, Chung-Li; Wang, Jung-Der; Chu, Po-Chin; Guo, Yue-Liang Leon

    2010-01-01

    Expanded perlite has been assumed as simple nuisance, however during an accidental spill out in Taiwan, among 24 exposed workers followed for more than 6 months, three developed persisted respiratory symptoms and positive provocation tests were compatible with reactive airway dysfunction syndrome. During simulation experiment expanded perlite is shown to be very dusty and greatly exceed current exposure permission level. Review of literature and evidence, though exposure of expanded perlite below permission level may be generally safe, precautionary protection of short term heavy exposure is warranted.

  9. Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs.

    OpenAIRE

    Gaskill, C L; Cribb, A E

    2000-01-01

    In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

  10. Pulmonary CT findings in acute mercury vapour exposure

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Manabu; Sato, Kimihiko; Heianna, Jyouiti; Hirano, Yoshinori; Omachi, Kohiti; Izumi, Jyunichi; Watarai, Jiro

    2001-01-01

    AIM: We describe the pulmonary computed tomography (CT) findings in acute mercury poisoning. MATERIALS AND METHODS: Initial (n= 8) and follow-up (n= 6) chest CT examinations in eight patients exposed to mercury vapour while cutting pipes in a sulphuric acid plant were reviewed. Of the eight patients, two were asymptomatic and had normal CT results, two were asymptomatic but had abnormalities on CT, and four had both acute symptoms and positive CT results. The patients were all men whose ages ranged from 37 to 54 years (mean, 49 years). RESULTS: Poorly defined nodules were present in five of six patients with positive CT findings, present alone in two patients or as part of a mixed pattern in three. They were random in distribution. Alveolar consolidation (n= 3) and areas of ground-glass opacity (n= 4) were observed and were more prominent in the most severely affected patients with the highest blood and urine level of mercury, predominantly in the upper and/or middle zone. These abnormal findings on CT resolved with (n= 1) or without (n= 5) steroid therapy. Pathological findings (n= 1) demonstrated acute interstitial changes predominantly with oedema. CONCLUSION: We report CT findings in eight patients acutely exposed to mercury vapour. The pulmonary injury was reversible on CT in these cases. Hashimoto, M. (2001)

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

    Science.gov (United States)

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

    2012-01-01

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

  12. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years.

    Science.gov (United States)

    Yasiry, Zeid; Shorvon, Simon D

    2012-12-01

    Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912. This article tells the story of the discovery of its antiepileptic action, its early development, and the subsequent course of its clinical use over the 100-year period. The side effects, pharmacokinetics, and misuse of barbiturates are considered, along with the more recent clinical trials and the drug's current clinical utilization. The introduction of controlled drug regulations, the comparative cost of phenobarbital, and its inclusion on the World Health Organization (WHO) essential drug list are discussed. It is one of the few drugs on the formulary in 1912 that is still listed today, and remarkably its efficacy in epilepsy has not been significantly bettered. The current recommendation by the WHO is that phenobarbital should be offered as the first option for therapy for convulsive epilepsy in adults and children if availability can be ensured. This is rated as a strong recommendation because of the proven efficacy and low cost of phenobarbital, and despite its perceived side-effect profile and the practical problems of access. Whether this recommendation puts "a hierarchy on the brain," as has been suggested, is arguable. Much still needs to be learned about the drug's effects, and the issues raised by phenobarbital have lessons for all antiepileptic drug therapy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  13. Phenobarbital-induced DRESS: a lichenoïd picture.

    Science.gov (United States)

    Chaabane, Amel; Ben Fadhel, Najah; Chadli, Zohra; Ben Fredj, Nadia; Boughattas, Naceur A; Aouam, Karim

    2014-12-01

    We describe, the first case of phenobarbital-induced DRESS syndrome presenting as a lichenoïd eruption. A 49-year-old man had received phenobarbital for a cerebral metastasis. Twenty-five days later, he developed a purplish skin eruption, odynophagia, oral mucosal erosion and fever. Physical examination revealed a cervical lymphadenopathy and facial edema associated to a diffuse violaceous maculo-papular itchy rash. Laboratory findings showed a 1200/mm³ eosinophil's cell count. Alanine aminotransferase was 169 IU/l. Lactate dehydrogenase and creatinine phosphokinase were at 768 and 90 IU/l, respectively. All symptoms resolved completely five weeks after phenobarbital withdrawal. Few days later, the patient died because of a cardio-respiratory arrest.

  14. Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli

    Directory of Open Access Journals (Sweden)

    Elizabeth Brooke Riley

    2015-08-01

    Full Text Available Psychostimulants have many effects on visual function, from adverse, following acute and prenatal exposure to therapeutic, on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF and dark (DF flashes elicited similar responses in the optic tectum neuropil (TOn, while the dorsal telencephalon (dTe responded only to LF. Acute cocaine (0.5 μM reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals, responses to LF are more complex, involving dTe (homologous to the cerebral cortex, and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that prenatal cocaine exposure modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by prenatal cocaine exposure may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological

  15. Behavioral and neurochemical changes in response to acute stressors: influence of previous chronic exposure to immobilization.

    Science.gov (United States)

    Pol, O; Campmany, L; Gil, M; Armario, A

    1992-07-01

    The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4-hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to shock was similar. In the forced swim test, acute IMO decreased struggling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Phenobarbital-responsive sialadenosis in dogs: case series.

    Science.gov (United States)

    Alcoverro, Emili; Tabar, Maria Dolores; Lloret, Albert; Roura, Xavier; Pastor, Josep; Planellas, Marta

    2014-12-01

    Phenobarbital-responsive sialadenosis (PRS) is a rare idiopathic disease in dogs. Vomiting, retching, and gulping with bilateral enlargement of the submandibular salivary glands are the more frequent clinical signs. A thorough diagnostic examination must be performed to rule out the most important systemic etiologies involved with chronic vomiting, as there is no specific test to diagnose PRS. Diagnosis is confirmed clinically by a rapid and dramatic improvement of clinical signs after instauration of phenobarbital treatment. The aim of this article is to describe the clinical presentation, diagnostic findings, and outcome of a case series of 4 dogs with presumptive PRS. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Phenobarbital versus diazepam for delirium tremens--a retrospective study

    DEFF Research Database (Denmark)

    Hjermø, Ida; Anderson, John Erik; Fink-Jensen, Anders;

    2010-01-01

    Delirium tremens (DT) is a severe and potentially fatal condition that may occur during withdrawal from chronic alcohol intoxication. The purpose of the present study was to compare the effects and the rates of complications of phenobarbital and diazepam treatment in DT.......Delirium tremens (DT) is a severe and potentially fatal condition that may occur during withdrawal from chronic alcohol intoxication. The purpose of the present study was to compare the effects and the rates of complications of phenobarbital and diazepam treatment in DT....

  18. Catalase Activity in Brown Mussels (Perna perna) under Acute Cadmium, Lead, and Copper Exposure and Depuration Tests

    National Research Council Canada - National Science Library

    Boudjema, Kamel; Kourdali, Sidali; Bounakous, Nabila; Meknachi, Abdellah; Badis, Abdelmalek

    2014-01-01

      Brown mussels (Perna perna) were exposed to cadmium (Cd), lead (Pb), and copper (Cu) concentrations under acute exposure and exposure-depuration tests for the estimation of biochemical biomarker catalase...

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

    OpenAIRE

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

    2016-01-01

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

  20. Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

    OpenAIRE

    Park, Hye Jung; Sohn, Jung-Ho; Kim, Yoon-Ju; Park, Yoon Hee; Han, Heejae; Park, Kyung Hee; Lee, Kangtaek; Choi, Hoon; Um, Kiju; Choi,In-Hong; Park, Jung-Won; Lee, Jae-Hyun

    2015-01-01

    Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c ...

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

    Science.gov (United States)

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

    2016-11-01

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

  2. Commuters’ air pollution exposure and acute health effects

    NARCIS (Netherlands)

    Zuurbier, M.M.M.

    2011-01-01

    People spend a substantial proportion of their time in traffic. In Europe, the average daily time in traffic is one to one and a half hour. Because of high in-traffic exposures and because most of the journeys are made during rush hours, the one to one and a half hour in traffic contributes dispropo

  3. Commuters’ air pollution exposure and acute health effects

    NARCIS (Netherlands)

    Zuurbier, M.M.M.

    2011-01-01

    People spend a substantial proportion of their time in traffic. In Europe, the average daily time in traffic is one to one and a half hour. Because of high in-traffic exposures and because most of the journeys are made during rush hours, the one to one and a half hour in traffic contributes

  4. Humoral immunodepression following acute NO/sub 2/ exposure in normal and adrenalectomized mice

    Energy Technology Data Exchange (ETDEWEB)

    Azoulay-Dupuis, E.; Levacher, M.; Muffat-Joly, M.; Pocidalo, J.J.

    1985-01-01

    The effects following 20 ppm NO/sub 2/ exposure on humoral immunity were investigated in C57BI/6 mice after 48, 72, and 96 h exposure. Both spleen plaque-forming cell (PFC) responses and serum hemagglutinins (HA) using sheep red blood cells (SRBC) as antigen were studied. Splenic and thymic weight and cellularity decreased on acute exposure to NO/sub 2/. PFC were markedly depressed after 48 h exposure and continued to decrease as exposure time was lengthened. HA titers were also depressed. The same significant suppression of PFC and HA titers was observed in adrenalectomized mice after 96 h NO/sub 2/ exposure. The depression of humoral immunity in NO/sub 2/-exposed mice was independent of stress-induced endogeneous steroids.

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

    Science.gov (United States)

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

    2010-10-01

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

  6. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia.

    Science.gov (United States)

    Shellhaas, Renée A; Ng, Chee M; Dillon, Christina H; Barks, John D E; Bhatt-Mehta, Varsha

    2013-02-01

    Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on phenobarbital pharmacokinetics, taking into account maturational changes. Level 3 neonatal ICU. Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. None. A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). Data on phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of phenobarbital. Therapeutic hypothermia does not influence the clearance of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

  7. Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

    Science.gov (United States)

    Mathur, Priya; Guo, Su

    2011-06-01

    Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

    Science.gov (United States)

    Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

    2013-12-01

    Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Occupational exposure to particles and incidence of acute myocardial infarction and other ischaemic heart disease.

    Science.gov (United States)

    Wiebert, Pernilla; Lönn, Maria; Fremling, Karin; Feychting, Maria; Sjögren, Bengt; Nise, Gun; Kauppinen, T; Plato, Nils; Gustavsson, Per

    2012-09-01

    Ambient particulate air pollution has been linked to cardiovascular disease. Occupational particle exposure levels may be several times higher than ambient levels but has been less studied. The authors investigated the association between occupational exposure to particles and the incidence of ischaemic heart disease (IHD). The cohort included all manual workers in the Swedish national census of 1980 with information on demographic data and occupation. Information on hospital admissions for acute myocardial infarction or other IHDs and cause of death were obtained from nation-wide registers. A job-exposure matrix for exposure to small (1 μm) particles was developed. HRs were calculated with Cox regression with adjustment for sex, age, socioeconomic group and urban/rural residential area. Exposure to small particles was associated with an increased HR for acute myocardial infarction of 1.12 (95% CI 1.09 to 1.15), and HR for exposure to large particles was 1.14 (95% CI 1.10 to 1.18). The association was somewhat stronger for workers exposed to small particles for more than 5 years, 1.21 (95% CI 1.11 to 1.31), but no trend with exposure intensity was found. The risk associated with exposure to small particles was higher among women than among men, 1.30 (95% CI 1.12 to 1.51) and 1.10 (95% CI 1.07 to 1.14), respectively. Findings were essentially similar for other IHDs. This explorative study gives some support to the hypothesis that occupational exposure to particles increases the risk of acute myocardial infarction and other IHD. The findings must be interpreted cautiously due to lack of smoking data.

  10. Self-reported acute health symptoms and exposure to companion animals#

    Science.gov (United States)

    Self-reported acute health symptoms and exposure to companion animalsWhitney S. Krueger1,2, Elizabeth D. Hilborn2, Timothy J. Wade21Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA2Environmental Public Health Division, Office of Research and Development, U...

  11. ACUTE BEHAVORIAL EFFECTS FROM EXPOSURE TO TWO-STROKE ENGINE EXHAUST

    Science.gov (United States)

    Benefits of changing from two-stroke to four-stroke engines (and other remedial requirements) can be evaluated (monetized) from the standpoint of acute behavioral effects of human exposure to exhaust from these engines. The monetization process depends upon estimates of the magn...

  12. In Utero Exposure to Lipopolysaccharide Alters the Postnatal Acute Phase Response in Beef Heifers

    Science.gov (United States)

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

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

    Science.gov (United States)

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

  14. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  15. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  16. Striatal dopamine dynamics in mice following acute and repeated toluene exposure.

    Science.gov (United States)

    Apawu, Aaron K; Mathews, Tiffany A; Bowen, Scott E

    2015-01-01

    The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene's mechanism of action is unknown. The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry. Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene's locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25-50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice. These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.

  17. Neurobehavorial effects of acute exposure to four solvents: meta-abalyses

    Science.gov (United States)

    Meta-and re-analyses of the available data for the neurobehavioral effects of acute inhalation exposure to toluene were reported by Benignus et al. (2007). The present study was designed to test the generality of the toluene results in as many other solvents as possible by furthe...

  18. Pathogenesis of Acute and Delayed Corneal Lesions after Ocular Exposure to Sulfur Mustard Vapor

    Science.gov (United States)

    2012-01-01

    had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae...can cause a permanent reduction in visual acuity or complete loss of eyesight [6]. The pathogenesis of MGK has been clinically described as a chronic

  19. A Method for Quantifying the Acute Health Impacts of Residential Non-Biological Exposure Via Inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Logue, Jennifer M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Singer, Bret C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-01

    The inability to monetize the health costs of acute exposures in homes and the benefits of various control options is a barrier to justifying policies and approaches that can reduce exposure and improve health.We synthesized relationships between short-term outdoor concentration changes and health outcomes to estimate the health impacts of short-term in-home exposures. Damage and cost impacts of specific health outcomes were taken from the literature. We assessed the impact of vented and non-vented residential natural gas cooking burners on Southern California occupants for two pollutants (NO2 and CO).

  20. Acute phase proteins in cattle after exposure to complex stress

    DEFF Research Database (Denmark)

    Lomborg, S. R.; Nielsen, L. R.; Heegaard, Peter M. H.

    2008-01-01

    Abstract Stressors such as weaning, mixing and transportation have been shown to lead to increased blood concentrations of acute phase proteins (APP), including serum amyloid A (SAA) and haptoglobin, in calves. This study was therefore undertaken to assess whether SAA and haptoglobin levels...... in blood mirror stress in adult cattle. Six clinically healthy Holstein cows and two Holstein heifers were transported for four to six hours to a research facility, where each animal was housed in solitary tie stalls. Blood samples for evaluation of leukocyte counts and serum SAA and haptoglobin...... concentrations were obtained before (0-sample) and at 8, 24 and 48 hours after the start of transportation. Upon arrival the animals gave the impression of being anxious, and they appeared to have difficulty coping with isolation and with being tied on the slippery floors of the research stable. Serum...

  1. Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli.

    Science.gov (United States)

    Riley, Elizabeth; Kopotiyenko, Konstantin; Zhdanova, Irina

    2015-01-01

    Psychostimulants have many effects on visual function, from adverse following acute and prenatal exposure to therapeutic on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF) and dark (DF) flashes elicited similar responses in the optic tectum neuropil (TOn), while the dorsal telencephalon (dTe) responded only to LF. Acute cocaine (0.5 μM) reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation (RSP) led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure (PCE) prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals), responses to LF are more complex, involving dTe (homologous to the cerebral cortex), and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that PCE modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by PCE may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological interventions.

  2. Acute and Chronic Exposure to CO2 in Space Flight

    Science.gov (United States)

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

    2010-01-01

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

  3. Structural and functional changes of the human macula during acute exposure to high altitude.

    Directory of Open Access Journals (Sweden)

    M Dominik Fischer

    Full Text Available BACKGROUND: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO study. METHODOLOGY/PRINCIPAL FINDINGS: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m. High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT in all four outer ETDRS grid subfields during acute altitude exposure (TRT(outer = 2.80 ± 1.00 μm; mean change ± 95%CI. This change was inverted towards the inner four subfields (TRT(inner = -1.89 ± 0.97 μm with significant reduction of TRT in the fovea (TRT(foveal = -6.62 ± 0.90 μm at altitude. BCVA revealed no significant difference compared to baseline (0.06 ± 0.08 logMAR. Microperimetry showed stable mean sensitivity in all but the foveal subfield (MS(foveal = -1.12 ± 0.68 dB. At baseline recordings before and >2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. CONCLUSIONS/SIGNIFICANCE: During acute exposure to high altitude central retinal thickness is subject to minor, yet statistically significant changes. These alterations describe a function of eccentricity with an increase in regions with relatively higher retinal nerve fiber content and vascular arcades. However, these changes did not correlate with measures of central retinal function or acute mountain sickness. For the first time a quantitative approach has been used to assess these changes during acute

  4. Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

    Science.gov (United States)

    Fischer, M. Dominik; Willmann, Gabriel; Schatz, Andreas; Schommer, Kai; Zhour, Ahmad; Zrenner, Eberhart; Bartz-Schmidt, Karl U.; Gekeler, Florian

    2012-01-01

    Background This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.80±1.00 μm; mean change±95%CI). This change was inverted towards the inner four subfields (TRTinner = −1.89±0.97 μm) with significant reduction of TRT in the fovea (TRTfoveal = −6.62±0.90 μm) at altitude. BCVA revealed no significant difference compared to baseline (0.06±0.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = −1.12±0.68 dB). At baseline recordings before and >2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance During acute exposure to high altitude central retinal thickness is subject to minor, yet statistically significant changes. These alterations describe a function of eccentricity with an increase in regions with relatively higher retinal nerve fiber content and vascular arcades. However, these changes did not correlate with measures of central retinal function or acute mountain sickness. For the first time a quantitative approach has been used to assess these changes during acute, non

  5. Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine exposure in mice.

    Science.gov (United States)

    Tallarida, Christopher S; Corley, Gladys; Kovalevich, Jane; Yen, William; Langford, Dianne; Rawls, Scott M

    2013-11-27

    Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine exposure and attenuates development of behavioral sensitization produced by repeated cocaine exposure. An important question that has not yet been answered is whether or not CTX reduces behavioral sensitization to cocaine in cases in which the antibiotic is administered only during the period of cocaine absence that follows repeated cocaine exposure and precedes reintroduction to cocaine. We investigated this question using C57BL/6 mice. Mice pretreated with cocaine (15mg/kg×14 days) and then challenged with cocaine (15mg/kg) after 30 days of cocaine absence displayed sensitization of locomotor activity. For combination experiments, CTX injected during the 30 days of cocaine absence attenuated behavioral sensitization produced by cocaine challenge. In the case in which CTX was injected together with cocaine for 14 days, development of behavioral sensitization to cocaine challenge was also reduced. CTX attenuated the increase in locomotor activity produced by acute cocaine exposure; however, its efficacy was dependent on the dose of cocaine as inhibition was detected against 30mg/kg, but not 15mg/kg, of cocaine. These results from mice indicate that CTX attenuates locomotor activity produced by acute and repeated cocaine exposure and counters cocaine's locomotor activating properties in a paradigm in which the antibiotic is injected during the period of forced cocaine absence that follows repeated cocaine exposure.

  6. Factors affecting the estimated probabilistic acute dietary exposure to captan from apple consumption.

    Science.gov (United States)

    Zentai, A; Sali, J; Szabó, I J; Szeitzné-Szabó, M; Ambrus, A; Vásárhelyi, A

    2013-01-01

    The effect of the number of pesticide residue values below the LOQ/LOD of analytical methods, the variability of residues in individual fruits, mass of fruit units and the number of bootstrap iterations was studied on the probabilistically estimated acute exposure of consumers. The 4720 daily apple consumption data and the results of 1239 apple sample analyses for captan residues, performed within the Hungarian monitoring programme between 2005 and 2011, were used in this study as model matrix. Up to about 95th percentile exposure (µg/(kg bw·day)), simply multiplying each residue in composite samples with each consumption value gave similar estimates to those obtained with the complex procedure taking also into account the mass of and residues in individual fruits. However, the exposure above the 95th percentile calculated with the complex procedure gradually increased with increasing percentile level compared to the simple procedure. Including the high number of non-detects reduced the estimated exposure, which was the highest when only the residues measured in treated fruits were taken into account. The number of bootstrap iterations between 100 and 10,000 did not significantly affect the calculated exposure. The 99.99th percentile exposure amounted to 17.9% of the acute reference dose of 300 µg/(kg bw·day) for women of childbearing age.

  7. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  8. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Science.gov (United States)

    Laloy, J.; Lozano, O.; Alpan, L.; Masereel, B.; Toussaint, O.; Dogné, J. M.; Lucas, S.

    2015-08-01

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

  9. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Energy Technology Data Exchange (ETDEWEB)

    Laloy, J., E-mail: julie.laloy@unamur.be [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lozano, O. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Alpan, L.; Masereel, B. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Toussaint, O. [University of Namur (UNamur), Laboratory of Cellular Biochemistry and Biology (URBC), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Dogné, J. M. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lucas, S. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium)

    2015-08-15

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Effects of Acute Exposures to Carbon Dioxide Upon Cognitive Functions

    Science.gov (United States)

    Scully, R. R.; Alexander, D. J.; Ryder, V. E.; Lam, C. W.; Statish, U.; Basner, M.

    2016-01-01

    Large quantities of carbon dioxide (CO2) originate from human metabolism and typically, within spacecraft, remain about 10-fold higher in concentration than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the International Space Station (ISS) that associates CO2 levels with reports of headaches by crewmembers. Additionally, there is concern that CO2 may contribute to vision impairment and intracranial pressure that has been observed in some crewmembers. Consequently, flight rules have been employed to control the level of CO2 below 4 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. However, the flight rule imposed limit, which places additional demands upon resources and current technology, still exceeds the lower bound of the threshold range for reportable headaches (2 - 5 mm Hg). Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached. The causes of the headaches may elicit other subtle adverse effects that occur at CO2 levels well below that for headaches. The concern that CO2 may have effects at levels below the threshold for headaches appears to be substantiated in unexpected findings that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. If findings of the earlier study are confirmed in crew-like subjects, our findings would provide additional evidence that CO2 may need to be

  12. Investigating the synchronization of hippocampal neural network in response to acute nicotine exposure

    Directory of Open Access Journals (Sweden)

    Akay Metin

    2010-07-01

    Full Text Available Abstract Previous studies suggested that γ oscillations in the brain are associated with higher order cognitive function including selective visual attention, motor task planning, sensory perception, working memory and dreaming REM sleep. These oscillations are mainly observed in cortical regions and also occur in neocortical and subcortical areas and the hippocampus. In this paper, we investigate the influence of acute exposure to nicotine on the complexity of hippocampal γ oscillations. Using the approximate entropy method, the influence of acute nicotine exposure on the hippocampal γ oscillations was investigated. The hippocampal γ oscillations have been generated in response to the 100 Hz stimulus and isolated using the visual inspection and spectral analysis method. Our central hypothesis is that acute exposure to nicotine significantly reduces the complexity of hippocampal γ oscillations. We used brain-slice recordings and the approximate entropy method to test this hypothesis. The approximate entropy (complexity values of the hippocampal γ oscillations are estimated from the 14 hippocampal slices. Our results show that it takes at least 100 msec to see any hippocampal activities in response to the 100 Hz stimulus. These patterns noticeably changed after 100 msec until 300 msec after the stimulus Finally, they were less prominent after 300 msec. We have analyzed the isolated hippocampal γ oscillations (between 150 and 250 msec after the stimulus using the approximate entropy (ApEn method. Our results showed that the ApEn (complexity values of hippocampal γ oscillations during nicotine exposure were reduced compared to those of hippocampal γ oscillations during control, and washout. This reduction was much more significant in response to acute nicotine exposure (p

  13. Phenobarbital use and neurological problems in FMR1 premutation carriers

    Science.gov (United States)

    Saldarriaga, Wilmar; Lein, Pamela; Teshima, Laura Yuriko González; Isaza, Carolina; Rosa, Lina; Polyak, Andrew; Hagerman, Randi; Girirajan, Santhosh; Silva, Marisol; Tassone, Flora

    2016-01-01

    Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55–200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients. PMID:26802682

  14. Phenobarbital use and neurological problems in FMR1 premutation carriers.

    Science.gov (United States)

    Saldarriaga, Wilmar; Lein, Pamela; González Teshima, Laura Yuriko; Isaza, Carolina; Rosa, Lina; Polyak, Andrew; Hagerman, Randi; Girirajan, Santhosh; Silva, Marisol; Tassone, Flora

    2016-03-01

    Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55-200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Acute Respiratory Failure due to Alveolar Hemorrhage after Exposure to Organic Dust

    Directory of Open Access Journals (Sweden)

    Sun Mi Choi

    2016-05-01

    Full Text Available Diffuse alveolar hemorrhage (DAH is associated with severe outcomes. We report a case of acute respiratory failure that required mechanical ventilation and was clinically and pathologically diagnosed as DAH related to exposure to organic dust. A 39-year-old man, who had visited a warehouse to grade beans for purchase, was referred to our hospital for impending respiratory failure. His initial radiographic examinations revealed diffuse bilateral ground-glass opacities in his lungs and bronchoalveolar lavage resulted in progressively bloodier returns, which is characteristic of DAH. He underwent bedside open lung biopsy of his right lower lobe in the intensive care unit. Biopsy results revealed DAH and organization with accumulation of hemosiderin-laden macrophages and a few fibroblastic foci. The patient was treated with empirical antibiotics and high-dose corticosteroids and successfully weaned from mechanical ventilation. DAH might be considered in the differential diagnosis of patients with acute respiratory failure after exposure to organic particles.

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA.

    Science.gov (United States)

    Shields, Grant S; Lam, Jovian C W; Trainor, Brian C; Yonelinas, Andrew P

    2016-05-01

    Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol.

  18. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    Science.gov (United States)

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally.

  19. Disrupted Nitric Oxide Metabolism from Type II Diabetes and Acute Exposure to Particulate Air Pollution.

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    Ashley P Pettit

    Full Text Available Type II diabetes is an established cause of vascular impairment. Particulate air pollution is known to exacerbate cardiovascular and respiratory conditions, particularly in susceptible populations. This study set out to determine the impact of exposure to traffic pollution, with and without particle filtration, on vascular endothelial function in Type II diabetes. Endothelial production of nitric oxide (NO has previously been linked to vascular health. Reactive hyperemia induces a significant increase in plasma nitrite, the proximal metabolite of NO, in healthy subjects, while diabetics have a lower and more variable level of response. Twenty type II diabetics and 20 controls (ages 46-70 years were taken on a 1.5 hr roadway traffic air pollution exposure as passengers. We analyzed plasma nitrite, as a measure of vascular function, using forearm ischemia to elicit a reactive hyperemic response before and after exposure to one ride with and one without filtration of the particle components of pollution. Control subjects displayed a significant increase in plasma nitrite levels during reactive hyperemia. This response was no longer present following exposure to traffic air pollution, but did not vary with whether or not the particle phase was filtered out. Diabetics did not display an increase in nitrite levels following reactive hyperemia. This response was not altered following pollution exposure. These data suggest that components of acute traffic pollution exposure diminish vascular reactivity in non-diabetic individuals. It also confirms that type II diabetics have a preexisting diminished ability to appropriately respond to a vascular challenge, and that traffic pollution exposure does not cause a further measureable acute change in plasma nitrite levels in Type II diabetics.

  20. Acute lead exposure increases arterial pressure: role of the renin-angiotensin system.

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    Maylla Ronacher Simões

    Full Text Available BACKGROUND: Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were treated with lead acetate (i.v. bolus dose of 320 µg/Kg, and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na(+,K(+-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1 produced blood lead levels of 37±1.7 µg/dL, which is below the reference blood concentration (60 µg/dL; 2 increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg; 3 increased ACE activity (27% compared to Ct and Na(+,K(+-ATPase activity (125% compared to Ct; and 4 did not change the protein expression of the α1-subunit of Na(+,K(+-ATPase, AT(1 and AT(2. Pre-treatment with an AT(1 receptor blocker (losartan, 10 mg/Kg or an ACE inhibitor (enalapril, 5 mg/Kg blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg did not prevent lead's hypertensive effect. CONCLUSION: Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular disease.

  1. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    Science.gov (United States)

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    Energy Technology Data Exchange (ETDEWEB)

    Mehinto, Alvine C., E-mail: alvinam@sccwrp.org [Southern California Coastal Water Research Project, Costa Mesa, CA 92626 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Prucha, Melinda S. [Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Vulpe, Christopher D. [Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 (United States); Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States)

    2014-07-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  3. Chromosomal bands affected by acute oil exposure and DNA repair errors.

    Directory of Open Access Journals (Sweden)

    Gemma Monyarch

    Full Text Available BACKGROUND: In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. OBJECTIVES: We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. METHODS: Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. RESULTS: Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016. CONCLUSION: The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

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

    Directory of Open Access Journals (Sweden)

    Elke S. Reichwaldt

    2016-08-01

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

  5. Acute Exposure to Pacific Ciguatoxin Reduces Electroencephalogram Activity and Disrupts Neurotransmitter Metabolic Pathways in Motor Cortex.

    Science.gov (United States)

    Kumar, Gajendra; Au, Ngan Pan Bennett; Lei, Elva Ngai Yu; Mak, Yim Ling; Chan, Leanne Lai Hang; Lam, Michael Hon Wah; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-09-10

    Ciguatera fish poisoning (CFP) is a common human food poisoning caused by consumption of ciguatoxin (CTX)-contaminated fish affecting over 50,000 people worldwide each year. CTXs are classified depending on their origin from the Pacific (P-CTXs), Indian Ocean (I-CTXs), and Caribbean (C-CTXs). P-CTX-1 is the most toxic CTX known and the major source of CFP causing an array of neurological symptoms. Neurological symptoms in some CFP patients last for several months or years; however, the underlying electrophysiological properties of acute exposure to CTXs remain unknown. Here, we used CTX purified from ciguatera fish sourced in the Pacific Ocean (P-CTX-1). Delta and theta electroencephalography (EEG) activity was reduced remarkably in 2 h and returned to normal in 6 h after a single exposure. However, second exposure to P-CTX-1 induced not only a further reduction in EEG activities but also a 2-week delay in returning to baseline EEG values. Ciguatoxicity was detected in the brain hours after the first and second exposure by mouse neuroblastoma assay. The spontaneous firing rate of single motor cortex neuron was reduced significantly measured by single-unit recording with high spatial resolution. Expression profile study of neurotransmitters using targeted profiling approach based on liquid chromatography-tandem mass spectrometry revealed an imbalance between excitatory and inhibitory neurotransmitters in the motor cortex. Our study provides a possible link between the brain oscillations and neurotransmitter release after acute exposure to P-CTX-1. Identification of EEG signatures and major metabolic pathways affected by P-CTX-1 provides new insight into potential biomarker development and therapeutic interventions.

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

    Science.gov (United States)

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

    2015-10-01

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

  7. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    Science.gov (United States)

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  8. Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

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    Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S

    2003-03-01

    White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

  9. Acute toxicity effects of Prunus avium fruit extract and selection of optimum dose against radiation exposure.

    Science.gov (United States)

    Sisodia, Rashmi; Sharma, K; Singh, Smita

    2009-01-01

    The objective of the study was to evaluate the acute toxicity of different doses of the methanolic extract of the fruit pulp of Prunus avium (family Rosaceae), which is used ethno-medicinally for the treatment of various diseases, and to find out the optimal dose of Prunus avium extract against 10 Gy gamma-radiation exposure. To test acute toxicity in mice, different doses of PAE (Prunus avium fruit extract) were given orally for 15 consecutive days, after which the animals were observed for another 15 days; the LD50/15 of the methanolic extract was calculated to be 4.947 gm/kg body weight (b.wt). In optimum dose selection against radiation exposure, oral administration of 450 mg/kg b.wt/d of PAE for 15 consecutive days before exposure to 10 Gy of gamma-radiation was found to afford maximum protection in terms of body weight and survivability of the mice in comparison to other doses.

  10. Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.

    Directory of Open Access Journals (Sweden)

    Michael S Madejczyk

    Full Text Available U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na(2Cr(2O(7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH, resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.

  11. Temporal Changes in Rat Liver Gene Expression after Acute Cadmium and Chromium Exposure

    Science.gov (United States)

    Madejczyk, Michael S.; Baer, Christine E.; Dennis, William E.; Minarchick, Valerie C.; Leonard, Stephen S.; Jackson, David A.; Stallings, Jonathan D.; Lewis, John A.

    2015-01-01

    U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers. PMID:25993096

  12. Infants born to mothers under phenobarbital treatment: correlation between serum levels and clinical features of neonates.

    Science.gov (United States)

    Zuppa, Antonio A; Carducci, Chiara; Scorrano, Antonio; Antichi, Eleonora; Catenazzi, Piero; Piras, Andrea; Pozzoli, Giacomo; Cardiello, Valentina; D'Antuono, Annamaria; Romagnoli, Costantino

    2011-11-01

    Phenobarbital crosses the placenta quickly, and the balance between maternal and fetal blood is achieved in a few minutes. Data on the clinical outcomes of infants born to mothers under phenobarbital treatment during pregnancy show that they are at risk of adverse events, such as sedation and abstinence syndrome. The aim of this study was to analyse the correlation between serum levels of phenobarbital and clinical features of neonates. Twenty-three infants born between 2001 and 2008 were studied. Maternal, neonatal and pharmacological variables were considered. Eleven infants displayed symptoms related to phenobarbital. Withdrawal syndrome was seen in seven infants and sedation syndrome was seen in four infants. One infant had severe cardiorespiratory depression at birth. None of the infants had severe neonatal abstinence syndrome. No statistically significant differences were found between symptomatic and asymptomatic infants. At birth, the mean serum level of phenobarbital of the 23 infants was 15.4 [standard deviation (SD) 6.2] μg/ml. A peak (16.1 μg/ml, SD 5.5) was seen on Day 3, followed by a gradual decrease to non-therapeutic levels (Phenobarbital levels were higher in symptomatic infants than asymptomatic infants, although the difference was not statistically significant. Serum levels of phenobarbital remained in the therapeutic range for both mothers and infants, and reduced gradually in infants. However, some infants displayed symptoms related to phenobarbital. As such, a clinical pharmacological surveillance protocol is necessary. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

    Science.gov (United States)

    Oztekin, Osman; Kalay, Salih; Tezel, Gonul; Akcakus, Mustafa; Oygur, Nihal

    2013-08-01

    We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

  14. Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signalling in the mouse.

    Science.gov (United States)

    Diss, Lucy; Dyball, Sarah; Ghela, Tina; Golding, Jonathan; Morris, Rachel; Robinson, Stephen; Tucker, Rosemary; Walter, Talia; Young, Paul; Allen, Marcus; Fidalgo, Sara; Gard, Paul; Mabley, Jon; Patel, Bhavik; Chatterjee, Prabal; Yeoman, Mark

    2016-02-01

    Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects that these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20mM for 60 min) of paraquat on the GI tract, particularly the colon which is a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), which are major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat's mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signalling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat's ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.

  15. Leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital: a case report.

    Science.gov (United States)

    Zeng, Qinghai; Wu, Yuanqiang; Zhan, Yi; Tang, Ling; Zhou, Yangmei; Yin, Jun; Fan, Fan; Zhang, Guiying; Lu, Qianjin; Xiao, Rong

    2013-01-01

    The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10(9)/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.

  16. EFFECTS OF PHENOBARBITAL ON HYPERBILIRUBINEMIA IN 28 PATIENTS WITH ICTERIC VIRAL HEPATITIS B

    Institute of Scientific and Technical Information of China (English)

    龙尧

    2001-01-01

    To observe the effects of Phenobarbital on hyperbilirubinemia in patients with icteric viral?hepatitis.Methods Sixty-two patients with viral icteric hepatitis B were randomly divided into two groups: Phenobarbital group received orally phenobarbital 90rag daily (30mg tid) for 2 to 4 weeks in addition to 60mg before sleep, if itch presented in night, plus liver-protective drugs; control group received only liverprotective drugs.Results Therapeutic efficacy of phenobarbital group was significantly better than that of control group(Hc=4.035, P<0.05) particularly in eliminating serum bilirubin and alleviating itch. Synchronized decrease of serum ALT and bilirubin occurred. No obvious side-effects were observed but rash occurred in one case.Conclusion Phenobarbital is safe and efficacious in treating hyperbilirubinemia.

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

    Science.gov (United States)

    Stark, John D; Walthall, William K

    2003-12-01

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

  18. A comparison of Drosophila melanogaster detoxification gene induction responses for six insecticides, caffeine and phenobarbital.

    Science.gov (United States)

    Willoughby, Lee; Chung, Henry; Lumb, Chris; Robin, Charles; Batterham, Philip; Daborn, Phillip J

    2006-12-01

    Modifications of metabolic pathways are important in insecticide resistance evolution. Mutations leading to changes in expression levels or substrate specificities of cytochrome P450 (P450), glutathione-S-transferase (GST) and esterase genes have been linked to many cases of resistance with the responsible enzyme shown to utilize the insecticide as a substrate. Many studies show that the substrates of enzymes are capable of inducing the expression of those enzymes. We investigated if this was the case for insecticides and the enzymes responsible for their metabolism. The induction responses for P450s, GSTs and esterases to six different insecticides were investigated using a custom designed microarray in Drosophila melanogaster. Even though these gene families can all contribute to insecticide resistance, their induction responses when exposed to insecticides are minimal. The insecticides spinosad, diazinon, nitenpyram, lufenuron and dicyclanil did not induce any P450, GST or esterase gene expression after a short exposure to high lethal concentrations of insecticide. DDT elicited the low-level induction of one GST and one P450. These results are in contrast to induction responses we observed for the natural plant compound caffeine and the barbituate drug phenobarbital, both of which highly induced a number of P450 and GST genes under the same short exposure regime. Our results indicate that, under the insecticide exposure conditions we used, constitutive over-expression of metabolic genes play more of a role in insect survival than induction of members of these gene families.

  19. Acute Inhalation Exposure to Titanium Ethanolate as a Possible Cause of Metal Fume Fever

    Directory of Open Access Journals (Sweden)

    M Ahmadimanesh

    2014-04-01

    Full Text Available Occupational inhalation exposure to noxious agents is not uncommon. Herein, we present a 26-year-old male student who had accidental acute inhalation exposure to a large quantity of titanium ethanolate and hydrogen chloride in chemistry lab. He was referred to the emergency department of our hospital with low-grade fever, dyspnea, headache, fatigue and myalgia. After 24 hrs of symptomatic treatment (oxygen therapy and acetaminophen, the fever was subsided and the patient discharged home in a good clinical condition. The presented symptoms could be interpreted as a form of metal fume fever. It can therefore be concluded that organo-metallic compound of titanium metal may have the potential to produce metal fume fever in human.

  20. Genome-wide gene expression profiling of acute metal exposures in male zebrafish

    Directory of Open Access Journals (Sweden)

    Christine E. Baer

    2014-12-01

    Full Text Available To capture global responses to metal poisoning and mechanistic insights into metal toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate at concentrations corresponding to their respective 96 h LC20, LC40 and LC60 (i.e. 96 h concentrations at which 20%, 40% and 60% lethality is expected, respectively. Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal exposure. Here we describe in detail the contents and quality controls for the gene expression and other data associated with the study published by Hussainzada and colleagues in BMC Pharmacology and Toxicology (Hussainzada et al., 2014 with the data uploaded to Gene Expression Omnibus (accession number GSE50648.

  1. Genome-wide gene expression profiling of acute metal exposures in male zebrafish

    Science.gov (United States)

    Baer, Christine E.; Ippolito, Danielle L.; Hussainzada, Naissan; Lewis, John A.; Jackson, David A.; Stallings, Jonathan D.

    2014-01-01

    To capture global responses to metal poisoning and mechanistic insights into metal toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate at concentrations corresponding to their respective 96 h LC20, LC40 and LC60 (i.e. 96 h concentrations at which 20%, 40% and 60% lethality is expected, respectively). Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal exposure. Here we describe in detail the contents and quality controls for the gene expression and other data associated with the study published by Hussainzada and colleagues in BMC Pharmacology and Toxicology (Hussainzada et al., 2014) with the data uploaded to Gene Expression Omnibus (accession number GSE50648). PMID:26484131

  2. Acute vertigo in an anesthesia provider during exposure to a 3T MRI scanner.

    Science.gov (United States)

    Gorlin, Andrew; Hoxworth, Joseph M; Pavlicek, William; Thunberg, Christopher A; Seamans, David

    2015-01-01

    Vertigo induced by exposure to the magnetic field of a magnetic resonance imaging (MRI) scanner is a well-known phenomenon within the radiology community but is not widely appreciated by other clinical specialists. Here, we describe a case of an anesthetist experiencing acute vertigo while providing sedation to a patient undergoing a 3 Tesla MRI scan. After discussing previous reports, and the evidence surrounding MRI-induced vertigo, we review potential etiologies that include the effects of both static and time-varying magnetic fields on the vestibular apparatus. We conclude our review by discussing the occupational standards that exist for MRI exposure and methods to minimize the risks of MRI-induced vertigo for clinicians working in the MRI environment.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-01

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

  4. Gene expression changes in female zebrafish (Danio rerio) brain in response to acute exposure to methylmercury

    Science.gov (United States)

    Richter, Catherine A.; Garcia-Reyero, Natàlia; Martyniuk, Chris; Knoebl, Iris; Pope, Marie; Wright-Osment, Maureen K.; Denslow, Nancy D.; Tillitt, Donald E.

    2011-01-01

    Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5(mu or u)g MeHg/g. Gene expression changes in the brain were examined using a 22,000-feature zebrafish microarray. At a significance level of pgenes were up-regulated and 76 genes were down-regulated in response to MeHg exposure. Individual genes exhibiting altered expression in response to MeHg exposure implicate effects on glutathione metabolism in the mechanism of MeHg neurotoxicity. Gene ontology (GO) terms significantly enriched among altered genes included protein folding, cell redox homeostasis, and steroid biosynthetic process. The most affected biological functions were related to nervous system development and function, as well as lipid metabolism and molecular transport. These results support the involvement of oxidative stress and effects on protein structure in the mechanism of action of MeHg in the female brain. Future studies will compare the gene expression profile induced in response to MeHg with that induced by other toxicants and will investigate responsive genes as potential biomarkers of MeHg exposure.

  5. Exposure to Discrimination and Heart Rate Variability Reactivity to Acute Stress among Women with Diabetes.

    Science.gov (United States)

    Wagner, Julie; Lampert, Rachel; Tennen, Howard; Feinn, Richard

    2015-08-01

    Exposure to racial discrimination has been linked to physiological reactivity. This study investigated self-reported exposure to racial discrimination and parasympathetic [high-frequency heart rate variability (HF-HRV)] and sympathetic (norepinephrine and cortisol) activity at baseline and then again after acute laboratory stress. Lifetime exposure to racial discrimination was measured with the Schedule of Racist Events scale. Thirty-two women (16 Black and 16 White) with type 2 diabetes performed a public speaking stressor. Beat-to-beat intervals were recorded on electrocardiograph recorders, and HF-HRV was calculated using spectral analysis and natural log transformed. Norepinephrine and cortisol were measured in blood. Higher discrimination predicted lower stressor HF-HRV, even after controlling for baseline HF-HRV. When race, age, A1c and baseline systolic blood pressure were also controlled, racial discrimination remained a significant independent predictor of stressor HF-HRV. There was no association between lifetime discrimination and sympathetic markers. In conclusion, preliminary data suggest that among women with type 2 diabetes mellitus (T2DM), exposure to racial discrimination is adversely associated with parasympathetic, but not sympathetic, reactivity. Copyright © 2013 John Wiley & Sons, Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

    Schlesinger, R.B.; Driscoll, K.E.; Gunnison, A.F.; Zelikoff, J.T. (New York Univ. Medical Center, NY (USA))

    1990-12-01

    Ozone (O{sub 3}) and nitrogen dioxide (NO{sub 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{sub 3} at 0.1, 0.3, or 1 ppm; NO{sub 2} at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O{sub 3} and 3 ppm NO{sub 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{sub 3}. Exposure to 10 ppm NO{sub 2} resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO{sub 2} and depressed following 3 and 10 ppm. The O{sub 3}/NO{sub 2} mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O{sub 3}. This study has demonstrated that acute exposure to either O{sub 3} or NO{sub 2} can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively.

  7. Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects in adult rats.

    Science.gov (United States)

    Bortel, Aleksandra; Słomian, Lucyna; Nitka, Dariusz; Swierszcz, Michał; Jaksz, Mirella; Adamus-Sitkiewicz, Beata; Nowak, Przemysław; Jośko, Jadwiga; Kostrzewa, Richard M; Brus, Ryszard

    2008-01-01

    To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by approximately 40% in the hippocampus and by approximately 20% in other brain regions at 1 h. Ethanol reduced GABA content by approximately 15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.

  8. Acute health effects associated with exposure to volcanic air pollution (vog) from increased activity at Kilauea Volcano in 2008.

    Science.gov (United States)

    Longo, Bernadette M; Yang, Wei; Green, Joshua B; Crosby, Frederick L; Crosby, Vickie L

    2010-01-01

    In 2008, the Kilauea Volcano on the island of Hawai'i increased eruption activity and emissions of sulfurous volcanic air pollution called vog. The purpose of this study was to promptly assess for a relative increase in cases of medically diagnosed acute illnesses in an exposed Hawaiian community. Using a within-clinic retrospective cohort design, comparisons were made for visits of acute illnesses during the 14 wk prior to the increased volcanic emissions (low exposure) to 14 wk of high vog exposure when ambient sulfur dioxide was threefold higher and averaged 75 parts per billion volume per day. Logistic regression analysis estimated effect measures between the low- and high-exposure cohorts for age, gender, race, and smoking status. There were statistically significant positive associations between high vog exposure and visits for medically diagnosed cough, headache, acute pharyngitis, and acute airway problems. More than a sixfold increase in odds was estimated for visits with acute airway problems, primarily experienced by young Pacific Islanders. These findings suggest that the elevated volcanic emissions in 2008 were associated with increased morbidity of acute illnesses in age and racial subgroups of the general Hawaiian population. Continued investigation is crucial to fully assess the health impact of this natural source of sulfurous air pollution. Culturally appropriate primary- and secondary-level health prevention initiatives are recommended for populations in Hawai'i and volcanically active areas worldwide.

  9. Very high dose phenobarbital for refractory status epilepticus.

    Science.gov (United States)

    Tiamkao, Somsak; Mayurasakorn, Nattakarn; Suko, Panit; Jitpimolmard, Suthipun; Arunpongpaisal, Suwanna; Phuttharak, Warinthorn; Auevitchayapat, Narong; Vannaprasaht, Suda; Tiamkao, Siriporn; Phunikhom, Kutcharin; Chaiyakum, Aporanee; Saengsuwan, Jiamjit

    2007-12-01

    Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.v.) midazolam (MDL), or continuous i.v. propofol (PRO) as alternatives to phenobarbital (PB) or continuous i.v. pentobarbital (PTB). To study the efficacy of very-high-dose phenobarbital (VHDPB) for treatment RSE. Retrospective study The authors collected and analyzed data from adult patients who were diagnosed with RSE. The authors present 10 patients with RSE who were treated with VHDPB. All of them were generalized convulsive status epilepticus (GCSE). Ages ranged from 16-86 years old (mean.: 43 years). PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day). The duration of status epilepticus (SE) varied widely, ranged 1-44 days (mean: 7 days). PB level ranged 35.29-218.34 ug/mL (mean 88.1 ug/mL). RSE was controlled by VHDPB 70%, 30% were not controlled. VHDPB were considered as alternative treatment for RSE.

  10. Evaluating Systemic Toxicity in Rabbits after Acute Ocular Exposure to Irritant Chemicals

    Directory of Open Access Journals (Sweden)

    Reshma Sebastian Cherian

    2014-01-01

    Full Text Available Acute systemic toxicity via ocular exposure route is not a well understood aspect. Any material/drug/chemical that comes in contact with the eye can evade the first pass metabolism and enter the systemic circulation through the conjunctival blood vessels or via the nasolacrimal route. In this study, the effect of ocular irritant chemicals on the systemic toxicity was assessed in rabbit. Eyes of rabbits were exposed to known ocular irritant (cetyl pyridinium chloride, sodium salicylate, imidazole, acetaminophen, and nicotinamide for 24 h and scored. After a period of 72 h, blood was collected from the animals for examining the hematological and biochemical parameters. The animals were then sacrificed and the eyes were collected for histopathology and cytokine analysis by ELISA. Splenocyte proliferation was assessed by tritiated thymidine incorporation assay. The liver and brain of the treated animals were retrieved for evaluating oxidative damage. The chemicals showed moderate to severe eye irritation. Inflammation was not evident in the histopathology but proinflammatory markers were significantly high. The splenocyte proliferation capacity was undeterred. And there was minimal oxidative stress in the brain and liver. In conclusion, acute exposure of ocular irritants was incapable of producing a prominent systemic side effect in the current scenario.

  11. Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

    Science.gov (United States)

    Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

    2014-12-01

    Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis.

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

    Science.gov (United States)

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

    2013-05-15

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

  13. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    Science.gov (United States)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  14. [Reactive microglial changes in rat neocortex and hippocampus after exposure to acute perinatal hypoxia].

    Science.gov (United States)

    Khozhaĭ, L I; Otellin, V A

    2013-01-01

    The dynamics of reactive changes of a population density of microglial cells and the reversibility of their phenotypic forms were studied in the brain of neonatal rats at different time intervals after 1 hr-long exposure to acute normobaric hypoxia in the pressure chamber at the second postnatal day. Different areas of the neocortex (frontal, motor, somatosensory and visual) and of the hippocampus (CAI, CA3, CA4 and fascia dentata) were examined 1 hr, 3 hrs, 1 and 5 days after exposure to hypoxia. Microglial cells were demonstrated using an immunocytochemical staining with the monoclonal antibodies against Iba- 1 antigen. The results have shown that the reaction of microglia to acute hypoxia in both the neocortex and the hippocampus of the new-borns developed simultaneously and synchronously with the augmentation of cell death. The increase of a population density of amoeboid form of microglial cells in the brain areas studied was recorded already after 1 hour as a result of their migration from the subventricular region and the areas adjacent to large vessels from where they practically disappeared. The number of amoeboid microglial cells in this area has recovered rather quickly (in 3 hrs). The population densify of microglial cells, especially of amoeboid forms, sharply increased with the augmentation of cell death and remained unchanged for about 5 days.

  15. Role of carbon monoxide in impaired endothelial function mediated by acute second-hand tobacco, incense, and candle smoke exposures.

    Science.gov (United States)

    Weber, Lynn P; Al-Dissi, Ahmad; Marit, Jordan S; German, Timothy N; Terletski, Sharilyn D

    2011-05-01

    The aim of this study was to determine if carbon monoxide (CO) is responsible for acute adverse cardiovascular effects of different sources of smoke: second-hand tobacco smoke (SHS), incense and candle smoke. Endothelial function was tested using flow-mediated dilation (FMD) in pigs and was shown to be sensitive to nitric oxide synthase blockade. Subsequent experiments showed that FMD was significantly impaired compared to sham-exposed pigs at 30 min after a 30-min exposure to all three sources of smoke. In contrast, SHS significantly increased systolic, diastolic and pulse pressures compared to sham-exposure, while both incense and candle smoke exposure had no effect. The FMD impairment correlated well with CO levels in the exposure chamber, but not total particulates or venous CO-hemoglobin. Therefore, this study suggests a gas phase component of smoke that accompanies CO, but not CO itself, is responsible for acute endothelial dysfunction after SHS, incense or candle smoke exposure.

  16. Acute exposure to apolipoprotein A1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo

    Science.gov (United States)

    Iqbal, Asif J; Barrett, Tessa J; Taylor, Lewis; McNeill, Eileen; Manmadhan, Arun; Recio, Carlota; Carmineri, Alfredo; Brodermann, Maximillian H; White, Gemma E; Cooper, Dianne; DiDonato, Joseph A; Zamanian-Daryoush, Maryam; Hazen, Stanley L; Channon, Keith M

    2016-01-01

    Apolipoprotein A1 (apoA1) is the major protein component of high-density lipoprotein (HDL) and has well documented anti-inflammatory properties. To better understand the cellular and molecular basis of the anti-inflammatory actions of apoA1, we explored the effect of acute human apoA1 exposure on the migratory capacity of monocyte-derived cells in vitro and in vivo. Acute (20–60 min) apoA1 treatment induced a substantial (50–90%) reduction in macrophage chemotaxis to a range of chemoattractants. This acute treatment was anti-inflammatory in vivo as shown by pre-treatment of monocytes prior to adoptive transfer into an on-going murine peritonitis model. We find that apoA1 rapidly disrupts membrane lipid rafts, and as a consequence, dampens the PI3K/Akt signalling pathway that coordinates reorganization of the actin cytoskeleton and cell migration. Our data strengthen the evidence base for therapeutic apoA1 infusions in situations where reduced monocyte recruitment to sites of inflammation could have beneficial outcomes. DOI: http://dx.doi.org/10.7554/eLife.15190.001 PMID:27572261

  17. Sustained impairment of respiratory function and swim performance following acute oil exposure in a coastal marine fish.

    Science.gov (United States)

    Johansen, J L; Esbaugh, A J

    2017-06-01

    Acute exposure to crude oil polycyclic aromatic hydrocarbons (PAH) can severely impair cardiorespiratory function and swim performance of larval fish; however, the effects of acute oil exposure on later life stages and the capacity for subsequent recovery is less clear. Red drum (Sciaenops ocellatus) is an economically important apex predator native to the Gulf of Mexico, which was directly exposed to the 2010 Deep Water Horizon (DWH) oil spill. Here we examine impact and recovery of young adult red drum from exposure to concentrations of 0, 4.1, and 12.1μgL(-1) ΣPAH50 naturally weathered oil-water accommodated fractions (geometric mean), which are well within the range of concentrations measured during the DWH incident. We focused on aerobic scope (ASc), burst- and critical swimming speeds (Uburst and Ucrit), cost of transport (COT), as well as the capacity to repay oxygen debt following exhaustive exercise (EPOC), which are critical parameters for success of all life stages of fishes. A 24h acute exposure to 4.1μgL(-1) ΣPAH caused a significant 9.7 and 12.6% reduction of Uburst and Ucrit respectively, but no change in ASc, COT or EPOC, highlighting a decoupled effect on the respiratory and swimming systems. A higher exposure concentration, 12.1μgL(-1) ΣPAH, caused an 8.6 and 8.4% impairment of Uburst and Ucrit, as well as an 18.4% reduction in ASc. These impairments persisted six weeks post-exposure, suggesting that recorded impacts are entrenched. Large predatory fishes are critically dependent on the cardiorespiratory and swimming systems for ecological fitness, and long-term impairment of performance due to acute oil exposure suggests that even acute exposure events may have long lasting impacts on the ecological fitness of affected populations. Copyright © 2017. Published by Elsevier B.V.

  18. Urine phenobarbital drug screening: potential use for compliance assessment in neonates.

    Science.gov (United States)

    Guillet, Ronnie; Kwon, Jennifer M; Chen, Sixaio; McDermott, Michael P

    2012-02-01

    This study was done to determine if urine phenobarbital measurements provide a reliable indicator of presence of the drug in neonates. Urine was collected from neonates treated with phenobarbital for clinical indications within 4 to 6 hours of clinically indicated collection of serum phenobarbital levels. Urine samples were also collected from control neonates not treated with phenobarbital. One aliquot was assayed fresh, another frozen at -30°C and assayed 1 to 3 months later. Phenobarbital was assayed using the ONLINE TDM Roche/Hitachi automated clinical chemistry analyzer. Serum and urine concentrations were compared as were fresh and frozen urine measurements. Serum phenobarbital ranged from 5.6 to 52.7 μg/mL. Matched urine samples were 56.6 ± 12.5% of the serum level. Frozen samples were 98.3 ± 8.0% of the fresh samples. Urine phenobarbital concentrations, either fresh or frozen, can be used in neonates as a noninvasive estimate of drug levels.

  19. Carryover Effects of Acute DEHP Exposure on Ovarian Function and Oocyte Developmental Competence in Lactating Cows.

    Science.gov (United States)

    Kalo, Dorit; Hadas, Ron; Furman, Ori; Ben-Ari, Julius; Maor, Yehoshua; Patterson, Donald G; Tomey, Cynthia; Roth, Zvi

    2015-01-01

    We examined acute exposure of Holstein cows to di(2-ethylhexyl) phthalate (DEHP) and its carryover effects on ovarian function and oocyte developmental competence. Synchronized cows were tube-fed with water or 100 mg/kg DEHP per day for 3 days. Blood, urine and milk samples were collected before, during and after DEHP exposure to examine its clearance pattern. Ovarian follicular dynamics was monitored through an entire estrous cycle by ultrasonographic scanning. Follicular fluids were aspirated from the preovulatory follicles on days 0 and 29 of the experiment and analyzed for phthalate metabolites and estradiol concentration. The aspirated follicular fluid was used as maturation medium for in-vitro embryo production. Findings revealed that DEHP impairs the pattern of follicular development, with a prominent effect on dominant follicles. The diameter and growth rate of the first- and second-wave dominant follicles were lower (P 25 mm). The pattern of growth and regression of the corpus luteum differed between groups, with a lower volume in the DEHP-treated group (P < 0.05). The follicular fluid aspirated from the DEHP-treated group, but not the controls, contained 23 nM mono(2-ethylhexyl) phthalate. Culturing of cumulus oocyte complexes in the follicular fluid aspirated from DEHP-treated cows reduced the proportion of oocytes progressing to the MII stage, and the proportions of 2- to 4-cell-stage embryos (P < 0.04) and 7-day blastocysts (P < 0.06). The results describe the risk associated with acute exposure to DEHP and its deleterious carryover effects on ovarian function, nuclear maturation and oocyte developmental competence.

  20. Carryover Effects of Acute DEHP Exposure on Ovarian Function and Oocyte Developmental Competence in Lactating Cows

    Science.gov (United States)

    Kalo, Dorit; Hadas, Ron; Furman, Ori; Ben-Ari, Julius; Maor, Yehoshua; Patterson, Donald G.; Tomey, Cynthia; Roth, Zvi

    2015-01-01

    We examined acute exposure of Holstein cows to di(2-ethylhexyl) phthalate (DEHP) and its carryover effects on ovarian function and oocyte developmental competence. Synchronized cows were tube-fed with water or 100 mg/kg DEHP per day for 3 days. Blood, urine and milk samples were collected before, during and after DEHP exposure to examine its clearance pattern. Ovarian follicular dynamics was monitored through an entire estrous cycle by ultrasonographic scanning. Follicular fluids were aspirated from the preovulatory follicles on days 0 and 29 of the experiment and analyzed for phthalate metabolites and estradiol concentration. The aspirated follicular fluid was used as maturation medium for in-vitro embryo production. Findings revealed that DEHP impairs the pattern of follicular development, with a prominent effect on dominant follicles. The diameter and growth rate of the first- and second-wave dominant follicles were lower (P 25 mm). The pattern of growth and regression of the corpus luteum differed between groups, with a lower volume in the DEHP-treated group (P < 0.05). The follicular fluid aspirated from the DEHP-treated group, but not the controls, contained 23 nM mono(2-ethylhexyl) phthalate. Culturing of cumulus oocyte complexes in the follicular fluid aspirated from DEHP-treated cows reduced the proportion of oocytes progressing to the MII stage, and the proportions of 2- to 4-cell-stage embryos (P < 0.04) and 7-day blastocysts (P < 0.06). The results describe the risk associated with acute exposure to DEHP and its deleterious carryover effects on ovarian function, nuclear maturation and oocyte developmental competence. PMID:26154164

  1. Carryover Effects of Acute DEHP Exposure on Ovarian Function and Oocyte Developmental Competence in Lactating Cows.

    Directory of Open Access Journals (Sweden)

    Dorit Kalo

    Full Text Available We examined acute exposure of Holstein cows to di(2-ethylhexyl phthalate (DEHP and its carryover effects on ovarian function and oocyte developmental competence. Synchronized cows were tube-fed with water or 100 mg/kg DEHP per day for 3 days. Blood, urine and milk samples were collected before, during and after DEHP exposure to examine its clearance pattern. Ovarian follicular dynamics was monitored through an entire estrous cycle by ultrasonographic scanning. Follicular fluids were aspirated from the preovulatory follicles on days 0 and 29 of the experiment and analyzed for phthalate metabolites and estradiol concentration. The aspirated follicular fluid was used as maturation medium for in-vitro embryo production. Findings revealed that DEHP impairs the pattern of follicular development, with a prominent effect on dominant follicles. The diameter and growth rate of the first- and second-wave dominant follicles were lower (P 25 mm. The pattern of growth and regression of the corpus luteum differed between groups, with a lower volume in the DEHP-treated group (P < 0.05. The follicular fluid aspirated from the DEHP-treated group, but not the controls, contained 23 nM mono(2-ethylhexyl phthalate. Culturing of cumulus oocyte complexes in the follicular fluid aspirated from DEHP-treated cows reduced the proportion of oocytes progressing to the MII stage, and the proportions of 2- to 4-cell-stage embryos (P < 0.04 and 7-day blastocysts (P < 0.06. The results describe the risk associated with acute exposure to DEHP and its deleterious carryover effects on ovarian function, nuclear maturation and oocyte developmental competence.

  2. Anticholinergic drug exposure is associated with delirium and postdischarge institutionalization in acutely ill hospitalized older patients.

    Science.gov (United States)

    Egberts, Angelique; van der Craats, Saskia T; van Wijk, Melissa D; Alkilabe, Shams; van den Bemt, Patricia M L A; Mattace-Raso, Francesco U S

    2017-06-01

    Several studies investigated the possible association between anticholinergic drugs and diverse clinical outcomes in older persons, but the results are inconsistent. The aim of this study was to investigate whether anticholinergic drug exposure is associated with delirium on admission, length of hospital stay, postdischarge institutionalization and in-hospital mortality in acutely ill hospitalized older patients. In this observational chart review study, we included acutely ill patients aged 65 and older who were admitted to the geriatric ward of the Erasmus University Medical Center, Rotterdam, The Netherlands, between 2012 and 2015 (n = 905). Anticholinergic drug exposure on admission was defined as the use of anticholinergic drugs, total number of anticholinergic drugs and anticholinergic drug burden score (ADB), quantified with the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden scale (ACB) and the list of Chew et al. (Chew). Logistic regression analyses were performed to investigate possible associations between anticholinergic drug exposure and the aforementioned outcomes. Analyses were adjusted for age, sex, comorbidities, non-anticholinergic drugs and delirium, where appropriate. Moderate and high ADB measured with the ARS were associated with delirium on admission with odds ratios (OR) of 1.70 (95% confidence interval (CI) = 1.16-2.49) and 1.83 (95% CI = 1.06-3.15), respectively. High ADB measured with the ARS was also associated with postdischarge institutionalization (OR = 2.43, 95% CI = 1.24-4.75). No associations were found using the ACB and Chew. Future studies are warranted to investigate the clinical usefulness of the ARS in reducing complications in older persons.

  3. Acute and recent air pollution exposure and cardiovascular events at labour and delivery

    Science.gov (United States)

    Männistö, Tuija; Mendola, Pauline; Grantz, Katherine Laughon; Leishear, Kira; Sundaram, Rajeshwari; Sherman, Seth; Ying, Qi; Liu, Danping

    2017-01-01

    Objective To study the relationship between acute air pollution exposure and cardiovascular events during labour/delivery. Methods The Consortium on Safe Labor (2002–2008), an observational US cohort with 223 502 singleton deliveries provided electronic medical records. Air pollution exposure was estimated by modified Community Multiscale Air Quality models. Cardiovascular events (cardiac failure/arrest, stroke, myocardial infarcts and other events) were recorded in the hospital discharge records for 687 pregnancies (0.3%). Logistic regression with generalised estimating equations estimated the relationship between cardiovascular events and daily air pollutant levels for delivery day and the 7 days preceding delivery. Results Increased odds of cardiovascular events were observed for each IQR increase in exposure to nitric oxides at 5 and 6 days prior to delivery (OR=1.17, 99% CI 1.04 to 1.30 and OR=1.15, 1.03 to 1.28, respectively). High exposure to toxic air pollution species such as ethylbenzene (OR=1.50, 1.08 to 2.09), m-xylene (OR=1.54, 1.11 to 2.13), o-xylene (OR=1.51, 1.09 to 2.09), p-xylene (OR=1.43, 1.03 to 1.99) and toluene (OR=1.42, 1.02 to 1.97) at 5 days prior to delivery were also associated with cardiovascular events. Decreased odds of events were observed with exposure to ozone. Conclusions Air pollution in the days prior to delivery, especially nitrogen oxides and some toxic air pollution species, was associated with increased risk of cardiovascular events during the labour/delivery admission. PMID:26105036

  4. Developmental rates of immatures of three Chrysomya species (Diptera: Calliphoridae) under the effect of methylphenidate hydrochloride, phenobarbital, and methylphenidate hydrochloride associated with phenobarbital.

    Science.gov (United States)

    Rezende, Fábio; Alonso, Marcela A; Souza, Carina M; Thyssen, Patrícia J; Linhares, Arício X

    2014-05-01

    Entomotoxicology is focused on obtaining data on necrophagous entomofauna, for criminal investigations purposes. This study aimed to evaluate the effect of different concentrations of methylphenidate hydrochloride, phenobarbital, and their association on the developmental rate, larval and pupal survivorship, and the interval of emergence of adults of Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), and Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). Considering the therapeutic dose (TD) of methylphenidate hydrochloride (0.29 mg/Kg), the concentrations tested were 10× TD, 50× TD, and 100× TD. For phenobarbital, the concentrations used were 1× TD (=150 mg/Kg), 3.3× TD, and 6.7× TD. For the association of the drugs, the combinations used were 10× TD-methylphenidate hydrochloride plus 1× TD-phenobarbital, 50× TD-methylphenidate hydrochloride plus 3.3× TD-phenobarbital, and 100× TD-methylphenidate hydrochloride plus 6.7× TD-phenobarbital. The control group, without addition of drug, was maintained under the same conditions of temperature (25 ± 1 °C), humidity (70 ± 10%), and photoperiod (12 h). Specimens of each group were weighed every 12 h until pupariation. The developmental rate of the three Chrysomya species immatures was monitored. For C. albiceps the developmental time was delayed in 24 h for methylphenidate hydrochloride group and in 12 h for the phenobarbital and the drugs association groups. The effect was observed only at specific ages for C. megacephala, without altering the developmental time. For C. putoria, the developmental time was delayed in 12 h for methylphenidate hydrochloride group and in 24 h for the phenobarbital and the drugs association groups. The emergence interval was similar among all experimental groups, but larval and pupal viabilities were affected in different ways.

  5. Assessment of locomotion behavior in adult Zebrafish after acute exposure to different pharmacological reference compounds

    Directory of Open Access Journals (Sweden)

    Pankaj Gupta

    2014-01-01

    Full Text Available Objectives: The objective of the present study was to assess locomotor behavior of adult zebrafish after acute exposure to different pharmacological reference compounds. Materials and Methods: Adult zebrafish of 4-5-months-old were exposed to different concentrations of known reference compounds for 15 min. The test was conducted separately for each drug concentration as well as control. Locomotor activity parameters viz. distance travelled, speed, total mobile time, and total immobile time were recorded for each animal during the exposure period. Results: Out of 11 compounds tested, nine compounds showed decrease in locomotor behavior with significant changes in distance travelled, speed, total mobile time, and total immobile time. Caffeine exhibited biphasic response in locomotion behavior, while scopolamine failed to induce any significant changes. Conclusion: In view of the above findings, these results suggested that exposure of adult zebrafish with different known compounds produce the expected changes in the locomotion behavior; therefore, adult zebrafish can be used an alternative approach for the assessment of new chemical entities for their effect on locomotor behavior.

  6. Setting safe acute exposure limits for halon replacement chemicals using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Vinegar, A; Jepson, G W; Cisneros, M; Rubenstein, R; Brock, W J

    2000-08-01

    Most proposed replacements for Halon 1301 as a fire suppressant are halogenated hydrocarbons. The acute toxic endpoint of concern for these agents is cardiac sensitization. An approach is described that links the cardiac endpoint as assessed in dogs to a target arterial concentration in humans. Linkage was made using a physiologically based pharmacokinetic (PBPK) model. Monte Carlo simulations, which account for population variability, were used to establish safe exposure times at different exposure concentrations for Halon 1301 (bromotrifluoromethane), CF(3)I (trifluoroiodomethane), HFC-125 (pentafluoroethane), HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa (1,1,1,3,3,3-hexafluoropropane). Application of the modeling technique described here not only makes use of the conservative cardiac sensitization endpoint, but also uses an understanding of the pharmacokinetics of the chemical agents to better establish standards for safe exposure. The combined application of cardiac sensitization data and physiologically based modeling provides a quantitative approach, which can facilitate the selection and effective use of halon replacement candidates.

  7. ACUTE NEUROTOXIC EFFECTS OF INHALED PERCHLOROETHYLENE ON PATTERN VISUAL EVOKED POTENTIALS AS A FUNCTION OF EXPOSURE AND ESTIMATED BLOOD AND BRAIN CONCENTRATION.

    Science.gov (United States)

    Previous experiments have shown the effects of acute inhalation exposure to trichloroethylene (TCE) and toluene are related to the target tissue concentration at the time of testing. The current studies examined exposure to another volatile organic compound, perchloroethylene (P...

  8. ACUTE NEUROTOXIC EFFECTS OF INHALED PERCHLOROETHYLENE ON PATTERN VISUAL EVOKED POTENTIALS AS A FUNCTION OF EXPOSURE AND ESTIMATED BLOOD AND BRAIN CONCENTRATION.

    Science.gov (United States)

    Previous experiments have shown the effects of acute inhalation exposure to trichloroethylene (TCE) and toluene are related to the target tissue concentration at the time of testing. The current studies examined exposure to another volatile organic compound, perchloroethylene (P...

  9. [Respiratory depression in delirium tremens patients treated with phenobarbital. A retrospective study

    DEFF Research Database (Denmark)

    Lutzen, L.; Poulsen, L.M.; Ulrichsen, J.

    2008-01-01

    in DT patients treated with phenobarbital. MATERIALS AND METHODS: We examined the medical records of patients who were treated as inpatients in 1998-2006 and discharged with the ICD-10 diagnoses F10.4 (alcohol withdrawal delirium) or F10.5 (alcohol induced psychotic disorder). Patients with pre...... to ketoacidosis. The death could not be attributed to the phenobarbital treatment. CONCLUSION: In conclusion, we found that the frequency of phenobarbital-induced respiratory depression was low. However, if the DT was complicated with pneumonia, life-threatening respiratory insufficiency could be the outcome...

  10. The body weight loss during acute exposure to high-altitude hypoxia in sea level residents.

    Science.gov (United States)

    Ge, Ri-Li; Wood, Helen; Yang, Hui-Huang; Liu, Yi-Ning; Wang, Xiu-Juan; Babb, Tony

    2010-12-25

    Weight loss is frequently observed after acute exposure to high altitude. However, the magnitude and rate of weight loss during acute exposure to high altitude has not been clarified in a controlled prospective study. The present study was performed to evaluate weight loss at high altitude. A group of 120 male subjects [aged (32±6) years] who worked on the construction of the Golmud-Lhasa Railway at Kunlun Mountain (altitude of 4 678 m) served as volunteer subjects for this study. Eighty-five workers normally resided at sea level (sea level group) and 35 normally resided at an altitude of 2 200 m (moderate altitude group). Body weight, body mass index (BMI), and waist circumference were measured in all subjects after a 7-day stay at Golmud (altitude of 2 800 m, baseline measurements). Measurements were repeated after 33-day working on Kunlun Mountain. In order to examine the daily rate of weight loss at high altitude, body weight was measured in 20 subjects from the sea level group (sea level subset group) each morning before breakfast for 33 d at Kunlun Mountain. According to guidelines established by the Lake Louise acute mountain sickness (AMS) consensus report, each subject completed an AMS self-report questionnaire two days after arriving at Kunlun Mountain. After 33-day stay at an altitude of 4 678 m, the average weight loss for the sea level group was 10.4% (range 6.5% to 29%), while the average for the moderate altitude group was 2.2% (-2% to 9.1%). The degree of weight loss (Δ weight loss) after a 33-day stay at an altitude of 4 678 m was significantly correlated with baseline body weight in the sea level group (r=0.677, P0.05). In the sea level subset group, a significant weight loss was observed within 20 d, but the weight remained stable thereafter. AMS-score at high altitude was significantly higher in the sea level group (4.69±2.48) than that in the moderate altitude group (2.97±1.38), and was significantly correlated with baseline body weight

  11. Age-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

    Directory of Open Access Journals (Sweden)

    Seok Kyu eKang

    2015-05-01

    Full Text Available Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB, with NKCC1 antagonist bumetanide (BTN as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7, 10 and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

  12. A case of acute psychosis in a patient following exposure to a single high dose of styrene.

    Science.gov (United States)

    Moon, Eunsoo; Suh, Hwagyu; Lee, Byung Dae; Park, Je Min; Lee, Young Min; Jeong, Hee Jeong

    2015-09-01

    We report a case of acute psychotic symptoms following exposure to a single high dose of styrene monomer. The 24-year-old male patient showed psychotic and cognitive symptoms immediately after exposure. His psychotic symptoms included auditory hallucinations and delusions of reference. Brain magnetic resonance imaging, electroencephalography, and laboratory examinations were performed to evaluate any other causes. The clinical, neuroimaging, and laboratory review in this case suggested that the suddenly developed psychotic symptoms that led to chronic deterioration were caused by the single exposure to styrene monomer. This is the first recent report in which acute psychotic symptoms developed from a single high dose of styrene suffocation compared with previous findings showing symptoms because of long-term low-dose exposure.

  13. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    Science.gov (United States)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

  14. Phenobarbital and midazolam increase neonatal seizure-associated neuronal injury.

    Science.gov (United States)

    Torolira, Daniel; Suchomelova, Lucie; Wasterlain, Claude G; Niquet, Jerome

    2017-07-01

    Status epilepticus is common in neonates and infants, and is associated with neuronal injury and adverse developmental outcomes. γ-Aminobutyric acidergic (GABAergic) drugs, the standard treatment for neonatal seizures, can have excitatory effects in the neonatal brain, which may worsen the seizures and their effects. Using a recently developed model of status epilepticus in postnatal day 7 rat pups that results in widespread neuronal injury, we found that the GABAA agonists phenobarbital and midazolam significantly increased status epilepticus-associated neuronal injury in various brain regions. Our results suggest that more research is needed into the possible deleterious effects of GABAergic drugs on neonatal seizures and on excitotoxic neuronal injury in the immature brain. Ann Neurol 2017;82:115-120. © 2017 American Neurological Association.

  15. Comprehensive analysis of the renal transcriptional response to acute uranyl nitrate exposure

    Directory of Open Access Journals (Sweden)

    Argiles Angel

    2006-01-01

    Full Text Available Abstract Background Chemical and radiological toxicities related to uranium acute exposure have been widely studied in nuclear fuel workers and military personnel. It is well known that uranyl nitrate induces acute renal failure (ARF. However, the mechanisms of this metal-induced injury are not well defined at the molecular level. Results Renal function and histology were assessed in mice receiving uranyl nitrate (UN(+ and controls (UN(-. To identify the genomic response to uranium exposure, serial analysis gene expression (SAGE of the kidney was performed in both groups. Over 43,000 mRNA SAGE tags were sequenced. A selection of the differentially expressed transcripts was confirmed by real-time quantitative PCR and Western blotting. UN(+ animals developed renal failure and displayed the characteristic histological lesions of UN nephropathy. Of the >14,500 unique tags identified in both libraries, 224 had a modified expression level; they are known to participate in inflammation, ion transport, signal transduction, oxidative stress, apoptosis, metabolism, and catabolism. Several genes that were identified had not previously been evaluated within the context of toxic ARF such as translationally controlled tumor protein, insulin like growth factor binding protein 7 and ribosomal protein S29, all apoptosis related genes. Conclusion We report a comprehensive description of the UN induced modifications in gene expression levels, including the identification of genes previously unrelated to ARF. The study of these genes and the metabolisms they control should improve our understanding of toxic ARF and enlighten on the molecular targets for potential therapeutic interventions.

  16. Effect of zinc sacrificial anode degradation on the defence system of the Pacific oyster, Crassostrea gigas: chronic and acute exposures.

    Science.gov (United States)

    Mottin, Elmina; Caplat, Christelle; Latire, Thomas; Mottier, Antoine; Mahaut, Marie-Laure; Costil, Katherine; Barillier, Daniel; Lebel, Jean-Marc; Serpentini, Antoine

    2012-09-01

    Two types of exposures were performed to assess the effects of zinc released from sacrificial anode degradation: a chronic exposure, in which oysters were exposed to 0.53±0.04 mg Zn L(-1) for 10 weeks, and an acute exposure, where oysters were exposed to 10.2±1.2 mg Zn L(-1) for 1 week. At the end of the acute exposure experiment, 81.8% mortality was recorded. In contrast, no mortality was detected after 10 weeks exposure. Moreover, all of the immune system biomarkers studied, except the number of circulating haemocytes, were stimulated by a moderate level of zinc and inhibited by a high level. Our exposure conditions did not induce SOD or MXR mRNA expression in gills and digestive gland. However, an increase of MT mRNA is observed in these tissues. The results indicate that oysters are sensitive to acute zinc toxicity but are only moderately affected by a mild zinc concentration.

  17. Maternal metallothionein and zinc after acute ethanol exposure during gestation in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Harris, J.E. (Univ. of Kansas, Kansas City (United States))

    1992-02-26

    Acute exposure of the rat fetus to ethanol at critical periods can cause growth retardation and brain damage; the mechanism(s) is not known. Ethanol may cause redistribution of maternal zinc which results in fetal zinc deficiency and subsequent interruption of growth and development. The purpose was to determine if acute ethanol administration to the pregnant rat alters Zn and the Zn binding protein metallothionein (MT) in selected tissues. On gestational day (gd) 14, eighteen pregnant Sprague-Dawley rats were divided into groups. By intragastric tube, ethanol treated dams were given ethanol and pairfed controls were given a 0.85% NaCl solution. On gd 15, intragastric feedings were repeated. Throughout, the Lieber-DeCarli control diet was fed (adlibitum to untreated controls and ethanol treated dams and in appropriate quantities to pair fed controls). Blood ethanol concentrations at 90 minutes after the ethanol dose were 154 {plus minus} 46 and 265 {plus minus} 110 mg% on gd 14 and 15, respectively.

  18. Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.; Campbell, James A.; Lin, Yuehe

    2004-04-01

    There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. The system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk.

  19. Discrimination of tumorigenic triazole conazoles from phenobarbital by transcriptional analyses of mouse liver gene expression

    Science.gov (United States)

    Conazoles are fungicides used to control fungal growth in environmental settings and to treat humans with fungal infections. Mouse hepatotumorigenic conazoles display many of the same hepatic toxicologic responses as the mouse liver carcinogen phenobarbital (PB): constitutive and...

  20. [A substrate-type induction of liver microsomal monooxygenases by phenobarbital].

    Science.gov (United States)

    Tsyrlov, I B; Gromova, O A; Rivkind, N B; Vakulin, G M; Liakhovich, V V

    1977-07-01

    A possibility of step-wise induction of microsomal monooxygenases after injection of phenobarbital in the presence of 3-methylcholanthrene-caused induction was studied. It was found that the ratio of the high- and low-spin types of cytochrome, rather than the position of the CO-peak of its reduced form is a criterion for functional specificity of hemoprotein. Induction by phenobarbital appears possible under conditions when the inductor binding to microsomal hemoprotein is lacking, since cytochrome P-488 has no binding sites for phenobarbital. It is assumed that under microsomal monooxygenases induction by phenobarbital activation of genome and subsequent protein synthesis are operated by the substrate rather than by products of its primary metabolism in microsomes.

  1. Effects of a Model Inducer, Phenobarbital, on Thyroid Hormone Glucuronidation in Rat Hepatocytes

    Science.gov (United States)

    In vivo, hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations. This decrease in circulating TH occurs in part through extrathyroidal mechanisms. Specifically, through the induction of hepatic xenobiotic metabolizing enzymes...

  2. [Determination of phenobarbital in human urine and serum using flow injection chemiluminescence].

    Science.gov (United States)

    Li, X; Niu, L C; He, X L; Song, Z H

    2012-01-01

    A sensitive chemiluminescence method, based on the enhancive effect of phenobarbital on the chemiluminescence reaction between luminol and dissolved oxygen in a flow injection system, was proposed for the determination of phenobarbital. The chemiluminescence intensity responded to the concentration of phenobarbital linearly ranging from 0.05 to 10 ng x ml(-1) with the detection limit of 0.02 ng x ml(-1) (3 sigma). At a flow rate of 2.0 ml x min(-1), a complete determination of phenobarbital, including sampling and washing, could be accomplished in 0.5 min, offering the sampling efficiency of 120 h(-1) accordingly. The method was applied successfully in an assay of PB for pharmaceutical preparations, human urine and serum without any pretreatment with recovery from 95.7 to 106.7% and RSDs of less than 3.0%.

  3. Experimental Raman and infrared investigation of phenobarbital febarabamate, difebarbamate and tetrabamate

    Science.gov (United States)

    Buchet, R.; Bill, H.; Siegfried, B.

    The results of a Raman and an i.r. investigation show that the tetrabamate molecule is formed by the hydrogen bonded constituants phenobarbital, febarbamate. Detailed spectroscopic results are given on these four molecules.

  4. PHENOBARBITAL AFFECTS THYROID HISTOLOGY AND LARVAL DEVELOPMENT IN THE AFRICAN CLAWED FROG XENOPUS LAEVIS

    Science.gov (United States)

    The abstract highlights our recent study to explore endocrine disrupting effects of phenobarbital in the African clawed frog, Xenopus laevis. In mammals, this chemical is known to induce the biotransforming enzyme UDP-glucuronosyltransferase (UDPGT) resulting in increased thyroid...

  5. Discrimination of tumorigenic triazole conazoles from phenobarbital by transcriptional analyses of mouse liver gene expression

    Science.gov (United States)

    Conazoles are fungicides used to control fungal growth in environmental settings and to treat humans with fungal infections. Mouse hepatotumorigenic conazoles display many of the same hepatic toxicologic responses as the mouse liver carcinogen phenobarbital (PB): constitutive and...

  6. [Effect of training on treadmill performance, aerobic capacity and body reactions to acute cold exposure].

    Science.gov (United States)

    Iakushkin, A V; Akimov, E B; Andreev, R S; Kalenov, Iu N; Kozlov, A V; Kuznetsova, O V; Son'kin, V D

    2014-01-01

    An attempt was made to test the hypothesis that regular physical activity at the anaerobic threshold is able to stimulate an increase in the amount of body fat brown or beige, which can manifest itself in increasing lactate utilization during exercise and increase the reactivity in response to acute regional cooling. The methods used are: ramp test, regional acute cold exposure, measurement of gas exchange, lactate and glucose in the blood, heart rate, and heart rate variability, blood pressure and respiration variability at rest and during standard functional tests; infrared thermal imaging, statistical methods of results analysis. Workout 10 physically active volunteers (7 males and 3 females) on a treadmill at a speed corresponding to 75-80% of the persona VO2max for 30 minutes 3 times per week at a fixed ambient temperature 21-22°C for 6 weeks resulted in a significant (from 19 to 39%) increase in test work duration but VO2max on average changed little. The increase in power of anaerobic threshold was associated with a sharp slowdown in the accumulation of lactate in progress of ramp test. Lactate utilization rate during the recovery period, on the contrary, increased. In general, significantly increased work efficiency at a test load. Not revealed noticeable changes in the condition and response to a standard functional tests of autonomic systems, as judged by heart rate variability, blood pressure and respiration variability at rest and during orthostatic tests and imposed breathing rhythm. The functional response of the body to acute cold exposure (1 minute cooling of the feet in ice water) is not changed after a cycle of training--either in terms of metabolism (oxygen consumption, etc.), or the dynamics of the skin temperature in areas of most probable location of brown adipose tissue (BAT). These data do not confirm the previously expressed (2010) hypothesis about the function of BAT as a universal homeostatic instrument in the body. Probably, if under

  7. [Suicide attempt by means of phenobarbital overdose. Effective treatment with continuous veno-venous hemodialysis].

    Science.gov (United States)

    Ruhe, M; Grautoff, S; Kähler, J; Pohle, T

    2016-03-01

    A 68-year-old woman tried to commit suicide using phenobarbital, which was initially prescribed for her dog that suffered from seizures. At admission she was unconscious and ventilated. Five days of intensive care therapy did not improve her state of consciousness. Subsequent continuous veno-venous hemodialysis accelerated the elimination of phenobarbital compared to endogenous elimination by a factor of five. The patient survived without sequelae. Detailed history taking and well-timed indication for dialysis were crucial.

  8. Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach.

    Science.gov (United States)

    van den Broek, M P H; Groenendaal, F; Toet, M C; van Straaten, H L M; van Hasselt, J G C; Huitema, A D R; de Vries, L S; Egberts, A C G; Rademaker, C M A

    2012-10-01

    Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effect of phenobarbital on the continuous amplitude-integrated electroencephalography (aEEG) in a prospective study. Data were obtained from the prospective SHIVER study, performed in two of the ten Dutch level III neonatal intensive care units. Phenobarbital data were collected between 2008 and 2010. Newborns were eligible for inclusion if they had a gestational age of at least 36 weeks and presented with perinatal asphyxia and encephalopathy. According to protocol in both hospitals an intravenous (repeated) loading dose of phenobarbital 20 mg/kg divided in 1-2 doses was administered if seizures occurred or were suspected before or during the hypothermic phase. Phenobarbital plasma concentrations were measured in plasma using a fluorescence polarization immunoassay. aEEG was monitored continuously. A one-compartmental population pharmacokinetic/pharmacodynamic model was developed using a multi-level Markov transition model. No (clinically relevant) effect of moderate therapeutic hypothermia on phenobarbital pharmacokinetics could be identified. The observed responsiveness was 66%. While we still advise an initial loading dose of 20 mg/kg, clinicians should not be reluctant to administer an additional dose of 10-20 mg/kg. An additional dose should be given before switching to a second-line anticonvulsant drug. Based on our pharmacokinetic/pharmacodynamic model, administration of phenobarbital under hypothermia seems to reduce the transition rate from a continuous normal voltage (CNV) to discontinuous normal voltage aEEG background level in hypothermic asphyxiated newborns, which may be attributed to the additional neuroprotection of phenobarbital in infants with a CNV pattern.

  9. Long-term outcome of phenobarbital treatment for epilepsy in rural China: a prospective cohort study.

    Science.gov (United States)

    Kwan, Patrick; Wang, Wenzhi; Wu, Jianzhong; Li, Shichuo; Yang, Hongchao; Ding, Ding; Hong, Zhen; Dai, Xiuying; Yang, Bing; Wang, Taiping; Yuan, Chenglin; Ma, Guangyu; de Boer, Hanneke M; Sander, Josemir W

    2013-03-01

    To evaluate the long-term outcome of phenobarbital treatment for convulsive epilepsy in rural China, and to explore factors associated with overall seizure outcomes. We carried out follow-up assessments of people who took part in an epilepsy community management program conducted in rural counties of six provinces in China. People with convulsive epilepsy who were previously untreated (or on irregular treatment) were commenced on regular treatment with phenobarbital. Information was collected using a standardized questionnaire by face-to-face interviews of the individuals (and their families where necessary). Information collected included treatment status, medication change, seizure frequency, and mortality. Among the 2,455 people who participated in the original program, outcomes were successfully ascertained during the follow-up assessment in 1986. Among them, 206 had died. Information on treatment response was obtained in 1,780 (56% male; mean age 33.9 years, range 3-84; mean duration of follow-up 6.4 years). Among them, 939 (53%) were still taking phenobarbital. The most common reasons for stopping phenobarbital were seizure freedom or substantial seizure reduction, socioeconomic reasons, and personal preference. Four hundred fifty-three individuals (25%) became seizure-free for at least 1 year while taking phenobarbital, 88% of whom did so at daily doses of 120 mg or below. Four hundred six (23%) reported adverse events, which led to withdrawal of phenobarbital in phenobarbital for convulsive epilepsy in rural China. One hundred years after the discovery of its antiepileptic effect, phenobarbital is still playing an important role in the management of epilepsy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  10. The effect of phenobarbital on the metabolism and excretion of thyroxine in rats

    Energy Technology Data Exchange (ETDEWEB)

    McClain, R.M.; Levin, A.A.; Posch, R.; Downing, J.C.

    1989-06-15

    The effect of phenobarbital on thyroid function and the metabolism and biliary excretion of thyroxine in rats was determined. Phenobarbital, administered for 2 weeks at a dose of 100 mg/kg/day, resulted in an increase in hepatic and thyroid gland weights, decreased circulating levels of T4, T3 and rT3, and increased TSH levels in male and female rats. After 3 months of treatment liver and thyroid weights were still increased; however, hormone values were not as markedly affected indicating that the rats had partially compensated for the effect on thyroid function. In thyroidectomized rats the plasma clearance of thyroxine was increased with phenobarbital. In bile duct cannulated phenobarbital-treated male rats the hepatic uptake at 4 hr was markedly increased. Bile flow was increased and the 4-hr cumulative biliary excretion of administered radioactivity was increased by 42%. Most of the increase in the excretion (76%) was accounted for by an increase in the excretion of thyroxine-glucuronide in phenobarbital-treated rats. Hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats expressed as picomoles per milligram of protein was increased by 40%; enzyme activity per gram of liver was increased by about twofold which, coupled with increased hepatic weight, resulted in about a threefold increase in total hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats as compared to that of controls. Qualitatively similar effects on metabolism, excretion, and enzyme induction were noted in female rats; however, the magnitude of increase was less than that observed in male rats. It is concluded that the effect of phenobarbital on thyroid function in rats is primarily a result of its effects on the hepatic disposition of thyroid hormone.

  11. Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a patient receiving phenobarbital.

    Science.gov (United States)

    Duncan, K O; Tigelaar, R E; Bolognia, J L

    1999-03-01

    Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that most often appears as an adverse reaction to a medication. There have been 21 reported cases of atypical erythema multiforme, toxic epidermal necrolysis, and SJS arising in patients receiving radiation therapy in addition to phenytoin, phenobarbital, or carbamazepine. We report the second case of SJS resulting from concomitant phenobarbital and radiation therapy, in which the eruption was limited to the sites of radiation, which were multiple.

  12. Acute vertigo in an anesthesia provider during exposure to a 3T MRI scanner

    Directory of Open Access Journals (Sweden)

    Gorlin A

    2015-03-01

    Full Text Available Andrew Gorlin,1 Joseph M Hoxworth,2 William Pavlicek,2 Christopher A Thunberg,1 David Seamans1 1Department of Anesthesiology, 2Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ, USA Abstract: Vertigo induced by exposure to the magnetic field of a magnetic resonance imaging (MRI scanner is a well-known phenomenon within the radiology community but is not widely appreciated by other clinical specialists. Here, we describe a case of an anesthetist experiencing acute vertigo while providing sedation to a patient undergoing a 3 Tesla MRI scan. After discussing previous reports, and the evidence surrounding MRI-induced vertigo, we review potential etiologies that include the effects of both static and time-varying magnetic fields on the vestibular apparatus. We conclude our review by discussing the occupational standards that exist for MRI exposure and methods to minimize the risks of MRI-induced vertigo for clinicians working in the MRI environment. Keywords: occupational medicine, MRI worker safety, vestibular dysfunction, magnetic field, 3T MRI scanner

  13. Acute Exposure to Stress Improves Performance in Trace Eyeblink Conditioning and Spatial Learning Tasks in Healthy Men

    Science.gov (United States)

    Duncko, Roman; Cornwell, Brian; Cui, Lihong; Merikangas, Kathleen R.; Grillon, Christian

    2007-01-01

    The present study investigated the effects of acute stress exposure on learning performance in humans using analogs of two paradigms frequently used in animals. Healthy male participants were exposed to the cold pressor test (CPT) procedure, i.e., insertion of the dominant hand into ice water for 60 sec. Following the CPT or the control procedure,…

  14. Performance, acute health symptoms and physiological responses during exposure to high air temperature and carbon dioxide concentration

    DEFF Research Database (Denmark)

    liu, weiwei; Zhong, Weidi; Wargocki, Pawel

    2017-01-01

    subjects to report feeling uncomfortably warm, to rate the air quality as worse, to report increased sleepiness and higher intensity of several acute health symptoms. Eardrum temperature, skin temperature, heart rate and body weight loss all increased significantly at this exposure, arterial oxygen...

  15. Impact of acute exposure to air pollution on the cardiorespiratory performance of military firemen

    Directory of Open Access Journals (Sweden)

    R.S. Oliveira

    2006-12-01

    Full Text Available The objective of the present study was to determine the impact of acute short-term exposure to air pollution on the cardiorespiratory performance of military fireman living and working in the city of Guarujá, São Paulo, Brazil. Twenty-five healthy non-smoking firemen aged 24 to 45 years had about 1 h of exposure to low and high levels of air pollution. The tests consisted of two phases: phase A, in Bertioga, a town with low levels of air pollution, and phase B, in Cubatão, a polluted town, with a 7-day interval between phases. The volunteers remained in the cities (Bertioga/Cubatão only for the time required to perform the tests. Cumulative load 10 ± 2 min-long exertion tests were performed on a treadmill, consisting of a 2-min stage at a load of 7 km/h, followed by increasing exertion of 1 km h-1 min-1 until the maximum individual limit. There were statistically significant differences (P < 0.05 in anaerobic threshold (AT between Cubatão (35.04 ± 4.91 mL kg-1 min-1 and Bertioga (36.98 ± 5.62 mL kg-1 min-1; P = 0.01, in the heart rate at AT (AT HR; Cubatão 152.08 ± 14.86 bpm, Bertioga 157.44 ± 13.64 bpm; P = 0.001, and in percent maximal oxygen consumption at AT (AT%VO2max; Cubatão 64.56 ± 6.55%, Bertioga 67.40 ± 5.35%; P = 0.03. However, there were no differences in VO2max, maximal heart rate or velocity at AT (ATvel observed in firemen between towns. The acute exposure to pollutants in Cubatão, SP, caused a significant reduction in the performance at submaximal levels of physical exertion.

  16. Effects of Acute Exposure to Moderate Altitude on Vascular Function, Metabolism and Systemic Inflammation

    Science.gov (United States)

    Stöwhas, Anne-Christin; Latshang, Tsogyal D.; Lo Cascio, Christian M.; Lautwein, Sina; Stadelmann, Katrin; Tesler, Noemi; Ayers, Lisa; Berneis, Kaspar; Gerber, Philipp A.; Huber, Reto; Achermann, Peter; Bloch, Konrad E.; Kohler, Malcolm

    2013-01-01

    Background Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. Objectives To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. Methods In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Results Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Conclusions Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. Trial Registration ClinicalTrials.gov NCT01130948 PMID:23936377

  17. Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Anne-Christin Stöwhas

    Full Text Available BACKGROUND: Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. OBJECTIVES: To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. METHODS: In 51 healthy male subjects with a mean (SD age of 26.9 (9.3 years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL particle size, insulin resistance (HOMA-index, highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich and during two days at 2590 m, (Davos Jakobshorn, Switzerland in randomized order. The largest differences in outcomes between the two altitudes are reported. RESULTS: Mean (SD oxygen saturation was significantly lower at 2590 m, 91.0 (2.0%, compared to 490 m, 96.0 (1.0%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001 and heart rate (mean difference +3.3 bpm, p<0.001 were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001, LDL particle size increased (median difference +0.45 nm, p=0.048 and hsCRP decreased (median difference -0.18 mg/l, p=0.024 compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. CONCLUSIONS: Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01130948.

  18. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    Science.gov (United States)

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. Photocatalytic degradation kinetics and mechanism of phenobarbital in TiO(2) aqueous solution.

    Science.gov (United States)

    Cao, Hua; Lin, Xiulian; Zhan, Haiying; Zhang, Hong; Lin, Jingxin

    2013-01-01

    5-Ethyl-5-phenylpyrimidine-2,4,6(1H, 3H, 5H)-trione is an anti-convulsant used to treat disorders of movement, e.g. tremors. This work deals with the transformation of phenobarbital by UV/TiO(2) heterogeneous photocatalysis, to assess the decomposition of the pharmaceutical compound, to identify intermediates, as well as to elucidate some mechanistic details of the degradation. The photocatalytic removal efficiency of 100 μm phenobarbital is about 80% within 60 min, while the degradation efficiency of phenobarbital was better in alkaline solution. The study on contribution of reactive oxidative species (ROSs) has shown that ()OH is responsible for the major degradation of phenobarbital, while the photohole, photoelectrons and the other ROSs have the minor contribution to the degradation. Finally, based on the identification of degradation intermediates, two main photocatalytic degradation pathways have been tentatively proposed, including the hydroxylation and cleavage of pyrimidine ring in the phenobarbital molecule respectively. Certainly, the phenobarbital can be mineralized when the photocatalytic reaction time prolongs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Single-pass albumin dialysis in a child aged six months with phenobarbital poisoning.

    Science.gov (United States)

    Kıhtır, Hasan Serdar; Yıldırım, Hamdi Murat; Yeşilbaş, Osman; Duramaz, Burcu Bursal; Şevketoğlu, Esra

    2016-12-01

    A girl aged six months was hospitalized because of resistant seizures and was discharged with phenobarbital and carbamazepine therapy. She was admitted to a state hospital with symptoms of inability to waken and difficulty in breathing. It was learned that phenobarbital had been used incorrectly and the patient was sent to our pediatric intensive care unit because of severe phenobarbital overdose. The decision was taken for hemodialysis. Single-pass albumin dialysis was planned because phenobarbital can bind to high levels of plasma protein. The process was undertaken with 1% albumin-containing dialysate, which was prepared manually. After 6 hours of dialysis, the phenobarbital blood level measured 62 mcg/mL (>140 mcg/mL on admission) and the patient's clinical findings were markedly regressed. There are no case reports about phenobarbital overdose treated with single-pass albumin dialysis in the literature. We conclude that single-pass albumin dialysis may be a useful treatment, especially with intoxications of drugs that bind protein at high levels.

  1. Acute lung injury following inhalation exposure to nerve agent VX in guinea pigs.

    Science.gov (United States)

    Wright, Benjamin S; Rezk, Peter E; Graham, Jacob R; Steele, Keith E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2006-05-01

    A microinstillation technique of inhalation exposure was utilized to assess lung injury following chemical warfare nerve agent VX [methylphosphonothioic acid S-(2-[bis(1-methylethyl)amino]ethyl) O-ethyl ester] exposure in guinea pigs. Animals were anesthetized using Telazol-meditomidine, gently intubated, and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4 microg/m3, 70.4 micro g/m(m3), 90.4 microg/m(m3)) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 h of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 microg/m(m3) and 90.4 microg/m(m3) VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 microg/m(m3), indicating that this dose of VX caused lung injury that persisted at 24 h. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

  2. Chronic and acute exposures to the world trade center disaster and lower respiratory symptoms: area residents and workers.

    Science.gov (United States)

    Maslow, Carey B; Friedman, Stephen M; Pillai, Parul S; Reibman, Joan; Berger, Kenneth I; Goldring, Roberta; Stellman, Steven D; Farfel, Mark

    2012-06-01

    We assessed associations between new-onset (post-September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center-area residents and workers enrolled in the World Trade Center Health Registry. World Trade Center-area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects.

  3. Neurobehavioral and neurophysiological effects after acute exposure to a single peak of 200 ppm toluene in healthy volunteers.

    Science.gov (United States)

    Kobald, S Oliver; Wascher, Edmund; Blaszkewicz, Meinolf; Golka, Klaus; van Thriel, Christoph

    2015-05-01

    The solvent toluene has neurotoxic properties that are especially relevant in the working environment. Short-term exposure limits (STELs) vary from 50 ppm up to 300 ppm across countries but their acute effects remain elusive in humans. Several in vitro and in vivo studies elucidated that toluene acutely acts by perturbations of different neurotransmitter systems. More specifically visual evoked potentials (VEPs) of rats are decreased after acute toluene exposure, leading to the assumption that particularly visual attention processes might be a target of toluene in humans. Therefore a visual change detection task was applied to measure both neurobehavioral and neurophysiological effects by using electroencephalography (EEG) after a single peak exposure to 200 ppm toluene. Performance and event-related components of the EEG were examined before and after exposure in a toluene-exposed and a control group. Thirty-three young healthy volunteers participated in this study. The behavioral results of the experiment indicate that toluene impairs the rate of correct responses especially in task conditions in which an irrelevant distractor is given, while the response times did not differ between both groups. The neurophysiological findings hint toward a less efficient visual processing of behaviorally relevant stimuli and an increased distractibility by irrelevant distractors. Thus the present results are a promising starting point for further research specifically targeting visual attention after toluene exposure and the reconsideration of the presently very heterogeneous STELs.

  4. Effects of acute exposure to WIFI signals (2.45GHz) on heart variability and blood pressure in Albinos rabbit.

    Science.gov (United States)

    Saili, Linda; Hanini, Amel; Smirani, Chiraz; Azzouz, Ines; Azzouz, Amina; Sakly, Mohsen; Abdelmelek, Hafedh; Bouslama, Zihad

    2015-09-01

    Electrocardiogram and arterial pressure measurements were studied under acute exposures to WIFI (2.45GHz) during one hour in adult male rabbits. Antennas of WIFI were placed at 25cm at the right side near the heart. Acute exposure of rabbits to WIFI increased heart frequency (+22%) and arterial blood pressure (+14%). Moreover, analysis of ECG revealed that WIFI induced a combined increase of PR and QT intervals. By contrast, the same exposure failed to alter maximum amplitude and P waves. After intravenously injection of dopamine (0.50ml/kg) and epinephrine (0.50ml/kg) under acute exposure to RF we found that, WIFI alter catecholamines (dopamine, epinephrine) action on heart variability and blood pressure compared to control. These results suggest for the first time, as far as we know, that exposure to WIFI affect heart rhythm, blood pressure, and catecholamines efficacy on cardiovascular system; indicating that radiofrequency can act directly and/or indirectly on cardiovascular system.

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

    Science.gov (United States)

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

    2015-10-01

    A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100mGy and 1Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the level of mutation were found comparing different dose rates. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Persistence of Breakage in Specific Chromosome Bands 6 Years after Acute Exposure to Oil

    Science.gov (United States)

    Francés, Alexandra; Hildur, Kristin; Barberà, Joan Albert; Rodríguez-Trigo, Gema; Zock, Jan-Paul; Giraldo, Jesús; Monyarch, Gemma; Rodriguez-Rodriguez, Emma; de Castro Reis, Fernanda; Souto, Ana; Gómez, Federico P.; Pozo-Rodríguez, Francisco; Templado, Cristina; Fuster, Carme

    2016-01-01

    analyses were performed in 47 exposed individuals. A total of 251 breakpoints in exposed individuals) were identified, showing a non-uniform distribution in the human ideogram. Ten chromosome bands were found to be especially prone to breakage through both statistical methods. By comparing these bands with those observed in certain exposed individuals who had already participated the previous study, it was found in both studies that four bands (2q21, 3q27, 5q31 and 17p11.2) are particularly sensitive to breakage. Additionally, the dysfunction in DNA repair mechanisms was not significantly higher in oil-exposed individuals than in non-exposed individuals. Limitations The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the high number of individuals who participated occasionally in clean-up tasks. Conclusion Our findings show the existence of at least four target bands (2q21, 3q27, 5q31 and 17p11.2) with a greater propensity to break over time after an acute exposure to oil. The breaks in these bands, which are commonly involved in hematological cancer, may explain the increase of cancer risk reported in chronically benzene-exposed individuals. In addition, a more efficiency of the DNA repair mechanisms has been detected six years after in fishermen who were highly exposed to the oil spill. To date, only this study, performed by our group on the previous and present genotoxic effects, has analyzed the chromosomal regions affected by breakage after an acute oil exposure. PMID:27479010

  7. Low-frequency electrical stimulation enhances the effectiveness of phenobarbital on GABAergic currents in hippocampal slices of kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi-Chameh, Homeira; Ghafouri, Samireh; Sheibani, Vahid; Mirnajafi-Zadeh, Javad

    2016-08-25

    Low frequency stimulation (LFS) has been proposed as a new approach in the treatment of epilepsy. The anticonvulsant mechanism of LFS may be through its effect on GABAA receptors, which are the main target of phenobarbital anticonvulsant action. We supposed that co-application of LFS and phenobarbital may increase the efficacy of phenobarbital. Therefore, the interaction of LFS and phenobarbital on GABAergic inhibitory post-synaptic currents (IPSCs) in kindled and control rats was investigated. Animals were kindled by electrical stimulation of basolateral amygdala in a semi rapid manner (12 stimulations/day). The effect of phenobarbital, LFS and phenobarbital+LFS was investigated on GABAA-mediated evoked and miniature IPSCs in the hippocampal brain slices in control and fully kindled animals. Phenobarbital and LFS had positive interaction on GABAergic currents. In vitro co-application of an ineffective pattern of LFS (100 pulses at afterdischarge threshold intensity) and a sub-threshold dose of phenobarbital (100μM) which had no significant effect on GABAergic currents alone, increased the amplitude and area under curve of GABAergic currents in CA1 pyramidal neurons of hippocampal slices significantly. Interestingly, the sub-threshold dose of phenobarbital potentiated the GABAergic currents when applied on the hippocampal slices of kindled animals which received LFS in vivo. Post-synaptic mechanisms may be involved in observed interactions. Obtained results implied a positive interaction between LFS and phenobarbital through GABAA currents. It may be suggested that a combined therapy of phenobarbital and LFS may be a useful manner for reinforcing the anticonvulsant action of phenobarbital. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

    Science.gov (United States)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

  9. Medication side effects among people with epilepsy taking phenobarbital in Zambia.

    Science.gov (United States)

    Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

    2014-11-01

    Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional

  10. Influence of acute exposure to high altitude on basal and postprandial plasma levels of gastroenteropancreatic peptides.

    Directory of Open Access Journals (Sweden)

    Rudolf L Riepl

    Full Text Available Acute mountain sickness (AMS is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland, over the course of three days. In a second study (n = 5, the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m. and stimulated (evening 8 p.m. plasma levels of pancreatic polypeptide (PP and cholecystokinin (CCK were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively. Mean O(2-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

  11. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M. [University of Extremo Catarinense, Criciuma, SC (Brazil)

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  12. Exploring the molecular mechanism of acute heat stress exposure in broiler chickens using gene expression profiling.

    Science.gov (United States)

    Luo, Q B; Song, X Y; Ji, C L; Zhang, X Q; Zhang, D X

    2014-08-10

    The process of heat regulation is complex and its exact molecular mechanism is not fully understood. In this study, to investigate the global gene regulation response to acute heat exposure, gene microarrays were exploited to analyze the effects of heat stress on three tissues (brain, liver, leg muscle) of the yellow broiler chicken (Gallus gallus). We detected 166 differentially expressed genes (DEGs) in the brain, 219 in the leg muscle and 317 in the liver. Six of these genes were differentially expressed in all three tissues and were validated by qRT-PCR, and included heat shock protein genes (HSPH1, HSP25), apoptosis-related genes (RB1CC1, BAG3), a cell proliferation and differentiation-related gene (ID1) and the hunger and energy metabolism related gene (PDK). All these genes might be important factors in chickens suffering from heat stress. We constructed gene co-expression networks using the DEGs of the brain, leg muscle and liver and two, four and two gene co-expression modules were identified in these tissues, respectively. Functional enrichment of these gene modules revealed that various functional clusters were related to the effects of heat stress, including those for cytoskeleton, extracellular space, ion binding and energy metabolism. We concluded that these genes and functional clusters might be important factors in chickens under acute heat stress. Further in-depth research on the newly discovered heat-related genes and functional clusters is required to fully understand their molecular functions in thermoregulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Acute exposure to 17α-ethinylestradiol disrupts audience effect on male-female interactions in Betta splendens.

    Science.gov (United States)

    Forette, Lindsay M; Mannion, Krystal L; Dzieweczynski, Teresa L

    2015-04-01

    Endocrine disrupting chemicals can negatively impact the morphology and behavior of organisms inhabiting polluted waters. Male-typical behaviors are often reduced after exposure, suggesting that exposure may have population-level effects. One way in which exposure may exert population-level effects is by interfering with communication within a network of individuals. Acute exposure to the estrogen mimic 17α-ethinylestradiol (EE2) disrupts the ability of male Siamese fighting fish, Betta splendens, to modify their behavior during male-male interactions when an audience is present. However, it is unknown whether audience effects during male-female interactions may be similarly altered. To examine this, male-female pairs that were given an acute exposure to EE2 or remained unexposed interacted in the presence of a female, male, or no audience. Sex differences were found between unexposed males and females. More interactant-directed gill flaring was displayed by control males when a male audience was present while control females performed this behavior more in the presence of an audience, regardless of sex. Both males and females in the control group performed more interactant-directed tail beats in the presence of a female audience. EE2 exposure made all audience effects disappear as treated males and females did not differ in their responses between audience types. These results demonstrate that acute exposure to EE2 may disrupt behavioral adjustments to audience type within a social network. This disruption may, in turn, influence population dynamics in this species as both males and females use information obtained from observing interactions in later encounters with the observed individuals.

  14. Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns.

    Science.gov (United States)

    Šíma, M; Pokorná, P; Hronová, K; Slanař, O

    2015-01-01

    Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

  15. High-dose phenobarbital or erythropoietin for the treatment of perinatal asphyxia in term newborns.

    Science.gov (United States)

    Avasiloaiei, Andreea; Dimitriu, Cristina; Moscalu, Mihaela; Paduraru, Luminita; Stamatin, Maria

    2013-10-01

    The aim of this study was to compare two neuroprotective strategies to supportive care in the treatment of perinatal asphyxia. A total of 67 term newborns with perinatal asphyxia were included and randomized into three groups: one group received supportive treatment; another group received a single dose of 40 mg/kg phenobarbital; and the third received three daily doses of 1000 IU/kg erythropoietin. The following parameters were analyzed: gestational age, birthweight, Apgar scores, cord blood pH, total serum antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). The newborns were included in the follow-up program and examined up to 18 months of age. TAS was higher in the erythropoietin group than in the other groups. SOD and GPx were lower for infants treated with phenobarbital or erythropoietin compared to control infants. MDA was lower in the erythropoietin group compared to the other groups, although the difference was not statistically significant (P > 0.05). The mortality rate was lower in the phenobarbital and erythropoietin groups (both 4.6%) than in the control group (17.4%). Long-term neurologic follow up showed a high incidence of sequelae in the control group compared to the phenobarbital and erythropoietin groups. Follow-up results were better in the phenobarbital group than in the erythropoietin group for motor and cognitive function at 3 and 6 months and worse for expressive language. At 18 months, however, the differences between these two groups were not significant. High-dose phenobarbital or erythropoietin along with supportive treatment has a positive influence on the outcome of newborns with perinatal asphyxia. Phenobarbital has the advantage of low cost and simplicity. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  16. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Rosiane V da Silva

    Full Text Available Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS, which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

  17. Effect of acute exposure to moderate altitude on muscle power: hypobaric hypoxia vs. normobaric hypoxia.

    Science.gov (United States)

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch-Góngora, Juan G; Galilea, Pedro A; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest P(mean) obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to P(max) (∼ 3%) and maximal strength (1 RM) (∼ 6%) in G1 attributable to the climb to altitude (Ppress.

  18. Phenobarbital loaded microemulsion: development, kinetic release and quality control

    Directory of Open Access Journals (Sweden)

    Kayo Alves Figueiredo

    Full Text Available ABSTRACT This study aimed to obtain and characterize a microemulsion (ME containing phenobarbital (PB. The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol(r, ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV = 242 nm. The kinetics of the in vitro release (Franz model of the ME and the emulsion (EM containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.

  19. Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital.

    Science.gov (United States)

    Nardou, Romain; Yamamoto, Sumii; Chazal, Geneviève; Bhar, Asma; Ferrand, Nadine; Dulac, Olivier; Ben-Ari, Yehezkel; Khalilov, Ilgam

    2011-04-01

    Phenobarbital produces its anti-epileptic actions by increasing the inhibitory drive of γ-aminobutyric acid. However, following recurrent seizures, γ-aminobutyric acid excites neurons because of a persistent increase of chloride raising the important issue of whether phenobarbital could aggravate persistent seizures. Here we compared the actions of phenobarbital on initial and established ictal-like events in an in vitro model of mirror focus. Using the in vitro three-compartment chamber preparation with the two hippocampi and their commissural fibres placed in three different chambers, kainate was applied to one hippocampus and phenobarbital contralaterally, either after one ictal-like event or after many recurrent ictal-like events that produce an epileptogenic mirror focus. Field, perforated patch and single-channel recordings were used to determine the effects of γ-aminobutyric acid and their modulation by phenobarbital, and alterations of the chloride cotransporters were investigated using sodium-potassium-chloride cotransporter 1 and potassium chloride cotransporter 2 antagonists, potassium chloride cotransporter 2 immunocytochemistry and sodium-potassium-chloride cotransporter 1 knockouts. Phenobarbital reduced initial ictal-like events and prevented the formation of a mirror focus when applied from the start. In contrast, phenobarbital aggravated epileptiform activities when applied after many ictal-like events by enhancing the excitatory actions of γ-aminobutyric acid due to increased chloride. The accumulation of chloride and the excitatory actions of γ-aminobutyric acid in mirror foci neurons are mediated by the sodium-potassium-chloride cotransporter 1 chloride importer and by downregulation and internalization of the chloride-exporter potassium-chloride cotransporter 2. Finally, concomitant applications of the sodium-potassium-chloride cotransporter 1 antagonist bumetanide and phenobarbital decreased excitatory actions of γ-aminobutyric acid and

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  1. Assessment of locomotion behavioral defects induced by acute toxicity from heavy metal exposure in nematode Caenorhabditis elegans

    Institute of Scientific and Technical Information of China (English)

    WANG Dayong; XING Xiaojuan

    2008-01-01

    Locomotion behaviors are susceptible to disruption by a broad spectrum of chemicals and environmental stresses. However, no systematic testing of locomotion behavior defects induced by metal exposure has been conducted in the model organism of nematode Caenorhabditis elegans. In this study, the acute toxicity from heavy metal exposure on the locomotion behaviors was analyzed in nematodes. Endpoints of head thrash, body bend, forward turn, backward turn, and Omega/U turn were chosen to evaluate the locomotion behavioral defects. Our data suggest that the endpoints of head thrash, body bend, and forward turn will be useful for the evaluation of heavy metal toxicity in nematodes. The endpoint of head thrash could detect the toxicity from Cd, Co, Cr, Cu, Hg, and Pb exposures at a low concentration (2.5 μmol/L). The endpoint of body bend could be explored to evaluate the toxicity from all assayed heavy metal exposures at different concentrations, whereas the endpoint of forward turn will be more useful for the evaluation of heavy metal toxicity at high concentrations. Thus, endpoints of these locomotion behaviors establish a fast and economic way to assess the presence of acute toxicity from heavy metal exposure in nematode C. elegans.

  2. Phenobarbital and temperature profile during hypothermia for hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Sant'Anna, Guilherme; Laptook, Abbot R; Shankaran, Seetha; Bara, Rebecca; McDonald, Scott A; Higgins, Rosemary D; Tyson, Jon E; Ehrenkranz, Richard A; Das, Abhik; Goldberg, Ronald N; Walsh, Michele C

    2012-04-01

    Data from the whole-body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (T (e)) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic-ischemic encephalopathy and clinical seizures and lower T (e) and cord pH than infants that have not received phenobarbital (-PB). There was a significant effect of phenobarbital itself and an interaction between phenobarbital and time in the T (e) profile. Mean T (e) in the +PB group was lower than in the -PB group, and the differences decreased over time. In +PB infants, the time to surpass target T (e) of 33.5°C and to reach the minimum T (e) during overshoot were shorter. In conclusion, the administration of phenobarbital before cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates.

  3. Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: an isobolographic analysis.

    Science.gov (United States)

    Fleck, Juliana; Marafiga, Joseane Righes; Jesse, Ana Cláudia; Ribeiro, Leandro Rodrigo; Rambo, Leonardo Magno; Mello, Carlos Fernando

    2015-04-01

    Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases the anticonvulsant action of classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well as isobolographic analysis, are used to show that the CysLT1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown that LTD4 reverses the effect of montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) of montelukast plus phenobarbital was 0.06±0.02 μmol, whereas the additively calculated ED50add value was 0.49±0.03 μmol. The calculated interaction index was 0.12, indicating a synergistic interaction. The association of montelukast significantly decreased the antiseizure ED50 for phenobarbital (0.74 and 0.04 μmol in the absence and presence of montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. The demonstration of a strong synergism between montelukast and phenobarbital is particularly relevant because both drugs are already used in the clinics, foreseeing an immediate translational application for epileptic patients who have drug-resistant seizures. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

    Mager, Edward M; Grosell, Martin

    2011-06-01

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

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

    OpenAIRE

    Ana ePalomino; Francisco Javier ePavon; Eduardo eBlanco Calvo; Antonia eSerrano; Sergio eArrabal; Patricia eRivera; Antonio eVargas; Ainhoa eBilbao; Leticia eRubio; Fernando eRodriguez de Fonseca; Juan eSuarez

    2014-01-01

    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 {cannabinoid recept...

  7. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Maria

    2008-01-01

    Full Text Available Abstract Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s. In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an

  8. Association between exposure to environmental tobacco smoke and biomarkers of oxidative stress among patients hospitalised with acute myocardial infarction.

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    Ian L Megson

    Full Text Available OBJECTIVE: To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction. DESIGN: An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction. SETTING: Nine acute hospitals in Scotland. PARTICIPANTS: Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL. INTERVENTION: None. MAIN OUTCOME MEASURES: Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA and oxidised low-density lipoprotein (ox-LDL were measured on admission blood samples and adjusted for potential confounders. RESULTS: After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031 and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001 but not ox-LDL (beta coefficient 2.14, 95% CI -8.94, 13.21, p = 0.703. CONCLUSIONS: Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.

  9. Exposure medium: key in identifying free Ag+ as the exclusive species of silver nanoparticles with acute toxicity to Daphnia magna.

    Science.gov (United States)

    Shen, Mo-Hai; Zhou, Xiao-Xia; Yang, Xiao-Ya; Chao, Jing-Bo; Liu, Rui; Liu, Jing-Fu

    2015-04-10

    It is still not very clear what roles the various Ag species play in the toxicity of silver nanoparticles (AgNPs). In this study, we found that traditional exposure media result in uncontrollable but consistent physicochemical transformation of AgNPs, causing artifacts in determination of median lethal concentration (LC50) and hindering the identification of Ag species responsible for the acute toxicity of AgNPs to Daphnia magna. This obstacle was overcome by using 8 h exposure in 0.1 mmol L(-1) NaNO3 medium, in which we measured the 8-h LC50 of seven AgNPs with different sizes and coatings, and determined the concentrations of various Ag species. The LC50 as free Ag(+) of the seven AgNPs (0.37-0.44 μg L(-1)) agreed very well with that of AgNO3 (0.40 μg L(-1)), and showed the lowest value compared to that as total Ag, total Ag(+), and dissolved Ag, demonstrating free Ag(+) is exclusively responsible for the acute toxicity of AgNPs to D. magna, while other Ag species in AgNPs have no contribution to the acute toxicity. Our results demonstrated the great importance of developing appropriate exposure media for evaluating risk of nanomaterials.

  10. Exposure Medium: Key in Identifying Free Ag+ as the Exclusive Species of Silver Nanoparticles with Acute Toxicity to Daphnia magna

    Science.gov (United States)

    Shen, Mo-Hai; Zhou, Xiao-Xia; Yang, Xiao-Ya; Chao, Jing-Bo; Liu, Rui; Liu, Jing-Fu

    2015-04-01

    It is still not very clear what roles the various Ag species play in the toxicity of silver nanoparticles (AgNPs). In this study, we found that traditional exposure media result in uncontrollable but consistent physicochemical transformation of AgNPs, causing artifacts in determination of median lethal concentration (LC50) and hindering the identification of Ag species responsible for the acute toxicity of AgNPs to Daphnia magna. This obstacle was overcome by using 8 h exposure in 0.1 mmol L-1 NaNO3 medium, in which we measured the 8-h LC50 of seven AgNPs with different sizes and coatings, and determined the concentrations of various Ag species. The LC50 as free Ag+ of the seven AgNPs (0.37-0.44 μg L-1) agreed very well with that of AgNO3 (0.40 μg L-1), and showed the lowest value compared to that as total Ag, total Ag+, and dissolved Ag, demonstrating free Ag+ is exclusively responsible for the acute toxicity of AgNPs to D. magna, while other Ag species in AgNPs have no contribution to the acute toxicity. Our results demonstrated the great importance of developing appropriate exposure media for evaluating risk of nanomaterials.

  11. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

    Energy Technology Data Exchange (ETDEWEB)

    Marchini, T.; Magnani, N.D. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Paz, M.L. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Vanasco, V. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Tasat, D. [CESyMA, Facultad de Ciencia Tecnología, Universidad Nacional de General San Martín, Martín de Irigoyen 3100, 1650 San Martín, Buenos Aires (Argentina); González Maglio, D.H. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); and others

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN

  12. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

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    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  13. Comparative study of behavioural problems among epileptic children treated with phenobarbital with epileptic children treated with phenytoin

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    Mohsen Javadzadeh

    2011-01-01

    Full Text Available Background: Phenobarbital is recommended by WHO as the first line drug for the treatment of partial and generalized tonic clonic epilepsies in developing countries, however several clinical trials have recorded higher frequencies of behavioural problems associated with Phenobarbital than with other drugs or no treatment. We compared the frequency of behavioural problems among epileptic children treated with phenobarbital with epileptic children treated with phenytoin. Materials and Method: We conducted a case-control study to comparing of epileptic children treatment with neurological with epileptic children treated with phenytoin. Between November 2006 to March 2007, 74 children referred from child neurologic clinic who treated with phenobarbital or phenytoin for more than 2 months in Zahedan, assessed consecutively by the Rutters behaviour scale for children aged 6 years and older and by the preschool behaviour questionnaire for those 2-5 years.Results: The mean scores on the behaviour scales did not differ significantly between the phenobarbital and phenytoin groups in children aged 6 years and older. Irretability, attention deficit, disobedience and lack of energy in phenobarbital group more than phenytoin group in 2-5 years old children. Conclusion: Several clinical trials have recorded higher frequencies (20-60% of behavioural problems associated with phenobarbital than with other drugs but in our study evidence supports the acceptability of phenobarbital for epileptic children in developing countries

  14. High Resolution ECG for Evaluation of QT Interval Variability during Exposure to Acute Hypoxia

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    Zupet, P.; Finderle, Z.; Schlegel, Todd T.; Starc, V.

    2010-01-01

    Ventricular repolarization instability as quantified by the index of QT interval variability (QTVI) is one of the best predictors for risk of malignant ventricular arrhythmias and sudden cardiac death. Because it is difficult to appropriately monitor early signs of organ dysfunction at high altitude, we investigated whether high resolution advanced ECG (HR-ECG) analysis might be helpful as a non-invasive and easy-to-use tool for evaluating the risk of cardiac arrhythmias during exposure to acute hypoxia. 19 non-acclimatized healthy trained alpinists (age 37, 8 plus or minus 4,7 years) participated in the study. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position breathing room air and then after breathing 12.5% oxygen for 30 min. For beat-to-beat RR and QT variability, the program of Starc was utilized to derive standard time domain measures such as root mean square of the successive interval difference (rMSSD) of RRV and QTV, the corrected QT interval (QTc) and the QTVI in lead II. Changes were evaluated with paired-samples t-test with p-values less than 0.05 considered statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with p = 0.000 and p = 0.005, respectively. Significant increases were found in both the rMSSDQT and the QTVI in lead II, with p = 0.002 and p = 0.003, respectively. There was no change in QTc interval length (p = non significant). QT variability parameters may be useful for evaluating changes in ventricular repolarization caused by hypoxia. These changes might be driven by increases in sympathetic nervous system activity at ventricular level.

  15. Successful use of sustained low efficiency dialysis in a case of severe phenobarbital poisoning

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    Sayandeep Jana

    2014-01-01

    Full Text Available A 30-year-old female presented with coma and subsequent cardiac arrest caused by phenobarbital overdosage, requiring ventilatory and vasopressor support. She had also developed severe hypoxia following gastric aspiration. Initial therapy, including activated charcoal and forced alkaline diuresis, failed to significantly lower her drug levels and there was minimal neurological improvement. As she was hemodynamically unstable, and unsuitable for conventional dialysis, she was put on sustained low efficiency dialysis (SLED to facilitate drug removal. SLED resulted in marked reduction in plasma level of phenobarbital, which eventually led to early extubation, improved cognition and aided full recovery. Thus, we concluded that SLED can be an effective alternative in cases of severe phenobarbital poisoning, where conventional hemodialysis or hemoperfusion cannot be initiated, to hasten drug elimination and facilitate early recovery.

  16. Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

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    Walailuk Kerdsan

    2009-01-01

    Full Text Available Methamphetamine (METH is a psychostimulant drug of abuse that produces long-term behavioral changes including behavioral sensitization, tolerance, and dependence. METH has been reported to induce neurotoxic effects in several areas of the brain via the dopaminergic system. Changes of dopamine function can induce malfunction of the glutamatergic system. Therefore, the aim of the present study was to examine the effects of METH administration on the expression of glutamate N-methyl-D-aspartate receptor subunit 1 (NMDAR1 in frontal cortex, striatum, and hippocampal formation after acute and subacute exposure to METH by western blotting. Male Sprague-Dawley rats were injected intraperitoneally with a single dose of 8 mg/kg METH, 4 mg/kg/day METH for 14 days and saline in acute, subacute, and control groups, respectively. A significant increase in NMDAR1 immunoreactive protein was found in frontal cortex in the subacute group (P=.036 but not in the acute group (P=.580. Moreover, a significant increase in NMDAR1 was also observed in striatum in both acute (P=.025 and subacute groups (P=.023. However, no significant differences in NMDAR1 in hippocampal formation were observed in either acute or subacute group. The results suggest that an upregulation of NMDA receptor expression may be a consequence of glutamatergic dysfunction induced by METH.

  17. Genotype and toxicity relationships among Hyalella azteca: I. Acute exposure to metals or low pH

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    Duan, Y.; Guttman, S.I.; Oris, J.T.; Bailer, A.J.

    2000-05-01

    Comparative genotype and toxin interactions at three polymorphic enzyme loci were examined in a laboratory population of amphipods (Hyalella azteca) during acute exposure to cadmium, zinc, copper, lead, or low pH. Significant toxin-genotype interactions were observed using logistic regression to model mortality in ten of 15 analyses. Both stressor-specific and nonspecific modes of selection were observed. In general, low pH selected for different genotypes than those selected by metals, especially zinc. Different modes of selection were also observed when amphipods were exposed to different metals. These results suggest that exposure to low pH would significantly reduce the ability of H. azteca to survive subsequent contamination by metals; exposure to stressors in the reverse order would also compromise a population's chance of survival. A genetic distance analysis showed that the magnitude of genetic differentiation consistently increased among survivors compared with that of the initial populations. These increases in genetic divergence estimates suggest that acute exposure to metals or low pH may have an evolutionarily significant impact on the species. They also suggest that both genotype frequency and genetic distance measures (based on allozyme data) may be used as bioindicators for environmental monitoring programs. Validation of such bioindicators requires an understanding of the population's genetic background, genetic structure, and history.

  18. Chronic and Acute Ozone Exposure in the Week Prior to Delivery Is Associated with the Risk of Stillbirth

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    Pauline Mendola

    2017-07-01

    Full Text Available Chronic and acute air pollution has been studied in relation to stillbirth with inconsistent findings. We examined stillbirth risk in a retrospective cohort of 223,375 singleton deliveries from 12 clinical sites across the United States. Average criteria air pollutant exposure was calculated using modified Community Multiscale Air Quality models for the day of delivery and each of the seven days prior, whole pregnancy, and first trimester. Poisson regression models using generalized estimating equations estimated the relative risk (RR of stillbirth and 95% confidence intervals (CI in relation to an interquartile range increase in pollutant with adjustment for temperature, clinical, and demographic factors. Ozone (O3 was associated with a 13–22% increased risk of stillbirth on days 2, 3, and 5–7 prior to delivery in single pollutant models, and these findings persisted in multi-pollutant models for days 5 (RR = 1.22, CI = 1.07–1.38 and 6 (RR = 1.18, CI = 1.04–1.33. Whole pregnancy and first trimester O3 increased risk 18–39% in single pollutant models. Maternal asthma increased stillbirth risk associated with chronic PM2.5 and carbon monoxide exposures. Both chronic and acute O3 exposure consistently increased stillbirth risk, while the role of other pollutants varied. Approximately 8000 stillbirths per year in the US may be attributable to O3 exposure.

  19. Clinical evaluation of a combination therapy of imepitoin with phenobarbital in dogs with refractory idiopathic epilepsy.

    Science.gov (United States)

    Neßler, Jasmin; Rundfeldt, Chris; Löscher, Wolfgang; Kostic, Draginja; Keefe, Thomas; Tipold, Andrea

    2017-01-25

    Imepitoin was tested as a combination treatment with phenobarbital in an open-label mono-centre cohort study in dogs with drug-resistant epilepsy. Diagnosis of idiopathic epilepsy was based on clinical findings, magnetic resonance imaging and cerebrospinal fluid analysis. Three cohorts were treated. In cohort A, dogs not responding to phenobarbital with or without established add-on treatment of potassium bromide or levetiracetam were treated add-on with imepitoin, starting at 10 mg/kg BID, with titration allowed to 30 mg/kg BID. In cohort B, the only difference to cohort A was that the starting dose of imepitoin was reduced to 5 mg/kg BID. In cohort C, animals not responding to imepitoin at >20 mg/kg BID were treated with phenobarbital add-on starting at 0.5 mg/kg BID. The add-on treatment resulted in a reduction in monthly seizure frequency (MSF) in all three cohorts. A reduction of ≥50% was obtained in 36-42% of all animals, without significant difference between cohorts. The lower starting dose of 5 mg/kg BID imepitoin was better tolerated, and an up-titration to on average of 15 mg/kg BID was sufficient in cohort A and B. In cohort C, a mean add-on dose of 1.5 mg/kg BID phenobarbital was sufficient to achieve a clinically meaningful effect. Six dogs developed a clinically meaningful increase in MSF of ≥ 50%, mostly in cohort A. Neither imepitoin nor phenobarbital add-on treatment was capable of suppressing cluster seizure activity, making cluster seizure activity an important predictor for drug-resistance. A combination treatment of imepitoin and phenobarbital is a useful treatment option for a subpopulation of dogs with drug-resistant epilepsy, a low starting dose with 5 mg/kg BID is recommended.

  20. Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial.

    Science.gov (United States)

    Nayeri, Fatemeh; Sheikh, Mahdi; Kalani, Majid; Niknafs, Pedram; Shariat, Mamak; Dalili, Hosein; Dehpour, Ahmad-Reza

    2015-05-15

    Evaluating the efficacy of the loading and tapering dose of Phenobarbital versus oral Morphine in the management of NAS. This randomized, open-label, controlled trial was conducted on 60 neonates born to illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran, Iran, who exhibited NAS requiring medical therapy. The neonates were randomized to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital followed by a tapering dose. The duration of treatment required for NAS resolution, the total hospital stay and the requirement for additional second line treatment were compared between the treatment groups. The Mean ± Standard Deviation for the duration of treatment required for the resolution of NAS was 8.5 ± 5 days in the Morphine group and 8.5 ± 4 days in the Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 ± 5.6 days in the Morphine group and 12.5 ± 5.3 days in the Phenobarbital group (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group required adjunctive treatment (P = 0.5). There were no significant differences in the duration of treatment, duration of hospital stay, and the requirement for adjunctive treatment, between the neonates with NAS who received Morphine Sulfate and neonates who received a loading and tapering dose of Phenobarbital. This study is registered at the Iranian Registry of Clinical Trials ( www.irct.ir ) which is a Primary Registry in the WHO Registry Network. (Registration Number =  IRCT201406239568N8 ).

  1. Prophylactic Effects of Levamisole and Vitamin E on Phenobarbital-induced Cleft Palate and Spina Bifida in Rat Embryos

    Science.gov (United States)

    Khaksary Mahabady, Mahmood; Najafzadeh Varzi, Hossein

    2011-01-01

    There are many reports that show the teratogenic effects of phenobarbital can be decreased by stimulation of maternal immune system. Therefore, in this study, the prophylactic effects of levamisole and vitamin E on teratogenic effects of phenobarbital were compared. This study was performed on 20 pregnant rats that were divided into four groups. Control group received normal saline and test groups received phenobarbital (120 mg/kg), phenobarbital (120 mg/kg) plus levamisole (10 mg/kg) and phenobarbital (120 mg/kg) plus vitamin E (100 mg/kg) intraperitoneally at 9-11th days of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red - Alcian blue method. Cleft palate and spina bifida incidence were 66.66% and 69.44% in fetuses of rats that had received only phenobarbital. Cleft palate and spina bifida incidence were 65.45% and 38.18% had in the group which had received phenobarbital plus levamisole. However, Cleft palate and spina bifida incidence were 54.54% and 27.27% in the group which had received phenobarbital plus vitamin E. The arithmetic means of the weight and length of fetuses the rats that had received levamisole and vitamin E were significantly greater than that of those that had received only phenobarbital. Vitamin E had a greater prophylactic effect than levamisole on the incidence of phenobarbital-induced cleft palate and spina bifida. However, the difference was not significant. PMID:24363692

  2. Canine Pancreas-Specific Lipase and C-reactive Protein in Dogs Treated With Anticonvulsants (Phenobarbital and Potassium Bromide).

    Science.gov (United States)

    Albarracín, Viviana; Teles, Mariana; Meléndez-Lazo, Antonio; Rodón, Jaume; Pastor, Josep

    2015-06-01

    Animals treated with anticonvulsant drugs may have increased canine pancreas-specific lipase (cPLI) values. Inflammatory conditions and specifically acute pancreatitis are of major concern in these animals. Elevation in C-reactive protein is being associated with inflammatory status in dogs and it has been correlated with the clinical severity of pancreatitis. In the present study, we investigated if there is a correlation between the cPLI increase, changes in C-reactive protein and hepatic enzymes, as well as the incidence of severe acute pancreatitis (AP) in dogs with anticonvulsant treatment (phenobarbital, or potassium bromide or both). Increased values of pancreas-specific lipase were found in 6.8% of the animals in treatment with anticonvulsants, and this increase is correlated with the increase in triglycerides, alkaline phosphatase, and alanine aminotransferase but not with C-reactive protein levels, which suggests a possible induction or release phenomenon rather than a clear severe AP. C-reactive protein levels did not affect cPLI values on the population studied. Only 2 animals had clinical and analytical data suggestive of AP, indicating a low prevalence (0.6%). In conclusion, cPLI may be increased in a low percentage of animals with anticonvulsants treatment and its increase may not be associated with severe AP. It may be induced by the anticonvulsants drugs; however, further studies are advised to rule out other possible causes that increased cPLI.

  3. Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

    Science.gov (United States)

    Kokwaro, Gilbert O; Ogutu, Bernhards R; Muchohi, Simon N; Otieno, Godfrey O; Newton, Charles R J C

    2003-01-01

    Aims Phenobarbital is commonly used to treat status epilepticus in resource-poor countries. Although a dose of 20 mg kg−1 is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15-mg kg−1 intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus. Methods Twelve children (M/F: 11/1), aged 7–62 months, received a loading dose of phenobarbital (15 mg kg−1) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg−1 at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx® fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to predict the optimum dosage regimen that would maintain plasma phenobarbital concentrations between 15 and 20 mg l−1 for 72 h. Results All the children achieved plasma concentrations above 15 mg l−1 by the end of the infusion. Mean (95% confidence interval or median and range for Cmax) pharmacokinetic parameters were: area under curve [AUC (0, ∞) ]: 4259 (3169, 5448) mg l−1.h, t½: 82.9 (62, 103) h, CL: 5.8 (4.4, 7.3) ml kg−1 h−1, Vss: 0.8 (0.7, 0.9) l kg −1, CSF: plasma phenobarbital concentration ratio: 0.7 (0.5, 0.8; n = 6) and Cmax: 19.9 (17.9–27.9) mg l−1. Eight of the children had their convulsions controlled and none of them had recurrence of convulsions. Simulations suggested that a loading dose of 15 mg kg−1 followed by two maintenance doses of 2.5 mg kg−1 at 24 h and 48 h would maintain plasma phenobarbital concentrations between 16.4 and 20 mg l−1 for 72 h. Conclusions Phenobarbital, given as an i.v. loading dose, 15 mg kg−1

  4. A review of epidemiological data on epilepsy, phenobarbital, and risk of liver cancer.

    Science.gov (United States)

    La Vecchia, Carlo; Negri, Eva

    2014-01-01

    Phenobarbital is not genotoxic, but has been related to promotion of liver cancer (as well as inhibition) in rodents. In October 2012, we carried out a systematic literature search in the Medline database and searched reference lists of retrieved publications. We identified 15 relevant papers. Epidemiological data on epileptics/anticonvulsant use and liver cancer were retrieved from eight reports from seven cohort (record linkage) studies of epileptics, and data on phenobarbital use from a pharmacy-based record linkage investigation of patients treated with phenobarbital (three reports), plus a case-control study nested in one of the cohort studies and including information on phenobarbital use. Of the studies of cancer in epileptics, two showed no excess risk of liver cancer. A long-term (1933-1984) Danish cohort study of epileptics found relative risks (RRs) of 4.7 [95% confidence interval (CI) 3.2-6.8] of liver cancer and of 2.2 (95% CI 1.2-3.5) of biliary tract cancers. Such apparent excess risks could, however, be largely or completely attributed to thorotrast, a contrast medium used in the past in epileptic patients for cerebral angiography. A Finnish cohort study of epileptics obtained an RR of 1.7 (95% CI 1.2-2.4). Such an apparent excess risk, however, was not related to phenobarbital or to any specific anticonvulsant drug. The long-term follow-up of two UK cohorts found some excess risk of liver cancer among severe, but not among mild, epileptics. Some excess risk of liver cancer was also found in cohort studies of patients hospitalized for epilepsy in Sweden and Taiwan, in the absence, however, of association with any specific drugs. A UK General Practice database, comparing epileptics treated with valproate with unexposed ones, found a very low incidence of liver cancer. Of the studies of cancer in patients treated with phenobarbital, a large US pharmacy-based cohort investigation showed no excess risk of liver cancer. In a case-control study, nested in

  5. Inhibition of methadone and phenobarbital percutaneous absorption by parenterally administered ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, D.N.; Briggs, J.R.

    Four hours after the topical administration of either aqueous methadone hydrochloride or sodium phenobarbital to hairless (SKH, hr-1/hr-1) mice, the mean drug concentration in liver was significantly lower in ethanol-treated mice than in control animals that had received only water. No statistically significant difference was noted between the mean concentrations for test and control mice when either methadone or phenobarbital were given by intraperitoneal injection instead of topically, suggesting that ethanol inhibits the percutaneous absorption of these drugs in vivo.

  6. Critical role of matrix metalloproteinase-9 in acute cold exposure-induced stroke in renovascular hypertensive rats.

    Science.gov (United States)

    Li, Chunguang; Li, Xiangpen; Shen, Qingyu; Li, Yi; He, Lei; Li, Mei; Tang, Yamei; Wang, Yidong; He, Qingyu; Peng, Ying

    2013-11-01

    Our objectives are to investigate the role of MMP-9 in cold exposure-induced stroke and assess the preventive effect of doxycycline, a total of 200 rats were assigned to a control group, sham group, 2-kidney, 2-clip (2K-2C) group, and doxycycline-received 2K-2C group (2K-2C+doxy) (N=50, each), and subsequently, each group were randomly assigned to 2 groups: acute cold exposure (ACE) and nonacute cold exposure (NACE) (N=25, each). After the blood pressure was stabilized, rats were maintained on a 12-h light (22°C)/dark (4°C) cycle (ACE group) or a 12-h light (22°C)/dark (22°C) cycle (NACE group) for 3 cycles. The results showed that ACE upregulated Ang II and MMP-9 protein levels in brains and aortas and considerably enhanced stroke incidence in 2K-2C rats. In contrast, doxycycline treatment prevented upregulation of MMP-9 protein expression and activity in brains and aortas in response to ACE and significantly decreased stroke incidence. These findings suggest that cold exposure-induced MMP-9 via activation of RAS might play a critical role in the initiation of cold exposure-induced stroke during chronic hypertension and doxycycline shows protective effects against cold exposure-induced stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience.

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    Shaukat Ali

    Full Text Available BACKGROUND: In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS. Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts. METHODOLOGY/PRINCIPAL FINDINGS: Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient to severely malformed. Ethanol exposure at early stages caused high mortality (≥88%. At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent. CONCLUSIONS: Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16 for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience.

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

    Science.gov (United States)

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

    2014-08-15

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

  9. Sensitivity of a green alga to atrazine is not enhanced by previous acute exposure.

    Science.gov (United States)

    Baxter, Leilan; Brain, Richard; Prosser, Ryan; Solomon, Keith; Hanson, Mark

    2013-10-01

    Exposure to atrazine in small lotic systems can be episodic, with short-term pulses (peaks) followed by lower, decreasing concentrations. Algae and macrophytes recover rapidly from pulsed exposure to atrazine, but reported observations of population response to subsequent exposures are minimal and inconclusive. Consequently, the sensitivity of Pseudokirchneriella subcapitata to atrazine following a pulsed exposure was assessed. Exposure concentrations reflected amplifications of those observed in streams from highly vulnerable watersheds in regions of intense use. Initial pulsed atrazine exposure at 0, 150 or 300 μg/L for 24-h was followed by 72-h exposure to 0, 5, 10, 25, or 50 μg/L. Measured responses were cell density, growth rate, chlorophyll-a, and maximum quantum yield of photosystem II. Algal recovery was rapid and prior pulsed exposure to atrazine did not significantly affect subsequent sensitivity (EC10s, EC25s) for any endpoint, indicating no changes in tolerance at the population level for this species.

  10. SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

    Science.gov (United States)

    We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

  11. Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update.

    Science.gov (United States)

    Yukawa, M; Yukawa, E; Suematsu, F; Takiguchi, T; Ikeda, H; Aki, H; Mimemoto, M

    2011-12-01

    Optimal use of phenobarbital in the neonatal population requires information regarding the drug's pharmacokinetics and the influence of various factors, such as different routes of administration, on the drug's disposition. However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in neonates and infants. This study was conducted to establish the role of patient characteristics in estimating doses of phenobarbital for neonates and infants using routine therapeutic drug monitoring data. The population pharmacokinetics of phenobarbital was evaluated using 109 serum concentration measurements obtained from routine phenobarbital monitoring of 70 neonates and infants. The data were analysed using the non-linear mixed effects model. A one-compartment pharmacokinetic model with first-order elimination was used. Covariates screened were current total bodyweight (TBW), gestational age, postnatal age (PNA), post-conceptional age, gender and neonates-infants clearance factor (serum concentration of phenobarbital; Conc). The final pharmacokinetic parameters were CL/F (mL/h) = (5.95.TBW (kg) +1.41.PNA (weeks)) Conc (serum phenobarbital concentration >50 μg/mL)(-0.221),Vd/F(L) =1.01.TBW (kg), and F = 0.483 for oral administration and F = 1 was assumed for suppository. Conc(-0.221) is 1 for phenobarbital concentration phenobarbital clearance in this study were TBW, PNA and Conc. Phenobarbital clearance increases proportionately with increasing TBW, and an older newborn was expected to have a higher rate of clearance than a younger newborn of equal bodyweight. Moreover, the clearance of phenobarbital decreased nonlinearly with increasing serum concentration of phenobarbital >50 μg/mL (Conc(-0.221) ). We developed a new model for neonate and infant dosing of phenobarbital with good predictive performance. Clinical application of our model should permit more accurate selection of initial and maintenance doses to achieve

  12. Is hair analysis for dialkyl phosphate metabolites a suitable biomarker for assessing past acute exposure to organophosphate pesticides?

    Science.gov (United States)

    Tsatsakis, A M; Tutudaki, M; Tzatzarakis, M N; Dawson, A; Mohamed, F; Christaki, M; Alegakis, A K

    2012-03-01

    In the present paper, the possibility to use dialkyl phosphate metabolites (DAPs) hair segmental analysis as a biomarker of past acute exposure to organophosphates is examined. Hair samples of four acute poisoning survivors were collected and segmental hair analysis was performed. The total hair samples were divided to 1 cm segments and analysed by gas chromatography-mass spectrometry (GC-MS) for the presence of four DAP metabolites, dimethyl phosphate (DMP), diethyl phosphate (DEP), diethyl thiophosphate (DETP) and diethyl dithiophosphate (DEDTP). Results were examined under the light of pesticide type and time of hair sample collection. Although DAPs were detected all along the hair shaft, higher concentrations (peaks) were detected in the segments proximate to the suicide period. It was also observed that the elevated concentrations of the present metabolites corresponded to the ones produced by the ingested parent compound. Conclusively, measurements of DAPs in the appropriate hair segments of OP-poisoned patients can be used for assessing past acute exposure to organophosphates in certain cases.

  13. Acute Free-Iron Exposure Does Not Explain the Impaired Haemorheology Associated with Haemochromatosis.

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    Antony P McNamee

    Full Text Available Given the severity of the current imbalance between blood donor supply and recipient demand, discarded blood drawn from the routine venesections of haemochromatosis (HFE-HH patients may serve as a valuable alternative source for blood banks and transfusion. We investigated whether functional or biochemical differences existed between HFE-HH and control blood samples, with particular focus upon the haemorheological properties, to investigate the viability of venesected blood being subsequently harvested for blood products.Blood samples were collected from HFE-HH patients undergoing venesection treatment (n = 19 and healthy volunteers (n = 8. Moreover, a second experiment investigated the effects of a dose-response of iron (0, 40, 80, 320 mM FeCl3 on haemorheology in healthy blood samples (n = 7. Dependent variables included basic haematology, iron status, haematocrit, red blood cell (RBC aggregation (native and standardised haematocrit and "aggregability" (RBC tendency to aggregate in a standard aggregating medium; 0.4 L/L haematocrit in a Dx70, and RBC deformability.Indices of RBC deformability were significantly decreased for HFE-HH when compared with healthy controls: RBC deformability was significantly decreased at 1-7 Pa (p < 0.05, and the shear stress required for half maximal deformability was significantly increased (p < 0.05 for HFE-HH. RBC aggregation in plasma was significantly increased (p < 0.001 for HFE-HH, although when RBC were suspended in plasma-free Dx70 no differences were detected. No differences in RBC deformability or RBC aggregation/aggregability were detected when healthy RBC were incubated with varying dose of FeCl3.HFE-HH impairs the haemorheological properties of blood; however, RBC aggregability was similar between HFE-HH and controls when cells were suspended in a plasma-free medium, indicating that plasma factor(s may explain the altered haemorheology in HFE-HH patients. Acute exposure to elevated iron levels does

  14. The use of self-reported symptoms as a proxy for acute organophosphate poisoning after exposure to chlorpyrifos 50 % plus cypermethrin 5 % among Nepali farmers

    DEFF Research Database (Denmark)

    Kofod, Dea Haagensen; Jørs, Erik; Varma, Anshu

    2016-01-01

    cholinesterase (PchE) activity, in addition to the symptoms, when assessing occupational acute pesticide poisoning. This study evaluated self-reported symptoms as a proxy for acute organophosphate poisoning among Nepali farmers by examining self-reported acute organophosphate poisoning symptoms and PchE activity......%: moderately hazardous) spray session or a 2-h placebo spray session, and after 7 days' washout, the farmers were assigned to the other spray session. Before and after each spray session farmers were interviewed about acute organophosphate poisoning symptoms and PchE activity was measured. Analyses were...... symptoms among the farmers regardless of organophosphate exposure or poisoning. Thus, self-reported acute organophosphate symptoms seem to be a poor proxy for acute organophosphate poisoning as the occurrence of these symptoms is not necessarily associated with acute organophosphate poisoning. TRIAL...

  15. Quantifying fish swimming behavior in response to acute exposure of aqueous copper using computer assisted video and digital image analysis

    Science.gov (United States)

    Calfee, Robin D.; Puglis, Holly J.; Little, Edward E.; Brumbaugh, William G.; Mebane, Christopher A.

    2016-01-01

    Behavioral responses of aquatic organisms to environmental contaminants can be precursors of other effects such as survival, growth, or reproduction. However, these responses may be subtle, and measurement can be challenging. Using juvenile white sturgeon (Acipenser transmontanus) with copper exposures, this paper illustrates techniques used for quantifying behavioral responses using computer assisted video and digital image analysis. In previous studies severe impairments in swimming behavior were observed among early life stage white sturgeon during acute and chronic exposures to copper. Sturgeon behavior was rapidly impaired and to the extent that survival in the field would be jeopardized, as fish would be swept downstream, or readily captured by predators. The objectives of this investigation were to illustrate protocols to quantify swimming activity during a series of acute copper exposures to determine time to effect during early lifestage development, and to understand the significance of these responses relative to survival of these vulnerable early lifestage fish. With mortality being on a time continuum, determining when copper first affects swimming ability helps us to understand the implications for population level effects. The techniques used are readily adaptable to experimental designs with other organisms and stressors.

  16. Risk Analysis of Acute Or Chronic Exposure to Arsenic of the Inhabitants in a District of Buenos Aires, Argentina

    Directory of Open Access Journals (Sweden)

    Cristina Vázquez

    2016-09-01

    Full Text Available The arsenic occurrence in the water constitutes a serious world health concern due to its toxicity. Depending on the intensity and duration of exposure, this element can be acutely lethal or may have a wide range of health effects in humans and animals. In Argentina, the origin of arsenic is mainly natural, and related to different geological processes. The Argentinean concern about arsenic and its influence on human health dates back to the previous century. The disease ascribed to arsenic contamination was called ‘chronic regional endemic hydroarsenism’. It is produced by the consumption of water with high levels of this element. In our study, we focused in La Matanza district, a very populated site in the Buenos Aires Province. An increasing concern of the inhabitants of the area regarding health problems was detected. In order to establish a full view of arsenic exposure in the area, several matrices and targets were analyzed. As matrices, water and soil samples were analyzed. As targets, canine and human hair was studied. The aim of this study was to investigate acute and chronically exposure to arsenic of La Matanza inhabitants.

  17. Effects of acute exercise on fear extinction in rats and exposure therapy in humans: Null findings from five experiments.

    Science.gov (United States)

    Jacquart, Jolene; Roquet, Rheall F; Papini, Santiago; Powers, Mark B; Rosenfield, David; Smits, Jasper A J; Monfils, Marie-H

    2017-08-01

    Exposure therapy is an established learning-based intervention for the treatment of anxiety disorders with an average response rate of nearly 50%, leaving room for improvement. Emerging strategies to enhance exposure therapy in humans and fear extinction retention in animal models are primarily pharmacological. These approaches are limited as many patients report preferring non-pharmacological approaches in therapy. With general cognitive enhancement effects, exercise has emerged as a plausible non-pharmacological augmentation strategy. The present study tested the hypothesis that fear extinction and exposure therapy would be enhanced by a pre-training bout of exercise. We conducted four experiments with rats that involved a standardized conditioning and extinction paradigm and a manipulation of exercise. In a fifth experiment, we manipulated vigorous-intensity exercise prior to a standardized virtual reality exposure therapy session among adults with fear of heights. In experiments 1-4, exercise did not facilitate fear extinction, long-term memory, or fear relapse tests. In experiment 5, human participants showed an overall reduction in fear of heights but exercise did not enhance symptom improvement. Although acute exercise prior to fear extinction or exposure therapy, as operationalized in the present 5 studies, did not enhance outcomes, these results must be interpreted within the context of a broader literature that includes positive findings. Taken all together, this suggests that more research is necessary to identify optimal parameters and key individual differences so that exercise can be implemented successfully to treat anxiety disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The effects of acute waterborne exposure to sublethal concentrations of molybdenum on the stress response in rainbow trout, Oncorhynchus mykiss.

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    Chelsea D Ricketts

    Full Text Available To determine if molybdenum (Mo is a chemical stressor, fingerling and juvenile rainbow trout (Oncorhynchus mykiss were exposed to waterborne sodium molybdate (0, 2, 20, or 1,000 mg l-1 of Mo and components of the physiological (plasma cortisol, blood glucose, and hematocrit and cellular (heat shock protein [hsp] 72, hsp73, and hsp90 in the liver, gills, heart, and erythrocytes and metallothionein [MT] in the liver and gills stress responses were measured prior to initiation of exposure and at 8, 24, and 96 h. During the acute exposure, plasma cortisol, blood glucose, and hematocrit levels remained unchanged in all treatments. Heat shock protein 72 was not induced as a result of exposure and there were no detectable changes in total hsp70 (72 and 73, hsp90, and MT levels in any of the tissues relative to controls. Both fingerling and juvenile fish responded with similar lack of apparent sensitivity to Mo exposure. These experiments demonstrate that exposure to waterborne Mo of up to 1,000 mg l(-1 did not activate a physiological or cellular stress response in fish. Information from this study suggests that Mo water quality guidelines for the protection of aquatic life are highly protective of freshwater fish, namely rainbow trout.

  19. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  20. Slow and stepped re-warming after acute low temperature exposure do not improve survival of Drosophila melanogaster larvae.

    Science.gov (United States)

    Sinclair, Brent J; Rajamohan, Arun

    2008-01-01

    We tested that hypothesis that slow re-warming rates would improve the ability of Drosophila melanogaster Meigen larvae to survive acute low temperature exposure. Four larval stages (1(st), 2(nd), 3(rd) instars and wandering stage 3(rd) instars) of four wild-type strains were exposed to -7 degrees C for periods of time expected to result in 90 % mortality. Larvae were then either directly transferred to their rearing temperature (21 degrees C), or returned to this temperature in a stepwise fashion (pausing at 0 and 15 degrees C) or by slow warming at 1 or 0.1 degrees C/min. We observed a reduced rapid cold-hardening effect and no general increase in survival of acute chilling in larvae re-warmed in a stepwise or slow fashion, and hypothesise that slow re-warming may result in accumulation of further chill injuries.

  1. Surface hydrophilic modification with a sugar moiety for a uniform-sized polymer molecularly imprinted for phenobarbital in serum.

    Science.gov (United States)

    Hua, Kuichang; Zhang, Lei; Zhang, Zhenhui; Guo, Yong; Guo, Tianying

    2011-08-01

    A uniform-sized polymer molecularly imprinted for phenobarbital, which is surface modified by a sugar moiety, has been prepared through a two-step swelling polymerization method using polystyrene beads as seeds, phenobarbital as the template, 4-vinylpyridine as a functional monomer, ethylene glycol dimethacrylate as a cross-linker and 2-O-meth-acryloyloxyethoxyl-(2,3,4,6- tetra-O-acetyl-β-d-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-β-d-glucopyranoside as a surface-modifying glycomonomer, respectively. After deprotecting the glycopolymer, a surface sugar moiety-modified, hydrophilic, molecularly imprinted polymer for phenobarbital (glyco-MIP) was obtained. The resulting polymer beads were packed into a stainless steel column to evaluate their chromatographic characteristics by high-performance liquid chromatography (HPLC). Good selectivity for phenobarbital was obtained with the glyco-MIP compared to the unmodified molecularly imprinted polymer, which revealed that the recognition sites of phenobarbital were unchanged with sugar moiety surface modification. Furthermore, bovine serum albumin was almost completely recovered from the glyco-MIP column, which indicates that the glyco-MIP materials can be used to separate and analyze drugs in complex samples, such as biological samples. The results of pretreatment with and analysis of phenobarbital in serum suggest that this material can be used to analyze phenobarbital in serum through a pretreatment and reverse-phase HPLC analysis process. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions

    NARCIS (Netherlands)

    Patel, NJ; Zamek-Gliszczynski, MJ; Zhang, PJ; Han, YH; Jansen, PLM; Meier, PJ; Stieger, B; Brouwer, KLR

    Phenobarbital (PB) treatment impairs the biliary excretion of some organic anions. One mechanism may involve direct competition for biliary excretion by PB and/or a PB metabolite. Alternatively, PB may alter the expression and/or function of hepatic organic anion transport proteins. The role of

  3. Analysis of connectivity map: Control to glutamate injured and phenobarbital treated neuronal network

    Science.gov (United States)

    Kamal, Hassan; Kanhirodan, Rajan; Srinivas, Kalyan V.; Sikdar, Sujit K.

    2010-04-01

    We study the responses of a cultured neural network when it is exposed to epileptogenesis glutamate injury causing epilepsy and subsequent treatment with phenobarbital by constructing connectivity map of neurons using correlation matrix. This study is particularly useful in understanding the pharmaceutical drug induced changes in the neuronal network properties with insights into changes at the systems biology level.

  4. Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.

    Science.gov (United States)

    Muñana, K R; Nettifee-Osborne, J A; Papich, M G

    2015-01-01

    Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs. Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6). Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point. Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P phenobarbital in dogs. Copyright © 2015 by the American College of Veterinary Internal Medicine.

  5. Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

    Science.gov (United States)

    Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

    2013-01-01

    Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

  6. Polymorphism in phenobarbital: discovery of a new polymorph and crystal structure of elusive form V.

    Science.gov (United States)

    Roy, Saikat; Goud, N Rajesh; Matzger, Adam J

    2016-03-21

    This report highlights the discovery of a new polymorph of the anticonvulsant drug phenobarbital (PB) using polymer-induced heteronucleation (PIHn) and unravelling the crystal structure of the elusive form V. Both forms are characterized by structural, thermal and VT-Raman spectroscopy methods to elucidate phase transformation behavior and shed light on stability relationships.

  7. Methoxyethanol biotransformation by liver and testis of rats is modulated by phenobarbital pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, L.; Au, W.; Moslen, M.T. (Univ. of Texas, Galveston (United States))

    1992-02-26

    Toxicity of 2-methoxyethanol (ME), a widely used solvent, is known to be dependent on its biotransformation by alcohol dehydrogenase to methoxyacetaldehyde (MA) and then by aldehyde dehydrogenase to methoxyacetic acid (MAA). However, little is known about the effects of enzyme inducers on the biotransformation of ME by liver or target organs such as the testis. The authors objective was to examine effects of phenobarbital pretreatment of Sprague Dawley rats on hepatic and testicular biotransformation of ME {r arrow} MA and MA {r arrow} MAA. Phenobarbital diminished hepatic ME {r arrow} MA activity by 80% when activity was calculated per mg prot and by 50% per liver/kg body weight. Hepatic MA {r arrow} MA activity was increased 25% by phenobarbital without an appreciable change in testicular MA {r arrow} MAA activity. Further studies are needed to determine if these effects of phenobarbital pretreatment on tissue biotransformation of ME and MA are associated with changes in the kinetics or toxicity of this solvent.

  8. Short-term exposure to ambient particulate matter and emergency ambulance dispatch for acute illness in Japan.

    Science.gov (United States)

    Tasmin, Saira; Ueda, Kayo; Stickley, Andrew; Yasumoto, Shinya; Phung, Vera Ling Hui; Oishi, Mizuki; Yasukouchi, Shusuke; Uehara, Yamato; Michikawa, Takehiro; Nitta, Hiroshi

    2016-10-01

    Short-term exposure to air pollution may be linked to negative health outcomes that require an emergency medical response. However, few studies have been undertaken on this phenomenon to date. The aim of this study therefore was to examine the association between short-term exposure to ambient suspended particulate matter (SPM) and emergency ambulance dispatches (EADs) for acute illness in Japan. Daily EAD data, daily mean SPM and meteorological data were obtained for four prefectures in the Kanto region of Japan for the period from 2007 to 2011. The area-specific association between daily EAD for acute illness and SPM was explored using generalized linear models while controlling for ambient temperature, relative humidity, seasonality, long-term trends, day of the week and public holidays. Stratified analyses were conducted to evaluate the modifying effects of age, sex and medical conditions. Area-specific estimates were combined using meta-analyses. For the total study period the mean level of SPM was 23.7μg/m(3). In general, higher SPM was associated with a significant increase in EAD for acute illness [estimated pooled relative risk (RR): 1.008, 95% CI: 1.007 to 1.010 per 10μg/m(3) increase in SPM at lag 0-1]. The effects of SPM on EAD for acute illness were significantly greater for moderate/mild medical conditions (e.g. cases that resulted in 3weeks hospitalization or which resulted in death). Using EAD data, this study has shown the adverse health effects of ambient air pollution. This highlights the importance of reducing the level of air pollution in order to maintain population health and well-being.

  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. Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

    -fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (Ptumor necrosis factor...... an induced acute phase response is impaired in long-term ethanol-fed rats. METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide...... (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins. RESULTS: Ethanol...

  11. Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

    DEFF Research Database (Denmark)

    Bengtson, Stefan; Knudsen, KB; Kyjovska, ZO

    2017-01-01

    the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90...... without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

  12. Combined effects of epileptic seizure and phenobarbital induced overexpression of P-glycoprotein in brain of chemically kindled rats

    Science.gov (United States)

    Jing, Xinyue; Liu, Xiang; Wen, Tao; Xie, Shanshan; Yao, Dan; Liu, Xiaodong; Wang, Guangji; Xie, Lin

    2010-01-01

    Background and purpose: The multidrug resistance of epilepsy may result from the overexpression of P-glycoprotein, but the mechanisms are unclear. We investigated whether the overexpression of P-glycoprotein in the brains of subjects with pharmacoresistant epilepsy resulted from both drug effects and seizure activity. Experimental approach: Kindled rats were developed by injecting a subconvulsive dose of pentylenetetrazole (33 mg·kg−1·day−1, i.p.) for 28 days. Groups were then treated with an oral dose of phenobarbital (45 mg·kg−1·day−1) for 40 days. In accord with behavioural observations, P-glycoprotein activity in brain was assessed using brain-to-plasma concentration ratios of rhodamine 123. P-glycoprotein levels in the brain regions were further evaluated using RT-PCR and Western blot analysis. The distribution of phenobarbital in the brain was assessed by measuring phenobarbital concentrations 1 h following its oral administration. Key results: The kindling significantly increased P-glycoprotein activity and expression. Good associations were found among P-glycoprotein activity, expression and phenobarbital concentration in the hippocampus. Short-term treatment with phenobarbital showed good anti-epileptic effect; the maximum effect occurred on day 14 when overexpression of P-glycoprotein was reversed. Continuous treatment with phenobarbital had a gradually reduced anti-epileptic effect and on day 40, phenobarbital exhibited no anti-epileptic effect; this was accompanied by both a re-enhancement of P-glycoprotein expression and decreased phenobarbital concentration in the hippocampus. P-glycoprotein function and expression were also increased in age-matched normal rats treated with phenobarbital. Conclusions and implications: The overexpression of P-glycoprotein in the brain of subjects with pharmacoresistant epilepsy is due to a combination of drug effects and epileptic seizures. PMID:20233212

  13. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs.

    Science.gov (United States)

    Boothe, Dawn Merton; Dewey, Curtis; Carpenter, David Mark

    2012-05-01

    To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs. Double-blinded, randomized, parallel, clinical trial. 46 AED-naïve dogs with naturally occurring epilepsy. Study inclusion was based on age, history, findings on physical and neurologic examinations, and clinicopathologic test results. For either phenobarbital treatment (21 dogs) or bromide treatment (25), a 7-day loading dose period was initiated along with a maintenance dose, which was adjusted on the basis of monthly monitoring. Efficacy and safety outcomes were compared between times (baseline and study end [generally 6 months]) and between drugs. Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). Seizure activity worsened in 3 bromide-treated dogs only. In dogs with seizure eradication, mean ± SD serum phenobarbital concentration was 25 ± 6 μg/mL (phenobarbital dosage, 4.1 ± 1.1 mg/kg [1.9 ± 0.5 mg/lb], p.o., q 12 h) and mean serum bromide concentration was 1.8 ± 0.6 mg/mL (bromide dosage, 31 ± 11 mg/kg [14 ± 5 mg/lb], p.o., q 12 h). Ataxia, lethargy, and polydipsia were greater at 1 month for phenobarbital-treated dogs; vomiting was greater for bromide-treated dogs at 1 month and study end. Both phenobarbital and bromide were reasonable first-choice AEDs for dogs, but phenobarbital was more effective and better tolerated during the first 6 months of treatment.

  14. Effects of Acute Oral 5-aminotetrazole (5-AT) Exposure to Rats (Rattus norvegicus)

    Science.gov (United States)

    2015-02-12

    Micronucleus Assay (MNA) Male rats from the 5-AT study (three highest dose groups and the vehicle control) were tested for DNA damage in their peripheral...Dose Test (Sub-acute Study) - Sperm Collection and Analysis 09/25/2013 10/07/2013 14-Day Repeated Dose Test (Sub-acute Study) - Micronucleus Assay...2015 Prepared by: Valerie H Adams, Ph.D. Approved for public release; distribution unlimited. Specialty: 500C Toxicity Test Toxicity Report No. S

  15. Renal effects of acute exposure to toluene. A controlled clinical trial

    DEFF Research Database (Denmark)

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

    1985-01-01

    Urinary excretion rates of beta 2-microglobulin and albumin were measured in 43 male printing trade workers and 43 age-matched male controls before and during exposure to toluene, 382 mg/m3, for 6 1/2 hours in a climate chamber. There were no significant changes in renal excretion rates of albumin...... and beta 2-microglobulin during toluene exposure indicating that no causal relationship exists between moderate exposure to organic solvents and renal injury....

  16. Probabilistic assessment of the cumulative dietary acute exposure of the population of Denmark to organophosphorus and carbamate pesticides

    DEFF Research Database (Denmark)

    Jensen, Bodil Hamborg; Petersen, Annette; Christensen, Tue

    2009-01-01

    Organophosphorus and carbamate pesticides are acetylcholinesterase-inhibiting pesticides and as such have a common mode of action. We assessed the cumulative acute exposure of the population of Denmark to 25 organophosphorus and carbamate pesticide residues from the consumption of fruit, vegetables...... the nationwide dietary survey conducted in 2000-2002. Contributions from 43 commodities were included in the calculations. We used the relative potency factor (RPF) approach to normalize the toxicity of the various organophosphorus and carbamate pesticides to the two index compounds chlorpyriphos...

  17. Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.

    Science.gov (United States)

    Luisier, Raphaëlle; Lempiäinen, Harri; Scherbichler, Nina; Braeuning, Albert; Geissler, Miriam; Dubost, Valerie; Müller, Arne; Scheer, Nico; Chibout, Salah-Dine; Hara, Hisanori; Picard, Frank; Theil, Diethilde; Couttet, Philippe; Vitobello, Antonio; Grenet, Olivier; Grasl-Kraupp, Bettina; Ellinger-Ziegelbauer, Heidrun; Thomson, John P; Meehan, Richard R; Elcombe, Clifford R; Henderson, Colin J; Wolf, C Roland; Schwarz, Michael; Moulin, Pierre; Terranova, Rémi; Moggs, Jonathan G

    2014-06-01

    The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CAR(KO)-PXR(KO)), double humanized CAR and PXR (CAR(h)-PXR(h)), and wild-type C57BL/6 mice. Wild-type and CAR(h)-PXR(h) mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CAR(KO)-PXR(KO) mouse livers and largely reversible in wild-type and CAR(h)-PXR(h) mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CAR(h)-PXR(h) mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.

  18. PHENOBARBITAL FOR THE PREVENTION OF INTRACRANIAL DAMAGE IN CHINESE NEONATES WITH SEVERE ASPHYXIA

    Institute of Scientific and Technical Information of China (English)

    陈惠金; 吴圣楣; 黄萍; 孙建华; 陈冠仪; 储凇雯

    2000-01-01

    Objective To evaluate the effect of phenobarbital on preventing intracranial damage and seizure in Chinese neonates with severe asphyxia. Methods A control trial was carried out in 60 Chinese neonates with severe asphyxia. 30 neonates received loading dose of phenobarbital on an average of 5.6h of age. Results The mean value of phenobarbital serum level obtained at the 4th day after birth was 21.9μg/ml. No significant difference was observed in the two groups in terms of birth weight, gestational age, Apgar scores, sex, etc. The imaging diagnosis within 3d of age in all subjects showed normal brain in 14, brain edema in 9 and intraventricular hemorrhage (IVH) in 7 in the treated group with a 53.3% of total complication rate, and normal brain in 5, brain edema in 15, IVH in 9 and subarachnoid hemorrhage (SAH) in 1 in the untreated group with a 83.3% of total complication rate. The incidence of intracranial damage in the untreated group was significantly higher than that in the treated group (83.3% vs 53.3%, P<0.05). In the treated group, 4 neonates with seizure symptom were effectively controlled soon, and none of the other 26 developed seizure. The period of seizure in the treated group was significantly shorter than that in the untreated group (P<0. 05). Other clinical symptoms were also sooner improved and no side effects were observed among the neonates treated with phenobarbital. Conclusion The incidence of postasphyxiated intracranial damage was obviously decreased, and seizure could be prophylactically intervened by phenobarbital. It is recommended that early application of preventive phenobarbitalin severely asphyxiated neonates is reasonable in reducing the incidence of intracranial lesions and subsequent seizures.

  19. Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

    Science.gov (United States)

    Sokoloff, Max D; Plegue, Melissa A; Chervin, Ronald D; Barks, John D E; Shellhaas, Renée A

    2015-07-01

    Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction. For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002). Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

  20. Toluene metabolism in isolated rat hepatocytes: effects of in vivo pretreatment with acetone and phenobarbital

    Energy Technology Data Exchange (ETDEWEB)

    Smith-Kielland, A.; Ripel, A. (National Inst. of Forensic Toxicology, Oslo (Norway))

    1993-02-01

    Hepatocytes isolated from control, acetone- and phenobarbital-pretreated rats were used to study the metabolic conversion of toluene to benzyl alcohol, benzaldehyde, benzoic acid and hippuric acid at low (<100 [mu]M) and high (100-500 [mu]M) toluene concentrations. The baseline formation rates of toluene metabolites (benzyl alcohol, benzoic acid and hippuric acid) were 2.9[+-]1.7 and 10.0[+-]2.3 nmol/mg cell protein/60 min at low and high toluene concentrations, respectively. In vivo pretreatment of rats with acetone and phenobarbital increased the formation of metabolites: at low toluene concentrations 3- and 5-fold, respectively; at high toluene concentrations no significant increase (acetone) and 8-fold increase (phenobarbital). Apparent inhibition by ethanol, 7 and 60 mM, was most prominent at low toluene concentrations: 63% and 69%, respectively, in control cells; 84% and 91% in acetone-pretreated cells, and 32% (not significant) and 51% in phenobarbital-pretreated cells. Ethanol also caused accumulation of benzyl alcohol. The apparent inhibition by isoniazid was similar to that of ethanol at low toluene concentrations. Control and acetone-pretreated cells were apparently resistant towards metyrapone; the decrease was 49% and 64% in phenobarbital-pretreated cells at low and high toluene concentrations, respectively. In these cells, the decrease in presence of combined ethanol and metyrapone was 95% (low toluene concentrations). 4-Methylpyrazole decreased metabolite formation extensively in all groups. Benzaldehyde was only found in the presence of an aldehyde dehydrogenase inhibitor. Increased ratio benzoic/hippuric acid was observed at high toluene concentrations. These results demonstrate that toluene oxidation may be studied by product formation in isolated hepatocytes. However, the influence of various enzymes in the overall metabolism could not be ascertained due to lack of inhibitor specificity. (orig.).

  1. Probabilistic acute dietary exposure assessments to captan and tolylfluanid using several European food consumption and pesticide concentration databases

    DEFF Research Database (Denmark)

    Boon, Polly E.; Svensson, Kettil; Moussavian, Shahnaz

    2009-01-01

    Probabilistic dietary acute exposure assessments of captan and tolylfluanid were performed for the populations of the Czech Republic, Denmark, Italy, the Netherlands and Sweden. The basis for these assessments was national databases for food consumption and pesticide concentration data harmonised...... at the level of raw agricultural commodity. Data were obtained from national food consumption surveys and national monitoring programmes and organised in an electronic platform of databases connected to probabilistic software. The exposure assessments were conducted by linking national food consumption data...... to national food consumption surveys. In this way it is possible to exchange or merge concentration data between countries in situations of data scarcity. This electronic platform in connection with probabilistic software can be seen as a prototype of a data warehouse, including a harmonised approach...

  2. Quantification of optic disc edema during exposure to high altitude shows no correlation to acute mountain sickness.

    Directory of Open Access Journals (Sweden)

    Gabriel Willmann

    Full Text Available BACKGROUND: The study aimed to quantify changes of the optic nerve head (ONH during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS. This work is related to the Tuebingen High Altitude Ophthalmology (THAO study. METHODOLOGY/PRINCIPAL FINDINGS: A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3® was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m. Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL and AMS-cerebral (AMS-c scores; oxygen saturation (SpO₂ and heart rate (HR were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation changed significantly at high altitude compared to baseline (p<0.05 and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO₂ or HR. CONCLUSIONS/SIGNIFICANCE: Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO₂ and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS.

  3. Quantification of Optic Disc Edema during Exposure to High Altitude Shows No Correlation to Acute Mountain Sickness

    Science.gov (United States)

    Willmann, Gabriel; Fischer, M. Dominik; Schatz, Andreas; Schommer, Kai; Messias, Andre; Zrenner, Eberhart; Bartz-Schmidt, Karl U.; Gekeler, Florian

    2011-01-01

    Background The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO2) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO2 or HR. Conclusions/Significance Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO2 and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS. PMID:22069483

  4. Probabilistic acute risk assessment of cumulative exposure to organophosphorus and carbamate pesticides from dietary vegetables and fruits in Shanghai populations.

    Science.gov (United States)

    Li, Fan; Yuan, Yaqun; Meng, Pai; Wu, Min; Li, Shuguang; Chen, Bo

    2017-05-01

    Organophosphorus pesticides (OPs) and carbamate pesticides (CPs) are among the most widely used pesticides in China, playing a major role in protecting agricultural commodities. In this study, we determined the cumulative acute exposure to OPs and CPs of Shanghai residents from vegetables and fruits (VFs). The food consumption data were obtained from the Shanghai Food Consumption Survey (SHFCS) of 2012-14 including a total of 1973 participants aged 2-90 years. The pesticide residue data were obtained from the Shanghai monitoring programme during 2008-11 with 34 organophosphates and 11 carbamates analysed in a total of 5335 samples of VFs. A probabilistic approach was performed as recommended by the EFSA, using the optimistic model with non-detects set as zero and with processing factors (PFs) being used and the pessimistic model with non-detects replaced by limit of detection (LOD) and without PFs. We used the relative potency factor (RPF) method to normalise the various pesticides to the index compound (IC) of methamidophos and chlorpyrifos separately. Only in the pessimistic model using methamidophos as the IC was there was small risk of exposure exceeding the ARfD (3 µg kg(-)(1) bw day(-)(1)) in the populations of preschool children (0.029%), school-age children (0.022%) and adults (0.002%). There were no risk of exposure exceeding the ARfD of methamidophos in the optimistic model and of chlorpyrifos (100 µg kg(-)(1) bw day(-)(1)) in both optimistic and pessimistic models in all three populations. Considering the Chinese habits of overwhelmingly eating processed food (vegetables being cooked, and fruits being washed or peeled), we conclude that little acute risk was found for the exposure to VF-sourced OPs and CPs in Shanghai.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Aquatic toxicity testing of nanoparticles (NPs) is challenged by their dynamic behavior in test suspensions. The resulting difficulties in controlling and characterizing exposure concentrations are detrimental to the generation of concentration-response data needed for hazard identification of NPs...... concentrations during 1–3 h pulses than for 24–48 h continuous exposures. For AgNPs, preparation of test suspensions in medium 24 h before toxicity testing (aging) increased stability during the short-term pulses. In pulse tests, organisms were exposed to the test materials, AgNPs and CuONPs for 1, 2 and 3 h...... (observed after 48 h post-exposure) as 24 h continuous exposure, as evidenced by overlapping 95% confidence intervals of EC50-values. In the 21 d post-exposure period, no trends in mortality or body length were identified. AgNP and AgNO3 pulses had no effect on the number of moltings, days to first live...

  6. Moderate (2%, v/v Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Krutika T. Deshpande

    2016-01-01

    Full Text Available Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  7. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.

    Science.gov (United States)

    Deshpande, Krutika T; Liu, Shinlan; McCracken, Jennifer M; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N; Richard, Zachary C; O'Neil, Maura F; Pritchard, Michele T

    2016-01-06

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  8. Contributing Factors for Acute Illness/Injury from Childhood Pesticide Exposure in North Carolina, USA, 2007–2013

    Directory of Open Access Journals (Sweden)

    Nirmalla Barros

    2016-02-01

    Full Text Available Between 2007 and 2013, there were 685 events with evidence of a relationship between pesticide exposure and acute illness/injury among persons less than 18 years old in North Carolina (United States. Median age of children affected was 4.3 years (range: 0.2–17.9. Distribution by gender was similar across all age groups. One fatality and four high severity events were observed. The greatest proportion (42% of events had ocular exposures, followed by dermal (25% and inhalation (18% exposures. When more than one route of exposure occurred, dermal and ocular routes were the most common (46%. Almost all events took place indoors and 32 events involved contact with pets. Insecticides (53% and insect repellants (31% were the most frequent agents contributing to these events. Manual application of pesticides contributed to the greatest number of events (25%, while application through a pressurized can and use of a trigger pump were involved in 21% and 15% of events, respectively. Additional contributors were due to inappropriate storage of pesticides and improper use of the pesticide. These contributing factors can be removed or minimized if pesticides are stored outside the residence or out of the reach of children and pets, and adequate ventilation is ensured whenever pesticides are applied.

  9. Probabilistic acute dietary exposure assessments to captan and tolylfluanid using several European food consumption and pesticide concentration databases.

    Science.gov (United States)

    Boon, Polly E; Svensson, Kettil; Moussavian, Shahnaz; van der Voet, Hilko; Petersen, Annette; Ruprich, Jiri; Debegnach, Francesca; de Boer, Waldo J; van Donkersgoed, Gerda; Brera, Carlo; van Klaveren, Jacob D; Busk, Leif

    2009-12-01

    Probabilistic dietary acute exposure assessments of captan and tolylfluanid were performed for the populations of the Czech Republic, Denmark, Italy, the Netherlands and Sweden. The basis for these assessments was national databases for food consumption and pesticide concentration data harmonised at the level of raw agricultural commodity. Data were obtained from national food consumption surveys and national monitoring programmes and organised in an electronic platform of databases connected to probabilistic software. The exposure assessments were conducted by linking national food consumption data either (1) to national pesticide concentration data or (2) to a pooled database containing all national pesticide concentration data. We show that with this tool national exposure assessments can be performed in a harmonised way and that pesticide concentrations of other countries can be linked to national food consumption surveys. In this way it is possible to exchange or merge concentration data between countries in situations of data scarcity. This electronic platform in connection with probabilistic software can be seen as a prototype of a data warehouse, including a harmonised approach for dietary exposure modelling.

  10. Enhanced biosynthesis of quercetin occurs as A photoprotective measure in Lycopersicon esculentum mill. under Acute UV-B exposure

    Directory of Open Access Journals (Sweden)

    Abhilasha Shourie

    2014-06-01

    Full Text Available Lycopersicon esculentum respond to UV-B by enhanced synthesis of flavonoid quercetin, a strong antioxidant that helps the plants to well acclimatize to UV-B stress. Three weeks old plants of L. esculentum were subjected to acute UV-B irradiation for 20, 40 and 60 minutes daily until 28 days and analyzed for the morphological and biochemical changes. UV-B exposure for 40 and 60 minutes considerably affected the growth and biomass of L. esculentum. The leaves were deformed, developed chlorosis and abscised early as compared to the unexposed plants. Biomass declined by 35% and total chlorophyll decreased by 24.7% due to disintegration of chloroplasts. Enhancement was seen in the content of carotenoids, anthocyanins and total flavonoids by 15, 33.3 and 22.8%, respectively, which was attributed to the photoprotective role of these compounds as potential quenchers of excess excitation energy. Quercetin content decreased on UV-B exposure to 20 and 40 min, and thereafter increased significantly by 5.19% on 60 min of exposure. This pattern probably indicated that the over-expression of genes involved in its biosynthesis such as phenylalanine ammonia lyase (PAL, chalcone synthase (CHS, flavanone 3-hydroxylase (F3H and dihydroflavonol 4-reductase (DFR occurred only after certain threshold exposure (60 min, which could be the strategy for developing tolerance against UV-B stress in L. esculentum.

  11. Influence of acclimation and exposure temperature on the acute toxicity of cadmium to the freshwater snail Potamopyrgus antipodarum (Hydrobiidae)

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, V.; Forbes, V.E.; Depledge, M.H. (Odense Univ. (Denmark). Ecotoxicology Group)

    1994-09-01

    Forty-eight-hour acute toxicity tests were performed to determine the influence of acclimation temperature (5, 15, and 20 C) and exposure temperature (5, 15, and 20 C) on the toxicity of cadmium to the freshwater gastropod Potamopyrgus antipodarum. Mortality varied with cadmium concentration and treatment conditions, but did not conform to conventional sigmoid concentration-response relationships. Because the shapes of the concentration-response curves were treatment dependent, a nontraditional approach for data analysis was employed. Regardless of acclimation temperature, mortality increased with increasing exposure temperature, and at all exposure temperatures snails acclimated at 15 C were most susceptible to cadmium toxicity. Estimated LC50 values were within 1 to 4 mg Cd/L. Although the shapes of the concentration-response curves were different for each treatment, the slopes were generally quite steep, indicating a uniform response for the whole population. At a given Cd concentration, acclimation temperature and exposure temperature accounted for 57 and 40%, respectively, of the variation in mortality, and LC50s changed by a factor of four. The results indicate that changes in environmental variables can alter both the degree of response and the response distribution of a population, and that past as well as prevailing environmental conditions can influence organismic responses to toxicants.

  12. Clinical, cardiopulmonary and haemocytological effects of xylazine in goats after acute exposure to different environmental temperature and humidity conditions

    Directory of Open Access Journals (Sweden)

    E.G.M. Mogoa

    2000-07-01

    Full Text Available This study was carried out to assess the influence of xylazine administration on clinical, cardiopulmonary and haemocytological variables after acute exposure to different environmental conditions. Xylazine hydrochloride was administered intravenously at 0.1 mg/kg body mass to 6 clinically healthy, castrated male goats. All animals were exposed for 60 min to 3 sets of climatic conditions: 14 °C, 33% relative humidity; 24 °C, 55% RH, and 34 °C, 65% RH. The variables that were measured for a period of 60 min after xylazine administration were sedation, analgesia, salivation, urination, ventilation rate, heart-rate, mean arterial blood pressure, oesophageal temperature, haematocrit, mean corpuscular volume and mean corpuscular haemoglobin concentration. Xylazine induced sedation, analgesia, salivation and urination independently of the 3 environmental conditions. Environment had no influence on the onset, duration and recovery from sedation. In the 14 °C environment, xylazine resulted in a significant decrease in ventilation and heart-rate from baseline values. Significant changes in mean arterial blood pressure, haemoglobin concentration, mean corpuscular volume, haematocrit and red cell count were observed in the 3 environments. Total plasma protein was significantly altered at 24 °C and 34 °C. Acute exposure of goats to different environmental conditions had no significant influence on the clinical, cardiopulmonary and haemocytological variables. Physiological changes induced by xylazine were therefore independent of the environment.

  13. 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure.

    Science.gov (United States)

    Dordevic, Aimee L; Konstantopoulos, Nicky; Cameron-Smith, David

    2014-01-01

    Preadipocytes contribute to the inflammatory responses within adipose tissue. Whilst fatty acids are known to elicit an inflammatory response within adipose tissue, the relative contribution of preadipocytes and mature adipocytes to this is yet to be determined. We aimed to examine the actions of common dietary fatty acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes and differentiated mature adipocytes. Gene expression levels of key adipokines in 3T3-L1 preadipocytes and adipocytes were determined following incubation with palmitic acid, myristic acid or oleic acid and positive inflammatory control, lipopolysaccharide for 2 and 4 h. Inflammatory kinase signalling was assessed by analysis of nuclear factor-κB, p38-mitogen-activated protein kinase and c-jun amino-terminal kinase phosphorylation. Under basal conditions, intracellular monocyte chemoattractant protein-1 and interleukin-6 gene expression levels were increased in preadipocytes, whereas mature adipocytes expressed increased gene expression levels of leptin and adiponectin. Fatty acid exposure at 2 and 4 h increased both monocyte chemoattractant protein-1 and interleukin-6 gene expression levels in preadipocytes to greater levels than in mature adipocytes. There was an accompanying increase of inhibitor of κB-α degradation and nuclear factor-κB (p65) (Ser536) phosphorylation with fatty acid exposure in the preadipocytes only. The current study points to preadipocytes rather than the adipocytes as the contributors to both immune cell recruitment and inflammatory adipokine secretion with acute increases in fatty acids.

  14. Cellular distribution of uranium after acute exposure of renal epithelial cells: SEM, TEM and nuclear microscopy analysis

    Science.gov (United States)

    Carrière, Marie; Gouget, Barbara; Gallien, Jean-Paul; Avoscan, Laure; Gobin, Renée; Verbavatz, Jean-Marc; Khodja, Hicham

    2005-04-01

    The major health effect of uranium exposure has been reported to be chemical kidney toxicity, functional and histological damages being mainly observed in proximal tubule cells. Uranium enters the proximal tubule as uranyl-bicarbonate or uranyl-citrate complexes. The aim of our research is to investigate the mechanisms of uranium toxicity, intracellular accumulation and repartition after acute intoxication of rat renal proximal tubule epithelial cells, as a function of its chemical form. Microscopic observations of renal epithelial cells after acute exposure to uranyl-bicarbonate showing the presence of intracellular precipitates as thin needles of uranyl-phosphate localized in cell lysosomes have been published. However the initial site of precipitates formation has not been identified yet: they could either be formed outside the cells before internalization, or directly inside the cells. Uranium solubility as a function and initial concentration was specified by ICP-MS analysis of culture media. In parallel, uranium uptake and distribution in cell monolayers exposed to U-bicarbonate was investigated by nuclear microprobe analyses. Finally, the presence of uranium precipitates was tested out by scanning electron microscopic observations (SEM), while extracellular and/or intracellular precipitates were observed on thin sections of cells by transmission electron microscopy (TEM).

  15. Cellular distribution of uranium after acute exposure of renal epithelial cells: SEM, TEM and nuclear microscopy analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carriere, Marie [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: carriere@drecam.cea.fr; Gouget, Barbara [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gallien, Jean-Paul [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Avoscan, Laure [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gobin, Renee [Laboratoire d' imagerie cellulaire et moleculaire, DBJC/SBFM/LTMD, CEA/Saclay, 91191 Gif sur Yvette (France); Verbavatz, Jean-Marc [Laboratoire d' imagerie cellulaire et moleculaire, DBJC/SBFM/LTMD, CEA/Saclay, 91191 Gif sur Yvette (France); Khodja, Hicham [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)

    2005-04-01

    The major health effect of uranium exposure has been reported to be chemical kidney toxicity, functional and histological damages being mainly observed in proximal tubule cells. Uranium enters the proximal tubule as uranyl-bicarbonate or uranyl-citrate complexes. The aim of our research is to investigate the mechanisms of uranium toxicity, intracellular accumulation and repartition after acute intoxication of rat renal proximal tubule epithelial cells, as a function of its chemical form. Microscopic observations of renal epithelial cells after acute exposure to uranyl-bicarbonate showing the presence of intracellular precipitates as thin needles of uranyl-phosphate localized in cell lysosomes have been published. However the initial site of precipitates formation has not been identified yet: they could either be formed outside the cells before internalization, or directly inside the cells. Uranium solubility as a function and initial concentration was specified by ICP-MS analysis of culture media. In parallel, uranium uptake and distribution in cell monolayers exposed to U-bicarbonate was investigated by nuclear microprobe analyses. Finally, the presence of uranium precipitates was tested out by scanning electron microscopic observations (SEM), while extracellular and/or intracellular precipitates were observed on thin sections of cells by transmission electron microscopy (TEM)

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

    Science.gov (United States)

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

    2010-11-01

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

  17. Impact of acute kidney injury exposure period among liver transplantation patients

    Science.gov (United States)

    2013-01-01

    Background Acute kidney injury is a common complication of liver transplantation. In this single-centre retrospective observational study, we investigated the impact of acute kidney disease on liver recipient survival. Methods The study population consisted of patients who underwent a liver engraftment between January 2002 and November 2006, at a single transplantation centre in São Paulo, Brazil. Acute kidney injury diagnosis and staging were according to the recommendations of the Acute Kidney Injury Network and consisted of scanning the daily serum creatinine levels throughout the hospital stay. Patients requiring renal replacement therapy prior to transplantation, those who developed acute kidney injury before the procedure or those receiving their second liver graft were excluded from the study. Results A total of 444 liver transplantations were performed during the study period, and 129 procedures (29%) were excluded. The remaining 315 patients constituted the study population. In 207 procedures, the recipient was male (65%). The mean age of the population was 51 years. Cumulative incidence of acute kidney injury within 48 h, during the first week after transplantation, and throughout the hospital stay was 32, 81 and 93%, respectively. Renal replacement therapy was required within a week after the transplantation in 31 procedures (10%), and another 17 (5%) required replacement therapy after that period. Mean follow-up period was 2.3 years. Time in days from acute kidney injury diagnosis to initiation of replacement therapy or reaching serum creatinine peak was associated with lower overall survival even when adjusted for significant potential confounders (HR 1.03; 95% CI 1.01, 1.05; p=0.002). Overall, patients experiencing acute kidney injury lasting for a week or more before initiation of replacement therapy experienced a threefold increase in risk of death (HR 3.02; 95% CI 2.04, 4.46; ptransplantation is remarkably frequent and has a substantial impact

  18. The effects of acute stress exposure on neural correlates of Pavlovian conditioning with monetary gains and losses

    Directory of Open Access Journals (Sweden)

    Andrea H Lewis

    2014-05-01

    Full Text Available Pavlovian conditioning involves the association of an inherently neutral stimulus with an appetitive or aversive outcome, such that the neutral stimulus itself acquires reinforcing properties. Across species, this type of learning has been shown to involve subcortical brain regions such as the striatum and the amygdala. It is less clear, however, how the neural circuitry involved in the acquisition of Pavlovian contingencies in humans is affected by acute stress. In the current study, we investigate the effect of acute stress exposure on Pavlovian conditioning using monetary reinforcers. Participants underwent a partial reinforcement conditioning procedure in which neutral stimuli were paired with high and low magnitude monetary gains and losses. A between-subjects design was used, such that half of the participants were exposed to cold stress while the remaining participants were exposed to a no stress control procedure. Cortisol measurements and subjective ratings were used as measures of stress. We observed an interaction between stress, valence and magnitude in the ventral striatum, with the peak in the putamen. More specifically, the stress group exhibited an increased sensitivity to magnitude in the gain domain. This effect was driven by those participants who experienced a larger increase in circulating cortisol levels in response to the stress manipulation. Taken together, these results suggest that acute stress can lead to individual differences in circulating cortisol levels which influence brain regions involved in associative learning such as the ventral striatum.

  19. The effects of acute stress exposure on striatal activity during Pavlovian conditioning with monetary gains and losses.

    Science.gov (United States)

    Lewis, Andrea H; Porcelli, Anthony J; Delgado, Mauricio R

    2014-01-01

    Pavlovian conditioning involves the association of an inherently neutral stimulus with an appetitive or aversive outcome, such that the neutral stimulus itself acquires reinforcing properties. Across species, this type of learning has been shown to involve subcortical brain regions such as the striatum and the amygdala. It is less clear, however, how the neural circuitry involved in the acquisition of Pavlovian contingencies in humans, particularly in the striatum, is affected by acute stress. In the current study, we investigate the effect of acute stress exposure on Pavlovian conditioning using monetary reinforcers. Participants underwent a partial reinforcement conditioning procedure in which neutral stimuli were paired with high and low magnitude monetary gains and losses. A between-subjects design was used, such that half of the participants were exposed to cold stress while the remaining participants were exposed to a no stress control procedure. Cortisol measurements and subjective ratings were used as measures of stress. We observed an interaction between stress, valence, and magnitude in the ventral striatum, with the peak in the putamen. More specifically, the stress group exhibited an increased sensitivity to magnitude in the gain domain. This effect was driven by those participants who experienced a larger increase in circulating cortisol levels in response to the stress manipulation. Taken together, these results suggest that acute stress can lead to individual differences in circulating cortisol levels which influence the striatum during Pavlovian conditioning with monetary reinforcers.

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

    Directory of Open Access Journals (Sweden)

    Yunji Hwang

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

  1. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    Science.gov (United States)

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  2. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

    Science.gov (United States)

    Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

    2013-05-07

    Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

  3. Intermittent diazepam and continuous phenobarbital to treat recurrence of febrile seizures: a systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Masuko Alice Hatsue

    2003-01-01

    Full Text Available Convulsions triggered by fever are the most common type of seizures in childhood, and 20% to 30% of them have recurrence. The prophylactic treatment is still controversial, so we performed a systematic review to find out the effectiveness of continuous phenobarbital and intermittent diazepam compared to placebo for febrile seizure recurrence. METHOD: Only randomized, double-blind, placebo-controlled trials were analyzed. The recurrence of febrile seizure was assessed for each drug. RESULTS: Ten eligible clinical trials were included. Febrile seizure recurrence was smaller in children treated with diazepam or phenobarbital than in placebo group. Prophylaxis with either phenobarbital or diazepam reduces recurrences of febrile seizures. The studies were clinical, methodological, and statistically heterogeneous. CONCLUSION: The effectiveness of phenobarbital and diazepam could not be demonstrated because clinical trials were heterogeneous, and the recommendation for treatment recurrence should rely upon the experience of the assistant physician yet.

  4. Exploring uncoupling proteins and antioxidant mechanisms under acute cold exposure in brains of fish.

    Directory of Open Access Journals (Sweden)

    Yung-Che Tseng

    Full Text Available Exposure to fluctuating temperatures accelerates the mitochondrial respiration and increases the formation of mitochondrial reactive oxygen species (ROS in ectothermic vertebrates including fish. To date, little is known on potential oxidative damage and on protective antioxidative defense mechanisms in the brain of fish under cold shock. In this study, the concentration of cellular protein carbonyls in brain was significantly increased by 38% within 1 h after cold exposure (from 28 °C to 18 °C of zebrafish (Danio rerio. In addition, the specific activity of superoxide dismutase (SOD and the mRNA level of catalase (CAT were increased after cold exposure by about 60% (6 h and by 60%-90% (1 and 24 h, respectively, while the specific glutathione content as well as the ratio of glutathione disulfide to glutathione remained constant and at a very low level. In addition, cold exposure increased the protein level of hypoxia-inducible factor (HIF by about 50% and the mRNA level of the glucose transporter zglut3 in brain by 50%-100%. To test for an involvement of uncoupling proteins (UCPs in the cold adaptation of zebrafish, five UCP members were annotated and identified (zucp1-5. With the exception of zucp1, the mRNA levels of the other four zucps were significantly increased after cold exposure. In addition, the mRNA levels of four of the fish homologs (zppar of the peroxisome proliferator-activated receptor (PPAR were increased after cold exposure. These data suggest that PPARs and UCPs are involved in the alterations observed in zebrafish brain after exposure to 18°C. The observed stimulation of the PPAR-UCP axis may help to prevent oxidative damage and to maintain metabolic balance and cellular homeostasis in the brains of ectothermic zebrafish upon cold exposure.

  5. Acute exposure to high environmental ammonia (HEA) triggers the emersion response in the green shore crab.

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    Zimmer, Alex M; Wood, Chris M

    2017-02-01

    The physiological effects of high environmental ammonia (HEA) exposure have been well documented in many aquatic species. In particular, it has recently been demonstrated that exposure to ammonia in fish leads to a similar hyperventilatory response as observed during exposure to hypoxia. In littoral crabs, such as the green crab (Carcinus maenas), exposure to severe hypoxia triggers an emersion response whereby crabs escape hypoxia to breathe air. We hypothesized that exposure to HEA in green crabs would lead to a similar behavioural response which is specific to ammonia. Using an experimental arena containing a rock bed onto which crabs could emerse, we established that exposure to HEA (4mmol/l NH4HCO3) for 15min triggers emersion in crabs. In experiments utilizing NaHCO3 controls and NH4HCO3 injections, we further determined that emersion was triggered specifically by external ammonia and was independent of secondary acid-base or respiratory disturbances caused by HEA. We then hypothesized that emersion from HEA provides a physiological benefit, similar to emersion from hypoxia. Exposure to 15min of HEA without emersion (no rock bed present) caused significant increases in arterial haemolymph total ammonia (Tamm), pH, and [HCO3(-)]. When emersion was allowed, arterial haemolymph Tamm and [HCO3(-)] increased, but no alkalosis developed. Moreover, emersion decreased haemolymph partial pressure of NH3 relative to crabs which could not emerse. Overall, we demonstrate a novel behavioural response to HEA exposure in crabs which we propose may share similar mechanistic pathways with the emersion response triggered by hypoxia.

  6. Renal excretion in coho salmon (Oncorhynchus kisutch) after acute exposure to 3-trifluoromethyl-4-nitrophenol

    Science.gov (United States)

    Hunn, J.B.; Allen, J.L.

    1975-01-01

    COHO SALMON (ONCORHYNCHUS KISUTCH) EXPOSED TO AN ACUTE, SUBLETHAL CONCENTRATION OF 3-TRIFLUOROMETHLY 1-4 NITROPHENOL (TFM) EXHIBITED AN INCREASED OUTPUT OF URINE WHEN COMPARED WITH CONTROLS, BUT THE URINARY EXCRETION OF NA, K, CA, MG AND C1 WAS NOT AFFECTED. ABOUT 35 TIMES MORE CONJUGATED TFM THAN FREE TFM WAS EXCRETED DURING THE 24-HOUR STUDY PERIOD.

  7. Effect of Acute Noise Exposure on Salivary Cortisol: A Randomized Controlled Trial.

    Science.gov (United States)

    Pouryaghoub, Gholamreza; Mehrdad, Ramin; Valipouri, Alireza

    2016-10-01

    Cardiovascular adverse effects are interesting aspects of occupational noise exposure. One possible mechanism of these effects is an alternation in hypothalamic-pituitary-adrenal axis. Our aim was to measure salivary cortisol response to relatively high-intensity noise exposure in a controlled randomized trial study. We exposed 50 male volunteers to 90 dBA noise for 20 minutes and compared their level of salivary cortisol with 50 non-exposed controls. Salivary samples obtained before and after exposure. Before intervention means (SD) salivary cortisol level were 3.24 (0.47)ng/ml and 3.25 (0.41)ng/ml for exposed and non-exposed groups respectively. Mean salivary cortisol level increased to 4.17 ng/mlafter intervention in exposure group. This increment was statistically significant (P=0.00). Mean salivary cortisol level of the non-exposed group had statistically non-significant decrement after this period (0.2 ng/ml). The difference between salivary cortisol level of non-exposed and exposed groups after the intervention was statistically significant. Noise exposure may affect the hypothalamic-pituitary-adrenal axis activity, and this may be one of the mechanisms of noise exposure cardiovascular effects.

  8. Mimicking exposures to acute and lifetime concentrations of inhaled silver nanoparticles by two different in vitro approaches

    Directory of Open Access Journals (Sweden)

    Fabian Herzog

    2014-08-01

    Full Text Available In the emerging market of nano-sized products, silver nanoparticles (Ag NPs are widely used due to their antimicrobial properties. Human interaction with Ag NPs can occur through the lung, skin, gastrointestinal tract, and bloodstream. However, the inhalation of Ag NP aerosols is a primary concern. To study the possible effects of inhaled Ag NPs, an in vitro triple cell co-culture model of the human alveolar/airway barrier (A549 epithelial cells, human peripheral blood monocyte derived dendritic and macrophage cells together with an air–liquid interface cell exposure (ALICE system was used in order to reflect a real-life exposure scenario. Cells were exposed at the air–liquid interface (ALI to 0.03, 0.3, and 3 µg Ag/cm2 of Ag NPs (diameter 100 nm; coated with polyvinylpyrrolidone: PVP. Ag NPs were found to be highly aggregated within ALI exposed cells with no impairment of cell morphology. Furthermore, a significant increase in release of cytotoxic (LDH, oxidative stress (SOD-1, HMOX-1 or pro-inflammatory markers (TNF-α, IL-8 was absent. As a comparison, cells were exposed to Ag NPs in submerged conditions to 10, 20, and 30 µg Ag/mL. The deposited dose per surface area was estimated by using a dosimetry model (ISDD to directly compare submerged vs ALI exposure concentrations after 4 and 24 h. Unlike ALI exposures, the two highest concentrations under submerged conditions promoted a cytotoxic and pro-inflammatory response after 24 h. Interestingly, when cell cultures were co-incubated with lipopolysaccharide (LPS, no synergistic inflammatory effects were observed. By using two different exposure scenarios it has been shown that the ALI as well as the suspension conditions for the lower concentrations after 4 h, reflecting real-life concentrations of an acute 24 h exposure, did not induce any adverse effects in a complex 3D model mimicking the human alveolar/airway barrier. However, the highest concentrations used in the ALI setup, as well

  9. Transient activation of microglia following acute alcohol exposure in developing mouse neocortex is primarily driven by BAX-dependent neurodegeneration.

    Science.gov (United States)

    Ahlers, Katelin E; Karaçay, Bahri; Fuller, Leah; Bonthius, Daniel J; Dailey, Michael E

    2015-10-01

    Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in the developing brain in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice, we found that alcohol-induced neuroapoptosis in the neocortex is closely correlated in space and time with the appearance of activated microglia near dead cells. The timing and molecular pattern of microglial activation varied with the level of cell death. Although microglia rapidly mobilized to contact and engulf late-stage apoptotic neurons, apoptotic bodies temporarily accumulated in neocortex, suggesting that in severe cases of alcohol toxicity the neurodegeneration rate exceeds the clearance capacity of endogenous microglia. Nevertheless, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, there was a transient increase in expression of pro-inflammatory factors, TNFα and IL-1β, after severe (5 g/kg) but not moderate (3 g/kg) EtOH levels. Alcohol-induced microglial activation and pro-inflammatory factor expression were largely abolished in BAX null mice lacking neuroapoptosis, indicating that microglial activation is primarily triggered by apoptosis rather than the alcohol. Therefore, acute alcohol exposure in the developing neocortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain.

  10. Maternal benzene exposure during pregnancy and risk of childhood acute lymphoblastic leukemia: a meta-analysis of epidemiologic studies.

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    Yanfeng Zhou

    Full Text Available The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.Relevant studies up to September 1st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR with 95% confidence interval (CI for ALL was 1.25 (1.09, 1.45 for solvent, 1.23 (1.02, 1.47 for paint, 1.42 (1.10, 1.84 for petroleum exposure, and 0.99 (0.93, 1.06 for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.

  11. Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera).

    Science.gov (United States)

    Burden, Christina M; Elmore, Christopher; Hladun, Kristen R; Trumble, John T; Smith, Brian H

    2016-05-01

    A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium-contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony.

  12. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash.

    Science.gov (United States)

    Marchini, T; Magnani, N D; Paz, M L; Vanasco, V; Tasat, D; González Maglio, D H; Alvarez, S; Evelson, P A

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3h. The onset of an adaptive response was observed at 5h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.

  13. Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Enrrico Bloise

    2017-02-01

    Full Text Available Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB. As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C, increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5 were injected (i.p. with PolyI:C (5 mg/kg or 10 mg/kg or vehicle (saline. [3H]digoxin (P-gp substrate was injected (i.v. 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus, and fetal brains were collected. Results: PolyI:C exposure (4h significantly elevated maternal plasma IL-6 (P<0.001 and increased [3H]digoxin accumulation in the fetal brain (P<0.05. In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.

  14. Oxidative DNA damage after acute exposure to arsenite and monomethylarsonous acid in biomethylation-deficient human cells.

    Science.gov (United States)

    Orihuela, Ruben; Kojima, Chikara; Tokar, Erik J; Person, Rachel J; Xu, Yuanyuan; Qu, Wei; Waalkes, Michael P

    2013-07-01

    The carcinogen inorganic arsenic (iAs) undergoes biomethylation (BMT) in some cells. The methylated metabolite, monomethylarsonous (MMA(3+)), may cause oxidative DNA damage (ODD). With chronic iAs exposure, BMT-competent cells show ODD while BMT-deficient do not. To further define these events, we studied ODD produced by acute iAs or MMA(3+) in the BMT-deficient human prostate cell line, RWPE-1. ODD, measured by the immuno-spin trapping method, was assessed after exposure to iAs or MMA(3+) alone, with the arsenic BMT inhibitor selenite or after glutathione (GSH) depletion. The expression of oxidative stress-related genes (HO-1, SOD-1, SOD-2, Nrf2 and Keap-1) was also assessed. Exposure to iAs at 24 h (0-20 µM), stimulated ODD only at levels above the LC50 of a 48 h exposure (17 µM). If iAs induced ODD, it also activated oxidative stress-related genes. Selenium did not alter iAs-induced ODD. MMA(3+) at 24 h (0-0.5 µM) caused ODD at levels below the LC50 of a 48 h exposure (1.5 µM), which were greatly increased by GSH depletion but not selenite. MMA(3+) induced ODD at levels not activating oxidant stress response genes. Overall, iAs induced ODD in BMT-deficient cells only at toxic levels. MMA(3+) caused ODD at non-toxic levels, independently of cellular BMT capacity and in a fashion not requiring further BMT.

  15. Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy.

    Science.gov (United States)

    Ashtarinezhad, Azadeh; Panahyab, Ataollah; Shaterzadeh-Oskouei, Shahrzad; Khoshniat, Hessam; Mohamadzadehasl, Baharak; Shirazi, Farshad H

    2016-09-05

    Biospectroscopic investigations have attracted attention of both the clinicians and basic sciences researchers in recent years. Scientists are discovering new areas for FTIR biospectroscopy applications in medicine. The aim of this study was to measure the possibility of FTIR-MSP application for the recognition and detection of fetus abnormalities after exposure of pregnant mouse to phenobarbital (PB) and levamisole (LEV) alone or in combination. PB is one of the most widely used antiepileptic drugs (AEDs), with sedative and hypnotic effects. When used by pregnant women, it is known to be a teratogenic agent. LEV is an antihelminthic drug with some applications in immune-deficiency as well as colon cancer therapy. Four groups of ten pregnant mice were selected for the experiments as follows: one control group received only standard diet, one group was injected with 120mg/kg of BP, one group was injected with 10mg/kg of LEV, and the last group was treated simultaneously with both BP and LEV at the above mentioned doses. Drugs administration was performed on gestation day 9 and fetuses were dissected on pregnancy day 15. Each dissected fetus was fixed, dehydrated and embedded in paraffin. Sections of liver (10μm) were prepared from control and treated groups by microtome and deparaffinized with xylene. The spectra were taken by FTIR-MSP in the region of 4000-400cm(-1). All the spectra were normalized based on amide II band (1545cm(-1)) after baseline correction of the entire spectrum, followed by classification using PCA, ANN and SVM. Both morphological and spectral changes were shown in the treated fetuses as compared to the fetuses in the control group. While cleft palate and C-R elongation were seen in PB injected fetuses, developmental retardation was mostly seen in the LEV injected group. Biospectroscopy revealed that both drugs mainly affected the cellular lipids and proteins, with LEV causing more changes in amide I and lipid regions than PB. Application of

  16. Age-dependence of responses to acute ozone exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gunnison, A.F.; Weideman, P.A.; Sobo, M.; Koenig, K.L.; Chen, L.C. (Institute of Environmental Medicine, New York University Medical Center, New York (United States))

    1992-04-01

    In the study reported here, we have extended our initial investigation to include the influence of animal age on temporal aspects of pulmonary AA metabolism and several other responses to brief exposures to 1 ppm ozone. Rats of discrete ages ranging from 13 days to 16 weeks were exposed to 1 ppm ozone or to air for 2, 4, or 6 hr. Immediately following exposure the lungs were lavaged with six consecutive volumes of phosphate-buffered saline and the acellular fluid from the first lavage volume recovered was analyzed for its content of prostaglandin E2 (PGE2), protein, and lactate dehydrogenase. Leukocytes recovered by lavage were quantitated and characterized by viability and percentage of polymorphonuclear (PMN) cells. Several lines of evidence verified that PGE2 was produced by the lung as a consequence of ozone exposure and that its concentration in the fluid from the first lavage was a reasonably good index of pulmonary AA metabolism to prostanoids. We also demonstrated that the lavage process itself stimulates the lung, resulting in increased AA metabolism to prostanoids that were recovered in the second and following lavage volumes. The time course of PGE2 production by the ozone-exposed lung varied considerably with animal age. Neonatal rats 13 days of age were the most sensitive to ozone stimulation. At 2 hr of exposure, PGE2 concentration in the first lung lavage of these animals peaked at values approximately two orders of magnitude above controls and then decreased sharply with continued exposure. Adults and older neonates (18 days of age) were much less responsive to 2-hr exposures; however, continued exposure of these rats for up to 6 hr resulted in increasing PGE2 concentration in the first lung lavage. Other responses showed various degree of age dependence.

  17. Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection.

    Science.gov (United States)

    Mathieson, Sean R; Livingstone, Vicki; Low, Evonne; Pressler, Ronit; Rennie, Janet M; Boylan, Geraldine B

    2016-10-01

    Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Post-phenobarbital seizures showed significantly lower amplitude (pphenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Effect of high-dose phenobarbital on oxidative stress in perinatal asphyxia: an open label randomized controlled trial.

    Science.gov (United States)

    Gathwala, Geeta; Marwah, Ashish; Gahlaut, Veena; Marwah, Poonam

    2011-08-01

    To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia. Open label, Randomized controlled trial. Neonatal intensive care unit of a tertiary care teaching hospital. 72 full term inborn neonates with severe birth asphyxia. Neonates were randomized to Study (phenobarbital) group and Control group. The infants in the study group received phenobarbital infusion (40 mg/kg) within first two hours of life while babies in the control group did not receive any phenobarbital. Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy. A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde. 60 neonates were followed up at 1 month of age when a detailed neurological examination was done. Four neonates in the study group and six neonates in the control group died during the study. Two neonates in the study group were lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group. The neurological outcome at one month follow up was found to be comparable between the two groups. Phenobarbital (40 mg/kg) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life.

  19. Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

    Science.gov (United States)

    Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

    2016-12-01

    Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng‑1 bee), or one of two low doses (0.377 or 0.091 ng‑1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

  20. Acute non-cancer mortality excess after polychlorinated biphenyls and polychlorinated dibenzofurans mixed exposure from contaminated rice oil: Yusho.

    Science.gov (United States)

    Kashima, Saori; Yorifuji, Takashi; Tsuda, Toshihide

    2011-08-15

    In Japan in 1968, rice-oil contaminated by polychlorinated biphenyls and polychlorinated dibenzofurans caused severe food poisoning, termed "Yusho" (oil disease). Several previous studies attempted to evaluate the effects targeting officially-certified Yusho patients. However, these studies have several limitations such as the left-truncated nature of the registry or residual confounding arising from the referent population selection. We thus conducted an area-based standardized mortality ratios (SMRs) study using vital statistics. A severely affected area (Tamanoura area) was adopted as the exposure group, with a reference population from Nagasaki prefecture in Kyushu, which included the Tamanoura. A large number of residents in Tamanoura were exposed to the rice-oil (28% of all the certified cases as of 2009). We estimated SMRs of non-cancer and cancer diseases for the years 1968-2002. Shortly after the exposure, SMRs of all causes, diabetes mellitus, cardiovascular disease, pneumonia/bronchitis, and bronchus/lung cancer were elevated. In particular, SMRs of heart disease were 1.97 [95% confidence intervals (CI): 1.09-3.56] in 1968, 2.05 (95% CI: 1.16-3.60) in 1969, and 1.89 (95% CI: 1.05-3.41) in 1975. However, we did not observe clear increase in SMRs more than 10 years after the exposure. This study provides further evidence in Yusho, especially on acute effects on non-cancer mortality. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Associations of acute exposure to fine and coarse particulate matter and mortality among older people in Tokyo, Japan.

    Science.gov (United States)

    Yorifuji, Takashi; Kashima, Saori; Doi, Hiroyuki

    2016-01-15

    Recent studies have reported adverse health effects of short-term exposure to coarse particles independent of particulate matter less than 2.5 μm in diameter (PM2.5), but evidence in Asian countries is limited. We therefore evaluated associations between short-term exposure to particulate matter (PM) and mortality among older people in Tokyo, Japan. We used a time-stratified, case-crossover design. Study participants included 664,509 older people (≥65 years old) in the 23 urbanized wards of the Tokyo Metropolitan Government, who died between January 2002 and December 2013. We obtained PM2.5 and suspended particulate matter (SPM; PMrespiratory diseases; for example, both pollutants were positively associated with increased risk of all-cause mortality even after simultaneous adjustment for each pollutant: OR of 1.006 (95% CI: 1.003, 1.009) for PM2.5 and 1.016 (95% CI: 1.011, 1.022) for PM7-2.5. Even below concentrations stipulated by the Japanese air quality guidelines for PM2.5 and SPM (PM7), we observed adverse health effects. This study provides further evidence that acute exposure to PM2.5 and coarse particles is associated with increased risk of mortality among older people. Rigorous evaluation of air quality guidelines for daily average PM2.5 and larger particles should be continued.

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

    Science.gov (United States)

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

    2008-08-01

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

  3. Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze.

    Science.gov (United States)

    Samuelson, Elizabeth E W; Chen-Wishart, Zachary P; Gill, Richard J; Leadbeater, Ellouise

    2016-12-13

    Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng(-1) bee), or one of two low doses (0.377 or 0.091 ng(-1)) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

  4. Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

    Science.gov (United States)

    2010-09-01

    The "Bradypnea" stage was generally preceded by episodes of ataxic or dyspneic breathing. Seizures and convulsions typically continued during...acute agent exposure. These included oro-facial movements (indicative of immoderate secretion), mild degree of dystonia/ ataxia , and a short period of...periods of acute cholinergic effects (mucoid-salivary secretion, dystonia, ataxia , tremors and fasciculations) were seen shortly after intoxication

  5. Strain- and context-dependent behavioural responses of acute alarm substance exposure in zebrafish.

    Science.gov (United States)

    Quadros, Vanessa A; Silveira, Ariane; Giuliani, Giulie S; Didonet, Fernanda; Silveira, Alessandra S; Nunes, Mauro E; Silva, Tális O; Loro, Vania L; Rosemberg, Denis B

    2016-01-01

    We investigate the behavioural responses of wild type (WT) and leopard (leo) zebrafish elicited by alarm substances of conspecifics at three contexts: during the exposure period (Experiment 1); after exposure, in habituation to novelty (Experiment 2); or after exposure, in the light-dark preference test (Experiment 3), and analyse their influence on pigment response. During the exposure, leo showed decreased vertical drifts, increased number and duration of erratic movements, while WT had increased erratic movements and latency to enter the top. In the novel tank, we observed that angular velocity decreased in WT exposed to alarm substance, which also presented increased fear responses. Contrastingly, leo increased the number of entries and time in top, indicating differences in habituation profile. Alarm substance increased the number of erratic movements in the light-dark test, but elicited different responses between strains in scototaxis, latency to enter the dark compartment and risk assessment episodes. Moreover, the body colour of zebrafish did not change after alarm substance exposure. Principal component analyses suggest that burst swimming, anxiety-like behaviours, and locomotion/exploration were the components that most accounted for total variances of Experiments 1, 2, and 3, respectively. We conclude that chemical cue from conspecifics triggers strain- and context-dependent responses.

  6. Acute respiratory distress syndrome following cutaneous exposure to Lysol: a case report.

    Science.gov (United States)

    Liu, Y Y; Lu, C C; Perng, R P

    1999-12-01

    Lysol (mixed cresols) is a brand of popular detergent commonly used to disinfect toilets and floors in Taiwan. We report a patient with acute respiratory failure immediately following chemical burns caused by skin contact with Lysol solution. On admission, chest radiography showed bilateral diffuse pulmonary infiltrates and an arterial blood gas analysis disclosed hypoxemia refractory to a high concentration of oxygen by inhalation. Under the impression of acute respiratory distress syndrome, our patient was admitted to the intensive care unit for respiratory care. Poor clinical improvement was noted, despite aggressive respiratory therapy. High-dose steroid therapy (hydrocortisone 30 mg/kg/day) was administered from the seventh day after mechanical ventilation began and the ratio of arterial partial pressure of oxygen to fractional concentration of oxygen in inspired gas improved thereafter. The amount of steroid was gradually tapered to the maintenance dose and the patient was successfully weaned from the ventilator after a 93-day course of mechanical ventilation.

  7. Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

    Directory of Open Access Journals (Sweden)

    Shiliang Li

    Full Text Available BACKGROUND: Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1 to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2 to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation. METHODS: Rats received saline or ethanol (3.45 g/kg, ip. We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively. RESULTS: Ethanol administration resulted in decreased load-dependent (-34 ± 9% and load-independent (-33 ± 12% contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47 ± 10%, elongated QT-interval (+38 ± 4%, enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial

  8. Acute short-term dim light exposure can lower muscle strength endurance

    Institute of Scientific and Technical Information of China (English)

    Arnold G. Nelson; Joke Kokkonen; Megan Mickenberg

    2015-01-01

    Background:Since it has been shown that spending 18 h under dim light conditions can result in reduced handgrip endurance, it was questioned whether or not a shorter exposure to dim light (i.e., 1 h) would have similar influence upon muscular endurance. Therefore this study compared the number of weighted knee extension lifts that could be done after spending 1 h in either dim or bright light. Methods:Participants (5 women, 11 men, college students 19-26 years) performed knee extension lifts to exhaustion with a load approximating 40%of their body weight. The lifts to exhaustion were measured immediately following 1 h of exposure to each of the following three con-ditions:dark (DL), room light (RL), and room light plus 5 mg melatonin (RLM). A minimum of 48 h separated each condition, and all par-ticipants started the exposures in a rested fed condition. Results:Average (±SD) number of knee extension lifts for RL (62.0 ± 22.0) was significantly ( p<0.05) greater than DL (51.4 ± 14.7) and RLM (57.8 ± 22.9). The number of RLM knee extension lifts was not significantly different from DL. Exposure to 1 h of dim light immediately prior to activity can result in a reduction in thigh muscle endurance. The decline in performance to short-term dim light exposure was similar to that found following longer-term exposure. Conclusion: It appears that light intensity can influence muscle endurance, however, at this time this effect cannot be directly related to endogenous melatonin production.

  9. Assessment of toxicologic interactions resulting from acute inhalation exposure to sulfuric acid and ozone mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Schlesinger, R.B.; Zelikoff, J.T.; Chen, L.C.; Kinney, P.L. (Department of Environmental Medicine, New York University Medical Center, NY (United States))

    1992-08-01

    Studies examining effects of air pollutants often use single compounds, while real world' exposures are to more than one chemical. Thus, it is necessary to assess responses following inhalation of chemical mixtures. Rabbits were exposed for 3 hr to sulfuric acid aerosol at 0, 50, 75, or 125 micrograms/m3 in conjunction with ozone at 0, 0.1, 0.3, or 0.6 ppm, following which broncho-pulmonary lavage was performed. Various pulmonary response endpoints related to general cytotoxicity and macrophage function were examined. In addition, a goal of the study was to define an improved approach to the analysis of data sets involving binary pollutant mixtures. Results were evaluated using analysis of variance with multiple linear contrasts to determine the significance of any effect in the pollutant-exposed groups compared to sham control animals and to assess the type, and extent, of any toxicological interaction between acid and ozone. Interaction was considered to occur when the effects of combined exposure were either significantly greater or less than additive. Pollutant exposures had no effect on lavage fluid levels of lactate dehydrogenase, prostaglandins E2 and F2 alpha, nor on the numbers, viability, or types of immune cells recovered by lavage. Phagocytic activity of macrophages was depressed at the two highest acid levels and at all levels of ozone. Superoxide production by stimulated macrophages was depressed by acid exposure at the two highest concentrations, while ozone alone had no effect. Significant antagonistic interaction was observed following exposure to mixtures of 75 or 125 micrograms/m3 acid with 0.1 or 0.3 ppm ozone. The activity of tumor necrosis factor elicited from stimulated macrophages was depressed by acid at 75 and 125 micrograms/m3 while ozone had no effect. Exposure to mixtures of 125 micrograms/m3 acid with 0.3 or 0.6 ppm ozone resulted in synergistic interaction.

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

    Science.gov (United States)

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    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 {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] 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-arachidonylglycerol (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

  11. Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants.

    Science.gov (United States)

    Smit, Elisa; Odd, David; Whitelaw, Andrew

    2013-08-13

    Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals. To determine the effect of postnatal administration of phenobarbital on the risk of IVH, neurodevelopmental impairment or death in preterm infants. We used the search strategy of the Neonatal Collaborative Review Group. The original review author (A Whitelaw) was an active trialist in this area and had personal contact with many groups in this field. He handsearched journals from 1976 (when cranial computed tomography (CT) scanning started) to October 2000; these included: Pediatrics, Journal of Pediatrics, Archives of Disease in Childhood, Pediatric Research, Developmental Medicine and Child Neurology, Acta Paediatrica, European Journal of Pediatrics, Neuropediatrics, New England Journal of Medicine, Lancet and British Medical Journal. We searched the National Library of Medicine (USA) database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, 2012, Issue 10) through to 31 October 2012. We did not limit the searches to the English language, as long as the article included an English abstract. We read identified articles in the original language or translated. We included randomised or quasi-randomised controlled trials in which phenobarbital was given to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birthweight below 1500 g or respiratory failure. Adequate determination of IVH by ultrasound or CT was also required. In addition to details of patient selection and control of bias, we extracted the details of the administration of phenobarbital. We

  12. Purification and immunochemical detections of ?-naphthoflavone- and phenobarbital-induced avian cytochrome P450 enzymes

    Science.gov (United States)

    Brown, R.L.; Levi, P.E.; Hodgson, E.; Melancon, M.J.

    1996-01-01

    Livers from mallards (Anas platyrhynchos) were treated with either -naphthoflavone (50 mg/kg) or phenobarbital (70 mg/kg). Purification of induced hepatic cytochrome P450 was accomplished using both DEAE and hydroxyapatite columns, as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis separation. Polyclonal antibodies to these proteins were then produced in young male New Zealand White rabbits. ?-naphthoflavone (?NF)- and phenobarbital(PB)-treated red-winged blackbird, screech owl, European starling and lesser scaup liver microsomes were analyzed in western blots for species cross-reactivity. Although all four of these avian species exhibited cross-reactivity with antibodies to ?NF-induced mallard P450, all but the lesser scaup revealed a protein of higher molecular weight than that of the ?NF-induced mallard. In addition, only the lesser scaup exhibited cross-reactivity with the anti-PB-induced mallard P450 antibodies.

  13. Exacerbation of benign familial neonatal epilepsy induced by massive doses of phenobarbital and midazolam.

    Science.gov (United States)

    Maeda, Tomoki; Shimizu, Miki; Sekiguchi, Kazuhito; Ishii, Atsushi; Ihara, Yukiko; Hirose, Shinichi; Izumi, Tatsuro

    2014-08-01

    Barbiturates and benzodiazepines are the first-line anticonvulsants for neonatal seizures. However, in immature brains, those drugs may lead to paradoxical neuronal excitation. A patient with benign familial neonatal epilepsy developed epileptic encephalopathy after massive doses of phenobarbital that were followed by a continuous infusion of midazolam on postnatal day 3. Electroencephalography revealed rhythmic delta activity in clusters with migrating epileptic foci. After discontinuation of both drugs, the patient's consciousness promptly improved and her electroencephalography normalized on postnatal day 5. This baby developed persistent electroencephalographic seizures due to massive doses of phenobarbital and midazolam. Clinicians should be aware of this anticonvulsant-induced paradoxical neuronal excitation and the uncoupling phenomenon, especially in individuals with benign familial neonatal epilepsy, who have low seizure thresholds. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Effects of midazolam and phenobarbital on brain oxidative reactions induced by pentylenetetrazole in a convulsion model.

    Science.gov (United States)

    Arai, Yukiko; Maeda, Shigeru; Higuchi, Hitoshi; Tomoyasu, Yumiko; Shimada, Masahiko; Miyawaki, Takuya

    2012-04-01

    Brain oxidative reactions are involved in epilepsy as well as neurodegenerative diseases. In animal convulsion models, some anticonvulsants have been found to suppress oxidative reactions associated with convulsions. However, the effect of anticonvulsants on brain oxidative reactions has not fully been clarified. Midazolam and phenobarbital are often used as an intravenous anesthetic, and are known to have anticonvulsive effect, but antioxidative effect of these drugs has rarely been studied. Thus, the purpose of this study was to evaluate the effects of these drugs on the degree of convulsions and brain oxidative reactions in an animal convulsion model. In order to evaluate brain oxidative reactions, we measured malondialdehyde (MDA) level and heme oxygenase (HO)-1 mRNA expression level in the brain of mice in a convulsion model generated by a single injection of pentylenetetrazole (PTZ). We evaluated the effects of midazolam and phenobarbital on the degree of PTZ-induced convulsions and on the changes in brain MDA level and HO-1 mRNA expression level. After PTZ injection, severe convulsions were observed in all mice. MDA level was increased in the whole brain, while HO-1 mRNA expression level was increased only in the hippocampus. Both midazolam and phenobarbital prevented the convulsions and suppressed the increase in both MDA level and HO-1 mRNA expression level in the brain. In this study, both midazolam and phenobarbital suppressed PTZ-induced MDA and HO-1 reactions in the brain, suggesting that these drugs inhibit brain oxidative reactions in a convulsion model.

  15. Bumetanide is not capable of terminating status epilepticus but enhances phenobarbital efficacy in different rat models.

    Science.gov (United States)

    Töllner, Kathrin; Brandt, Claudia; Erker, Thomas; Löscher, Wolfgang

    2015-01-05

    In about 20-40% of patients, status epilepticus (SE) is refractory to standard treatment with benzodiazepines, necessitating second- and third-line treatments that are not always successful, resulting in increased mortality. Rat models of refractory SE are instrumental in studying the changes underlying refractoriness and to develop more effective treatments for this severe medical emergency. Failure of GABAergic inhibition is a likely cause of the development of benzodiazepine resistance during SE. In addition to changes in GABAA receptor expression, trafficking, and function, alterations in Cl(-) homeostasis with increased intraneuronal Cl(-) levels may be involved. Bumetanide, which reduces intraneuronal Cl(-) by inhibiting the Cl(-) intruding Na(+), K(+), Cl(-) cotransporter NKCC1, has been reported to interrupt SE induced by kainate in urethane-anesthetized rats, indicating that this diuretic drug may be an interesting candidate for treatment of refractory SE. In this study, we evaluated the effects of bumetanide in the kainate and lithium-pilocarpine models of SE as well as a model in which SE is induced by sustained electrical stimulation of the basolateral amygdala. Unexpectedly, bumetanide alone was ineffective to terminate SE in both conscious and anesthetized adult rats. However, it potentiated the anticonvulsant effect of low doses of phenobarbital, although this was only seen in part of the animals; higher doses of phenobarbital, particularly in combination with diazepam, were more effective to terminate SE than bumetanide/phenobarbital combinations. These data do not suggest that bumetanide, alone or in combination with phenobarbital, is a valuable option in the treatment of refractory SE in adult patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach.

    Science.gov (United States)

    Marsot, Amélie; Brevaut-Malaty, Véronique; Vialet, Renaud; Boulamery, Audrey; Bruguerolle, Bernard; Simon, Nicolas

    2014-08-01

    Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated. Routine clinical pharmacokinetic data were retrospectively collected from 48 neonates and infants (weight: 0.7-10 kg; patient's postnatal age: 0-206 days; GA: 27-42 weeks) treated with phenobarbital, who were administered as intravenous or suspension by oral routes and hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg (3.1-10.6 mg/kg) per day was administered by 30-min infusion or by oral route. Pharmacokinetic analysis was performed using a nonlinear mixed-effect population model software). Data were modelled with an allometric pharmacokinetic model, using three-fourths scaling exponent for clearance (CL). The population typical mean [per cent relative standard error (%RSE)] values for CL, apparent volume of distribution (Vd ) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg (15%) and 48.9% (22%), respectively. The interindividual variability of CL, Vd , F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and 7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in neonates and infants was estimated. The dose should be increased when switching from intravenous to oral administration. © 2013 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.

  17. Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats.

    Science.gov (United States)

    Shenoy, A K; Miyahara, J T; Swinyard, E A; Kupferberg, H J

    1982-08-01

    The 1.5-benzodiazepine (clobazam), the 1,4-benzodiazepine (diazepam), and two nonbenzodiazepine antiepileptic drugs (phenobarbital and valproate) were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that clobazam and valproate exhibit a wider range of experimental anticonvulsant activity than either diazepam or phenobarbital. Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine). Clobazam is effective by the MES test in rats only in doses that exceed the median minimal toxic dose. Phenobarbital is effective against all of the above tests, but minimal toxic doses must be employed to prevent strychnine seizures. Diazepam, on the other hand, is effective in nontoxic doses against seizures induced by Metrazol, bicuculline, and picrotoxin, but protects animals from maximal electroshock and strychnine seizures only when given in toxic doses. When compared on the basis of protective indices (PI = TD50/ED50) calculated from intraperitoneal data, the PIs for clobazam were 1.6 to 13 times higher than those for diazepam. Overall, except for the MES test in rats, the PIs for clobazam were from 1.5 to 44 times higher than those for any of the other three substances. With respect to the MES test in rats, the PI for clobazam was 10.8 times higher than that for diazepam; however, the PIs for phenobarbital and valproate were 3.5 and 4.4 times higher, respectively, than that for clobazam. These data suggest that the spectrum of anticonvulsant activity for the 1,5-benzodiazepine (clobazam) is superior to that for the 1,4-benzodiazepine (diazepam). Also, the broad experimental profile of anticonvulsant activity of clobazam agrees well with its reported broad clinical efficacy.

  18. Phenytoin induced chorea in a pediatric patient: An interaction between phenytoin, phenobarbital and clobazam

    Directory of Open Access Journals (Sweden)

    Manish Barvaliya

    2011-01-01

    Full Text Available A 3-year-old female patient developed chorea possibly due to an interaction between phenytoin, phenobarbital and clobazam used for generalized tonic clonic seizures. Phenytoin withdrawal resulted in recovery within 24 hours. Post reaction computerized tomography (CT-scan of brain was normal. Combined use of anti-seizure drugs and interactions between them may be responsible for the reaction. Therapeutic drug monitoring is important while prescribing two or more anti-seizure drugs.

  19. Electrocardiographic and autonomic effects of acute particulate matter (PM) exposure in a rat model of cardiomyopathy

    Science.gov (United States)

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiac disease--especially heart failure (HF). Cardiomyopathy is the most common cause of heart failure. The mechanisms ...

  20. Antioxidant responses and bioaccumulation in green-lipped mussels (Perna viridis) under acute tributyltin chloride exposure.

    Science.gov (United States)

    Chen, Hai-Gang; Jia, Xiao-Ping; Cai, Wen-Gui; Lin, Qin; Ma, Sheng-Wei

    2011-11-01

    Green-lipped mussels (Perna viridis) were exposed to waterborne tributyltin chloride (TBTCl) at different concentrations (0.2, 0.4 and 0.8 μg L(-1)) for up to 72 h. Accumulated TBTCl in Perna viridis correlated linearly with the exposure concentrations of 0.2 μg L(-1)(R(2) = 0.772), 0.4 μg L(-1)(R(2) = 0.952), and 0.8 μg L(-1)(R(2) = 0.909). The results of superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) all decreased in gill tissues after 24 h of exposure, but the hepatic SOD and the hepatic GPx showed either little or no effect on exposure of TBTCl solutions. Analysis using the Spearman rank correlation coefficient showed the hepatic GPx activity appeared to have a significant negative correlativity (R(s) = -0.42) with the exposed TBTCl concentrations, and the hepatic MDA was significantly negatively correlated (R(s) = -0.33) with the tissue TBTCl concentrations. Conversely, a significant positive correlation (R(s) = 0.60) was shown between the gill MDA contents and exposure time. This study illustrates oxyradical scavenger GPx best correlated with stress level of pollutants among the various antioxidant parameters.

  1. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Rats.

    Science.gov (United States)

    Smith, Catherine A; Farmer, Kyle; Lee, Hyunmin; Holahan, Matthew R; Smith, Jeffrey C

    2015-10-27

    Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl) phthalate (DEHP) disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

  2. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl Phthalate in Rats

    Directory of Open Access Journals (Sweden)

    Catherine A. Smith

    2015-10-01

    Full Text Available Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl phthalate (DEHP disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

  3. Acute Atrazine Exposure has Lasting Effects on Chemosensory Responses to Food Odors in Crayfish (Orconectes virilis).

    Science.gov (United States)

    Belanger, Rachelle M; Mooney, Lauren N; Nguyen, Hung M; Abraham, Noor K; Peters, Tyler J; Kana, Maria A; May, Lauren A

    2016-02-01

    The herbicide atrazine is known to impact negatively olfactory-mediated behaviors in aquatic animals. We have shown that atrazine exposure has deleterious effects on olfactory-mediated behavioral responses to food odors in crayfish; however, recovery of chemosensory abilities post-atrazine exposure has not been investigated. We examined whether crayfish (Orconectes virilis) recovered chemosensory abilities after a 96-h exposure to sublethal, environmentally relevant concentrations of 80 ppb (µg/L) atrazine. Following treatment, we analyzed the ability of the crayfish to locate a food source using a Y-maze with one arm containing fish-flavored gelatin and the other containing unflavored gelatin. We compared the time spent in the food arm of the Y-maze, near the food source, as well as moving and walking speed of control and atrazine-treated crayfish. We also compared the number of crayfish that handled the food source and the amount of food consumed. Following 24-, 48-, and 72-h recovery periods in fresh water, behavioral trials were repeated to determine if there was any observable recovery of chemosensory-mediated behaviors. Atrazine-treated crayfish spent less time in the food arm, at the odor source, and were less successful at finding the food odor source than control crayfish for all times tested. Additionally, atrazine-treated crayfish consumed less fish-flavored than control crayfish; however, treatment did not affect locomotion. Overall, we found that crayfish are not able to recover chemosensory abilities 72 h post-atrazine exposure. Because crayfish rely heavily on their chemosensory abilities to acquire food, the negative impacts of atrazine exposure could affect population size in areas where atrazine is heavily applied.

  4. [Retrospective Cytogenetic Dose Evaluation. I. Chromosome Aberration Levels in Remote Periods after Acute External Exposure in Different Situations].

    Science.gov (United States)

    Nugs, V Yu; Khvostunov, I K; Goloub, E V; Kozlova, M G; Nadejina, N M; Galstian, I A

    2015-01-01

    Cytogenetic analysis of peripheral blood lymphocyte cultures of 22 persons was performed in remote terms after acute external γ-, γ-β- or γ-neutron irradiation as a result of various accidents using the classical me- thod. The initial dose estimates were obtained using physical calculations, the method of measuring the EPR signal in tooth enamel, according to haematological and/or cytogenetic parameters. The purpose of this study was to obtain evidence about the state of the lymphocyte chromosome apparatus of people approxi- mately 17-50 years after an accidental radiation exposure. In general, elevated levels of chromosome aberra- tions were detected. An average correlation was observed between the atypical chromosome frequency and absorbed dose. It is proposed to use the obtained results in the future to explore the possibility of retrospective dose evaluation on the basis of a special computer program.

  5. Histopathological Alterations of Hybrid Walking Catfish (Clarias macrocephalus x Clarias gariepinus in Acute and Subacute Cadmium Exposure

    Directory of Open Access Journals (Sweden)

    Nuntiya Pantung

    2008-01-01

    Full Text Available Histopathological alterations occur in the gills, livers and kidneys of 3-month old hybrid walking catsfich (Clarias macrocephalus x Clarias gariepinos after acute and subacute cadmium exposure in water, and after intraperitoneal injection.The 96-h LC50 for cadmium in recirculation open systems was 13.6 mg/l, and the 96-h LD50 1.6 mg/kg of fish. Light microscopic studies were carried out in gills, livers and kidneys. Gill alterations included an increased number of chloride cells, breakdown of the pillar cells and edema of the epithelial cells. In the liver there was blood conjestion in sinusoids and swelling of hepatocytes. The kidneys showed vacuolation and necrosis of proximal tubular cells.

  6. Changes of autonomic nervous system function in healthy young men during initial phase at acute high-altitude exposure

    Institute of Scientific and Technical Information of China (English)

    Qin Jun; Huang Lan; Tian Kaixin; Yu Shiyong; Yu Yang; Long Min

    2008-01-01

    Objective: To investigate the changes of autonomic nervous system (ANS) function during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level male residents were studied in Chengdu plain and then Tibet plateau. Heart rate variability (HRV), cold pressor test (CPT), resting heart rate (HR) and blood pressure (BP) were measured at baseline (560 m altitude) and in 2 to 4 d after arriving at Tibet plateau (3 675 m altitude) to assess the ANS function. Results: Compared with baseline, on day 2 in Tibet the standard deviation of normal to normal intervals (SDNN), high-frequency (HF) power, total power (TP), root mean square of delta RR (rMSSD), percentage of delta RR>50 ms (PNN50), normalized high-frequency (Hfnu) and fractal dimension (FD) decreased significantly (SDNN, HF,TP P<0.01, rMSSD, PNNs0, Hfnu, FD P<0.05), while the normalized low-frequency (Lfnu) and LF/HF increased significantly (P<0.01). During day 3-4 in Tibet, SDNN, rMSSD, HF, TP and Hfnu tended to rebound while Lfnu and LF/HF decreased towards baseline day by day. In addition, in Tibet the increase in systolic pressure (SP) and diastolic pressure (DP) during CPT decreased significantly (P<0.01, 0.05), but resting HR increased compared with baseline (P<0.01). Conclusion: ANS modulation is generally blunted, and the relatively predominant sympathetic control is enhanced originally, then it reverts to the sea level states gradually during the initial days of acute high-altitude exposure.

  7. Acute Meteorite Dust Exposure and Pulmonary Inflammation - Implications for Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness [1-3]" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure [4]. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles [1]. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern [5]. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive [2, 6-9], and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz [6]. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary

  8. Epidemiology of adult acute myeloid leukemia: Impact of exposures on clinical phenotypes and outcomes after therapy.

    Science.gov (United States)

    Finn, Laura; Sproat, Lisa; Heckman, Michael G; Jiang, Liuyan; Diehl, Nancy N; Ketterling, Rhett; Tibes, Raoul; Valdez, Ricardo; Foran, James

    2015-12-01

    An increased risk of adult myeloid leukemia (AML) has recently been associated with lifestyle and environmental exposures, including obesity, smoking, some over the counter medications, and rural/farm habitats in case control studies. The association of these exposures with AML cytogenetic categories, outcomes after therapy, and overall survival is unknown. Relevant exposures were evaluated in a cohort of 295 consecutive AML patients diagnosed and treated at Mayo Clinic in Florida and Arizona. Standard cytogenetic risk categories were applied and reviewed in a central cytogenetic laboratory. The association of epidemiologic exposures with cytogenetic risk, complete remission after therapy, and overall survival was evaluated using logistic and Cox regression models. A significant association between obesity and intermediate-abnormal cytogenetics was identified (OR: 1.94, P=0.025). Similarly, those with secondary AML were more likely to have poor risk (OR: 2.55, P<0.001) and less likely to have intermediate normal (OR: 0.48, P=0.003) cytogenetics. In multivariate analysis, overall survival was improved for patients ≥ 60 years receiving intensive (RR: 0.21, P<0.001) and non-intensive therapy (RR: 0.40, P<0.001 compared to no treatment, and was lower for users of tobacco (RR 1.39, P=0.032), and those with poor risk cytogenetics (RR: 3.96, P=0.002) or poor performance status (RR: 1.69, P<0.001). Furthermore, an association between statin use at the time of diagnosis (OR: 2.89, P=0.016) and increased complete remission after intensive chemotherapy was identified, while prior solid organ transplantation was associated with significantly lower complete remission rate after therapy (OR: 0.10, P=0.035). Our results provide evidence that specific epidemiologic exposures, including obesity, are significantly associated with unique AML cytogenetic risk categories and response to therapy. This supports a link between patient lifestyles, clinical exposures, and leukemogenesis

  9. Pulmonary Inflammatory Responses To Acute Meteorite Dust Exposures - Implications For Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive, and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative

  10. C57BL/6 Substrains Exhibit Different Responses to Acute Carbon Tetrachloride Exposure: Implications for Work Involving Transgenic Mice.

    Science.gov (United States)

    McCracken, Jennifer M; Chalise, Prabhakar; Briley, Shawn M; Dennis, Katie L; Jiang, Lu; Duncan, Francesca E; Pritchard, Michele T

    2017-07-07

    Biological differences exist between strains of laboratory mice, and it is becoming increasingly evident that there are differences between substrains. In the C57BL/6 mouse, the primary substrains are called 6J and 6N. Previous studies have demonstrated that 6J and 6N mice differ in response to many experimental models of human disease. The aim of our study was to determine if differences exist between 6J and 6N mice in terms of their response to acute carbon tetrachloride (CCl4) exposure. Mice were given CCl4 once and were euthanized 12 to 96 h later. Relative to 6J mice, we found that 6N mice had increased liver injury but more rapid repair. This was because of the increased speed with which necrotic hepatocytes were removed in 6N mice and was directly related to increased recruitment of macrophages to the liver. In parallel, enhanced liver regeneration was observed in 6N relative to 6J mice. Hepatic stellate cell activation occurred earlier in 6N mice, but there was no difference in matrix metabolism between substrains. Taken together, these data demonstrate specific and significant differences in how the C57BL/6 substrains respond to acute CCl4, which has important implications for all mouse studies utilizing this model.

  11. Cellular metabolic, stress, and histological response on exposure to acute toxicity of endosulfan in tilapia (Oreochromis mossambicus).

    Science.gov (United States)

    Kumar, Neeraj; Sharma, Rupam; Tripathi, Gayatri; Kumar, Kundan; Dalvi, Rishikesh S; Krishna, Gopal

    2016-01-01

    Endosulfan is one of the most hazardous organochlorines pesticides responsible for environmental pollution, as it is very persistent and shows bio-magnification. This study evaluated the impact of acute endosulfan toxicity on metabolic enzymes, lysozyme activities, heat shock protein (Hsp) 70 expression, and histopathology in Tilapia (Oreochromis mossambicus). Among the indicators that were induced in dose dependent manner were the enzymes of amino acid metabolism (serum alanine aminotransferase and aspartate aminotransferase), carbohydrate metabolism (serum lactate dehydrogenase), pentose phosphate pathway (Glucose-6-phosphate dehydrogenase) as well as lysozyme and Hsp70 in liver and gill, while liver and gill Isocitrate dehydrogenase (TCA cycle enzyme) and marker of general energetics (Total adenosine triphosphatase) were inhibited. Histopathological alterations in gill were clubbing of secondary gill lamellae, marked hyperplasia, complete loss of secondary lamellae and atrophy of primary gill filaments. Whereas in liver, swollen hepatocyte, and degeneration with loss of cellular boundaries were distinctly noticed. Overall results clearly demonstrated the unbalanced metabolism and damage of the vital organs like liver and gill in Tilapia due to acute endosulfan exposure.

  12. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures. (ACR)

  13. The Acute Effects of Single Exposures to White Phosphorus Smoke in Rats and Guinea Pigs

    Science.gov (United States)

    1980-09-01

    males and three females per dose, were used. The animals, weighing between 200 and 300 grams, were fasted overnight prior to desing . The liquid used in...min_’u n, nfinc animals died during exposure. The sunivine animal had respirator, problems far i houlr and t!-_- gradually recovered. 3. Hematology and...ATTN: MAJ Borges APO San Francisco 96328) Defense- Technical Information Center ATTN: DTIC-DDA-2 2 Commander Cau;icon Station, Building 5 2d Infantry

  14. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    Act of 1979, as amended, Title 50, U.S.C., App. 2401 et seq. Violations of these export laws are subject to severe criminal penalties ...DTRA-TR-16-059 DISTRIBUTION A. Approved for public release: distribution is unlimited. Exposure to burn and radiation elicit epithelial cell death in...villus cells, promoting early cell death before migration is complete (Carter et al., 2014, Wolf et al., 1999). This response is fast and strong but

  15. Estimating the acute health effects of coarse particulate matter accounting for exposure measurement error.

    Science.gov (United States)

    Chang, Howard H; Peng, Roger D; Dominici, Francesca

    2011-10-01

    In air pollution epidemiology, there is a growing interest in estimating the health effects of coarse particulate matter (PM) with aerodynamic diameter between 2.5 and 10 μm. Coarse PM concentrations can exhibit considerable spatial heterogeneity because the particles travel shorter distances and do not remain suspended in the atmosphere for an extended period of time. In this paper, we develop a modeling approach for estimating the short-term effects of air pollution in time series analysis when the ambient concentrations vary spatially within the study region. Specifically, our approach quantifies the error in the exposure variable by characterizing, on any given day, the disagreement in ambient concentrations measured across monitoring stations. This is accomplished by viewing monitor-level measurements as error-prone repeated measurements of the unobserved population average exposure. Inference is carried out in a Bayesian framework to fully account for uncertainty in the estimation of model parameters. Finally, by using different exposure indicators, we investigate the sensitivity of the association between coarse PM and daily hospital admissions based on a recent national multisite time series analysis. Among Medicare enrollees from 59 US counties between the period 1999 and 2005, we find a consistent positive association between coarse PM and same-day admission for cardiovascular diseases.

  16. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

  17. Acute ozone exposure increases plasma prostaglandin F2 alpha in ozone-sensitive human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Schelegle, E.S.; Adams, W.C.; Giri, S.N.; Siefkin, A.D.

    1989-07-01

    Twenty O/sub 3/-sensitive and /sup 2/O O/sub 3/-nonsensitive subjects participated in a study to investigate the effects of disparate O/sub 3/ sensitivity on plasma prostaglandin F2 alpha responses consequent to exposure to ambient O3 concentrations. Subjects were selected from a pool of 75 normal healthy college-aged males who had been previously exposed to 0.35 ppm O3 for 1 h at an exercising VE of 60 L/min. The selection criterion used was the observed decrement in FEV1 after the O/sub 3/ exposure: O/sub 3/-sensitive, FEV1 decrement greater than 24%; O/sub 3/-nonsensitive, FEV1 decrement less than 11%. Each subject was exposed to filtered air and to 0.20 and 0.35 ppm O/sub 3/ for 80 min while exercising at a VE of 50 L/min. These experimental protocols were divided into two 40-min sessions separated by a period of 4 to 10 min. PGF2 alpha, FVC, FEV1, and FEF25-75 were evaluated before, during, and after each protocol. SGaw and Vtg were measured before and after each protocol. Plasma PGF2 alpha was significantly increased in the O/sub 3/-sensitive group during and after the 0.35-ppm O/sub 3/ exposure.

  18. Partial recovery of erythrocyte glycogen in diabetic rats treated with phenobarbital

    Directory of Open Access Journals (Sweden)

    da-Silva C.A.

    1997-01-01

    Full Text Available Erythrocytes may play a role in glucose homeostasis during the postprandial period. Erythrocytes from diabetic patients are defective in glucose transport and metabolism, functions that may affect glycogen storage. Phenobarbital, a hepatic enzyme inducer, has been used in the treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM, increasing the insulin-mediated glucose disposal. We studied the effects of phenobarbital treatment in vivo on glycemia and erythrocyte glycogen content in control and alloxan-diabetic rats during the postprandial period. In control rats (blood glucose, 73 to 111 mg/dl in femoral and suprahepatic veins the erythrocyte glycogen content was 45.4 ± 1.1 and 39.1 ± 0.8 µg/g Hb (mean ± SEM, N = 4-6 in the femoral artery and vein, respectively, and 37.9 ± 1.1 in the portal vein and 47.5 ± 0.9 in the suprahepatic vein. Diabetic rats (blood glucose, 300-350 mg/dl presented low (P<0.05 erythrocyte glycogen content, i.e., 9.6 ± 0.1 and 7.1 ± 0.7 µg/g Hb in the femoral artery and vein, respectively, and 10.0 ± 0.7 and 10.7 ± 0.5 in the portal and suprahepatic veins, respectively. After 10 days of treatment, phenobarbital (0.5 mg/ml in the drinking water did not change blood glucose or erythrocyte glycogen content in control rats. In diabetic rats, however, it lowered (P<0.05 blood glucose in the femoral artery (from 305 ± 18 to 204 ± 45 mg/dl and femoral vein (from 300 ± 11 to 174 ± 48 mg/dl and suprahepatic vein (from 350 ± 10 to 174 ± 42 mg/dl, but the reduction was not sufficient for complete recovery. Phenobarbital also stimulated the glycogen synthesis, leading to a partial recovery of glycogen stores in erythrocytes. In treated rats, erythrocyte glycogen content increased to 20.7 ± 3.8 µg/g Hb in the femoral artery and 30.9 ± 0.9 µg/g Hb in the suprahepatic vein (P<0.05. These data indicate that phenobarbital activated some of the insulin-stimulated glucose metabolism steps which were

  19. Impact of acute exposure to WTC dust on ciliated and goblet cells in lungs of rats.

    Science.gov (United States)

    Cohen, Mitchell D; Vaughan, Joshua M; Garrett, Brittany; Prophete, Colette; Horton, Lori; Sisco, Maureen; Ghio, Andrew; Zelikoff, Judith; Lung-chi, Chen

    2015-01-01

    Clinical studies and the World Trade Center (WTC) Health Registry have revealed increases in the incidence of chronic (non-cancer) lung disorders among first responders (FR) who were at Ground Zero during the initial 72 h after the collapse. Our previous analyses of rats exposed to building-derived WTC dusts using exposure scenarios/levels that mimicked FR mouth-breathing showed that a single WTC dust exposure led to changes in expression of genes whose products could be involved in the lung ailments, but few other significant pathologies. We concluded that rather than acting as direct inducers of many of the FR health effects, it was more likely inhaled WTC dusts instead may have impacted on toxicities induced by other rescue-related co-pollutants present in Ground Zero air. To allow for such effects to occur, we hypothesized that the alkaline WTC dusts induced damage to the normal ability of the lungs to clear inhaled particles. To validate this, rats were exposed on two consecutive days (2 h/d, by intratracheal inhalation) to WTC dust (collected 12-13 September 2001) and examined over a 1-yr period thereafter for changes in the presence of ciliated cells in the airways and hyperplastic goblet cells in the lungs. WTC dust levels in the lungs were assessed in parallel to verify that any changes in levels of these cells corresponded with decreases in host ability to clear the particles themselves. Image analyses of the rat lungs revealed a significant decrease in ciliated cells and increase in hyperplastic goblet cells due to the single series of WTC dust exposures. The study also showed there was only a nominal non-significant decrease (6-11%) in WTC dust burden over a 1-yr period after the final exposure. These results provide support for our current hypothesis that exposure to WTC dusts caused changes in airway morphology/cell composition; such changes could, in turn, have led to potential alterations in the clearance/toxicities of other pollutants inhaled

  20. The bumetanide prodrug BUM5, but not bumetanide, potentiates the antiseizure effect of phenobarbital in adult epileptic mice.

    Science.gov (United States)

    Erker, Thomas; Brandt, Claudia; Töllner, Kathrin; Schreppel, Philipp; Twele, Friederike; Schidlitzki, Alina; Löscher, Wolfgang

    2016-05-01

    The loop diuretic bumetanide has been reported to potentiate the antiseizure activity of phenobarbital in rodent models of neonatal seizures, most likely as a result of inhibition of the chloride importer Na-K-Cl cotransporter isoform 1 (NKCC1) in the brain. In view of the intractability of neonatal seizures, the preclinical findings prompted a clinical trial in neonates on bumetanide as an add-on to phenobarbital, which, however, had to be terminated because of ototoxicity and lack of efficacy. We have recently shown that bumetanide penetrates only poorly into the brain, so that we developed lipophilic prodrugs such as BUM5, the N,N-dimethylaminoethylester of bumetanide, which penetrate more easily into the brain and are converted to bumetanide. In the present study, we used a new strategy to test whether BUM5 is more potent than bumetanide in potentiating the antiseizure effect of phenobarbital. Adult mice were made epileptic by pilocarpine, and the antiseizure effects of bumetanide, BUM5, and phenobarbital alone or in combination were determined by the maximal electroshock seizure threshold test. In nonepileptic mice, only phenobarbital exerted seizure threshold-increasing activity, and this was not potentiated by the NKCC1 inhibitors. In contrast, a marked potentiation of phenobarbital by BUM5, but not bumetanide, was determined in epileptic mice. Thus, bumetanide is not capable of potentiating phenobarbital's antiseizure effect in an adult mouse model, which, however, can be overcome by using the prodrug BUM5. These data substantiate that BUM5 is a promising tool compound for target validation and proof-of-concept studies on the role of NKCC1 in brain diseases. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  1. MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor.

    Science.gov (United States)

    Shizu, Ryota; Shindo, Sawako; Yoshida, Takemi; Numazawa, Satoshi

    2012-01-01

    Constitutive androstane receptor (CAR) is a nuclear receptor that regulates the transcription of target genes, including CYP2B and 3A. Phenobarbital activates CAR, at least in part, in an AMP-activated protein kinase (AMPK)-dependent manner. However, the precise mechanisms underlying phenobarbital activation of AMPK are still unclear. In the present study, it was demonstrated that phenobarbital administration to mice decreases hepatic miR-122, a liver-enriched microRNA involved in both hepatic differentiation and function. The time-course change in the phenobarbital-mediated down-regulation of miR-122 was inversely correlated with AMPK activation. Phenobarbital decreased primary miR-122 to approximately 25% of the basal level as early as 1 h and suppressed transactivity of mir-122 promoter in HuH-7 cells, suggesting that the down-regulation occurred at the transcriptional level. AMPK activation by metformin or 5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside had no evident effect on miR-122 levels. An inhibitory RNA specific for miR-122 increased activated AMPK and CAR-mediated trancactivation of the phenobarbital-responsive enhancer module in HepG2 cells. Conversely, the reporter activity induced by the ectopic CAR was almost completely suppressed by co-transfection with the miR-122 mimic RNA. GFP-tagged CAR was expressed in the cytoplasm in addition to the nucleus in the majority of HuH-7 cells in which miR-122 was highly expressed. Co-transfection of the mimic or the inhibitor RNA for miR-122 further increased or decreased, respectively, the number of cells that expressed GFP-CAR in the cytoplasm. Taken together, these results suggest that phenobarbital-mediated down-regulation of miR-122 is an early and important event in the AMPK-dependent CAR activation and transactivation of its target genes.

  2. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

    Science.gov (United States)

    Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

    2016-04-01

    Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs.

  3. [Case report of acute death on the 7th day due to exposure to the vapor of the insecticide chlorfenapyr].

    Science.gov (United States)

    Hoshiko, Michiko; Naito, Shinji; Koga, Mitsuaki; Mori, Mihoko; Hara, Kunio; Ishitake, Tatsuya

    2007-04-01

    We present the case of a 55-year-old male agricultural worker who complained of severe general fatigue and hyperperspiration after exposure to an insecticide vapor. He worked in a tea plantation and used chlorfenapyr, a broad spectrum for harmful insects, without any protective mask or clothes. After one day of insecticide spray work, he gradually began to complain of general fatigue, hyperperspiration, nausea and vomiting. At first, he was diagnosed as being dehydrated and was treated with fluid replacement therapy. Although he received this conservative therapy, there was no effect on the above mentioned symptoms. On the 7th day of the onset of his symptoms, his consciousness level deteriorated rapidly and body temperature exceeded 40 degrees C. No cerebral vascular disease or meningitis was observed. Finally, he died despite intensive care. The findings of the clinical course and laboratory data suggest a clinical diagnosis of acute pesticide poisoning due to exposure to chlorfenapyr vapor. We suggest that agricultural workers should use this insecticide with caution and sufficient protective gear.

  4. Early changes in gene expression induced by acute UV exposure in leaves of Psychotria brachyceras, a bioactive alkaloid accumulating plant.

    Science.gov (United States)

    do Nascimento, Naíla Cannes; Menguer, Paloma Koprovski; Sperotto, Raul Antonio; de Almeida, Márcia Rodrigues; Fett-Neto, Arthur Germano

    2013-05-01

    UV-B radiation can damage biomolecules, such as DNA, RNA, and proteins, halting essential cellular processes; this damage is partly due to ROS generation. Plant secondary metabolites may protect against UV-B. Psychotria brachyceras Müll. Arg. (Rubiaceae), a subtropical shrub, produces brachycerine, a monoterpene indole alkaloid mainly accumulated in leaf tissues, which displays antioxidant and antimutagenic activities. Exposure of P. brachyceras cuttings to UV-B radiation significantly increases leaf brachycerine concentration. It has been suggested that this alkaloid might contribute to protection against UV-B damage both through its quenching activity on ROS and as UV shield. To identify differentially expressed genes of P. brachyceras in response to UV-B and investigate a possible influence of this stimulus on putative brachycerine-related genes, suppressive subtractive hybridization was applied. Complementary DNA from UV-B-treated leaves for 24 h was used as tester, and cDNA from untreated leaves, as driver. After BLASTX alignments, 134 sequences matched plant genes. Using quantitative RT-PCR, selected genes potentially related to brachycerine showed significant increases in transcription after UV-B exposure: tryptophan decarboxylase, ACC oxidase, UDP-glucose glucosyltransferase, lipase, and serine/threonine kinase. Results suggest a possible involvement of brachycerine in acute UV-B responses and show that alkaloid accumulation seems at least partly regulated at transcriptional level.

  5. Effect of acute and chronic arsenic exposure on growth, structure and virulence of Aeromonas hydrophila isolated from fish.

    Science.gov (United States)

    Goswami, Ramansu; Ghosh, Debabrata; Saha, Dhira Rani; Padhy, Pratap Kumar; Mazumder, Shibnath

    2011-02-01

    Aeromonas hydrophila being a ubiquitous bacterium is prone to arsenic exposure. The present study was designed to determine the role of arsenic on growth and virulence of A. hydrophila. Exposure to arsenic (1 mg L(-1) and 2 mg L(-1)) had no effect on growth but significantly inhibited the hemolytic and cytotoxic potential of exposed bacteria. Transmission electron microscopy revealed loss of membrane integrity and presence of condensed cytoplasm suggestive of acute stress in bacteria exposed to arsenic. Arsenic-adapted bacteria were developed by repeated sub-culturing in presence of arsenic. Arsenic-adaptation led to significant recovery in hemolytic and cytotoxic potential. The arsenic-adapted bacteria exhibited normal membrane integrity, decreased cytoplasmic condensation and possessed scattered polysome like structures in the cytoplasm. A positive correlation was observed between arsenic tolerance and resistance to several antimicrobials. Arsenic-adaptation failed to confer cross-protection to mercury and cadmium stress. SDS-PAGE analysis revealed the expression of two new proteins of approximately 85 kDa and 79 kDa respectively in arsenic-adapted A. hydrophila. Plasmid-curing and transformation studies clearly indicate plasmid has no role on arsenic resistance trait of the bacteria. Our study, for the first time, reports a structure and function relationship of xenobiotics on bacteria.

  6. Intermittent Exposure to Social Defeat and Open-field Test in Rats : Acute and Long-term Effects on ECG, Body Temperature and Physical Activity

    NARCIS (Netherlands)

    Sgoifo, Andrea; Pozzato, Chiara; Meerlo, Peter; Costoli, Tania; Manghi, Massimo; Stilli, Donatella; Olivetti, Giorgio; Musso, Ezio

    2002-01-01

    This study investigated the effects of exposure to an intermittent homotypic stressor on: (i) habituation of acute autonomic responsivity (i.e. cardiac sympathovagal balance and susceptibility to arrhythmias), and (ii) circadian rhythmicity of heart rate, body temperature, and physical activity. Aft

  7. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

    Science.gov (United States)

    To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

  8. DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.

    2015-01-01

    by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary acute phase response was analysed by Saa3 mRNA levels by real-time quantitative polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx 1 and 3 days, but not 28 days post-exposure. Saa3 m...

  9. Occupational exposure levels of bioaerosol components are associated with serum levels of the acute phase protein Serum Amyloid A in greenhouse workers

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Thilsing, Trine; Bælum, Jesper;

    2016-01-01

    to elevated levels of bioaerosols. The objective of this study is to assess whether greenhouse workers personal exposure to bioaerosol components was associated with serum levels of the acute phase proteins Serum Amyloid A (SAA) and C-reactive protein (CRP). METHODS: SAA and CRP levels were determined...

  10. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

    Science.gov (United States)

    To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

  11. Virtual reality jogging as a novel exposure paradigm for the acute urge to be physically active in patients with eating disorders: Implications for treatment.

    Science.gov (United States)

    Paslakis, Georgios; Fauck, Vanessa; Röder, Kathrin; Rauh, Elisabeth; Rauh, Manfred; Erim, Yesim

    2017-08-11

    The acute urge to be physically active is a relevant clinical phenomenon in patients suffering from eating disorders. In this study with n = 20 female patients with anorexia nervosa and n = 10 female patients with bulimia nervosa, a virtual reality (VR) jogging paradigm was applied as a novel highly immersive 3-D exposure paradigm. Patients were asked to rate their acute urge to be physically active during the exposure procedure. A 10-item self-report questionnaire (smQ) was developed to capture the cognitive, emotional, and behavioral aspects of the acute urge to move. We hypothesized that exposure would lead to habituation of the urge to be physically active. We also hypothesized that leptin levels would be associated with the degree of the subjective urge to be physically active, while habituation would be associated with a decrease in stress hormones (α-amylase, cortisol, and cortisone in saliva). A statistically significant change in subjective scores in the smQ from baseline to postexposure was seen. Our novel VR paradigm may serve as a therapeutic tool for exposure and habituation of the urge of acutely engaging in physical activity in patients with eating disorders. © 2017 Wiley Periodicals, Inc.

  12. USE OF THE FUNGICIDE CARBENDAZIM AS A MODEL COMPOUND TO DETERMINE THE IMPACT OF ACUTE CHEMICAL EXPOSURE DURING OOCYTE MATURATION AND FERTILIZATION ON PREGNANCY OUTCOME IN THE HAMSTER

    Science.gov (United States)

    Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected...

  13. Intermittent Exposure to Social Defeat and Open-field Test in Rats : Acute and Long-term Effects on ECG, Body Temperature and Physical Activity

    NARCIS (Netherlands)

    Sgoifo, Andrea; Pozzato, Chiara; Meerlo, Peter; Costoli, Tania; Manghi, Massimo; Stilli, Donatella; Olivetti, Giorgio; Musso, Ezio

    2002-01-01

    This study investigated the effects of exposure to an intermittent homotypic stressor on: (i) habituation of acute autonomic responsivity (i.e. cardiac sympathovagal balance and susceptibility to arrhythmias), and (ii) circadian rhythmicity of heart rate, body temperature, and physical activity. Aft

  14. DNA breaks induced by micromolar concentrations of dimethylnitrosamine in liver primary cell cultures from untreated and phenobarbital treated rats.

    Science.gov (United States)

    Mendoza-Figueroa, T; López-Revilla, R; Villa-Treviño, S

    1983-05-01

    Direct genotoxic effects of the alkylating agent dimethylnitrosamine (DMN) have been difficult to detect in several short-term tests. We simplified our method to detect DNA breaks induced by DMN in rat liver primary cell cultures, and increased its sensitivity about 150 times by changing the conditions of ultracentrifugation and exposure to DMN. Additionally we increased 4 times the sensitivity of the improved assay by isolating hepatocytes from rats treated with phenobarbital (PB). Treatment for 24 h with 60 microM and 13.5 microM DMN of hepatocytes isolated from untreated and PB-treated rats, respectively, decreased the molecular weight of DNA by 50%. After 24 h exposure to 13.5 microM [14C]DMN, hepatocytes from PB-treated rats incorporated 3 times more radioactivity into trichloroacetic acid precipitable material than hepatocytes from untreated rats. Also PB-treatment increased remarkably cytotoxic effects of DMN while it did not modify the cytotoxicity nor the genotoxicity of the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. These results show that DMN is more genotoxic for hepatocytes from PB-treated rats, and suggest that the enhanced genotoxicity is probably due to an augmented metabolism of DMN by these cultures. Our improved assay of DNA breaks as an indicator of DMN genotoxicity is now as sensitive but faster to perform than hepatocyte-mediated mutagenesis. It could be used to explore genotoxic effects of other alkylating agents and the action of microsomal enzyme modifiers on genotoxicity.

  15. Integrated risk analysis for acute and chronic exposure to toxic chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Gurjar, B.R.; Mohan, Manju

    2003-10-01

    The traditional practice to assess and evaluate different types of risk in isolation to each other are liable to give erroneous results. Integrated risk assessment is an answer to overcome this problem. This paper presents the cumulative or integrated assessment of acute risk posed by accidental release of hazardous chemical (e.g. chlorine) and chronic risk induced by toxic chemicals (e.g. cadmium, chromium and nickel) present in the ambient environment. The present study has been carried out in a most simplified way to demonstrate and appreciate the broader context of integrated risk analysis (IRA). It has been observed that the inclusion of background risk factors (BRF) in individual risk factors (IRF) related to an industry may significantly alter the siting and planning strategies of that industry.

  16. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness.

    Science.gov (United States)

    Hamilton, Trevor James; Kwan, Garfield T; Gallup, Joshua; Tresguerres, Martin

    2016-01-25

    Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab.

  17. Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

    Directory of Open Access Journals (Sweden)

    Tornero-Velez Rogelio

    2008-11-01

    Full Text Available Abstract Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg or permethrin (1 – 100 mg/kg followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM and isotonic regression (PIR methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1 was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25% in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of

  18. Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.

    Science.gov (United States)

    Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu; Rousseau, Bernard

    2016-10-01

    Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases.

  19. Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2004-04-15

    Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.

  20. Oxidative stress in toadfish (Halobactrachus didactylus) cardiac muscle. Acute exposure to vanadate oligomers.

    Science.gov (United States)

    Aureliano, M; Joaquim, N; Sousa, A; Martins, H; Coucelo, J M

    2002-06-07

    Vanadate solutions as "metavanadate" (containing ortho and metavanadate species) and "decavanadate" (containing mainly decameric species) (5 mM; 1 mg/kg) were injected intraperitoneously in Halobatrachus didactylus (toadfish), in order to evaluate the contribution of decameric vanadate species to vanadium (V) intoxication on the cardiac tissue. Following short-term exposure (1 and 7 days), different changes on antioxidant enzyme activities-superoxide dismutase (SOD), catalase (CAT), selenium-glutathione peroxidase (Se-GPx), total glutathione peroxidase (GPx), lipid peroxidation and subcellular vanadium distribution were observed in mitochondrial and cytosolic fractions of heart ventricle toadfish. After 1 day of vanadium intoxication, SOD, CAT and Se-GPx activities were decreased up to 25%, by both vanadate solutions, except mitochondrial CAT activity that increased (+23%) upon decavanadate administration. After 7 days of exposure, decavanadate versus metavanadate solutions promoted different effects mainly on cytosolic CAT activity (-56% versus -5%), mitochondrial CAT activity (-10% versus +10%) and total GPx activity (+1% versus -35%), whereas lipid peroxidation products were significantly increased (+82%) upon 500 microM decavanadate intoxication. Accumulation of vanadium in total (0.137+/-0.011 microg/g) and mitochondrial (0.022+/-0.001 microg/g) fractions was observed upon 7 days of metavanadate exposure, whereas for decavanadate, the concentration of vanadium increased in cytosolic (0.020+/-0.005 microg/g) and mitochondrial (0.021+/-0.009 microg/g) fractions. It is concluded that decameric vanadate species are responsible for a strong increase on lipid peroxidation and a decrease in cytosolic catalase activity thus contributing to oxidative stress responses upon vanadate intoxication, in the toadfish heart.

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

    Science.gov (United States)

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

    2011-09-01

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

  2. Efficacy of multiple exposure with low level He-Ne laser dose on acute wound healing: a pre-clinical study

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

    2014-02-01

    Investigations on the use of Low Level Laser Therapy (LLLT) for wound healing especially with the red laser light have demonstrated its pro-healing potential on a variety of pre-clinical and surgical wounds. However, until now, in LLLT the effect of multiple exposure of low dose laser irradiation on acute wound healing on well-designed pre-clinical model is not much explored. The present study aimed to investigate the effect of multiple exposure of low dose Helium Neon laser on healing progression of full thickness excision wounds in Swiss albino mice. Further, the efficacy of the multiple exposure of low dose laser irradiation was compared with the single exposure of optimum dose. Full thickness excision wounds (circular) of 15 mm diameter were created, and subsequently illuminated with the multiple exposures (1, 2, 3, 4 and 5 exposure/ week until healing) of He-Ne (632.8 nm, 4.02 mWcm-2) laser at 0.5 Jcm-2 along with single exposure of optimum laser dose (2 J/cm-2) and un-illuminated controls. Classical biophysical parameters such as contraction kinetics, area under the curve and the mean healing time were documented as the assessment parameters to examine the efficacy of multiple exposures with low level laser dose. Experimental findings substantiated that either single or multiple exposures of 0.5 J/cm2 failed to produce any detectable alterations on wound contraction, area under the curve and mean healing time compared to single exposure of optimum dose (2 Jcm-2) and un-illuminated controls. Single exposure of optimum, laser dose was found to be ideal for acute wound healing.

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

    Directory of Open Access Journals (Sweden)

    Tukov A.R.

    2016-12-01

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

  4. Temporal Changes in Rat Liver Gene Expression after Acute Cadmium and Chromium Exposure

    Science.gov (United States)

    2015-05-19

    centri- fuged and cells placed in ice cold PBS at 1 x 105 cells/mL. The cells were combined with low melting point agarose, and then pipetted onto a...after a sin- gle exposure to CdCl2 or Na2Cr2O7. Both metals accumulated dose -dependently in the liver and generated ROS, including hydroxyl radical...studies have demonstrated the use of intraperitoneal injections of CdCl2 [26–34] and Na2CrO4 [35–38] in these dose ranges to induce tissue injury

  5. Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells.

    Science.gov (United States)

    Briffa, Jessica F; Grinfeld, Esther; Mathai, Michael L; Poronnik, Phillip; McAinch, Andrew J; Hryciw, Deanne H

    2015-02-05

    Increased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-β1 (TGF-β1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-β1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-β1 secretion (0.50 µg/ml) and phosphorylated AMPKα (at 0.25, and 0.50 µg/ml), and downregulates megalin expression at all concentrations (0.05-0.50 µg/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-β1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 µg/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-β1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway.

  6. Acute high-intensity sound exposure alters responses of place cells in hippocampus.

    Science.gov (United States)

    Goble, T J; Møller, A R; Thompson, L T

    2009-07-01

    Overstimulation is known to activate neural plasticity in the auditory nervous system causing changes in function and re-organization. It has been shown earlier that overstimulation using high-intensity noise or tones can induce signs of tinnitus. Here we show in studies in rats that overstimulation causes changes in the way place cells of the hippocampus respond as rats search for rewards in a spatial maze. In familiar environments, a subset of hippocampal pyramidal neurons, known as place cells, respond when the animal moves through specific locations but are relatively silent in others. This place-field activity (i.e. location-specific firing) is stable in a fixed environment. The present study shows that activation of neural plasticity through overstimulation by sound can alter the response of these place cells. Rats implanted with chronic drivable dorsal hippocampal tetrodes (four microelectrodes) were assessed for stable single-unit place-field responses that were extracted from multiunit responses using NeuroExplorer computer spike-sorting software. Rats then underwent either 30 min exposure to a 4 kHz tone at 104 dB SPL or a control period in the same sound chamber. The place-field activity was significantly altered after sound exposure showing that plastic changes induced by overstimulation are not limited to the auditory nervous system but extend to other parts of the CNS, in this case to the hippocampus, a brain region often studied in the context of plasticity.

  7. Cholinesterase inhibition and depression of the photic after discharge of flash evoked potentials following acute or repeated exposures to a mixture of carbaryl and propoxur.

    Science.gov (United States)

    Mwanza, Jean-Claude; Lyke, Danielle F; Hertzberg, Richard C; Haber, Lynne; Kohrman-Vincent, Melissa; Li, Ruosha; Pan, Yi; Lyles, Robert H; Simmons, Jane Ellen; Macmillan, Denise K; Zehr, R Dan; Swank, Adam E; Herr, David W

    2012-06-01

    Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had

  8. Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

    Science.gov (United States)

    Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

    2006-01-01

    CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

  9. Cognitive and mood effects of phenobarbital treatment in people with epilepsy in rural China: a prospective study.

    Science.gov (United States)

    Ding, Ding; Zhang, Qing; Zhou, Dong; Lin, Weihong; Wu, Qingsheng; Sun, Jixin; Zhao, Qianhua; Yu, Peimin; Wang, Wenzhi; Wu, Jianzhong; Bell, Gail S; Kwan, Patrick; de Boer, Hanneke M; Li, Shichuo; Thompson, Pamela J; Hong, Zhen; Sander, Josemir W

    2012-12-01

    Phenobarbital is an effective treatment for epilepsy but concerns remain over its potential neurocognitive toxicity. This prospective study evaluated the effects of phenobarbital treatment on cognition and mood in people with epilepsy in rural China. We recruited 144 adults with convulsive seizures and 144 healthy controls from six sites in rural China. People with epilepsy were treated with phenobarbital monotherapy for 12 months. At baseline, and at 3, 6 and 12 months, cases and controls were evaluated with a battery of neuropsychological tests: the Mini-Mental State Examination, the Hamilton Depression Rating Scale, a digit span test, a verbal fluency test, an auditory verbal learning test and a digit cancellation test. Efficacy of phenobarbital treatment was evaluated at the end of follow-up for those with epilepsy. Cognitive test scores and mood ratings were available for 136 (94%) people with epilepsy and 137 (95%) controls at the 12 month follow-up. Both groups showed slightly improved performance on a number of neuropsychological measures. The people with epilepsy showed greater performance gains (p=0.012) in verbal fluency. Nine people with epilepsy complained of memory problems during the treatment period. In this study, phenobarbital was not found to have a major negative impact on cognitive function of people with convulsive seizures and some cognitive gains were observed, possibly due to improved seizure control.

  10. Acute maternal oxidant exposure causes susceptibility of the fetal brain to inflammation and oxidative stress.

    Science.gov (United States)

    Akhtar, Feroz; Rouse, Christopher A; Catano, Gabriel; Montalvo, Marcus; Ullevig, Sarah L; Asmis, Reto; Kharbanda, Kusum; Maffi, Shivani K

    2017-09-30

    Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive. Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16-17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) were administered to modulate glutathione (GSH) content in fetal and maternal brain. Twenty-four hours following ethanol exposure, GSH content and OS in brain tissues were analyzed. Cytokines and chemokines were selected based on their association with distinctive microglia phenotype M1-like (IL-1β, IFN γ, IL-6, CCL3, CCL4, CCL-7, CCL9,) or M2-like (TGF-β, IL-4, IL-10, CCL2, CCL22, CXCL10, Arg1, Chi1, CCR2 and CXCR2) and measured in the brain by qRT-PCR and ELISA. In addition, Western blot and confocal microscopy techniques in conjunction with EOC13.31 cells exposed to similar ethanol-induced oxidative stress and redox conditions were used to determine the underlying mechanism of microglia activation associated with the observed phenotypic changes. We show that a single episode of mild to moderate OS in the last trimester of gestation causes GSH depletion, increased protein and lipid peroxidation and inflammatory responses inclined towards a M1-like microglial phenotype (IL-1β, IFN-γ) in fetal brain tissue observed at 6-24 h post exposure. Maternal brain is resistant to many of these marked changes. Using EOC 13.31 cells, we show that GSH homeostasis in microglia is crucial to restore its anti-inflammatory state and modulate inflammation

  11. Long term impact of the endocrine disruptor tributyltin on male fertility following a single acute exposure.

    Science.gov (United States)

    Mitra, Sumonto; Srivastava, Ankit; Khandelwal, Shashi

    2017-10-01

    Declining rate of human fertility is a growing concern, where lifestyle and environmental factors play an important role. We recently demonstrated that tributyltin (TBT), an omnipresent endocrine disruptor, affects testicular cells in vitro. In this study, male Wistar rats were gavaged a single dose of 10, 20, and 30 mg/kg TBT-chloride (TBTC) (to mimic accidental exposure in vivo) and sacrificed on day 3 and day 7, respectively. TBT bioavailability was evaluated by estimating total tin content, and essential metal levels were analyzed along with redox molecules (ROS and GSH/GSSG) to understand the effect on physiological conditions. Blood-testicular barrier (BTB) disruption, levels of associated proteins and activity of proteolytic enzymes were evaluated to understand the effect on BTB. Histological analysis of tissue architecture and effect on protein expression of steroidogenic, stress and apoptotic markers were also evaluated. Widespread TBTC pollution can be an eventual threat to male fertility worldwide. © 2017 Wiley Periodicals, Inc.

  12. Telomere dynamics in human mesenchymal stem cells after exposure to acute oxidative stress

    DEFF Research Database (Denmark)

    Harbo, M.; Koelvraa, S.; Serakinci, N.;

    2012-01-01

    A gradual shortening of telomeres due to replication can be measured using the standard telomere restriction fragments (TRF) assay and other methods by measuring the mean length of all the telomeres in a cell. In contrast, stress-induced telomere shortening, which is believed to be just...... as important for causing cellular senescence, cannot be measured properly using these methods. Stress-induced telomere shortening caused by, e.g. oxidative damage happens in a stochastic manner leaving just a few single telomeres critically short. It is now possible to visualize these few ultra-short telomeres...... due to the advantages of the newly developed Universal single telomere length assay (STELA), and we therefore believe that this method should be considered the method of choice when measuring the length of telomeres after exposure to oxidative stress. In order to test our hypothesis, cultured human...

  13. Effects of Air Pollutant Exposure on Acute Myocardial Infarction, According to Gender

    Science.gov (United States)

    Tuan, Tássia Soldi; Venâncio, Taís Siqueira; Nascimento, Luiz Fernando Costa

    2016-01-01

    Background: There is evidence of the effects of air pollution on hospital admissions due to cardiovascular diseases, including myocardial infarction. Objective: To estimate the association between exposure to air pollutants and hospital admissions due to myocardial infarction according to gender, between January 1st 2012 and December 31st 2013, in São Jose dos Campos-SP. Methods: An ecological time series study was carried out with daily data of admissions due to AMI, pollutants CO, O3, PM10, SO2, and NO2, according to gender. We used the Poisson regression generalized linear model to estimate the relative risks of hospital admissions with lags of 0-5 days, adjusted for temperature, humidity, seasonality and days of the week. Results: There were 1837 admissions for ischemic heart diseases, with 636 women and 1201 men. For females, the risks were significant for CO in lag 0 (RR = 1,09), lag1 (RR = 1,08) and lag 5 (RR = 1,10) and SO2 in lag 0 (RR = 1,10) and 3 (RR = 1,09). For men there was significance of the CO in, lag 3 and lag 5 (RR = 1,05). There was significance, regardless of gender, for CO at lag 1 (RR = 1,05) and lag 5 (RR = 1,07) and lag 0 for SO2 (RR = 1,06). Conclusion: The data presented show the important role of CO and SO2 in the genesis of myocardial infarction admissions, and responses to pollutant exposure are different if analyzed by gender and together - hence the importance of a stratified analyses. PMID:27533257

  14. Atrazine in sub-acute exposure results in sperm DNA disintegrity and nuclear immaturity in rats

    Directory of Open Access Journals (Sweden)

    Rajab-Ali Sadrkhanloo

    2012-03-01

    Full Text Available This study was designed to evaluate the detrimental effect of atrazine (ATR on germinal epitheliums (GE cytoplasmic carbohydrate (CH and unsaturated fatty acids (UFA ratio and to clarify the effect of ATR on serum levels of FSH, LH, testosterone and inhibin-B (INH-B. The impact of ATR exposure on total antioxidant capacity (TAC, sperm DNA packing and integrity were also investigated. Seventy two Wistar rats were used. The rats in control group received vehicle and the animals in test groups received 100, 200 and 300 mg kg-1 BW of ATR orally on daily bases for 12, 24 and 48 days. In ATR-received groups the spermatogenesis cell were presented with dense reactive sites for lipidophilic staining associated with faint cytoplasmic CH accumulation. Dissociated germinal epithelium, negative tubular and repopulation indexes were manifested. The serum levels of testosterone, FSH, LH and INH-B decreased by 85% after 48 days exposure to high dose of ATR. TAC was reduced in a time- and dose-dependent manner. The sperm DNA damage was marked in animals which exposed to high dose of ATR (72.50 ± 2.25% and the percentage of nuclear immature sperm increased up to 83.40 ± 0.89%. In conclusion, ATR not only induced its detrimental effect on the endocrine function of the testes and pituitary gland but also affected the cytoplasmic CH ratio and consequently leads to inadequate energy supplement in spermatogenesis cells. Therefore the imbalanced oxidative stress occurs in testicular tissue, which in turn enhances the sperm DNA disintegrity and nuclear immaturity.

  15. Reinforcer devaluation as a consequence of acute nicotine exposure and withdrawal

    Science.gov (United States)

    Kirshenbaum, Ari; Green, John; Fay, Michael; Parks, Angelique; Phillips, Jesse; Stone, Jason; Roy, Tessa

    2014-01-01

    RATIONALE Nicotine discontinuation produces behaviors in rats that are congruent with anhedonia, and these symptoms may be related to the devaluation of non-nicotine reinforcers. OBJECTIVE Four separate experiments were performed to explore the parameters surrounding nicotine-induced reinforcer devaluation. METHODS In Experiments 1 and 2, nicotine (0.1 or 0.3 mg/kg) or 0.3 mg/kg nicotine plus 1.0 mg/kg mecamylamine was delivered to rats prior to progressive ratio (PR) schedule sessions in which sucrose was used as a reinforcer. In order to (a) evaluate reinforcer enhancement by nicotine, and (b) reinforcer devaluation in the absence of nicotine, all rats experienced two PR schedule sessions per day for 10 days. Experiment 3 involved nicotine (0.3 mg/kg) and a visual stimulus in place of sucrose reinforcement. In Experiment 4, rats received nicotine (0.3 mg/kg) either before or after a single PR-schedule session for 10 days. RESULTS Experiments 1 and 2 demonstrate that reinforcer devaluation is related to the occupation of nicotinic-acetylcholine receptors. Results from Experiment 3 provide some evidence that devaluation occurs with either sucrose or visual-stimulus reinforcement. Experiment 4 demonstrates that a necessary condition for reinforcer devaluation to occur is the concurrent exposure to the reinforcer and nicotine. CONCLUSIONS Reinforcer devaluation in rats emerges rapidly in a progressive, orderly fashion that coincides with accumulated exposure to nicotine. These results suggest that reinforcer devaluation may be a feature of nicotine that contributes to the abuse liability of tobacco products. PMID:25401169

  16. Effects of health intervention programs and arsenic exposure on child mortality from acute lower respiratory infections in rural Bangladesh.

    Science.gov (United States)

    Jochem, Warren C; Razzaque, Abdur; Root, Elisabeth Dowling

    2016-09-01

    Respiratory infections continue to be a public health threat, particularly to young children in developing countries. Understanding the geographic patterns of diseases and the role of potential risk factors can help improve future mitigation efforts. Toward this goal, this paper applies a spatial scan statistic combined with a zero-inflated negative-binomial regression to re-examine the impacts of a community-based treatment program on the geographic patterns of acute lower respiratory infection (ALRI) mortality in an area of rural Bangladesh. Exposure to arsenic-contaminated drinking water is also a serious threat to the health of children in this area, and the variation in exposure to arsenic must be considered when evaluating the health interventions. ALRI mortality data were obtained for children under 2 years old from 1989 to 1996 in the Matlab Health and Demographic Surveillance System. This study period covers the years immediately following the implementation of an ALRI control program. A zero-inflated negative binomial (ZINB) regression model was first used to simultaneously estimate mortality rates and the likelihood of no deaths in groups of related households while controlling for socioeconomic status, potential arsenic exposure, and access to care. Next a spatial scan statistic was used to assess the location and magnitude of clusters of ALRI mortality. The ZINB model was used to adjust the scan statistic for multiple social and environmental risk factors. The results of the ZINB models and spatial scan statistic suggest that the ALRI control program was successful in reducing child mortality in the study area. Exposure to arsenic-contaminated drinking water was not associated with increased mortality. Higher socioeconomic status also significantly reduced mortality rates, even among households who were in the treatment program area. Community-based ALRI interventions can be effective at reducing child mortality, though socioeconomic factors may

  17. Evidence for effects on thermoregulation after acute oral exposure to type I and type II pyrethroids in infant rats.

    Science.gov (United States)

    Bardullas, Ulises; Sosa-Holt, Carla Solange; Pato, Alejandro Martín; Nemirovsky, Sergio Iván; Wolansky, Marcelo Javier

    2015-01-01

    Most pyrethroid (PYR) insecticides may be classified either as type-I compounds, which produce whole body tremors and hyperthermia, or type-II compounds, which produce salivation, choreoathetosis, and hypothermia (i.e., producing T and CS neurobehavioral syndromes, respectively). This classification is based on clinical observations in adult rats and mice after intracerebroventricular or intravascular administration of highly effective acute (bolus) doses. PYR neurotoxicity in infant animals is not characterized as much as in adult animals. Endpoints informing on vital determinants of mammal's maturation, such as body temperature may help recognizing age-related differences in susceptibility to PYRs. In this work, body temperature (Tb) was monitored at 30-min intervals after acute oral exposure to T-syndrome PYR bifenthrin (BIF), CS-syndrome PYR cypermethrin (CYPM), and a BIF–CYPM mixture in weanling rats by using a subcutaneous temperature monitoring system. In both single-compound assays, a time- and dose-related decline of Tb was the most evident impact on thermoregulation observed starting at ~2–3 h after dosing.Moreover, 15–18 mg/kg BIF induced a mild increase in Tb before the hypothermic action was apparent. The lowest effective dose for temperature perturbation was 15mg/kg for BIF and 10mg/kg for CYPM, and moderate neurobehavioral alterations were evident at 12 and 10mg/kg, respectively. When low effective doses of BIF and CYPM were co-administered mild behavioral effects and a transient increase in Tb (p=0.02) were observed at 1–2 h, and no Tb decline was apparent afterwards compared to control animals. Noteworthy, the hypothermic action of BIF in infant rats was quite different from the hyperthermia consistently reported in studies using mature animals. Our results suggest that body temperature monitoring may be useful as a complementary assessment to reveal qualitative age-specific pesticide effects in rats.

  18. Acute ocular injuries caused by 60-Ghz millimeter-wave exposure.

    Science.gov (United States)

    Kojima, Masami; Hanazawa, Masahiro; Yamashiro, Yoko; Sasaki, Hiroshi; Watanabe, Soichi; Taki, Masao; Suzuki, Yukihisa; Hirata, Akimasa; Kamimura, Yoshitsugu; Sasaki, Kazuyuki

    2009-09-01

    The goal of this study was to examine the clinical course of 60-GHz millimeter-wave induced damages to the rabbit eye and to report experimental conditions that allow reproducible induction of these injuries. The eyes of pigmented rabbits (total number was 40) were irradiated with 60-GHz millimeter-waves using either a horn antenna or one of two lens antennas (6 and 9 mm diameter; phi6, phi9) Morphological changes were assessed by slit-lamp microscopy. Additional assessments included corneal fluorescein staining, iris fluorescein angiography, and lens epithelium light microscopy. Under the standardized eye-antenna positioning, the three antennas caused varying damages to the eyelids or eyeglobes. The most reproducible injuries without concurrent eyelid edema and corneal desiccation were achieved using the phi6 lens antenna: irradiation for 6 min led to an elevation of the corneal surface temperature (reaching 54.2 +/- 0.9 degrees C) plus corneal edema and epithelial cell loss. Furthermore, mitotic cells appeared in the pupillary area of the lens epithelium. Anterior uveitis also occurred resulting in acute miosis (from 6.6 +/- 1.4 to 2.2 +/- 1.4 mm), an increase in flares (from 6.7 +/- 0.9 to 334.3 +/- 130.8 photons per second), and iris vasodilation or vessel leakage. These findings indicate that the three types of millimeter-wave antennas can cause thermal injuries of varying types and levels. The thermal effects induced by millimeter-waves can apparently penetrate below the surface of the eye.

  19. In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model.

    Directory of Open Access Journals (Sweden)

    Barbara Ambruosi

    Full Text Available Phthalates are ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl phthalate (DEHP is the most abundant phthalate and it impairs fertility by acting as an endocrine disruptor. The aim of the present study was to analyze the effects of in vitro acute exposure to DEHP on oocyte maturation, energy and oxidative status in the horse, a large animal model. Cumulus cell (CC apoptosis and oxidative status were also investigated. Cumulus-oocyte complexes from the ovaries of slaughtered mares were cultured in vitro in presence of 0.12, 12 and 1200 µM DEHP. After in vitro maturation (IVM, CCs were removed and evaluated for apoptosis (cytological assessment and TUNEL and intracellular reactive oxygen species (ROS levels. Oocytes were evaluated for nuclear chromatin configuration. Matured (Metaphase II stage; MII oocytes were further evaluated for cytoplasmic energy and oxidative parameters. DEHP significantly inhibited oocyte maturation when added at low doses (0.12 µM; P<0.05. This effect was related to increased CC apoptosis (P<0.001 and reduced ROS levels (P<0.0001. At higher doses (12 and 1200 µM, DEHP induced apoptosis (P<0.0001 and ROS increase (P<0.0001 in CCs without affecting oocyte maturation. In DEHP-exposed MII oocytes, mitochondrial distribution patterns, apparent energy status (MitoTracker fluorescence intensity, intracellular ROS localization and levels, mt/ROS colocalization and total SOD activity did not vary, whereas increased ATP content (P<0.05, possibly of glycolytic origin, was found. Co-treatment with N-Acetyl-Cysteine reversed apoptosis and efficiently scavenged excessive ROS in DEHP-treated CCs without enhancing oocyte maturation. In conclusion, acute in vitro exposure to DEHP inhibits equine oocyte maturation without altering ooplasmic energy and oxidative stress parameters in matured oocytes which retain the potential to be fertilized and develop into

  20. Monitorização terapêutica de fenobarbital = Therapeutic control of phenobarbital

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    Marcela Elisa Pastore

    2007-07-01

    Full Text Available Apesar do desenvolvimento de novos fármacos, o fenobarbital ainda temdestaque no tratamento da epilepsia por ser completo, efetivo e apresentar baixo custo. A margem terapêutica relativamente estreita e o risco do desenvolvimento de crises convulsivas, caso a dosagem não esteja adequada, fazem da monitorização terapêutica um procedimento de rotina na conduta do tratamento. O objetivo deste trabalho de caracterizar o perfil dos pacientes que se submeteram à monitorização terapêutica de fenobarbital em um laboratório de ensino em análises clínicas, no Estado do Paraná, nos anos de 2004 e 2005. Foi realizado um levantamento das fichas do laboratório e obtidos dados de 104pessoas que realizaram 119 determinações séricas do fármaco, dentre as quais 116 foram para a monitorização terapêutica. A maioria dos pacientes era adulta e realizou exames por solicitação de um serviço público de saúde. Observou-se que 49,1% dos resultados estavamacima ou abaixo da faixa terapêutica considerada. Foram realizados 49 exames em pacientes que faziam uso do fenobarbital em regime de monoterapia e 67 exames em pacientes que utilizavam este fármaco em associação com outros agentes antiepilépticos. A monitorizaçãode níveis séricos de fenobarbital mostra-se vantajosa frente ao grande número de fatores que evidenciam a necessidade de se correlacionar a concentração do fármaco com o estado clínico do paciente.Despite the development of new drugs, the phenobarbital still has prominence in the treatment of the epilepsy for being complete, effective and to present low cost. The relatively narrow therapeutical range and the risk of the development of convulsive crises in case the dosage is not well adjusted, make the therapeutical control a routine procedure. The aim of this work is to characterize the profile of the patients submitted to the therapeutical control of phenobarbital in a laboratory of clinical analysis in Paraná State

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

    Science.gov (United States)

    Crawford, Charles G.

    2004-01-01

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

  2. Nose-to-brain transport of aerosolised quantum dots following acute exposure.

    Science.gov (United States)

    Hopkins, Laurie E; Patchin, Esther S; Chiu, Po-Lin; Brandenberger, Christina; Smiley-Jewell, Suzette; Pinkerton, Kent E

    2014-12-01

    Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots (QDs) are semiconductor nanocrystals possessing unique optical and electrical properties. Although QDs are commonly made of cadmium, a metal known to have neurological effects, potential transport of QDs directly to the brain has not been assessed. This study evaluated whether QDs (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of QDs for 1 h via nasal inhalation, and nanoparticles were detected 3 h post-exposure within the olfactory tract and olfactory bulb by a wide range of techniques, including visualisation via fluorescent and transmission electron microscopy. We conclude that, following short-term inhalation of solid QD nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response. To our knowledge, this is the first study to clearly demonstrate that QDs can be rapidly transported from the nose to the brain by olfactory uptake via axonal transport following inhalation.

  3. An Exploratory Study on the Development of an Animal Model of Acute Pancreatitis Following Nicotine Exposure

    Directory of Open Access Journals (Sweden)

    Chowdhury P

    2003-09-01

    Full Text Available Abstract Cigarette smoking is known to be a major risk factor for pancreatic cancer and pancreatitis is believed to be a predisposed condition for pancreatic cancer. As of this date, there is no established experimental animal model to conduct detailed studies on these two deadly diseases. Our aim is to establish a rodent model by which we can systematically study the pathogenesis of pancreatitis and pancreatic cancer. Methods Adult Male Sprague Dawley rats were exposed to graded doses of nicotine by various routes for periods of three to 16 weeks. Blood samples were measured for hormonal and metabolic parameters. The pancreas was evaluated for histopathological changes and its function was assessed in isolated pancreatic acini upon stimulation with cholecystokinin (CCK or carbachol (Cch. The pancreatic tissue was evaluated further for oncogene expression. Results Body weight, food and fluid intakes, plasma glucose and insulin levels were significantly reduced in animals with nicotine exposure when compared to control. However, CCK and gastrin levels in the blood were significantly elevated. Pancreatic function was decreased significantly with no alteration in CCK receptor binding. Pancreatic histology revealed vacuolation, swelling, cellular pyknosis and karyorrhexis. Mutant oncogene, H-ras, was overexpressed in nicotine-treated pancreatic tissue. Summary and conclusion The results suggest that alterations in metabolic, hormonal and pathologic parameters following nicotine-treatment appear consistent with diagnostic criteria of human pancreatitis. It is proposed that rats could be considered as a potential animal model to study the pathogenesis of pancreatitis.

  4. Coronary CT angiography for acute chest pain triage: Techniques for radiation exposure reduction; 128 vs. 64 multidetector CT

    Energy Technology Data Exchange (ETDEWEB)

    Goitein, Orly; Eshet, Yael; Konen, Eli (Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)), email: orly.goitein@sheba.health.gov.il; Matetzky, Shlomi (Heart Inst., Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)); Goitein, David (Surgery C, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)); Hamdan, Ashraf; Di Segni, Elio (Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel); Heart Inst., Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel))

    2011-10-15

    Background. Coronary CT angiography (CCTA) is used daily in acute chest pain triage, although exposing patients to significant radiation dosage. CCTA using prospective ECG gating (PG CCTA) enables significant radiation reduction Purpose. To determine whether the routine use of 128 vs. 64 multidetector CT (MDCT) can increase the proportion of patients scanned using PG CCTA technique, lowering radiation exposure, without decreasing image quality. Material and Methods. The study comprised 232 patients, 116 consecutive patients scanned using 128 MDCT (mean age 49 years, 79 men, BMI 28) and 116 consecutive patients (mean age 50 years, 75 men, BMI 28) which were scanned using 64 MDCT. PG CCTA was performed whenever technically permissible by each type of scanner: 64 MDCT = stable heart rate (HR) <60/min and weight <110 kg; 128 MDCT = stable HR < 70/min and weight <140 kg. All coronary segments were evaluated for image quality using a visual scale of 1-5. An estimated radiation dose was recorded. Results. PC CCTA was performed in 84% and 49% of the 128 and 64 MDCT groups, respectively (P < 0.0001). Average image quality score were 4.6 +- 0.3 and 4.7 +- 0.1 for the 128 and 64 MDCT, respectively (P = 0.08). The mean radiation dose exposure was 6.2 +- 4.8 mSv and 10.4 +- 7.5 mSv for the 128 and 64 MDCT, respectively (P = 0.008). Conclusion. The 128 MDCT scanner enables utilization of PG CCTA technique in a greater proportion of patients, thereby decreasing the related radiation significantly, without hampering image quality

  5. Comparison of waterborne and intraperitoneal exposure to fipronil in the Caspian white fish (Rutilus frisii) on acute toxicity and histopathology.

    Science.gov (United States)

    Ardeshir, Rashid Alijani; Zolgharnein, Hossein; Movahedinia, Abdolali; Salamat, Negin; Zabihi, Ebrahim

    2017-01-01

    Fipronil is an effective insecticide widely used in agriculture with potential ecotoxicological consequences. The median lethal dose (LD50) and concentration (LC50) of fipronil in 16.3 g Caspian white fish, Rutilus frisii kutum fingerlings were determined. To determine the LD50, a total of 133 fish were assigned to 19 tanks (7 fish/tank) including one control and 6 treatment groups (300, 450, 550, 650, 750, 850 mg/kg). Fish were injected intraperitoneally and monitored at 96 h. The LD50 of fipronil was 632 mg/kg suggesting it was slightly toxic to the Caspian white fish. To determine LC50, 114 fish were assigned to 19 tanks (6 fish/tank) including one control and 6 treatment groups (300, 400, 500, 600, 700, 800 μg/L). The LC50 of fipronil was 572 μg/L, which was highly toxic to the fish. The degree of tissue change (DTC) in vital organs from moribund fish exposed via waterborne exposure showed severe damage (DTC: 71 ± 52 for 700 μg/L) in the gill, including aneurisms, extensive fusion and necrosis. The fish exposed through the intraperitoneal route seemed to have severe lesions (DTC: 66 ± 50 for 750 mg/kg) in the kidney, involving hemorrhage, tubular degeneration and necrosis. The liver had no significant differences in DTC values between the two routes and showed pyknosis and sinusoid dilation. Hematoxylin and eosin staining did not show any histological alterations in the brain but nissl staining showed some alterations in distribution of purkinje cells. Generally, this study showed that the route of exposure to fipronil not only affects its acute toxicity but also determines the main target organs of toxicity and histopathological alterations in Caspian white fish.

  6. Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

    Directory of Open Access Journals (Sweden)

    Tiffany-Jane Evans

    Full Text Available Genome wide association studies (GWAS have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL. Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358 and population controls (n = 1192. Furthermore, we utilised family trio (n = 204 genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9, and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9. There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05. There were no interactions of risk genotypes with age or sex (P-values >0.2. Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.

  7. Mega-dose phenobarbital therapy for super-refractory status epilepticus.

    Science.gov (United States)

    Byun, Jung-Ick; Chu, Kon; Sunwoo, Jun-Sang; Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Jun, Jin-Sun; Lee, Han Sang; Lee, Woo-Jin; Lee, Doo Young; Jeon, Daejong; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Lee, Sang Kun

    2015-12-01

    To evaluate the efficacy and safety of mega-dose phenobarbital (MDPB; enteral or parenteral phenobarbital >10 mg/kg/day) for treating super-refractory status epilepticus (SRSE; continuous or recurrent status epilepticus for ≥24 hours after the onset of continuous anaesthetic treatment) in adult patients. Adult patients with SRSE who were treated with MDPB in our institution from March 2005 to September 2014 were reviewed. We collected data on basic demographics, clinical features, functional status, anticonvulsant treatment, and possible adverse events. SRSE outcome was divided into six categories: successful therapy, initial failure, breakthrough seizures, withdrawal seizures, intolerable side effects, and death during treatment. Ten adult patients with SRSE received MDPB. Median age at seizure onset was 38 years (range: 18-59), and half were male. All patients had no history of seizures and had symptoms suggestive of viral encephalitis. Median duration of status epilepticus was 17.5 days (range: 6-60) and anaesthetics were used for a median of 14.0 days (range: 2-54) before MDPB. Successful control of SRSE was achieved in half of the patients, however, only one of ten patients was able to fully recover at discharge. Median duration of the MDPB was 45.5 days and the maximum serum phenobarbital level reached a median of 151.5 μg/ml. Patients with successful MDPB therapy had normal brain imaging (80% vs. 0%; p=0.048) and better functional outcome at discharge and after three months of follow-up. Infection was the most critical complication, along with cardiorespiratory depression. MDPB is a therapeutic option for control of SRSE when other choices are exhausted.

  8. Effects of Air Pollutant Exposure on Acute Myocardial Infarction, According to Gender.

    Science.gov (United States)

    Tuan, Tássia Soldi; Venâncio, Taís Siqueira; Nascimento, Luiz Fernando Costa

    2016-09-01

    There is evidence of the effects of air pollution on hospital admissions due to cardiovascular diseases, including myocardial infarction. To estimate the association between exposure to air pollutants and hospital admissions due to myocardial infarction according to gender, between January 1st 2012 and December 31st 2013, in São Jose dos Campos-SP. An ecological time series study was carried out with daily data of admissions due to AMI, pollutants CO, O3, PM10, SO2, and NO2, according to gender. We used the Poisson regression generalized linear model to estimate the relative risks of hospital admissions with lags of 0-5 days, adjusted for temperature, humidity, seasonality and days of the week. There were 1837 admissions for ischemic heart diseases, with 636 women and 1201 men. For females, the risks were significant for CO in lag 0 (RR = 1,09), lag1 (RR = 1,08) and lag 5 (RR = 1,10) and SO2 in lag 0 (RR = 1,10) and 3 (RR = 1,09). For men there was significance of the CO in, lag 3 and lag 5 (RR = 1,05). There was significance, regardless of gender, for CO at lag 1 (RR = 1,05) and lag 5 (RR = 1,07) and lag 0 for SO2 (RR = 1,06). The data presented show the important role of CO and SO2 in the genesis of myocardial infarction admissions, and responses to pollutant exposure are different if analyzed by gender and together - hence the importance of a stratified analyses. Existem evidências sobre os efeitos da poluição do ar nas internações por doenças cardiovasculares, entre elas o infarto do miocárdio. Estimar a associação entre exposição a poluentes do ar e internações por infarto segundo gêneros, entre 01 de Janeiro de 2012 e 31 de Dezembro de 2013, em São José dos Campos - SP. Estudo ecológico de série temporal com dados diários de internações por IAM dos poluentes CO, O3, PM10, SO2, NO2, segundo gêneros. Utilizou-se modelo linear generalizado da Regressão de Poisson para estimar os riscos relativos para internações com defasagens de 0 a 5

  9. A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy.

    Science.gov (United States)

    Fredsø, N; Sabers, A; Toft, N; Møller, A; Berendt, M

    2016-02-01

    Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control. In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P = 0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy.

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

    Science.gov (United States)

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

    2012-01-18

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

  11. Short-term nitrogen dioxide exposure and geomagnetic activity interaction: contribution to emergency hospitalization for acute coronary syndrome.

    Science.gov (United States)

    Vencloviene, Jone; Grazuleviciene, Regina; Babarskiene, Ruta; Dedele, Audrius; Grazulevicius, Tomas

    2011-06-01

    We investigated whether extremely geomagnetic activity may modify the association between short-term nitrogen dioxide (NO₂) exposure and emergency hospitalization for acute coronary syndrome (ACS). A case-crossover study design was used to analyze ACS in 6,594 hospitalized patients at the Clinic of Kaunas, Lithuania. We evaluated the associations between NO₂, geomagnetic activity and the rate of emergency admissions for ACS by logistic regression controlling for seasonal variation, weekdays and meteorological factors. Ambient NO₂ pollution interquartile range increase (IQR) on the day of admission and previous day (lag 0-1) in patients below 65 years of age increase the risk of ACS equal to 24% (95% CI 0.96-1.60). Evidence of effect modification by combined NO₂ and geomagnetic activity was observed in relation to ACS, adjusted OR was 1.61; 95% CI 1.03-2.53. In conclusion, these findings suggest that geomagnetic activity variations may increase the traffic-related air pollution effect on ACS, and highlight environmental factors associated with ischemic heart disease course.

  12. Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus.

    Science.gov (United States)

    Martyniuk, Christopher J; Feswick, April; Spade, Daniel J; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2010-08-01

    Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis, but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after 7 days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20-30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (pdieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer's disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are also associated with the etiology of human neurological disorders. (c) 2010 Elsevier Inc. All rights reserved.

  13. Acute and subacute toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the shallow-water coral Porites divaricata: Application of a novel exposure protocol.

    Science.gov (United States)

    Renegar, D Abigail; Turner, Nicholas R; Riegl, Bernhard M; Dodge, Richard E; Knap, Anthony H; Schuler, Paul A

    2017-01-01

    Previous research evaluating hydrocarbon toxicity to corals and coral reefs has generally focused on community-level effects, and results often are not comparable between studies because of variability in hydrocarbon exposure characterization and evaluation of coral health and mortality during exposure. Toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the coral Porites divaricata was assessed in a constant exposure toxicity test utilizing a novel toxicity testing protocol uniquely applicable to shallow-water corals, which considered multiple assessment metrics and evaluated the potential for post-exposure mortality and/or recovery. Acute and subacute effects (gross morphological changes, photosynthetic efficiency, mortality, and histologic cellular changes) were evaluated during pre-exposure (4 wk), exposure (48 h), and post-exposure recovery (4 wk) periods. Coral condition scores were used to determine a 48-h median effective concentration of 7442 μg/L. Significant physical and histological changes resulted from exposure to 640 μg/L and 5427 μg/L 1-methylnaphthalene, with a 1-d to 3-d delay in photosynthetic efficiency effects (ΔF/Fm). Pigmented granular amoebocyte area was found to be a potentially useful sublethal endpoint for this species. Coral mortality was used to estimate a 48-h median lethal concentration of 12 123 μg/L. Environ Toxicol Chem 2017;36:212-219. © 2016 SETAC. © 2016 SETAC.

  14. Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment

    Directory of Open Access Journals (Sweden)

    Cherry eIgnacio

    2014-09-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of Social Enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or Social Enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by Social Enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for Social Enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression.

  15. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    Science.gov (United States)

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

  16. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  17. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    Energy Technology Data Exchange (ETDEWEB)

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  18. Phenobarbital-mediated tumor promotion in transgenic mice with humanized CAR and PXR.

    Science.gov (United States)

    Braeuning, Albert; Gavrilov, Alina; Brown, Susan; Wolf, C Roland; Henderson, Colin J; Schwarz, Michael

    2014-08-01

    The nuclear receptors CAR (constitutive androstane receptor) and possibly PXR (pregnane X receptor) mediate the hepatic effects of phenobarbital (PB) and similar-acting compounds. Although PB is a potent nongenotoxic tumor promoter in rodent liver, epidemiological data from epilepsy patients treated with phenobarbital do not show a specific role of PB in human liver cancer risk. That points to species differences in the susceptibility to tumor promotion by PB, which might be attributed to divergent functions of the PB receptors CAR and PXR in mice and humans. In the present study, male transgenic mice expressing human CAR and PXR were used to detect possible differences between wild-type (WT) and humanized mice in their response to CAR activation in a tumor initiation/promotion experiment with a single injection of the tumor initiator N-nitrosodiethylamine preceding chronic PB treatment for 10 months. Analysis of liver tumor burden revealed that PB strongly promoted the outgrowth of hepatocellular adenoma driven by activated β-catenin in WT mice, whereas the tumor-promoting effect of PB was much less pronounced in the humanized group. In conclusion, the present findings demonstrate that human CAR and PXR support tumor promotion by PB in mouse liver, but to a significantly lesser extent than the WT murine receptors. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Increase in phorbol ester binding in liver microsomes after chronic administration of phenobarbital

    Energy Technology Data Exchange (ETDEWEB)

    Menez, J.F.; Deitrich, R.A. (Univ. of Colorado, Denver (United States))

    1991-03-15

    The effect of chronic administration of phenobarbital on the binding of phorbol-12,13-dibutyrate (({sup 3}H)PDBu), an activator of protein kinase C (PKC), was examined in rat liver microsomes. A significant increase in the number of binding sites was observed in microsomes of Fisher 344 rats. However, no change appeared in liver cytosol binding of PDBu. Consequently, a translocation process of PKC is unlikely. The increase in ({sup 3}H)PDBu binding in liver microsomes is significant 24 h. after one injection of phenobarbital and reaches its maximum in 2 days. In other strains of rats (ACI and lean Zucker), significant differences were found in the increase of ({sup 3}H)PDBu binding in microsomes. Fisher 344 were the most sensitive, lean Zucker rats, the least sensitive. Those results parallel the pentoxy-resorufin O demethylase activity in the microsomes of the same animals. EC{sub 50} values for inhibition of ({sup 3}H)PDBu binding by pentobarbital were determined in control microsomes from Fisher and Zucker rats. In Fisher rats, ({sup 3}H)PDBu binding in microsomes was found to be more sensitive to the inhibitory effect of pentobarbital than in lean Zucker rats, which suggests that the more microsomes are inhibited in vitro the greater the increase in PKC in microsomes following chronic barbiturate treatment.

  20. Effects of Acute Exposure to Increased Plasma Branched-Chain Amino Acid Concentrations on Insulin-Mediated Plasma Glucose Turnover in Healthy Young Subjects

    OpenAIRE

    Sarah Everman; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

    2015-01-01

    Background Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. Objective To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Methods Ten healthy subjects were randomly assigned to...

  1. Acute Kidney Injury, Risk Factors, and Prognosis in Hospitalized HIV-Infected Adults in South Africa, Compared by Tenofovir Exposure

    Science.gov (United States)

    Martinson, Neil; Motlhaoleng, Katlego; Abraham, Pattamukkil; Mancama, Dalu; Naicker, Saraladevi; Variava, Ebrahim

    2017-01-01

    Abstract There are limited data describing acute kidney injury (AKI) in HIV-infected adult patients in resource-limited settings where tenofovir disoproxil fumarate (TDF), which is potentially nephrotoxic, is increasingly prescribed. We describe risk factors for and prognosis of AKI in HIV-infected individuals, stratified by those receiving and those naive to TDF. A prospective case cohort study of hospitalized HIV-infected adults with AKI stratified by TDF exposure. Adults (≥18 years) were recruited: clinical and biochemical data were collected at admission; their renal recovery, discharge, or mortality was ascertained as an in-patient and, subsequently, to a scheduled 3-month follow-up. Among this predominantly female (61%), almost exclusively black African cohort of 175 patients with AKI, 93 (53%) were TDF exposed; median age was 41 years (interquartile range 35–50). Median CD4 count and viral load and creatinine at baseline were 116 cells/mm3 and 110,159 copies/ml, respectively. A greater proportion of the TDF group had severe AKI on admission (61% vs. 43%, p = .014); however, both groups had similar rates of newly diagnosed tuberculosis (TB; 52%) and nonsteroidal anti-inflammatory drug (NSAID; 32%) use. Intravenous fluid was the therapeutic mainstay; only seven were dialyzed. Discharge median serum creatinine (SCr) was higher in the TDF group (p = .032) and fewer in the TDF group recovered renal function after 3 months (p = .043). Three-month mortality was 27% in both groups, but 55% of deaths occurred in hospital. Those that died had a higher SCr and more severe AKI than survivors; TB was diagnosed in 33 (70%) of those who died. AKI was more severe and renal recovery slower in the TDF group; comorbidities, risk factors, and prognosis were similar regardless of TDF exposure. Because TB is linked to higher mortality, TB coinfection in HIV-infected patients with AKI warrants more intensive monitoring. In all those with poor renal recovery, our

  2. Prior exposure to capture heightens the corticosterone and behavioural responses of little penguins (Eudyptula minor) to acute stress.

    Science.gov (United States)

    Carroll, Gemma; Turner, Emma; Dann, Peter; Harcourt, Rob

    2016-01-01

    Studies of physiology can provide important insight into how animals are coping with challenges in their environment and can signal the potential effects of exposure to human activity in both the short and long term. In this study, we measured the physiological and behavioural response of little penguins (Eudyptula minor) that were naïve to human activity over 30 min of capture and handling. We assessed relationships between corticosterone secretion, behaviour, sex and time of day in order to characterize the determinants of the natural stress response. We then compared the response of these naïve penguins with the responses of female little penguins that had been exposed to research activity (bimonthly nest check and weighing) and to both research activity (monthly nest check and weighing) and evening viewing by tourists. We found that corticosterone concentrations increased significantly over 30 min of capture, with naïve penguins demonstrating a more acute stress response during the day than at night. Penguins that had previously been exposed to handling at the research and research/visitor sites showed elevated corticosterone concentrations and consistently more aggressive behaviour after 30 min compared with naïve birds, although there were no significant differences in baseline corticosterone concentrations. Our findings demonstrate that these little penguins have not habituated to routine capture, but rather mount a heightened physiological and behavioural response to handling by humans. Less invasive research monitoring techniques, such as individual identification with PIT tags and automatic recording and weighing, and a reduction in handling during the day should be considered to mitigate some of the potentially negative effects of disturbance. Given the paucity of data on the long-term consequences of heightened stress on animal physiology, our study highlights the need for further investigation of the relationship between the corticosterone

  3. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.

    Science.gov (United States)

    Tipold, A; Keefe, T J; Löscher, W; Rundfeldt, C; de Vries, F

    2015-04-01

    The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  4. Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients with post-stroke seizure.

    Science.gov (United States)

    Siniscalchi, Antonio; Scaglione, Francesco; Sanzaro, Enzo; Iemolo, Francesco; Albertini, Giorgio; Quirino, Gianluca; Manes, Maria Teresa; Gratteri, Santo; Mercuri, Nicola Biagio; De Sarro, Giovambattista; Gallelli, Luca

    2014-12-01

    Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic drugs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke seizures. We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls. Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p phenobarbital prolonged QTc interval more so than levetiracetam.

  5. Influence of Phenobarbital and Carbon tetrachloride on the Modulation of Tissue Retention Profile of Hexachlorocyclohexane in Rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The study was designed to investigate the role of hepatic metabolic activity on body burden of HCH residue. Male albino rats were orally administered 0, 5, and 10 mg/kg HCH for 90 days, followed by either sodium phenobarbital or carbon tetrachloride treatment for 0, 15 and 30 days after withdrawal of their respective HCH administration. The liver weight was significantly increased at 30 days after the administration of phenobarbital and carbon tetrachloride in both 5 mg and 10 mg/kg HCH withdrawal groups when compared to control. HCH residue was maximun in fat followed by adrenal>thymus>liver>kidney>spleen>testes>brain>plasma. Carbon tetrachloride caused an accumul-ation of HCH residues in the liver 15 and 30 days after administration of both doses of HCH. Phenobarbital did not show significant variation in HCH residues in hepatic tissue. Phenobarbital treatment caused significant induction of hepatic RED, APD, AHH, GST and QR activities. Significant decreases in activities were observed by carbon tetrachloride when compared to animals treated with HCH alone. The overall results clearly suggest the role of P450 protein on the body burden of HCH residues.

  6. ACUTE AND CHRONIC TOXICITY OF ALUMINUM TO A UNIONID MUSSEL (LAMPSILIS SILIQUOIDEA) AND AN AMPHIPOD (HYALELLA AZTECA) IN WATER-ONLY EXPOSURES.

    Science.gov (United States)

    Wang, Ning; Ivey, Chris D; Brunson, Eric L; Cleveland, Danielle; Ingersoll, Chris G; Stubblefield, William A; Cardwell, Allison S

    2017-05-05

    The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity dataset to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about the sensitivity of mussels to Al. The objective of the present study was to evaluate acute 96-h and chronic 28-d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3 . Acute 50% effect concentration (EC50) for survival of both species was >6,200 µg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al dataset for freshwater species at pH range of 5.0 to azteca) as the 5th most sensitive species, indicating the two species were sensitive to Al in chronic exposures. The USEPA proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Postradiation-time dependant dose-response of bone-marrow-cell genetic structures in mice given acute gamma-ray exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, B.; Bulanova, M.; Praskova, L.; Filev, G. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1981-01-01

    Adult mice have received acute exposures to cesium-137 gamma rays at four dose lebels ranging from 0.029 to 0.129 K/kg. 20 hours after the exposure bone-marrow-cell metaphase slides were prepared for cytogemetic analysis. The findings indicated quantitative relations to exist between the scores of structural chromosome aberrations and radiation dose. The chromosome and chromatid fragment fitted to an equation of the Y = aDsup(n) type, chromosome and chromatid exchanges exhibited a linear relationship, and aberrant-cell data were described a linear-quadratic equation. The aberrant-cell percentage seen 20 hrs and 30 hrs after exposure to 0.03225 K/kg proved higher than the one observed at 40 hrs and 72 hrs postradiation.(A.B.).

  8. Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure.

    Science.gov (United States)

    Tolu, Pierluigi; Masi, Flavio; Leggio, Benedetta; Scheggi, Simona; Tagliamonte, Alessandro; De Montis, M Graziella; Gambarana, Carla

    2002-09-01

    Acetyl-L-carnitine (ALCAR) is the acetyl ester of carnitine that has been reported to be beneficial in depressive disorders and Alzheimer's disease. A 7-day administration of ALCAR in rats increased dopamine and serotonin output in the nucleus accumbens shell and it prevented the development of escape deficit produced by acute exposure to unavoidable stress. No tolerance developed to this protective effect, which appeared to be mediated by (1) the activation of 5-HT(1A) receptors, as it was antagonized by the administration of WAY100635 30 min before stress exposure; and (2) a process of neuronal plasticity dependent on NMDA receptor activity, as subcutaneous dizocilpine infusion during ALCAR treatment prevented the development of the protective effect on stress. Chronic stress exposure maintains an escape deficit condition that is reverted by a long-term treatment with antidepressants, but the same condition was not modified by long-term ALCAR administration. Thus, ALCAR cannot be defined as an antidepressant.

  9. Phenobarbital induction and chemical synergism demonstrate the role of UDP-glucuronosyltransferases in detoxification of naphthalophos by Haemonchus contortus larvae.

    Science.gov (United States)

    Kotze, Andrew C; Ruffell, Angela P; Ingham, Aaron B

    2014-12-01

    We used an enzyme induction approach to study the role of detoxification enzymes in the interaction of the anthelmintic compound naphthalophos with Haemonchus contortus larvae. Larvae were treated with the barbiturate phenobarbital, which is known to induce the activity of a number of detoxification enzymes in mammals and insects, including cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UDPGTs), and glutathione (GSH) S-transferases (GSTs). Cotreatment of larvae with phenobarbital and naphthalophos resulted in a significant increase in the naphthalophos 50% inhibitory concentration (IC50) compared to treatment of larvae with the anthelmintic alone (up to a 28-fold increase). The phenobarbital-induced drug tolerance was reversed by cotreatment with the UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, probenecid, and sulfinpyrazone. Isobologram analysis of the interaction of 5-nitrouracil with naphthalophos in phenobarbital-treated larvae clearly showed the presence of strong synergism. The UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, and probenecid also showed synergistic effects with non-phenobarbital-treated worms (synergism ratio up to 3.2-fold). This study indicates that H. contortus larvae possess one or more UDPGT enzymes able to detoxify naphthalophos. In highlighting the protective role of this enzyme group, this study reveals the potential for UDPGT enzymes to act as a resistance mechanism that may develop under drug selection pressure in field isolates of this species. In addition, the data indicate the potential for a chemotherapeutic approach utilizing inhibitors of UDPGT enzymes as synergists to increase the activity of naphthalophos against parasitic worms and to combat detoxification-mediated drug resistance if it arises in the field. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120 exposure.

    Directory of Open Access Journals (Sweden)

    Andrew J Shepherd

    Full Text Available Infection with human immunodeficiency virus-1 (HIV-1 within the brain has long been known to be associated with neurodegeneration and neurocognitive disorder (referred as HAND, a condition characterized in its early stages by declining cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat glycoprotein 120 (gp120 has been suggested to be a critical factor inducing apoptotic cell death in neurons via the activation of p38 mitogen-activated protein kinase (MAPK, upon chronic exposure to the virus. Here we show that acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which provides protection against non-apoptotic cell death, involving the major somatodendritic voltage-gated K⁺ (Kv channel Kv2.1 as the key mediator. The Kv2.1 channel has recently been shown to provide homeostatic control of neuronal excitability under conditions of seizures, ischemia and neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which ultimately leads to changes in specific sub-cellular localization and voltage-dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and subsequent activation of the protein phosphatase calcineurin. This leads to the overall suppression of neuronal excitability and provides neurons with a homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1 channel activity led to significant enhancement of non-apoptotic neuronal death upon acute gp120 treatment. These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections.

  11. Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120 exposure.

    Science.gov (United States)

    Shepherd, Andrew J; Loo, Lipin; Mohapatra, Durga P

    2013-01-01

    Infection with human immunodeficiency virus-1 (HIV-1) within the brain has long been known to be associated with neurodegeneration and neurocognitive disorder (referred as HAND), a condition characterized in its early stages by declining cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat glycoprotein 120 (gp120) has been suggested to be a critical factor inducing apoptotic cell death in neurons via the activation of p38 mitogen-activated protein kinase (MAPK), upon chronic exposure to the virus. Here we show that acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which provides protection against non-apoptotic cell death, involving the major somatodendritic voltage-gated K⁺ (Kv) channel Kv2.1 as the key mediator. The Kv2.1 channel has recently been shown to provide homeostatic control of neuronal excitability under conditions of seizures, ischemia and neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which ultimately leads to changes in specific sub-cellular localization and voltage-dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and subsequent activation of the protein phosphatase calcineurin. This leads to the overall suppression of neuronal excitability and provides neurons with a homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1 channel activity led to significant enhancement of non-apoptotic neuronal death upon acute gp120 treatment. These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections.

  12. Association of ABCB1 C3435T polymorphism with phenobarbital resistance in Thai patients with epilepsy.

    Science.gov (United States)

    Keangpraphun, T; Towanabut, S; Chinvarun, Y; Kijsanayotin, P

    2015-06-01

    One-third of patients with epilepsy are resistant to anti-epileptic drugs (AEDs). Drug-resistant epilepsy is believed to be multifactorial involving both genetic and non-genetic factors. Genetic variations in the ABCB1 gene encoding the drug efflux transporter, p-glycoprotein (p-gp), may influence the interindividual variability in AED response by limiting drugs from reaching their target. Phenobarbital (PB), one of the most cost-effective and widely used AEDs in developing countries, has been reported to be transported by p-gp. This study aimed to investigate the association of a genetic variant, ABCB1 3435C>T, and non-genetic factors with phenobarbital response in Thai patients with epilepsy. One hundred and ten Thai patients with epilepsy who were treated with PB maintenance doses were enrolled in this study. Two phenotypic groups, PB-responsive epilepsy and PB-resistant epilepsy, were defined according to the International League Against Epilepsy (ILAE) criteria. Subjects were genotyped for ABCB1 3435C>T (rs1045642). Multiple logistic regression analysis was tested for the association of ABCB1 3435C>T polymorphism and non-genetic factors with PB response. Sixty-two PB-responsive epilepsy subjects and 48 PB-resistant epilepsy subjects were identified. All genotype frequencies of the ABCB1 3435C>T SNP were consistent with the Hardy-Weinberg equilibrium (P > 0·05). The ABCB1 3435C>T polymorphism and type of epilepsy were associated with response to PB. Patients with PB-resistant epilepsy had a significantly higher frequency of ABCB1 3435CC genotype and had focal epilepsy more often than patients with PB-responsive epilepsy (adjusted OR = 3·962, 95% CI = 1·075-14·610, P-value = 0·039; adjusted OR = 5·936, 95% CI = 2·272-15·513, P-value phenobarbital. © 2015 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn (Poland); Wu, Dongmei, E-mail: dongmei.wu@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Wallin, Håkan, E-mail: hwa@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Vogel, Ulla, E-mail: ubv@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically

  15. No Effects of Acute Exposure t