WorldWideScience

Sample records for acute phenobarbital exposure

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

    Dow Jacky

    2010-01-01

    Full Text Available Abstract 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.

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

    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 postnata...

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

    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. PMID:25112558

  4. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures

    Maitre, Nathalie L.; Smolinsky, Ciaran; Slaughter, James C.; Stark, Ann R.

    2013-01-01

    Objective Compare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures. Study design Retrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures. Effect of cumulative exposure to LEV and PB on outcomes of death, cerebral palsy (CP), and Bayley Scales of Infant Development (BSID) scores were evaluated at 24 months corrected age. Analyses were adjusted for number of electrographic seizures and gestational age. Results In 280 in...

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

    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

  6. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

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

    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 of...

  7. Estimating risk from acute exposures- new concepts

    Risk from acute exposures at different ages is calculated by the ICRP-60 methodology using Indian and Swedish-ICRP baseline data. The results demonstrate a considerably lower significance for exposures at higher ages. For acute exposures in the age range 0-45 years, more than half the fatality probability and more than one fourth the person-years of life lost are expressed above age 65 years. The Indian values of these parameters are a factor of 2 to 3 lower than those for the Swedish-ICRP values. The results are compared with those obtained by the Biological Effects of Ionizing Radiation (BEIR V) method. (author). 4 refs., 1 tab., 1 fig

  8. In Vivo Nanodetoxication for Acute Uranium Exposure

    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.

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

    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.

  10. Compound list: phenobarbital [Open TG-GATEs

    Full Text Available phenobarbital PB 00004 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/phenobarbital.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/...in_vitro/phenobarbital.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vivo/Liver/Single/phenobarbital.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggat...es/LATEST/Rat/in_vivo/Liver/Repeat/phenobarbital.Rat.in_vivo.Liver.Repeat.zip ...

  11. Chromosome aberrations and environmental exposures in acute leukemia

    Lindquist, Ragnhild Rosengren

    2009-01-01

    The aims of this thesis are to evaluate the role of environmental exposures, especially professional exposure to organic solvents and petroleum products in the etiology of acute leukemia and to investigate if there is a correlation between the exposure to a specific leukemogen factor and a clonal chromosome aberration of the leukemic cells. Papers I and II present results of a case-control study of environmental exposures, in all occupations during life-time, medical treatm...

  12. Phenobarbital induced Stevens–Johnson syndrome in a child

    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.

  13. VISUAL SYSTEM DYSFUNCTION FOLLOWING ACUTE TRIMETHYLTIN EXPOSURE IN RATS

    Trimethyltin (TMT) has been shown to produce damage in the limbic system and several other brain areas. To date, damage to sensory systems has not been reported. The present study investigated the integrity of the visual system following acute exposure to TMT. Rats were chronical...

  14. Biomarkers of Acute Respiratory Allergen Exposure: Screening For Sensitization Potential

    Rationale: An in vitro assay to identify respiratory sensitizers will provide a rapid screen and reduce animal use. The study goal was to identify biomarkers that differentiate allergen versus non-allergen responses following an acute exposure. Methods: Female BALB/c mice rec...

  15. PREDICTORS OF INDIVIDUAL DIFFERENCES IN ACUTE RESPONSE TO OZONE EXPOSURE

    The purposes of this study were to identify personal characteristics which predict individual differences in acute response to ozone exposure and to develop a predictive model for decrements in FEV1 as a function of ozone concentration and individual predictors. esponse and predi...

  16. Health Impacts from Acute Radiation Exposure

    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.

  17. 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

    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...

  18. Explanation of nurse standard of external exposure acute radiation sickness

    National occupational health standard-Nurse Standard of External Exposure Acute Radiation Sickness has been approved and issued by the Ministry of Health. Based on the extensive research of literature, collection of the previous nuclear and radiation accidents excessive exposed personnel data and specific situations in China, this standard was enacted according to the current national laws, regulations, and the opinions of peer experts. It is mainly used for care of patients with acute radiation sickness, and also has directive significance for care of patients with iatrogenic acute radiation sickness which due to the hematopoietic stem cell transplantation pretreatment. To correctly carry out this standard and to reasonably implement nursing measures for patients with acute radiation sickness, the contents of this standard were interpreted in this article. (authors)

  19. Acute behavioural dysfunctions following exposure to γ-rays

    Exposure to ionizing radiations (IR) has been reported to have many ill effects. These are manifested immediately after exposure and may persist or develop long after the incident. The severity and manifestation is dependent on the absorbed dose and type of the IR. These have been reported extensively in human subjects; especially among the victims of the accidental exposure and radiotherapy patients. Additionally, there have been a plethora of studies in animal models which support these findings, and are being used to test radio-mitigative or radio-protective strategies. The vulnerability of neuronal tissue to IR is well known, however the acute dose-dependent behavioural consequences have yet to be understood. Thus, our laboratory has been trying to decipher the dose-dependent behavioural dysfunctions which have occurred 24-72 hours post IR exposure and possible radio-protective strategies. We are utilizing mouse models of studying the behavioural processes, in a test battery conceptualized to study the affective and cognitive skills as well as motor skills of the animals. Additionally, we have observed cellular damage to different areas of the brain and subsequent correlations to behavioural dysfunctions. This has being carried out by using single cell gel electrophoresis (SCGE) and Diffusion Tensor Imaging (DTI). The findings show that after exposure to sub-lethal γ-rays, there are significant changes that occur in all the behavioural parameters. The most sensitive area has been found to be the Hippocampus as visualized by DTI and the SCGE. Consequently, short term and long term memory functions have been shown to be disrupted within 24-72 hours of exposure. Acute dysfunctions of affective functions have also been demonstrated to materialise within 24 hours post exposure. Unexpectedly, the behavioural dysfunctions were seen to be dose independent. Thus, this study provides a foundation to help decipher the acute behavioural manifestations of IR exposure

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

    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. PMID:26924539

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

    Bælum, Jesper

    1991-01-01

    symptoms. The pharmacokinetics of toluene is complex and there is a large individual variation in the excretion of the metabolites. This variation can only to a limited extend be related to known variables. Intake of alcohol during exposure inhibits the metabolism of toluene and increases the internal dose...... 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 and...

  2. Toxicity levels to humans during acute exposure to hydrogen fluoride

    A literature review was conducted of the acute toxicity of hydrogen fluoride (HF) with emphasis on the effects of inhalation of gaseous HF. The data and findings of the relevant references were summarized under four categories: animal studies, controlled human studies, community exposure and industrial exposure. These were critically reviewed and then lethal concentration-time relationships were developed for humans, corresponding to LCsub(LO), LCsub(10) and LCsub(50) levels. The effects of age, health and other physiological variables on the sensitivity to HF were discussed, as well as antagonistic and synergistic effects with other substances

  3. Acute pulmonary alveolar proteinosis due to exposure to cotton dust

    Thind Gurcharan

    2009-01-01

    Full Text Available Secondary pulmonary alveolar proteinosis (PAP is rare but may occur in association with malignancy, certain infections, and exposure to inorganic or organic dust and some toxic fumes. This case report describes the second recorded case of PAP due to exposure to cotton dust. A 24-year-old man developed PAP after working as a spinner for eight years without respiratory protection. He was admitted as an emergency patient with very severe dyspnea for four months and cough for several years. Chest X-ray showed bilateral diffuse alveolar consolidation. He died 16 days later, and a diagnosis of acute pulmonary alveolar proteinosis was made at autopsy. The histopathology demonstrated alveoli and respiratory bronchioles filled with characteristic periodic acid Schiff-positive material, which also revealed birefringent bodies of cotton dust under polarized light. Secondary PAP can be fatal and present with acute respiratory failure. The occupational history and characteristic pathology can alert clinicians to the diagnosis.

  4. ACUTE PRENATAL EXPOSURE TO ETHANOL AND SOCIAL BEHAVIOR: EFFECT OF AGE, SEX, AND TIMING OF EXPOSURE

    Mooney, Sandra M.; Varlinskaya, Elena I.

    2010-01-01

    During development of the central nervous system, neurons pass through critical periods of vulnerability to environmental factors. Exposure to ethanol during gastrulation or during neuronal generation results in a permanent reduction in the number of neurons in trigeminal-associated cranial nerve nuclei. Normal functioning of the trigeminal system is required for social behavior, the present study examined the effects of acute prenatal exposure to ethanol on social interactions across ontogen...

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

    Dörr Harald; Meineke Viktor

    2011-01-01

    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 ab...

  6. Chromosomal abnormalities and environmental exposures in acute nonlymphocytic leukemia

    Chromosomal abnormalities are present in bone marrow of approximately 50% of newly diagnostic acute nonlymphatic leukemia (ANLL) patients, but their etiologic significance, if any, is unclear. The frequency of environmental exposures, gathered by questionnaire from patients or relatives, was compared in 127 newly diagnosed ANLL patients with marrow abnormalities (AA) and 109 ANLL patients with cytogenetically normal marrow. These represented 73% of de novo patients treated at M. D. Anderson Hospital between 1976 and 1983. AA patients were more likely than NN patients to: report cytotoxic treatment for prior medical conditions, smoke cigarettes, drink alcoholic beverages, and work at occupations with possible exposure to mutagens. No statistically significant associations between aneuploidy and use of other tobacco, avocational exposure to chemicals or exposure to animals were present. Associations between specific abnormalities and prior cytotoxic therapy (deletion of chromosome 7), smoking (extra chromosome 8, inversion chromosome 16), and occupation at the time of diagnosis (translocation between chromosomes 8 and 21) were noted. No association between occupational exposure to benzene or ionizing radiation and the 6 most common chromosomal abnormalities in ANLL patients were noted, although these agents are known to be leukemogenic. Problems with interpreting the above associations, including the high nonresponse rate, a high proportion of surrogate respondents, and the large number of significance tests that were performed, are discussed. These results are consistent with those from previously reported series, and suggest that tumor-specific markers may be present for some exposures in this disease

  7. Synthesis of phenobarbital 14C - 5 (1964)

    Phenobarbital (Luminal), well known as a hypnotic agent, plays also an important role in the medical treatment of epilepsy. With the object of studying the metabolism of this medicament in the living system, the synthesis of phenobarbital marked in position 2 of the pyrimidinic ring has been effected. It has been necessary, in order to carry out to research into the metabolism of this product, to have a phenobarbital marked in position 5 of the pyrimidinic ring. This synthesis, making it possible to introduce C-14 into position 5 of the pyrimidinic ring, consists of seven stages starting from C-14 carboxyl benzoic acid having a specific activity of 25 mc/mM. The melting point of the final product is 172 - 173 deg. C and its specific activity is 11.15 mc/mM. The overall radioactive yield of the pure product, with respect to the original benzoic acid (10 mM) is of the order of 3 per cent. The purity of the product has been controlled by paper chromatography; it is of the order of 99 per cent. (author)

  8. Lung oxidative response after acute coal dust exposure

    Coal dust exposure can induce an acute alveolar and interstitial inflammation that can lead to chronic pulmonary diseases. The objective of this study was to describe the acute and later effects of acute coal dust exposure in lung parenchyma and the involvement of reactive oxygen species in coal dust effects. Forty-eight male Wistar rats (200-250 mg) were separated into four groups: 48 h, 7 days, 30 days, and 60 days after coal dust instillation. Gross mineral coal dust (3 mg/0.5 mL saline) was administered directly in the lungs of the treatment group by intratracheal instillation. Control animals received only saline solution (0.5 mL). Lipid peroxidation was determined by the quantity of thiobarbituric acid-reactive species (TBARS), oxidative damage to protein was obtained by the determination of carbonyl groups, the total radical-trapping antioxidant parameter (TRAP) was estimated by luminol chemoluminescence emission, catalase activity was measured by the rate of decrease in hydrogen peroxide, and superoxide dismutase activity was assayed by the inhibition of adrenaline autooxidation. Histological evaluation of coal dust-treated rats demonstrated an inflammatory infiltration after 48 h of the exposure. Initially, this was a cellular infiltration suggestive of lymphocyte infiltration with lymphoid hyperplasia that remained until 7 days after induction. This initial response was followed by a chronic inflammatory infiltration characterized by aggregates of macrophages 30 days after induction. This inflammatory response tended to resolve 60 days after induction, being similar to that of control animals. During both the acute and chronic phases of lung inflammation we observed a decrease in the TRAP in the lung of coal dust-exposed animals compared to that in control animals. We also observed an activation of superoxide dismutase 60 days after coal dust exposition. TBARS were increased 60 days after coal dust exposure and protein carbonyl groups increased at all

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

    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.

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

    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. PMID:25101986

  11. Acute skin lesions due to localized ''hot particle'' radiation exposures

    Purpose of the studies was to determine incidence and severity of lesions resulting from localized deposition of dose to the skin from small (2 at 70μm depth) from isotopes having max beta particle energies from about 0.3-3 MeV. Incidence of erythema and scabs (indicating ulceration) were scored routinely for up to 71 days post-irradiation. Responses followed normal probability distributions, and thus, no true threshold could be defined. Ten and 50% incidence rates were deduced using probit analyses. Lowest dose producing 10% incidence was about 1 Gy for exposures to Yb-175 (0.5 MeV max energy) beta particles. Severity of lesions was estimated using diameters and persistence. From preliminary considerations of probability of induction, size, and persistence of acute lesions, a special limit for hot particle exposures in the range of 5-50 Gy may be reasonable, with an action level between about 1 Gy and the limit

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

    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.

  13. Impact of chronic and acute pesticide exposures on periphyton communities

    Aquatic ecosystems face variable exposure to pesticides, especially during floodings which are associated with short bursts of high contaminant concentrations that influence biological systems. A study was undertaken to highlight the impact of the herbicide diuron applied in mixture with the fungicide tebuconazole on natural periphyton during flooding events. Periphyton were grown in two series of two lotic outdoor mesocosms: one series was non-contaminated while the other was exposed to chronic contamination. After 4 weeks, one channel of each series was exposed to three successive pulses, with each pulse followed by one week of recovery. Impacts on periphyton were assessed by using Denaturing Gel Gradient Electrophoresis to characterize eukaryotic community structure. At a functional scale, photosynthetic efficiency was quantified during each pulse, and the induced tolerance to diuron was estimated by performing short-term inhibition tests based on photosynthetic efficiency. Moreover, pesticide concentrations in the water column and periphyton matrix were measured. Diuron was adsorbed in the periphyton during each pulse and desorbed 13 h after pulse end. The different pulses affected the eukaryotic community structures of the control biofilms, but not of the chronically exposed ones. During the first pulse, photosynthetic efficiency was correlated with pesticide concentration in the water phase, and there was no difference between periphyton from chronically contaminated channels and control channels. However, during the second and third pulses, the photosynthetic efficiency of periphyton chronically exposed to pesticides appeared to be less impacted by the acute pulsed exposure of pesticide. These changes were consistent with the acquisition of induced tolerance to diuron since only after the third pulse that periphyton from chronic channel became tolerant to diuron. Our experimental study indicates that the effects of pulsed acute exposures to pesticides on

  14. Acute effects of acrolein in human volunteers during controlled exposure

    Dwivedi, Aishwarya M.; Johanson, Gunnar; Lorentzen, Johnny C.; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

    2015-01-01

    Abstract Context: Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. Objective: The aim of the study was to determine thresholds for acute irritation for acrolein. Methods: Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. Results: The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p acrolein alone but not during any of the other five exposure conditions. Conclusion: Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein. PMID:26635308

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

    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

    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. Dose-response relationships of acute exposure to sulfur dioxide

    Acute toxicity effects of sulphur dioxide are reviewed, and the derivation of a dose-lethality curve (presented as LC50 vs. time) for human exposure to sulphur dioxide is attempted for periods ranging from ten seconds to two hours. As an aid to assessment of the hazards involved in operating heavy water manufacturing facilities, the fact that sulphur dioxide would be produced by the combustion of hydrogen sulphide was briefly considered in an appendix. It is suggested that sulphuric acid, a much more toxic substance than sulphur dioxide, may also be formed in such an event. It is concluded, therefore, that an overall hazard evaluation may have to address the contributory effects of sulphuric acid. (author)

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

    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.

  19. Successful use of haemodialysis to treat phenobarbital overdose

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

    2013-01-01

    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 elimin...

  20. Acute Exposure from RADON-222 and Aerosols in Drinking Water

    Bernhardt, George Paul, IV

    Radon-222 in water is released when the water is aerated, such as during showering. As a result, a temporary burst of radon-222 can appear as a short term, or acute, exposure. This study looked at homes with radon-222 concentrations in water from 800 picocuries per liter (pCi/l) to 53,000 pCi/l to determine the buildup of radon gas in a bathroom during showering. Samples from the tap and drain, compared to determine the percentage of radon-222 released, showed that between 58% and 88% of radon-222 in the water was released. The resultant radon-222 increase in air, measured with a flow-through detector, ranged from 2 pCi/l to 114 pCi/l in bathrooms due to a 10 to 15 minute shower with water flow rates ranging from 3 l/min to 6 l/min. Significantly, these rates did not fall rapidly but stayed approximately the same for up to 15 minutes after the water flow ceased. In examining exposures, the true danger is in the radon-222 progeny rather than the radon itself. The progeny can be inhaled and deposited in the tracheobronchial passages in the lung. Filter samples of bathroom air measured in a portable alpha spectrometer showed an increase in radon-222 progeny, notably polonium-218 and -214, in the air after showering. These increases were gradual and were on the order of 0.5 pCi/l at the highest level. Tap samples measured in a portable liquid scintillator showed that the progeny are present in the water but are not in true secular equilibrium with the radon-222 in the water. Therefore, the radon-222 does not have to decay to produce progeny since the progeny are already present in the water. A two stage sampler was used to examine the percentage of radiation available in aerosols smaller than 7 microns. Repeated trials showed that up to 85% of the radiation available in the aerosols is contained in the smaller, more respirable particles.

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

    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)....

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

    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...

  3. Continuous positive airway pressure increases haemoglobin O2 saturation after acute but not prolonged altitude exposure.

    p. Agostoni, Caldara G, Bussotti M, Revera M, Valentini M, Gregorini F, Faini A, Lombardi C, Bilo G, Giuliano A, Veglia F, Savia G, P.A. Modesti, Mancia G, Parati G

    2010-01-01

    Abstract: It is unknown whether subclinical high-altitude pulmonary oedema reduces spontaneously after prolonged altitude exposure. Continuous positive airway pressure (CPAP) removes extravascular lung fluids and improves haemoglobin oxygen saturation in acute cardiogenic oedema. We evaluated the presence of pulmonary extravascular fluid increase by assessing CPAP effects on haemoglobin oxygen saturation under acute and prolonged altitude exposure. We applied 7 cm H2O CPAP for 30 min to he...

  4. Brewing complications: the effect of acute ethanol exposure on wound healing

    Radek, Katherine A.; Ranzer, Matthew J.; DiPietro, Luisa A.

    2009-01-01

    Ethanol consumption is linked to a higher incidence of traumatic wounds and increases the risk for morbidity and mortality following surgical or traumatic injury. One of the most profound effects of acute ethanol exposure on wound healing occurs during the inflammatory response, and altered cytokine production is a primary component. Acute ethanol exposure also impairs the proliferative response during healing, causing delays in epithelial coverage, collagen synthesis, and blood vessel regrow...

  5. Acute leukaemia after exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid.

    Timonen, T T; Palva, I P

    1980-01-01

    Acute leukaemia is known to develop in many cases of benzene-induced pancytopenia [1]. This is a report of the development of acute leukaemia in a patient who had apparently recovered from pancytopenia after chronic exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid. PMID:6769284

  6. Modelling the effects of ionizing radiation on survival of animal population: acute versus chronic exposure.

    Kryshev, A I; Sazykina, T G

    2015-03-01

    The objective of the present paper was application of a model, which was originally developed to simulate chronic ionizing radiation effects in a generic isolated population, to the case of acute exposure, and comparison of the dynamic features of radiation effects on the population survival in cases of acute and chronic exposure. Two modes of exposure were considered: acute exposure (2-35 Gy) and chronic lifetime exposure with the same integrated dose. Calculations were made for a generic mice population; however, the model can be applied for other animals with proper selection of parameter values. In case of acute exposure, in the range 2-11 Gy, the population response was in two phases. During a first phase, there was a depletion in population survival; the second phase was a recovery period due to reparation of damage and biosynthesis of new biomass. Model predictions indicate that a generic mice population, living in ideal conditions, has the potential for recovery (within a mouse lifetime period) from acute exposure with dose up to 10-11 Gy, i.e., the population may recover from doses above an LD50 (6.2 Gy). Following acute doses above 14 Gy, however, the mice population went to extinction without recovery. In contrast, under chronic lifetime exposures (500 days), radiation had little effect on population survival up to integrated doses of 14-15 Gy, so the survival of a population subjected to chronic exposure was much better compared with that after an acute exposure with the same dose. Due to the effect of "wasted radiation", the integrated dose of chronic exposure could be about two times higher than acute dose, producing the same effect on survival. It is concluded that the developed generic population model including the repair of radiation damage can be applied both to acute and chronic modes of exposure; results of calculations for generic mice population are in qualitative agreement with published data on radiation effects in mice. PMID

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

    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.

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

    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 th...

  9. Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts.

    X. Hu; Wegman, D H; Eisen, E A; Woskie, S R; Smith, R G

    1992-01-01

    A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a d...

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

    Hjermø, Ida; Anderson, John Erik; Fink-Jensen, Anders; Allerup, Peter N.; Ulrichsen, Jakob

    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....

  11. Occupational exposure to solvents and acute myeloid leukemia

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

    2014-01-01

    660 controls matched by year of birth, sex, and country. Occupational records were linked with Nordic Occupational Cancer Study job exposure matrix (JEM) to estimate quantitative values for 26 occupational exposure factors. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated by...... for an excess risk in the groups of workers exposed to toluene, trichloroethylene and ARHC....

  12. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    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...

  13. Cardiac Autonomic Effects of Acute Exposures to Airborne Particulates in Men and Women

    Howarth, M. S.; Schlegel, T. T.; Knapp, C. F.; Patwardhan, A. R.; Jenkins, R. A.; Ilgner, R. H.; Evans, J. M.

    2007-01-01

    The aim of this research was to investigate cardiac autonomic changes associated with acute exposures to airborne particulates. Methods: High fidelity 12-lead ECG (CardioSoft, Houston, TX) was acquired from 19 (10 male / 9 female) non-smoking volunteers (age 33.6 +/- 6.6 yrs) during 10 minutes pre-exposure, exposure and post-exposure to environmental tobacco smoke (ETS), cooking oil fumes, wood smoke and sham (water vapor). To control exposure levels, noise, subject activity, and temperature, all studies were conducted inside an environmental chamber. Results: The short-term fractal scaling exponent (Alpha-1) and the ratio of low frequency to high frequency Heart Rate Variability (HRV) powers (LF/HF, a purported sympathetic index) were both higher in males (pcardiac responses to some acute airborne particulates are gender related.

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

    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 bl...

  15. Commuters’ air pollution exposure and acute health effects

    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 disproportionately to total daily exposure to traffic related air pollution. So far a limited number of studies compared particulate matter exposures of different groups of commuters. There is limited evid...

  16. Acute pulmonary alveolar proteinosis due to exposure to cotton dust

    Thind Gurcharan

    2009-01-01

    Secondary pulmonary alveolar proteinosis (PAP) is rare but may occur in association with malignancy, certain infections, and exposure to inorganic or organic dust and some toxic fumes. This case report describes the second recorded case of PAP due to exposure to cotton dust. A 24-year-old man developed PAP after working as a spinner for eight years without respiratory protection. He was admitted as an emergency patient with very severe dyspnea for four months and cough for several years. Ches...

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

    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.

  18. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction

    ATTAYA, SHARIFF; KANTHI, YOGENDRA; ASTER, RICHARD; MCCRAE, KEITH

    2015-01-01

    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies. PMID:19172524

  19. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction

    ATTAYA, SHARIFF; Kanthi, Yogendra; Aster, Richard; McCrae, Keith

    2009-01-01

    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies.

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

    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

  1. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    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......-water after contamination will not die as a result of Se toxicity and can safely be used for human consumption....

  2. Cumulative exposure to prior collective trauma and acute stress responses to the Boston marathon bombings.

    Garfin, Dana Rose; Holman, E Alison; Silver, Roxane Cohen

    2015-06-01

    The role of repeated exposure to collective trauma in explaining response to subsequent community-wide trauma is poorly understood. We examined the relationship between acute stress response to the 2013 Boston Marathon bombings and prior direct and indirect media-based exposure to three collective traumatic events: the September 11, 2001 (9/11) terrorist attacks, Superstorm Sandy, and the Sandy Hook Elementary School shooting. Representative samples of residents of metropolitan Boston (n = 846) and New York City (n = 941) completed Internet-based surveys shortly after the Boston Marathon bombings. Cumulative direct exposure and indirect exposure to prior community trauma and acute stress symptoms were assessed. Acute stress levels did not differ between Boston and New York metropolitan residents. Cumulative direct and indirect, live-media-based exposure to 9/11, Superstorm Sandy, and the Sandy Hook shooting were positively associated with acute stress responses in the covariate-adjusted model. People who experience multiple community-based traumas may be sensitized to the negative impact of subsequent events, especially in communities previously exposed to similar disasters. PMID:25896419

  3. Commuters’ air pollution exposure and acute health effects

    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

  4. Cumulative Exposure to Prior Collective Trauma and Acute Stress Responses to the Boston Marathon Bombings

    Garfin, DR; Holman, EA; Silver, RC

    2015-01-01

    © The Author(s) 2015 The role of repeated exposure to collective trauma in explaining response to subsequent community-wide trauma is poorly understood. We examined the relationship between acute stress response to the 2013 Boston Marathon bombings and prior direct and indirect media-based exposure to three collective traumatic events: the September 11, 2001 (9/11) terrorist attacks, Superstorm Sandy, and the Sandy Hook Elementary School shooting. Representative samples of residents of metrop...

  5. Working memory performance after acute exposure to the cold pressor stress in healthy volunteers

    Duncko, Roman; Johnson, Linda; Merikangas, Kathleen; Grillon, Christian

    2009-01-01

    Effects of acute stress exposure on learning and memory have been frequently studied in both animals and humans. However, only a few studies have focused specifically on working memory performance and the available data are equivocal. The present study examined working memory performance during the Sternberg item recognition task after exposure to a predominantly adrenergic stressor. Twenty four healthy subjects were randomly assigned to a stress group or a control group. The stress group was...

  6. Cement dust exposure and acute lung function: A cross shift study

    Moen Bente E

    2010-04-01

    Full Text Available Abstract Background Few studies have been carried out on acute effects of cement dust exposure. This study is conducted to investigate the associations between current "total" dust exposure and acute respiratory symptoms and respiratory function among cement factory workers. Methods A combined cross-sectional and cross-shift study was conducted in Dire Dawa cement factory in Ethiopia. 40 exposed production workers from the crusher and packing sections and 20 controls from the guards were included. Personal "total" dust was measured in the workers' breathing zone and peak expiratory flow (PEF was measured for all selected workers before and after the shift. When the day shift ended, the acute respiratory symptoms experienced were scored and recorded on a five-point Likert scale using a modified respiratory symptom score questionnaire. Results The highest geometric mean dust exposure was found in the crusher section (38.6 mg/m3 followed by the packing section (18.5 mg/m3 and the guards (0.4 mg/m3. The highest prevalence of respiratory symptoms for the high exposed workers was stuffy nose (85% followed by shortness of breath (47% and "sneezing" (45%. PEF decreased significantly across the shift in the high exposed group. Multiple linear regression showed a significant negative association between the percentage cross-shift change in PEF and total dust exposure. The number of years of work in high-exposure sections and current smoking were also associated with cross-shift decrease in PEF. Conclusions Total cement dust exposure was related to acute respiratory symptoms and acute ventilatory effects. Implementing measures to control dust and providing adequate personal respiratory protective equipment for the production workers are highly recommended.

  7. The effects of acute radiation exposure on the serum components

    The blood samples were collected from the experimental animals 24 hrs after irradiation of gamma doses upto 80 Gy. Native PAGE showed a decreasing trend in gamma globulin fraction of serum from the irradiated group compared to control, while SDS PAGE indicated an enhanced tendency in protein of molecular weight 30,000 to 40,000. Serum albumin slightly decreased with radiation doses as a result of decrease in total protein amount. Radiation exposure had little or no effects on such lipid related components as phospholipid, triglyceride, and cholesterol, respectively. Among others, glutamic pyryvic transaminase (GPT) showed a drastic decrease in its amount 24 hrs after radiation exposure, which can be applied to the health care program for radiation workers. (Author)

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

    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...

  9. Acute Lung Injury Due To Carbon Monoxide Exposure

    Uzkeser M et al.

    2012-10-01

    Full Text Available A 20-year-old woman, who was found unconscious in the bed by the morning, was brought to emergency department. Her carboxyhemoglobin level was 20.2%. The portable chest X-ray showed bilaterally alveolar and interstitial infiltration. Initial pO 2 /FIO 2 ratio was calculated as 119 mmHg. Acute lung injury due to carbon monoxide intoxication was considered. She was intubated and mechanical ventilation was applied. In the second day of hospitalization, a clear improvement was observed on the chest X-ray. She was discharged without any complication on the seventh day of hospitalization. Early diagnosis and treatment may prevent progression of ARDS and progression of permanent damage, and may lead to complete recovery.

  10. Effect of sodium valproate on phenobarbital serum levels in children and adults.

    Fernandez de Gatta, M R; Alonso Gonzalez, A C; Garcia Sanchez, M J; Dominguez-Gil Hurle, A; Santos Borbujo, J; Monzon Corral, L

    1986-01-01

    The influence of sodium valproate on serum levels of phenobarbital during combination treatment was studied in 29 children and 50 adults with epilepsy. Steady-state drug levels in serum were determined immediately prior to drug administration using immunoenzymatic analysis. The serum level/dose ratio of phenobarbital increased significantly (p less than 0.001) when sodium valproate was added to the treatment. The increase had a mean value of 50.9% in adults and 112.5% in children, suggesting marked interindividual variability in the intensity of the interaction. Almost half of the patients required a decrease in the dose of phenobarbital prescribed. The interaction was more pronounced in patients with high serum levels of phenobarbital, while the dose of phenobarbital and the serum levels and dose of sodium valproate did not seem to affect the extent of the interaction. Close monitoring of the serum levels of phenobarbital is recommended during simultaneous treatment with sodium valproate. PMID:3103264

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

    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. PMID:25098448

  12. Pathological Evaluation of Phenobarbital and Atorvastatin Co-Administration on Kidney of Rat

    Hossein Najafzadeh; Hassan Morovvati; Babak Mohammadian; Mohammad Razijalali; S.Mahsa Poormoosavi

    2012-01-01

    Background: Atorvastatin is a lipid-lowering drug used to treat hyperlipidemia. Phenobarbital is the inductor of cytochrome enzymes. This study examined the interfering effect of simultaneous consumption of these drugs on the biochemical and pathological changes in rat’s kidney.Materials and Methods: Drugs were administered to 4 groups of Wistar rats (8 per group) for 15 days as follows: normal saline, atorvastatin, atorvastatin phenobarbital and phenobarbital alone. After anesthesia, blood w...

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

    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

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

    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

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

    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. PMID:24120434

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

    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.

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

    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

  18. The brain is a target organ after acute exposure to depleted uranium

    The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144 ± 10 μg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 μg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70 ± 8 μg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed

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

    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

  20. Characterisation of cochlear inflammation in mice following acute and chronic noise exposure.

    Tan, Winston J T; Thorne, Peter R; Vlajkovic, Srdjan M

    2016-08-01

    Oxidative stress has been established as the key mechanism of the cochlear damage underlying noise-induced hearing loss, however, emerging evidence suggests that cochlear inflammation may also be a major contributor. This study aimed to improve our understanding of the cochlear inflammatory response associated with acute and chronic noise exposure. C57BL/6 mice were exposed to acute traumatic noise (100 dBSPL, 8-16 kHz for 24 h) and their cochleae collected at various intervals thereafter, up to 7 days. Using quantitative RT-PCR and immunohistochemistry, changes in expression levels of proinflammatory cytokines (TNF-α, IL-1β), chemokines (CCL2) and cell adhesion molecules (ICAM-1) were studied. All gene transcripts displayed similar dynamics of expression, with an early upregulation at 6 h post-exposure, followed by a second peak at 7 days. ICAM-1 immunoexpression increased significantly in the inferior region of the spiral ligament, peaking 24 h post-exposure. The early expression of proinflammatory mediators likely mediates the recruitment and extravasation of inflammatory cells into the noise-exposed cochlea. The occurrence of the latter expression peak is not clear, but it may be associated with reparative processes initiated in response to cochlear damage. Chronic exposure to moderate noise (90 dBSPL, 8-16 kHz, 2 h/day, up to 4 weeks) also elicited an inflammatory response, reaching a maximum after 2 weeks, suggesting that cochlear damage and hearing loss associated with chronic environmental noise exposure may be linked to inflammatory processes in the cochlea. This study thus provides further insight into the dynamics of the cochlear inflammatory response induced by exposure to acute and chronic noise. PMID:27109494

  1. Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

    In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LCLO, LC10 and LC50 levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs

  2. High precision liquid chromatography analysis of dopaminergic and serotoninergic responses to acute alcohol exposure in zebrafish

    Chatterjee, Diptendu; Gerlai, Robert

    2009-01-01

    Zebrafish is gaining popularity in behavioral neuroscience in general and in alcohol research in particular. Alcohol is known to affect numerous molecular mechanisms depending on dose and administration regimen. Prominent among these mechanisms are several neurotransmitter systems. Here we analyze the responses of the dopaminergic and serotoninergic neurotransmitter systems of zebrafish to acute alcohol treatment (1 h long exposure of adult fish to 0.00%, 0.25%, 0.50%, or 1.00% ethyl alcohol)...

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

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

    2015-01-01

    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 1mg K/L to 3mg 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.

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

    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. PMID:26874561

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

    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.

  6. Chemosensory effects during acute exposure to N-methyl-2-pyrrolidone (NMP).

    van Thriel, Christoph; Blaszkewicz, Meinolf; Schäper, Michael; Juran, Stephanie A; Kleinbeck, Stefan; Kiesswetter, Ernst; Wrbitzky, Renate; Stache, Jürgen; Golka, Klaus; Bader, Michael

    2007-12-10

    Organic solvents are still essential in many industrial applications. To improve safety and health in the working environment lower occupational thresholds limits have been established and less toxic substitutes were introduced. N-Methyl-2-pyrrolidone (NMP) is a versatile solvent that is used as a substitute for dichloromethane in paint strippers. Due to conflicting results, there is a debate whether NMP causes irritations of the upper airways/eyes or not. In a human experimental study we examined the chemosensory effects of NMP under controlled conditions. Fifteen healthy males were investigated in a cross-over study. NMP vapor concentrations were 10, 40 and 80 mg/m(3) for 2 x 4h with an exposure-free lunch break of 30 min. To maximize chemosensory effects a peak exposure scenario (25mg/m(3) baseline, 160 mg/m(3) peaks 4 x 15 min, time-weighted average: 72 mg/m(3)) was tested. The four different conditions were conducted with and without moderate physical workload. Chemosensory effects were measured physiologically by anterior rhinomanometry, eye blink rate and breathing frequency. Subjectively, ratings of acute health symptoms and intensity of olfactory and trigeminal sensations were collected repeatedly throughout the exposures. All physiological variables were unaffected by the different NMP concentrations and even the peak exposures were non-effective on these measures. Olfactory mediated health symptoms increased dose-dependently. For these symptoms a strong adaptation was observable, especially during the first 4h of the exposures. Other acute symptoms were not significantly affected. Comparable to the symptoms, only olfactory sensations increased dose-dependently. Trigeminal sensations (e.g. eye and nose irritations) were evaluated as being barely detectable during the different exposures, only during 160 mg/m(3) exposure peak weak and transient eye irritation were reported. The results clearly suggest that NMP concentrations of up to 160 mg/m(3) caused no

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

    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.

  8. Comparative sensitivity of three populations of the cladoceran Moinodaphnia macleayi to acute and chronic uranium exposure.

    Semaan, M; Holdway, D A; van Dam, R A

    2001-10-01

    Assessment of differences in the response of three different populations of the tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The populations tested included a laboratory stock (maintained for 10 years), a wild population collected from Bowerbird Billabong (an uncontaminated environment), and a population collected from Djalkmara Billabong (a relatively contaminated environment with elevated levels of uranium), located on the Ranger uranium mine site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was determined for all three populations. The no-observed-effect-concentration (NOEC; reproduction) and lowest observed-effect-concentration (LOEC; reproduction) for uranium ranged between 8-31 micrograms L-1 and 20-49 micrograms L-1, respectively, for all three populations. The 48 h EC50 (immobilization-lethality) for uranium ranged between 160-390 micrograms L-1 for all three populations. There was little difference in the response of the three populations of M. macleayi to acute and chronic uranium exposure, although the response of the laboratory population to chronic uranium exposure appeared more variable than the "wild" populations. There was no apparent tolerance in the population of M. macleayi obtained from Djalkmara Billabong when exposed to elevated levels of uranium. M. macleayi was significantly more sensitive to uranium exposure than other species previously tested. It was concluded that the sensitivity of the laboratory population (to uranium) is still representative of natural M. macleayi populations. PMID:11594022

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

    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

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

    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

  11. Effect of Alcohol Administration on Blood Sugar of Normal and Alcohol Habituated Rates during Acute Cold Exposure

    K. K. Srivastava

    1968-10-01

    Full Text Available Thermoregulatory failure of alcohol administered fasted rates has been studied under acute cold stress. Twentyfour hour fasted rates developed acute hypoglycemia on being given a single oral dose of ethanol (1.3g/kg body weight during a two hour exposure at -20 degree calcius. Alcohol habituated rates, under similar conditions, more or less maintained their blood sugar concentration.

  12. Acute exposure to a 60 Hz magnetic field increases DNA strand breaks in rat brain cells

    Lai, H.; Singh, N.P. [Univ. of Washington, Seattle, WA (United States)

    1997-05-01

    Acute exposure of rats to a 60 Hz magnetic field caused a dose-dependent increase in DNA strand breaks in brain cells of the animals (assayed by a microgel electrophoresis method at 4 h postexposure). An increase in single-strand DNA breaks was observed after exposure to magnetic fields of 0.1, 0.25, and 0.5 mT, whereas an increase in double-strand DNA breaks was observed at 0.25 and 0.5 mT. Because DNA strand breaks may affect cellular functions, lead to carcinogenesis and cell death, and be related to onset of neurodegenerative diseases, the data may have important implications for the possible health effects of exposure to 60 Hz magnetic fields.

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

    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.

  14. Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation.

    Ramadi, Khalil B; Mohamed, Yassir A; Al-Sbiei, Ashraf; Almarzooqi, Saeeda; Bashir, Ghada; Al Dhanhani, Aisha; Sarawathiamma, Dhanya; Qadri, Shahnaz; Yasin, Javed; Nemmar, Abderrahim; Fernandez-Cabezudo, Maria J; Haik, Yousef; Al-Ramadi, Basel K

    2016-10-01

    Nanoparticles (NPs) are increasingly being commercialized for use in biomedicine. NP toxicity following acute or chronic exposure has been described, but mechanistic insight into this process remains incomplete. Recent evidence from in vitro studies suggested a role for NLRP3 in NP cytotoxicity. In this study, we investigated the effect of systemic administration of composite inorganic NP, consisting of Ag:Cu:B (dose range 1-20 mg/kg), on the early acute (4-24 h post-exposure) and late phase response (96 h post-exposure) in normal and NLRP3-deficient mice. Our findings indicate that systemic exposure (≥2 mg/kg) was associated with acute liver injury due to preferential accumulation of NP in this organ and resulted in elevated AST, ALT and LDH levels. Moreover, within 24 h of NP administration, there was a dose-dependent increase in intraperitoneal neutrophil recruitment and upregulation in gene expression of several proinflammatory mediators, including TNF-α, IL-1β and S100A9. Histological analysis of liver tissue revealed evidence of dose-dependent hepatocyte necrosis, increase in sinusoidal Kupffer cells, lobular granulomas and foci of abscess formation which were most pronounced at 24 h following NP administration. NP deposition in the liver led to a significant upregulation in gene expression of S100A9, an endogenous danger signal recognition molecule of phagocytes, IL-1β and IL-6. The extent of proinflammatory cytokine activation and hepatotoxicity was significantly attenuated in mice deficient in the NLRP3 inflammasome, demonstrating the critical role of this innate immune system recognition receptor in the response to NP. PMID:26956548

  15. Self-Reported Acute Health Effects and Exposure to Companion Animals.

    Krueger, W S; Hilborn, E D; Dufour, A P; Sams, E A; Wade, T J

    2016-06-01

    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 animals can result in a variety of health symptoms related to infection, irritation and allergy; however, few studies have examined this association in a large-scale cohort setting. Cross-sectional data collected from 50 507 participants in the United States enrolled from 2003 to 2009 were used to examine associations between animal contact and acute health symptoms during a 10-12 day period. Fixed-effects multivariable logistic regression estimated adjusted odds ratios (AORs) and 95% confident intervals (CI) for associations between animal exposures and outcomes of GI illness, respiratory illness and skin/eye symptoms. Two-thirds of the study population (63.2%) reported direct contact with animals, of which 7.7% had contact with at least one unfamiliar animal. Participants exposed to unfamiliar animals had significantly higher odds of self-reporting all three acute health symptoms, when compared to non-animal-exposed participants (GI: AOR = 1.4, CI = 1.2-1.7; respiratory: AOR = 1.5, CI = 1.2-1.8; and skin/eye: AOR = 1.9, CI = 1.6-2.3), as well as when compared to participants who only had contact with familiar animals. Specific contact with dogs, cats or pet birds was also significantly associated with at least one acute health symptom; AORs ranged from 1.1 to 1.5, when compared to participants not exposed to each animal. These results indicate that contact with animals, especially unfamiliar animals, was significantly associated with GI, respiratory and skin/eye symptoms. Such associations could be attributable to zoonotic infections and allergic reactions. Etiological models for acute health symptoms should consider contact with companion animals, particularly exposure to unfamiliar animals

  16. Possibilities for exposure reduction in computed tomography examination of acute chest pain

    Electrocardiogram-gated (ECG) computed tomography (CT) investigations can be accompanied by high amounts of radiation exposure. This is particularly true for the investigation of patients with unclear and acute chest pain. The common approach in patients with acute chest pain is standard spiral CT of the chest. The chest pain or triple-rule-out CT protocol is a relatively new ECG-gated protocol of the entire chest. This article reviews and discusses different techniques for the CT investigation of patients with acute chest pain. By applying the appropriate scan technique, the radiation exposure for an ECG-gated protocol must not necessarily be higher than a standard chest CT scan Aortic pathologies are far better depicted by ECG-gated scan protocols and depending on the heart rate coronary artery disease can also be detected at the same time. The use of ECG-triggered scans will not support the diagnostics of the pulmonary arteries. However, in unspecific chest pain an ECG-triggered scan protocol can provide information on the differential diagnosis. (orig.)

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

    Reichwaldt, Elke S; Stone, Daniel; Barrington, Dani J; Sinang, Som C; Ghadouani, Anas

    2016-01-01

    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. PMID:27589798

  18. Associations between Chronic Community Noise Exposure and Blood Pressure at Rest and during Acute Noise and Non-Noise Stressors among Urban School Children in India

    Bang Hyun Kim; Evans, Gary W.; Stephen J. Lepore; Bhaskar Shejwal

    2010-01-01

    The present study builds on prior research that has examined the association between children’s chronic exposure to community noise and resting blood pressure and blood pressure dysregulation during exposure to acute stressors. A novel contribution of the study is that it examines how chronic noise exposure relates to blood pressure responses during exposure to both noise and non-noise acute stressors. The acute noise stressor was recorded street noise and the non-noise stressor was mental ar...

  19. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus)

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The...

  20. Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

    Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m3 concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m3 soman survived, while animals exposed to 841, and 1121 mg/m3 resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt50 for soman determined by probit analysis was 827.2 mg/m3. A majority of the animals that died at 1121 mg/m3 developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

  1. Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness

    Tang XG

    2014-07-01

    Full Text Available Xu-gang Tang,1 Ji-hang Zhang,1 Xu-bin Gao,1 Qian-ning Li,2 Jia-bei Li,1 Jie Yu1 Jun Qin,1 Lan Huang11Institute of Cardiovascular Diseases, 2Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of ChinaObjective: We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS. Methods: A total of 600 adult men were recruited. Subjects’ subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured. Results: Despite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314–1.464, P<0.001, whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS. Conclusion: Our results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep

  2. Medical management of severe local radiation injury after acute X-ray exposure

    Medical management during acute period in a case of severe local radiation injury after acute X-ray exposure includes 3 stages. During the fist stage patient got conservative treatment according to the common pathogenetic mechanisms of LRI (dis aggregating therapy, stimulation of regeneration, dis intoxication therapy, antibiotic therapy, pain relief therapy, Local anti-burn therapy-specific non-adhesive bandage with antiseptic and anti-burn medicaments); estimation of severity, deepness and area of injury by clinical picture and dates of instrumental methods of examining; defining necessity and volume of surgical treatment; preparing arrangements for surgical treatment. This stage ends with forming of demarcation line of a very hard severity of a Local Radiation Injure. The second stage includes necrectomy of the area of a very hard severity with microsurgical plastic by re vascularized flap and auto dermoplastic. The third stage - adaptation of re vascularized flap and total epithelization of injured area. (author)

  3. Acute Exposure to Crystalline Silica Reduces Macrophage Activation in Response to Bacterial Lipoproteins.

    Beamer, Gillian L; Seaver, Benjamin P; Jessop, Forrest; Shepherd, David M; Beamer, Celine A

    2016-01-01

    Numerous studies have examined the relationship between alveolar macrophages (AMs) and crystalline silica (SiO2) using in vitro and in vivo immunotoxicity models; however, exactly how exposure to SiO2 alters the functionality of AM and the potential consequences for immunity to respiratory pathogens remains largely unknown. Because recognition and clearance of inhaled particulates and microbes are largely mediated by pattern recognition receptors (PRRs) on the surface of AM, we hypothesized that exposure to SiO2 limits the ability of AM to respond to bacterial challenge by altering PRR expression. Alveolar and bone marrow-derived macrophages downregulate TLR2 expression following acute SiO2 exposure (e.g., 4 h). Interestingly, these responses were dependent on interactions between SiO2 and the class A scavenger receptor CD204, but not MARCO. Furthermore, SiO2 exposure decreased uptake of fluorescently labeled Pam2CSK4 and Pam3CSK4, resulting in reduced secretion of IL-1β, but not IL-6. Collectively, our data suggest that SiO2 exposure alters AM phenotype, which in turn affects their ability to uptake and respond to bacterial lipoproteins. PMID:26913035

  4. Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

    Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

    2011-01-01

    In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

  5. Reproductive performance of Bracon hebetor females following acute exposure to sulphur dioxide in air

    Petters, R.M.; Mettus, R.V.

    1982-02-01

    Bracon hebetor females were exposed to 3 ppm SO/sub 2/ for 3 h and 5 h and their reproductive performance was assayed for 20 days. Lifespan of the treated females and their egg production were not different from those of control wasps. Also, egg hatchability, an important indicator of fertility, was not consistently affected. These results indicate Bracon reproductive performance, a sensitive toxicological assay system, to be resistant to acute SO/sub 2/ exposure. Putative SO/sub 2/ effects on parasitic wasp populations in nature are therefore probably not due to interference with female fecundity and fertility.

  6. Rhabdomyolysis, acute kidney injury and transverse myelitis due to naive heroin exposure

    Ankur Gupta

    2011-01-01

    Full Text Available Heroin exposure can cause various complications like seizures, stroke, spongiform encephalopathy, transverse myelopathy, plexopathy, compartment syndrome, rhabdomyolysis and renal failure due to various mechanisms. We report here a young male who smoked heroin for the first time and developed transverse myelitis, rhabdomyolysis and acute kidney injury requiring dialysis. His renal recovery was complete by four weeks, while neurological improvement occurred 8 to 12 weeks later. This case suggests a common pathogenic mechanism of heroin intoxication involving multiple systems of the body.

  7. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus).

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L(-1) for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The OCRs in all groups were significantly different than control (P muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained. PMID:27382568

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

    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.

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

    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.

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

    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. PMID:24194397

  11. Modulation of pulmonary defense mechanisms by acute exposures to nitrogen dioxide

    The effect of acute exposures to NO2 on the antibacterial defenses of the murine lung was assessed following inhalation challenges with Staphylococcus aureus, Proteus mirabilis, and Pasteurella pneumotropica. With S. aureus pulmonary antibacterial defenses were suppressed at NO2 levels of 4.0 ppm and greater. Exposure to 10.0 ppm enhanced the intrapulmonary killing of P. mirabilis which correlated with an increase in the phagocytic cell populations lavaged from the lungs; at 20.0 ppm bactericidal activity against P. mirabilis was impaired. Pulmonary antibacterial defenses against P. pneumotropica were impaired at 10.0 ppm which correlated with a decrease in the retrieved phagocytic lung cell population. Reversing the order of treatment (ie., NO2 exposure prior to bacterial challenge) raised the threshold concentration for NO2-induced impairment of intrapulmonary bacterial killing. With S. aureus the effect was not observed at 5.0 ppm but at 10.0 ppm and with P. mirabilis not at 20.0 ppm but at 30.0 ppm intrapulmonary killing was enhanced. Exposures up to 20.0 ppm of NO2 did not effect the physical translocation mechanisms of the lung as quantitated by declines in pulmonary radiotracer activity following aerogenic challenge with 32P-labeled staphylococci

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

    Seok Kyu Kang

    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.

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

    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. In vivo proliferation of bone marrow stem cells of mice after combined long-term exposure to gamma radiation and acute exposure to X rays

    The aim of this paper was to ascertain whether a long-term exposure to gamma radiation at low dose rates, comparable to the professional permissible dose, can modify the response of bone marrow stem cells to single acute irradiation. The study was carried out by the method of exogenous spleen colonization. Continuous exposure to Co60 gamma rays was applied at dose rates of 0,223 mGy x h-1 and 1,25 mGy x h-1. The duration of exposure was 30-105 days, accumulated doses within this time were 0.16-0,56 Gy respectively. After the exposure was completed the mice were subjected to acute X-rays irradiation at the doses of 0,5-4,0 Gy. It was found the bone marrow stem cells, capable to form clones in the spleens, respond to the dose effect as well as at very low its values. The effect estimated by changed responsiveness to acute irradiation depends to accumulated dose only. The higher is the accumulated dose during long-term irradiation the greater is diminishing of repopulating ability of bone marrow cells after following acute irradiation. 4 refs., 3 figs., 1 tab. (author)

  15. Acute and long-term effects of exposure to sodium monofluoroacetate (1080 in sheep

    S. R. Gooneratne

    2008-08-01

    Full Text Available Acute and long-term effects of a single, relative lyhigh oral dose (0.25a nd 0.30 mg/kg of sodium monofluoroacetate (1080 on the survival and productivity of sheep were evaluated to establish a better understanding of 1080 poisoning and identify more specific changes diagnostic of toxicosis. In survivors, clinical signs of acute 1080 toxicosis such as salivation and lethar gywere generally very mild. Fasted animals were more prone to 1080 toxicity. In animals that died, more severe signs, including tachypnoea, dyspnoea, and tremors occurred for 15-20 min prior to death. 1080 concentrations were highest in the blood> heart> skeletal muscle> liver. 1080 could not be detected in any of these organs of the animals that survived. Serum citratec oncentratione were elevated for 4 days after dosing. No clinical or biochemical abnormalities were found in any animal after 4 days. Histopathological lesions were most marked in the heart and lung with inflammation, necrosis, and scattered foci of fibrous tissue in the myocardium, pulmonary oedema and inflammation of the lung. No adverse longterm effects on general health or reproductive performance were observed in any sheep that survived the first 4 days following exposure to 1080. The most reliable diagnostic in dicators of 1080 exposure in sheep were measurement of its residues in blood, skeletal muscle and ruminal contents, increased serum citratec oncentratione; l evated heart rate,and characteristic electrocardiograpchh anges(up to 4 days after exposure. Death from 1080 is most likely to occur within 96 h, and animals that survived this period appeared normal.

  16. Improvement of cold resistance and performance of broilers by acute cold exposure during late embryogenesis.

    Shinder, D; Ruzal, M; Giloh, M; Druyan, S; Piestun, Y; Yahav, S

    2011-03-01

    The aim of this study was to fine-tune previous acute cold exposure treatments of broiler embryos during late embryogenesis to improve lifelong cold resistance and performance. Six hundred Cobb hatching eggs were incubated under standard conditions and then exposed to 3 treatments: control; cold treatment in which embryos were exposed to 15°C for 30 min on d 18 and 19 of incubation (30 × 2); and cold treatment similar to 30 × 2 but with 60-min exposures (60 × 2). Egg shell temperature (T(egg)) and heart rate (HR) were monitored pre- and posttreatment. Upon hatching, hatchability, body weight, and body temperature were recorded. From 14 to 35 d of age, three quarters of the chickens in each treatment were raised under ascites-inducing conditions (AIC) and the remaining birds were raised under standard brooding conditions (SBC). The T(egg) and HR decreased significantly in response to increased exposure time on d 18 of incubation. On d 19 of incubation, before the second cold exposure, the 30 × 2 group showed greater T(egg) and HR than the controls, and during the second exposure they maintained these parameters better than the 60 × 2 embryos. No treatment effect on hatchability was observed. At 35 d of age ascites incidence among 30 × 2 chickens under AIC was significantly less than that among the controls (P ascites incidence and improved growth rate under either SBC or AIC. These results may be related to a prenatal epigenetic adaptation of the thermoregulatory and cardiovascular systems to low ambient temperature. PMID:21325235

  17. DOSE-RELATED GENE EXPRESSION CHANGES IN FOREBRAIN FOLLOWING ACUTE, LOW-LEVEL CHLORPYRIFOS EXPOSURE IN NEONATAL RATS

    Ray, Anamika; Liu, Jing; Ayoubi, Patricia; Pope, Carey

    2010-01-01

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 hr following acute CPF exposure in seven day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following e...

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

    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...

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

    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. Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.

    Capulli, Andrew K; MacQueen, Luke A; O'Connor, Blakely B; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. PMID:27174867

  1. Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure.

    Davranche, Karen; Casini, Laurence; Arnal, Pierrick J; Rupp, Thomas; Perrey, Stéphane; Verges, Samuel

    2016-10-01

    The present study aimed to assess specific cognitive processes (cognitive control and time perception) and hemodynamic correlates using functional near-infrared spectroscopy (fNIRS) during acute and prolonged high-altitude exposure. Eleven male subjects were transported via helicopter and dropped at 14 272 ft (4 350 meters) of altitude where they stayed for 4 days. Cognitive tasks, involving a conflict task and temporal bisection task, were performed at sea level the week before ascending to high altitude, the day of arrival (D0), the second (D2) and fourth (D4) day at high altitude. Cortical hemodynamic changes in the prefrontal cortex (PFC) area were monitored with fNIRS at rest and during the conflict task. Results showed that high altitude impacts information processing in terms of speed and accuracy. In the early hours of exposure (D0), participants displayed slower reaction times (RT) and decision errors were twice as high. While error rate for simple spontaneous responses remained twice that at sea level, the slow-down of RT was not detectable after 2 days at high-altitude. The larger fNIRS responses from D0 to D2 suggest that higher prefrontal activity partially counteracted cognitive performance decrements. Cognitive control, assessed through the build-up of a top-down response suppression mechanism, the early automatic response activation and the post-error adjustment were not impacted by hypoxia. However, during prolonged hypoxic exposure the temporal judgments were underestimated suggesting a slowdown of the internal clock. A decrease in cortical arousal level induced by hypoxia could consistently explain both the slowdown of the internal clock and the persistence of a higher number of errors after several days of exposure. PMID:27262217

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

    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

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

    da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    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. PMID:23844182

  4. Acute crack cocaine exposure induces genetic damage in multiple organs of rats.

    Moretti, Eduardo Gregolin; Yujra, Veronica Quispe; Claudio, Samuel Rangel; Silva, Marcelo Jose Dias; Vilegas, Wagner; Pereira, Camilo Dias Seabra; de Oliveira, Flavia; Ribeiro, Daniel Araki

    2016-04-01

    Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p crack cocaine at 9 and 18 mg/kg (p crack cocaine is able to induce genomic damage in multiple organs of Wistar rats. PMID:26825523

  5. Acute low-intensity microwave exposure increases DNA single-strand breaks in rat brain cells

    Lai, H.; Singh, N.P. [Univ. of Washington, Seattle, WA (United States)

    1995-08-01

    Levels of DNA single-strand break were assayed in brain cells from rats acutely exposed to low-intensity 2,450 MHz microwaves using an alkaline microgel electrophoresis method. Immediately after 2 h of exposure to pulsed (2 {mu}s width, 500 pulses/s) microwaves, no significant effect was observed, whereas a dose rate-dependent [0.6 and 1.2 W/kg whole body specific absorption rate (SAR)] increase in DNA single-strand breaks was found in brain cells of rats at 4 h postexposure. Furthermore, in rats exposed for 2 h to continuous-wave 2,450 MHz microwaves (SAR 1.2 W/kg), increases in brain cell DNA single-strand breaks were observed immediately as well as at 4 h postexposure.

  6. Caffeine improves performance in double poling during acute exposure to 2,000-m altitude.

    Stadheim, H K; Nossum, E M; Olsen, R; Spencer, M; Jensen, J

    2015-12-15

    There is limited research on the physiological effects of caffeine (CAF) ingestion on exercise performance during acute hypoxia. The aim of the present study was therefore to test the effect of placebo (PLA) and CAF (4.5 mg/kg) on double poling (DP) performance during acute hypoxia. Thirteen male subelite cross-country skiers (V̇o2max 72.6 ± 5.68 ml·kg(-1)·min(-1)) were included. Performance was assessed as 1) an 8-km cross-country DP time-trial (C-PT), and 2) time until task failure at a set workload equal to ∼90% of DP V̇o2max. Testing was carried out in a hypobaric chamber, at 800 mbar (Pio2: ∼125 mmHg) corresponding to ∼2,000 m above sea level in a randomized double-blinded, placebo-controlled, cross-over design. CAF improved time to task failure from 6.10 ± 1.40 to 7.22 ± 1.30 min (P exercise subjects reported lower pain in arms and rate of perceived exertion (RPE) following CAF ingestion. Throughout C-PTs similar RPE and pain was shown between treatments. However, higher heart rate was observed during the CAF 8 km (187 ± 7 vs. 185 ± 7; P < 0.05) and 90% C-PT (185 ± 7 vs. 181 ± 9) associated with increased ventilation, blood lactate, glucose, adrenaline, decreased pH, and bicarbonate. The present study demonstrates for the first time that CAF ingestion improves DP time to task failure although not consistently time trial performance during acute exposure to altitude. Mechanisms underpinning improvements seem related to reduced pain RPE and increased heart rate during CAF C-PTs. PMID:26494444

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

    Belén Feriche

    Full Text Available 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 (P<0.05. We also observed a stimulating effect of natural hypoxia on P(mean and P(peak in the middle-high part of the curve (≥ 60 kg; P<0.01 and a 7.8% mean increase in barbell displacement velocity (P<0.001. No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1 RM, movement velocity and power during the execution of a force-velocity curve in bench press.

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

    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 (P<0.05). We also observed a stimulating effect of natural hypoxia on P(mean) and P(peak) in the middle-high part of the curve (≥ 60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1 RM, movement velocity and power during the execution of a force-velocity curve in bench press. PMID:25474104

  9. Effects of Acutely Intermittent Hypoxic Exposure on Running Economy and Physical Performance in Basketball Players.

    Kilding, Andrew E; Dobson, Bryan P; Ikeda, Erika

    2016-07-01

    Kilding, AE, Dobson, BP, and Ikeda, E. Effects of acutely intermittent hypoxic exposure on running economy and physical performance in basketball players. J Strength Cond Res 30(7): 2033-2042, 2016-The aim of this study was to determine the effect of short duration intermittent hypoxic exposure (IHE) on physical performance in basketball players. Using a single-blind placebo-controlled group design, 14 trained basketball players were subjected to 15 days of passive short duration IHE (n = 7), or normoxic control (CON, n = 7), using a biofeedback nitrogen dilution device. A range of physiological, performance, and hematological variables were measured at baseline, and 10 days after IHE. After intervention, the IHE group, relative to the CON group, exhibited improvements in the Yo-Yo intermittent recovery level 1 (+4.8 ± 1.6%; effect size [ES]: 1.0 ± 0.4) and repeated high-intensity exercise test performance (-3.5 ± 1.6%; ES: -0.4 ± 0.2). Changes in hematological parameters were minimal, although soluble transferrin receptor increased after IHE (+9.2 ± 10.1%; ES: 0.3 ± 0.3). Running economy at 11 km·h (-9.0 ± 9.7%; ES: -0.7 ± 0.7) and 13 km·h was improved (-8.2 ± 6.9%; ES: -0.7 ± 0.5), but changes to V[Combining Dot Above]O2peak, HRpeak, and lactate were unclear. In summary, acutely IHE resulted in worthwhile changes in physical performance tests among competitive basketball players. However, physiological measures explaining the performance enhancement were in most part unclear. PMID:26677826

  10. Acute exposure to lead increases myocardial contractility independent of hypertension development

    We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension

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

    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

  12. MicroRNA-122 Down-Regulation Is Involved in Phenobarbital-Mediated Activation of the Constitutive Androstane Receptor

    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 hepati...

  13. Effects of acute exposure to magnetic field on ionic composition of frog sciatic nerve

    Objective: To evaluate the possible interaction between magnetic field and cadmium on ionic composition of frog sciatic nerve. Design: The combined effect of magnetic field and cadmium (1.5mg/kg; in lymphatic sac) were studied in frog sciatic nerves (Rana Esculenta). Sciatic nerve samples were extracted, weighed and mixed in bidistilled water in order to analyze by inductively coupled plasma (ICP) ionic composition. Setting: Frogs (Rana Esculenta) were reared in swimming-pool (Faculte des Sciences de Bizerte, Tunisia). Frogs were cared for under the Tunisian Code of Practice for the Care and Use of Animals for Scientific purpose and the Experimental Protocols were approved by the Ethics Committee. Subjects: Treated and control groups (n=6) weighing 50-100g at the time of experiments were housed in the same condition three weeks before the beginning of the experiments. Results: Acute exposure to magnetic field increased significantly the calcium (+298%, p<0.05) and iron (+50%, p<0.05) contents of frog sciatic nerve, whereas magnesium and copper contents remained unchanged. The association between magnetic field and cadmium, induced marked increase of calcium (+360%, p<0.05), whereas magnesium content remained stable. Conclusions: Magnetic field exposure alters the ionic composition in the frog sciatic nerve, especially calcium and iron. Magnetic field magnifies the effect of cadmium on calcium homeostasis. (author)

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

    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,…

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

    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. Modeling the acute health effects of astronauts from exposure to large solar particle events.

    Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

    2009-04-01

    Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed. PMID:19276707

  17. Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure.

    Michaeli, Avner; Matzner, Henry; Poltyrev, Tatyana; Yaka, Rami

    2012-03-01

    Excitatory synapses on dopamine (DA) neurons in the ventral tegmental area (VTA) are modulated following exposure to various addictive drugs, including cocaine. Previously we have shown that cocaine affects GABA(A) receptor (GABA(A)R)-mediated neurotransmission in VTA DA neurons. This finding led us to reexamine the modulation of the excitatory synapse on these neurons in response to cocaine exposure, while the activity of GABA(A)R is uninterrupted. Using rat brain slices, evoked post synaptic currents (ePSC) were monitored and inhibitors of NMDA receptor (NMDAR) and AMPA receptor (AMPAR) were gradually added to inhibitors-free bath solution. Modifications in the efficacy of the excitatory synapses were evaluated by comparing AMPAR-mediated and NMDAR-mediated currents (AMPA/NMDA ratio). The lack of GABA(A)R inhibitors enabled us to examine parallel changes in the relation between GABA(A)R-mediated and NMDAR-mediated currents (GABA(A)/NMDA ratio). First, we found that AMPA/NMDA ratio measured under complete availability of GABA(A)R, is significantly higher than the ratio measured under GABA(A)R blockade. In addition, GABA(A)/NMDA ratio, but not AMPA/NMDA ratio, is augmented a few hours following in vitro acute cocaine exposure. When measured 24 h after in vivo single cocaine injection, no change in GABA(A)/NMDA ratio was observed, however, the AMPA/NMDA ratio was found to be significantly higher. Finally, a decrease in both ratios was detected in rats repeatedly injected with cocaine. Taken together, these results lead to a better understanding of the means by which cocaine modifies synaptic inputs on VTA DA neurons. The parallel changes in GABA(A)/NMDA ratio may suggest an interaction between inhibitory and excitatory neural systems. PMID:22197515

  18. [Exposure to tobacco smoke and type of acute respiratory infections in children].

    Bielska, Dorota; Trofimiuk, Emil; Ołdak, Elzbieta; Cylwik, Bogdan; Chlabicz, Sławomir

    2010-01-01

    Respiratory diseases are the most common cause of the child and family practice physicians are one of the main reasons for referral to a specialist clinic and hospital pediatric wards. The severity of respiratory disease in adolescence influenced by various factors, endo- and exogenous. Some of them, especially environmental factors can be eliminated or reduced and thus reduce the risk of developing this disease. The most common source of pollutants in dwellings is tobacco smoke. The aim of this study was to assess exposure to tobacco smoke in three years old children of attending local kindergartens in Białystok and its influence on the type of recovery from acute respiratory infections by the respondents. The study included 313 children from among the 1,200 who attend the local 51-kindergartens in Bialystok. Information on the structure of tobacco use in three-years-old-children's families and respiratory illnesses among random children were obtained, based on anonymous questionnaires completed by their carers. Exposure to tobacco smoke was based on questionnaires and serum cotinine in relation to creatinine in the urine of patients (K/K). In the 150 families surveyed children found 210 smoking people. Every day smoked 37.3% of fathers and 23.6% of mothers. Of the children surveyed--34% of the houses which where there was a prohibition on tobacco use, 35% of the houses which were smoked in enclosed areas, in 31% of homes have not been established no-smoking rules. Children who during the six-month period to attend kindergarten gone lower respiratory tract infection had mean K/K (59.57 ng/mg) higher than the ones that were healthy and underwent upper respiratory tract infection. Used by the parents of the children tested in part to reduce the exposure to tobacco smoke in the home environment was ineffective and did not influence the decrease in the incidence of lower respiratory tract. PMID:21360910

  19. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

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

    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. PMID:26356390

  1. Development of short, acute exposure hazard estimates: a tool for assessing the effects of chemical spills in aquatic environments.

    Bejarano, Adriana C; Farr, James K

    2013-08-01

    Management decisions aimed at protecting aquatic resources following accidental chemical spills into rivers and coastal estuaries require estimates of toxic thresholds derived from realistic spill conditions: acute pulse exposures of short duration (h), information which often is unavailable. Most existing toxicity data (median lethal concentration or median effective concentration) come from tests performed under constant exposure concentrations and exposure durations in the 24-h to 96-h range, conditions not typical of most chemical spills. Short-exposure hazard concentration estimates were derived for selected chemicals using empirical toxicity data. Chemical-specific 5th percentile hazard concentrations (HC5) of species sensitivity distributions (SSD) from individual exposure durations (6-96 h) were derived via bootstrap resampling and were plotted against their original exposure durations to estimate HC5s and 95% confidence intervals (CIs) at shorter exposures (1, 2, and 4 h). This approach allowed the development of short-exposure HC5s for 12 chemicals. Model verification showed agreement between observed and estimated short-exposure HC5s (r(2) adjusted = 0.95, p overprotective, these were derived from environmentally realistic exposure durations, providing risk-assessors with a tool to manage field decisions. Environ Toxicol Chem 2013;32:1918-1927. © 2013 SETAC. PMID:23625642

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

    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

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

    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

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

    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.

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

    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. PMID:25684626

  6. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn Exposure on Sea Cucumbers (Apostichopus japonicus

    Li Li

    2016-01-01

    Full Text Available Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus exposed to heavy metals. Acute toxicity values (96 h LC50 were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR decreased. The OCRs in all groups were significantly different than control (P muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained.

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

    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

  8. Acute and chronic ethanol exposure differentially affect induction of hippocampal LTP.

    Fujii, Satoshi; Yamazaki, Yoshihiko; Sugihara, Toshimichi; Wakabayashi, Ichiro

    2008-05-23

    Using hippocampal slices, we found that chronic ethanol consumption by rats induces tolerance to the impairing effects of acute ethanol treatment on induction of long-term potentiation (LTP) in CA1 neurons. In hippocampal slices from pair-fed control rats, stable LTP was induced by tetanic stimulation consisting of 25 or more pulses at 100 Hz, but not by tetanic stimulation of 15 pulses at 100 Hz, and LTP induction was blocked if the tetanus was delivered in the presence of 8.6 mM ethanol, 1 microM muscimol, a gamma-aminobutyric acid (GABA) A receptor agonist, or 2.5 microM dl-2-amino-5-phosphonovaleric acid (AP5), an N-methyl-d-aspartate (NMDA) receptor antagonist. In hippocampal slices from rats chronically fed a liquid diet containing ethanol, a tetanus consisting of 15 pulses at 100 Hz did induce stable LTP, indicating a decrease in the stimulation threshold for inducing LTP. Application of ethanol, muscimol, or AP5 did not affect LTP induction in these cells, suggesting that the effects of chronic ethanol exposure on LTP induction are mediated by a reduction in GABAergic inhibition or an increase in NMDA receptor activity in hippocampal CA1 neurons. PMID:18423576

  9. Acute, whole-body microwave exposure and testicular function of rats

    Lebovitz, R.M.; Johnson, L.

    1987-01-01

    Male Sprague-Dawley rats were exposed for 8 h to continuous-wave microwave radiation (MWR, 1.3 Ghz) at a mean specific absorbed dose rate of 9 mW/g. MWR exposure and sham-irradiation took place in unidirectionally energized cylindrical waveguide sections, within which the animals were essentially unrestrained. The MWR treatment in this setting was determined to yield an elevation of deep rectal temperature to 4.5 degrees C. The animals were taken for analysis at 6.5, 13, 26, and 52 days following treatment, which corresponded to .5, 1, 2, and 4 cycles of the seminiferous epithelium. Net mass of testes, epididymides, and seminal vesicles; daily sperm production (DSP) per testis and per gram of testis; and the number of epididymal sperm were determined. The levels of circulating follicle-stimulating hormone (FSH) and leutinizing hormone (LH) were derived via radioimmunoassay of plasma samples taken at the time of sacrifice. Despite the evident acute thermogenesis of the MWR at 9 mW/g, no substantial decrement in testicular function was found. We conclude that, in the unrestrained rat, whole body irradiation at 9 mW/g, while sufficient to induce evident hyperthermia, is not a sufficient condition for disruption of any of these key measures of testicular function.

  10. Acute, whole-body microwave exposure and testicular function of rats

    Male Sprague-Dawley rats were exposed for 8 h to continuous-wave microwave radiation (MWR, 1.3 Ghz) at a mean specific absorbed dose rate of 9 mW/g. MWR exposure and sham-irradiation took place in unidirectionally energized cylindrical waveguide sections, within which the animals were essentially unrestrained. The MWR treatment in this setting was determined to yield an elevation of deep rectal temperature to 4.5 degrees C. The animals were taken for analysis at 6.5, 13, 26, and 52 days following treatment, which corresponded to .5, 1, 2, and 4 cycles of the seminiferous epithelium. Net mass of testes, epididymides, and seminal vesicles; daily sperm production (DSP) per testis and per gram of testis; and the number of epididymal sperm were determined. The levels of circulating follicle-stimulating hormone (FSH) and leutinizing hormone (LH) were derived via radioimmunoassay of plasma samples taken at the time of sacrifice. Despite the evident acute thermogenesis of the MWR at 9 mW/g, no substantial decrement in testicular function was found. We conclude that, in the unrestrained rat, whole body irradiation at 9 mW/g, while sufficient to induce evident hyperthermia, is not a sufficient condition for disruption of any of these key measures of testicular function

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

    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.

  12. Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness

    Tang XG; Zhang JH; Gao XB; Li QN; Li JB; Yu J; Qin J; Huang L

    2014-01-01

    Xu-gang Tang,1 Ji-hang Zhang,1 Xu-bin Gao,1 Qian-ning Li,2 Jia-bei Li,1 Jie Yu1 Jun Qin,1 Lan Huang11Institute of Cardiovascular Diseases, 2Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of ChinaObjective: We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (A...

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

    Acute Cl2 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 Cl2 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 Cl2 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. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3− or NO2−. 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. Cl2 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 Cl2 inhalation. - Highlights: • Effect of 60 ppm*hr Cl2 gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor. • Alterations in surfactant homeostasis and pulmonary mechanics

  14. Phenobarbital induction of cytochromes P-450. High-level long-term responsiveness of primary rat hepatocyte cultures to drug induction, and glucocorticoid dependence of the phenobarbital response.

    Waxman, D J; Morrissey, J J; Naik, S; Jauregui, H O

    1990-01-01

    The induction of hepatic cytochromes P-450 by phenobarbital (PB) was studied in rat hepatocytes cultured for up to 5 weeks on Vitrogen-coated plates in serum-free modified Chee's medium then exposed to PB (0.75 mM) for an additional 4 days. Immunoblotting analysis indicated that P-450 forms PB4 (IIB1) and PB5 (IIB2) were induced dramatically (greater than 50-fold increase), up to levels nearly as high as those achieved in PB-induced rat liver in vivo. The newly synthesized cytochrome P-450 was enzymically active, as shown by the major induction of the P-450 PB4-dependent steroid 16 beta-hydroxylase and pentoxyresorufin O-dealkylase activities in the PB-induced hepatocyte microsomes (up to 90-fold increase). PB induction of these P-450s was markedly enhanced by the presence of dexamethasone (50 nM-1 microM), which alone was not an affective inducing agent, and was inhibited by greater than 90% by 10% fetal bovine serum. The PB response was also inhibited (greater than 85%) by growth hormone (250 ng/ml), indicating that this hormone probably acts directly on the hepatocyte when it antagonizes the induction of P-450 PB4 in intact rats. In untreated hepatocytes, P-450 RLM2 (IIA2), P-450 3 (IIA1) and NADPH P-450 reductase levels were substantially maintained in the cultures for 10-20 days. The latter two enzymes were also inducible by PB to an extent (3-4 fold elevation) that is comparable with that observed in the liver in vivo. Moreover, P-450c (IA1) and P-450 3 (IIA1) were highly inducible by 3-methylcholanthrene (5 microM; 48 h exposure) even after 3 weeks in culture. In contrast, the male-specific pituitary-regulated P-450 form 2c (IIC11) was rapidly lost upon culturing the hepatocytes, suggesting that supplementation of appropriate hormonal factors may be necessary for its expression. The present hepatocyte culture system exhibits a responsiveness to drug inducers that is qualitatively and quantitatively comparable with that observed in vivo, and should prove

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

    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)

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

    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)

  17. Effect of phenobarbital on inducing insecticide tolerance and esterase changes in Aedes aegypti (Diptera: Culicidae

    Rita de Cássia Sousa-Polezzi

    2004-01-01

    Full Text Available The effect of phenobarbital (PB on the induction of tolerance to the organophosphorous insecticide temephos (TE was investigated in Aedes aegypti L4 larvae submitted to two different PB-treatments:(1 continuous treatment from the egg to the larval L4 stage and (2 discontinuous treatment in which L4 larvae were exposed for 30 h. Mosquitoes from two Brazilian cities were studied: São José do Rio Preto (SJ in São Paulo State and Goiânia (GO in Goiás State. According to criterions established by World Health Organization (WHO mosquitoes from SJ are organophosphate-susceptible while mosquitoes from GO are organophosphate-resistant. For both SJ and GO larvae the two different PB-treatments resulted in significantly increased tolerance (measured by reduced mortality to 0.01mg/L TE while for larvae exposed to 0.02 mg/L TE only continuous PB-treatment resulted in significantly increased TE-tolerance. The reduction of mortality rate was greater in SJ larvae than in GO larvae, confirming data from other organisms indicating that the effect of PB is more pronounced in susceptible strains. To test if oxidase enzymes were involved in PB-induced tolerance we treated PB-pretreated SJ and GO larvae with the oxidase inhibitor piperonyl butoxide (PBO before exposure to TE and observed increased (rather than decreased tolerance, suggesting that oxidases are not involved in the tolerance process and that PB and PBO can act in concert or synergistically. Esterase patterns of PB-pretreated larvae indicated that the cholinesterases EST-13 and EST-14 are involved in the PB-induced TE- tolerance, reinforcing a previous study carried out in our laboratory which suggested that increased esterase synthesis is the mechanism responsible for the development of insecticide resistance in Aedes aegypti.

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

    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.

  19. Effect of phenobarbital on the level of translatable rat liver epoxide hydrolase mRNA.

    Pickett, C B; Lu, A Y

    1981-01-01

    Liver poly(A)+RNA isolated from untreated and phenobarbital-treated rats has been translated in the rabbit reticulocyte cell-fre system in order to determine the level of translationally active epoxide hydrolase (EC 3.3.2.3) mRNA. The in vitro translation systems were immunoprecipitated with rabbit IgG prepared against purified epoxide hydrolase, and the amount of epoxide hydrolase synthesized by the lysate programmed with control and phenobarbital poly(A)+RNA was quantitated. The level of tr...

  20. The Influence of Age of Onset and Acute Anabolic Steroid Exposure on Cognitive Performance, Impulsivity, and Aggression in Men

    Hildebrandt, Tom; Langenbucher, James W.; Flores, Adrianne; Harty, Seth; Berlin, Heather A.

    2014-01-01

    A growing translational literature suggests that adolescent exposure to anabolic-androgenic steroids (AASs) leads to increased aggression and impulsivity. However, little is known about the cognitive effects of AASs among AAS users or the differences between adolescent and adult onset users. This study provides a test of the effects of acute naturalistic AAS use and age of onset (adolescent vs. adult) on measures of inhibitory control, planning and attention, and decision makin...

  1. Acute exposure to stress improves performance in trace eyeblink conditioning and spatial learning tasks in healthy men

    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, participants completed a trace eyeblink conditioning task followed by a virtual navigation Morris water task (VNMWT). Hypothalamic-pituitary-adreno...

  2. Changes of pathological and physiological indicators affecting drug metabolism in rats after acute exposure to high altitude

    Li, Wenbin; Wang, Rong; Xie, Hua; ZHANG, JUANHONG; Jia, Zhengping

    2014-01-01

    High altitude environments cause the human body to undergo a series of pathological, physiological and biochemical changes, which have a certain effect on drug pharmacokinetics. The objective of the present study was to observe changes in factors affecting pharmacokinetics in rats following acute exposure to high altitude and return to low altitude. A total of 21 male Wistar rats were randomly assigned to three groups. The rats in group A were maintained at low altitude in Shanghai, 55 m abov...

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

    Willmann, Gabriel, 1977-; 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 ...

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

    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.

  5. Age-related differences in pulmonary effects of acute and subchronic episodic ozone exposures in Brown Norway rats.

    Snow, Samantha J; Gordon, Christopher J; Bass, Virginia L; Schladweiler, Mette C; Ledbetter, Allen D; Jarema, Kimberly A; Phillips, Pamela M; Johnstone, Andrew F; Kodavanti, Urmila P

    2016-06-01

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O3 exposure. PMID:27097751

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

    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

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

    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

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

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

    2014-01-01

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

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

    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.

  10. Micronucleus assay in human lymphocytes as a bio dosimeter of in vivo acute and chronic exposures

    To assess the persistence over time of micronuclei (MN) in lymphocytes of cancer patients after radiotherapy and, consequently, to verify the suitability of MN test as a dosimeter for monitoring in vivo ionizing radiation damage, the cytokinesis-blocked MN assay was applied in peripheral blood lymphocytes of cervix and head and neck cancer patients (n = 34). The evaluation of data suggests that: 1) MN frequency increases linearly with the equivalent total-body absorbed dose (R2 = 0,9; P=0,015); 2) The distribution of the MN yields deviates significantly from Poisson with the increase of equivalent total-body dose (σ2/y = 1,14 mean value); 3) The comparison of spontaneous MN frequencies in healthy subjects with those in cancer patients, prior to radiotherapy, shows significant differences (p<0,01); and 4) It is observed a general decline in MN frequencies with time after radiotherapy, with considerable variations between patients. The kinetics of elimination of MN seems to follow a two-term exponential function, with a short and a long term. Patients with the highest equivalent total-body dose (total tumoral dose: 60-80 Gy) initially tend to have the fastest decline. At 6-18 months of follow-up time 11 of the 17 patients, evaluated 2-480 months post-treatment, showed higher frequencies of MN than their respective levels before radiation therapy, indicating persistence of radiation induced cytogenetic damage. Further studies modeling changes in chromosome aberrations with acute and chronic exposures should provide perspectives on biological dosimetry in accident situations in which there is a blood sampling delay and on biological monitoring of human populations exposed to ionizing radiation. (author)

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

    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.

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

    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

    2009-01-01

    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 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...

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

    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. -- Highlights: •Exposures in aquatic ecosystems to many herbicides are episodic. •Pulsed exposure to atrazine does not increase sensitivity of Pseudokirchneriella subcapitata in subsequent exposures. •Recovery of algal growth from a pulsed exposure to atrazine occurs within 24 h. -- A pulsed exposure to atrazine does not influence subsequent response to a second, reduced range of exposures in an alga. Recovery in all endpoints is rapid

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

    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.

  15. Comparative response of dogs and monkeys to sublethal acute and continuous low dose-rate gamma-ray exposure

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (injury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with 35 R/day until death to determine the amount of radiation-induced injury remaining in conditioned animals as a reduction in mean survival time. Dogs (50 percent) and monkeys (8 percent) died from injury incurred during the conditioning exposures. Thus, the comparative response of dogs and monkeys to dose protraction by acute dose fractionation was similar to what might be expected from a single acute dose. Mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approximately 1400 h). Thus, hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35 R/day gamma-ray challenge exposure were greater than for their control counterparts. Thus, the long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than four times the acute LD50-30 in dogs and approximately two times that of monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 R/day

  16. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

  17. An incident study about acute and chronic human exposure to uranium by high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS).

    Krystek, Petra; Ritsema, Rob

    2009-01-01

    From the year 2003 to 2005 around 1700 Dutch soldiers made a part of the international stabilisation force in Iraq. An incident happened as a group of four Dutch soldiers found a 30mm bullet identified as containing depleted uranium (DU). The main pathway of the acute exposure is via inhalation of small uranium containing particles, e.g. from a bullet during its explosion. To develop a method for acute exposure investigations were carried out about finding an efficient and suitable way to sample nasal mucus as medium of inhalation. Generally, in human exposure studies with regard to natural uranium (NU) or DU, urine is the matrix for analysis. Uranium concentrations in urine are based on daily ingestion depending on the composition of drinking water and food. A second possibility is the acute exposure to uranium after an incident, either through inhalation or impact. Nevertheless, the results deliver only interpretations in respect to chronic/long-term exposure. For the acute exposure procedures like sniffling out into cleansing tissues and rinsing the nose were tested with real-life samples from four soldiers involved in an incident with possibly acute exposure to uranium. For the quantification of uranium high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS) was applied. PMID:18187363

  18. Plants experiencing chronic internal exposure to ionizing radiation exhibit higher frequency of homologous recombination than acutely irradiated plants

    Kovalchuk, O.; Kovalchuk, I.; Hohn, B. [Friedrich Miescher Institute, P.O. Box 2543, CH-4002 Basel (Switzerland); Arkhipov, A. [Chernobyl Scientific and Technical Center of International Research, Shkolnaya Str. 6, 255620 Chernobyl (Ukraine); Barylyak, I.; Karachov, I. [Ukrainian Scientific Genetics Center, Popudrenko Str. 50, 253660 Kiev (Ukraine); Titov, V. [Ivano-Frankivsk State Medical Academy, Galitska Str.2, 284000 Ivano-Frankivsk (Ukraine)

    2000-04-03

    Ionizing radiation (IR) is a known mutagen responsible for causing DNA strand breaks in all living organisms. Strand breaks thus created can be repaired by different mechanisms, including homologous recombination (HR), one of the key mechanisms maintaining genome stability [A. Britt, DNA damage and repair in plants, Annu. Rev. Plant. Phys. Plant Mol. Biol., 45 (1996) 75-100; H. Puchta, B. Hohn, From centiMorgans to basepairs: homologous recombination in plants, Trends Plant Sci., 1 (1996) 340-348.]. Acute or chronic exposure to IR may have different influences on the genome integrity. Although in a radioactively contaminated environment plants are mostly exposed to chronic pollution, evaluation of both kinds of influences is important. Estimation of the frequency of HR in the exposed plants may serve as an indication of genome stability. We used previously generated Arabidopsis thaliana and Nicotiana tabacum plants, transgenic for non-active versions of the {beta}-glucoronidase gene (uidA) [P. Swoboda, S. Gal, B. Hohn, H. Puchta, Intrachromosomal homologous recombination in whole plants, EMBO J., 13 (1994) 484-489; H. Puchta, P. Swoboda, B. Hohn, Induction of homologous DNA recombination in whole plants, Plant, 7 (1995) 203-210.] serving as a recombination substrate, to study the influence of acute and chronic exposure to IR on the level of HR as example of genome stability in plants. Exposure of seeds and seedlings to 0.1 to 10.0 Gy 60Co resulted in increased HR frequency, although the effect was more pronounced in seedlings. For the study of the influence of chronic exposure to IR, plants were grown on two chemically different types of soils, each artificially contaminated with equal amounts of 137Cs. We observed a strong and significant correlation between the frequency of HR in plants, the radioactivity of the soil samples and the doses of radiation absorbed by plants (in all cases r0.9, n=6, P<0.05). In addition, we noted that plants grown in soils with

  19. Plants experiencing chronic internal exposure to ionizing radiation exhibit higher frequency of homologous recombination than acutely irradiated plants

    Ionizing radiation (IR) is a known mutagen responsible for causing DNA strand breaks in all living organisms. Strand breaks thus created can be repaired by different mechanisms, including homologous recombination (HR), one of the key mechanisms maintaining genome stability [A. Britt, DNA damage and repair in plants, Annu. Rev. Plant. Phys. Plant Mol. Biol., 45 (1996) 75-100; H. Puchta, B. Hohn, From centiMorgans to basepairs: homologous recombination in plants, Trends Plant Sci., 1 (1996) 340-348.]. Acute or chronic exposure to IR may have different influences on the genome integrity. Although in a radioactively contaminated environment plants are mostly exposed to chronic pollution, evaluation of both kinds of influences is important. Estimation of the frequency of HR in the exposed plants may serve as an indication of genome stability. We used previously generated Arabidopsis thaliana and Nicotiana tabacum plants, transgenic for non-active versions of the β-glucoronidase gene (uidA) [P. Swoboda, S. Gal, B. Hohn, H. Puchta, Intrachromosomal homologous recombination in whole plants, EMBO J., 13 (1994) 484-489; H. Puchta, P. Swoboda, B. Hohn, Induction of homologous DNA recombination in whole plants, Plant, 7 (1995) 203-210.] serving as a recombination substrate, to study the influence of acute and chronic exposure to IR on the level of HR as example of genome stability in plants. Exposure of seeds and seedlings to 0.1 to 10.0 Gy 60Co resulted in increased HR frequency, although the effect was more pronounced in seedlings. For the study of the influence of chronic exposure to IR, plants were grown on two chemically different types of soils, each artificially contaminated with equal amounts of 137Cs. We observed a strong and significant correlation between the frequency of HR in plants, the radioactivity of the soil samples and the doses of radiation absorbed by plants (in all cases r0.9, n=6, P<0.05). In addition, we noted that plants grown in soils with different

  20. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

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

    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.

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

    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.

  3. Effect of repetitive acute cold exposures during the last phase of broiler embryogenesis on cold resistance through the life span.

    Shinder, D; Rusal, M; Giloh, M; Yahav, S

    2009-03-01

    The time just before hatch is critical, because the embryo shifts toward internal and external pipping. This study aimed to determine the beneficial effect of repeated acute reductions of the incubation temperature during the last phase of broiler embryogenesis on posthatch cold tolerance and on the development of ascites syndrome. Fertile eggs were incubated at 37.8 degrees C and 56% RH. At 18 and 19 d of incubation, 3 treatments were conducted, comprising 2 or 3 exposures to 15 degrees C for 30 or 60 min each. During these cold exposures, egg temperature was measured by infrared thermography to determine sensible heat loss from the eggs. At hatch, BW and body temperature were measured. At 3 and 14 d of age, chicks were challenged by cold exposure to 10 degrees C for 3 h. From 14 d of age onward, three-quarters of the chicks were raised under ascites-inducing conditions (AIC) and the others were raised under regular conditions. The sensible heat loss from the eggs was 512 +/- 66 cal and 718 +/- 126 cal for 30 and 60 min of cold exposure, respectively. No effect of treatment on hatchability was observed, but body temperature and BW were greater to significantly greater in the treated chicks. Cold challenges at 3 and 14 d of age revealed a relative thermoregulatory advantage of embryos exposed to cold for 60 min. Under AIC, fewer treated chickens than controls developed ascites. At 38 d of age, BW and relative breast muscle weight were numerically to significantly greater in the treated chicks than in the control chicks when both were raised under regular conditions, whereas no differences were observed among the chicks raised under AIC. Repeated brief acute cold exposures during the last phase of embryogenesis appeared to improve the ability of growing broilers to withstand low ambient temperatures during their life span. Moreover, chickens treated during embryogenesis improved their performance under regular growth conditions. PMID:19211536

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

    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.

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

    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.

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

    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. PMID:27235903

  7. Acute stress, depression, and anxiety symptoms among English and Spanish speaking children with recent trauma exposure

    Barber, Beth A.; Kohl, Krista L.; Kassam-Adams, Nancy; Gold, Jeffrey I.

    2014-01-01

    A growing literature suggests the clinical importance of acute stress disorder (ASD) symptoms in youth following potentially traumatic events. A multisite sample of English and Spanish speaking children and adolescents (N=479) between the ages of 8 to 17, along with their caregivers completed interviews and self-report questionnaires between 2 days and one month following the event. The results indicate that children with greater total acute stress symptoms reported greater depressive (r = .4...

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

    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

  9. The implications of re-analysing radiation-induced leukaemia in atomic bomb survivors: risks for acute and chronic exposures are different

    Implications of risk estimates, as required for practical radiation protection purposes, were explored through a preliminary re-analysis of leukaemia in the Japanese atomic bomb survivors using a biologically based cancer model. The calculations for the risks posed for contracting leukaemia pointed to important differences between low-dose-rate ('chronic') and high-dose-rate ('acute') exposures. For example, the risks caused by long-term ('chronic') exposures are calculated to be substantially lower than those for 'acute' exposures. In view of these model predictions the results of epidemiological studies are discussed. (author)

  10. Adolescent mice are less sensitive to the effects of acute nicotine on context pre-exposure than adults.

    Kutlu, Munir Gunes; Braak, David C; Tumolo, Jessica M; Gould, Thomas J

    2016-07-01

    Adolescence is a critical developmental period associated with both increased vulnerability to substance abuse and maturation of certain brain regions important for learning and memory such as the hippocampus. In this study, we employed a hippocampus-dependent learning context pre-exposure facilitation effect (CPFE) paradigm in order to test the effects of acute nicotine on contextual processing during adolescence (post-natal day (PND) 38) and adulthood (PND 53). In Experiment 1, adolescent or adult C57BL6/J mice received either saline or one of three nicotine doses (0.09, 0.18, and 0.36mg/kg) prior to contextual pre-exposure and testing. Our results demonstrated that both adolescent and adult mice showed CPFE in the saline groups. However, adolescent mice only showed acute nicotine enhancement of CPFE with the highest nicotine dose whereas adult mice showed the enhancing effects of acute nicotine with all three doses. In Experiment 2, to determine if the lack of nicotine's effects on CPFE shown by adolescent mice is specific to the age when they are tested, mice were either given contextual pre-exposure during adolescence or adulthood and received immediate shock and testing during adulthood after a 15day delay. We found that both adolescent and adult mice showed CPFE in the saline groups when tested during adulthood. However, like Experiment 1, mice that received contextual pre-exposure during adolescence did not show acute nicotine enhancement except at the highest dose (0.36mg/kg) whereas both low (0.09mg/kg) and high (0.36mg/kg) doses enhanced CPFE in adult mice. Finally, we showed that the enhanced freezing response found with 0.36mg/kg nicotine in the 15-day experiment may be a result of decreased locomotor activity as mice that received this dose of nicotine traveled shorter distances in an open field paradigm. Overall, our results indicate that while adolescent mice showed normal contextual processing when tested both during adolescence and adulthood, they

  11. Effects of acute millimeter wave exposure on the expression of substance P and c-fos in rat spinal cord

    Yan-wen ZHANG; Yao, Quan; Shang-cheng XU; Yu, Zheng-Ping; Guang-bin ZHANG

    2013-01-01

    Objective  To observe the expression changes in substance P (SP) and c-fos in rat spinal cord after acute millimeter-wave (MMW) exposure, and explore the mechanism of thermal hyperalgesia at the spinal level. Methods  The back skin of SD rats was exposed to 35 GHz MMW (40W/cm2) for 0s (control group), 30s, 1min, or 3min. The corresponding segment of the spinal cord was taken at 0min, 5min, 10min, 1h and 3h after MMW irradiation for total RNA and protein extraction. The expressions of SP and c...

  12. Augmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13

    Williams, Alison Suzanne; Mathews, Joel Andrew; Kasahara, David Itiro; Chen, Lucas; Wurmbrand, Allison Patricia; Si, Huiqing; Shore, Stephanie Ann

    2013-01-01

    Background: Acute ozone (O3) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice. Objectives: We examined the hypothesis that these augmented responses to O3 are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13. Methods: We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2–/–) mice, and obese Cpefat and TNFR2-deficient Cpefat mice (Cpefat/TNFR2–/–), to O3 (2 ppm for 3 hr) either...

  13. Augmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13

    Williams, Alison Suzanne; Mathews, Joel Andrew; Kasahara, David Itiro; Chen, Lucas; Wurmbrand, Allison Patricia; Si, Huiqing; Shore, Stephanie Ann

    2013-01-01

    Background: Acute ozone (O3) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice. Objectives: We examined the hypothesis that these augmented responses to O3 are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13. Methods: We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2–/– ) mice, and obese Cpefat and TNFR2-deficient Cpefat mice (Cpefat /TNFR2–/– ), to O3 (2 ppm for 3 hr) eit...

  14. Left Ventricular Function during Acute High-Altitude Exposure in a Large Group of Healthy Young Chinese Men

    Rao, Mingyue; Li, Jiabei; Qin, Jun; Zhang, Jihang; Gao, Xubin; Yu, Shiyong; Yu, Jie; Chen, Guozhu; Xu, Baida; Li, Huijie; Rao, Rongsheng; Huang, Lan; JIN, JUN

    2015-01-01

    Objective The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males. Methods A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclim...

  15. Acute and sublethal effects of sequential exposure to the pesticide azinphos-methyl on juvenile earthworms (Eisenia andrei).

    Jordaan, Martine S; Reinecke, Sophié A; Reinecke, Adriaan J

    2012-04-01

    The use of organophosphate pesticides is an integral part of commercial farming activities and these substances have been implicated as a major source of environmental contamination and may impact on a range of non-target fauna. The extent to which soil dwelling non-target organisms are affected by exposure to the organophosphate azinphos-methyl was investigated through monitoring selected biomarker responses and life cycle effects under laboratory conditions in the earthworm Eisenia andrei. Standard acute toxicity tests were conducted followed by a sequential exposure regime experiment, in order to assess the effects of multiple pesticide applications on biomarker (cholinesterase activity and neutral red retention time), life-cycle (growth and reproduction) and behaviour (avoidance and burrowing activity) responses. The present study indicates that the time between exposure events was a more important variable than concentration and that a longer interval between exposures may mitigate the effects of pesticide exposure provided that the exposure concentration is low. Additionally, it was shown that E. andrei was unable to avoid the presence of azinphos-methyl in soil, even at concentrations as high as 50% of the LC(50) value, indicating that the presence of azinphos-methyl in the soil pose a realistic threat to earthworms and other soil dwelling organisms. The ChE inhibition test showed a high percentage inhibition of the enzyme in all exposure groups that survived and NRR times of exposed organisms were lower than that of the controls. The present study yielded important results that contribute to the understanding of biological impacts of pesticide pollution on the environment. Extrapolating these results can aid in optimising pesticide application regimes to mitigate the environmental effects thereof and thus ensuring sustained soil biodiversity in agricultural areas. PMID:22086221

  16. Intermittent diazepam and continuous phenobarbital to treat recurrence of febrile seizures: a systematic review with meta-analysis

    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.

  17. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja; Szarek, Jozef; Wu, Dongmei; Williams, Andrew; Andersen, Ole; Nicklas R. Jacobsen; Yauk, Carole L.; Wallin, Hakan; Halappanavar, Sabina; Vogel, Ulla Birgitte

    2015-01-01

    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 pla...

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

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

    2013-01-01

    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 questio...

  19. Acute cardiovascular effects of exposure to air pollution: components, vascular mechanisms and protecting the public

    Langrish, Jeremy Patrick

    2012-01-01

    Exposure to air pollution, particularly fine and ultrafine particulate matter derived from combustion sources, has been consistently associated with increased cardiovascular morbidity and mortality. Recent controlled exposure studies demonstrate that short-term exposure to diesel exhaust, which can contribute up to 40% of urban particulate air pollution, results in impaired vascular endothelial and fibrinolytic function in healthy volunteers, and increased exercise-induced m...

  20. Growth and biochemical responses of juvenile cod to acute and chronic exposure to production water from the Hibernia oil rig

    Burridge, L.; Lyons, M.; Blair, T.; Haya, K.; Lee, K. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Maritimes Region, Ocean Sciences Division

    2007-07-01

    A study was conducted in which the chemical characteristics of production water collected from the Hibernia oil production platform in June, 2006 were determined. Bioassays were also performed on juvenile cod in order to determine acute responses after 48 hour exposure to concentrations of production water ranging from 0.06 to 5 per cent. Of the 70 juvenile cod that were exposed continuously for 45 days to 0.05 per cent Hibernia production water, 8 were sacrificed and liver, gill muscle and plasma was collected for biochemical analysis at day 3, 14, 28 and 45 during the exposure. Length and weight data were also collected to compare growth rates of exposed fish with unexposed fish. Results did not reveal any difference in growth rate in cod exposed for 45 days to Hibernia production water compared to those held in untreated water under the same conditions. Tissues for mixed function oxygenase (MFO) induction are undergoing analysis.

  1. Growth and biochemical responses of juvenile cod to acute and chronic exposure to production water from the Hibernia oil rig

    A study was conducted in which the chemical characteristics of production water collected from the Hibernia oil production platform in June, 2006 were determined. Bioassays were also performed on juvenile cod in order to determine acute responses after 48 hour exposure to concentrations of production water ranging from 0.06 to 5 per cent. Of the 70 juvenile cod that were exposed continuously for 45 days to 0.05 per cent Hibernia production water, 8 were sacrificed and liver, gill muscle and plasma was collected for biochemical analysis at day 3, 14, 28 and 45 during the exposure. Length and weight data were also collected to compare growth rates of exposed fish with unexposed fish. Results did not reveal any difference in growth rate in cod exposed for 45 days to Hibernia production water compared to those held in untreated water under the same conditions. Tissues for mixed function oxygenase (MFO) induction are undergoing analysis

  2. Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy.

    Ashtarinezhad, Azadeh; Panahyab, Ataollah; Shaterzadeh-Oskouei, Shahrzad; Khoshniat, Hessam; Mohamadzadehasl, Baharak; Shirazi, Farshad H

    2016-09-01

    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

  3. Assessing chronic fish health: An application to a case of an acute exposure to chemically treated crude oil.

    Mauduit, F; Domenici, P; Farrell, A P; Lacroix, C; Le Floch, S; Lemaire, P; Nicolas-Kopec, A; Whittington, M; Zambonino-Infante, J L; Claireaux, G

    2016-09-01

    Human alteration of marine ecosystems is substantial and growing. Yet, no adequate methodology exists that provides reliable predictions of how environmental degradation will affect these ecosystems at a relevant level of biological organization. The primary objective of this study was to develop a methodology to evaluate a fish's capacity to face a well-established environmental challenge, an exposure to chemically dispersed oil, and characterize the long-term consequences. Therefore, we applied high-throughput, non-lethal challenge tests to assess hypoxia tolerance, temperature susceptibility and maximal swimming speed as proxies for a fish's functional integrity. These whole animal challenge tests were implemented before (1 month) and after (1 month) juvenile European sea bass (Dicentrarchus labrax) had been acutely exposed (48h) to a mixture containing 0.08gL(-1) of weathered Arabian light crude oil plus 4% dispersant (Corexit© EC9500A), a realistic exposure concentration during an oil spill. In addition, experimental populations were then transferred into semi-natural tidal mesocosm ponds and correlates of Darwinian fitness (growth and survival) were monitored over a period of 4 months. Our results revealed that fish acutely exposed to chemically dispersed oil remained impaired in terms of their hypoxia tolerance and swimming performance, but not in temperature susceptibility for 1 month post-exposure. Nevertheless, these functional impairments had no subsequent ecological consequences under mildly selective environmental conditions since growth and survival were not impacted during the mesocosm pond study. Furthermore, the earlier effects on fish performance were presumably temporary because re-testing the fish 10 months post-exposure revealed no significant residual effects on hypoxia tolerance, temperature susceptibility and maximal swimming speed. We propose that the functional proxies and correlates of Darwinian fitness used here provide a useful

  4. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna.

    Sarapultseva, Elena I; Dubrova, Yuri E

    2016-10-01

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000mGy of acute γ-rays. Exposure to 1000 and 10,000mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F0 and F1Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F0Daphnia exposed to 1000 and 10,000mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000mGy. We propose that the decreased fertility observed among the F2 progeny of parents exposed to 10,000mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F2 progeny of irradiated F0Daphnia exposed to the lower doses of acute γ-rays. PMID:27288911

  5. Oxidative stress related to chlorpyrifos exposure in rainbow trout: Acute and medium term effects on genetic biomarkers.

    Benedetto, A; Brizio, P; Squadrone, S; Scanzio, T; Righetti, M; Gasco, L; Prearo, M; Abete, M C

    2016-05-01

    Organophosphates (OPs) are derivatives of phosphoric acid widely used in agriculture as pesticides. Chlorpyrifos (CPF) is an OP that is extremely toxic to aquatic organisms. Rainbow trout (Oncorhynchus mykiss) is considered as a sentinel model species for ecotoxicology assessment in freshwater ecosystems. An exposure study was carried out on rainbow trout to investigate genetic responses to CPF-induced oxidative stress by Real-Time PCR, and to determine the accumulation dynamics of CPF and toxic metabolite chlorpyrifos-oxon (CPF-ox) in edible parts, by HPLC-MS/MS. Among the genes considered to be related to oxidative stress, a significant increase in HSP70 mRNA levels was observed in liver samples up to 14days after CPF exposure (0.05mg/L). CPF concentrations in muscle samples reach mean values of 285.25ng/g within 96hours of exposure, while CPF-ox concentrations were always under the limit of quantification (LOQ) of the applied method. Our findings lead us to consider HSP70 as a suitable genetic marker in rainbow trout for acute and medium-term monitoring of CPF exposure, complementary to analytical determinations. PMID:27017883

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

    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.

  7. Modulation of pulmonary defense mechanisms by acute exposures to nitrogen dioxide. [Staphylococcus aureus; Proteus mirabilis; Pasteurella pneumotropica

    Jakab, G.J.

    1987-02-01

    The effect of acute exposures to NO/sub 2/ on the antibacterial defenses of the murine lung was assessed following inhalation challenges with Staphylococcus aureus, Proteus mirabilis, and Pasteurella pneumotropica. With S. aureus pulmonary antibacterial defenses were suppressed at NO/sub 2/ levels of 4.0 ppm and greater. Exposure to 10.0 ppm enhanced the intrapulmonary killing of P. mirabilis which correlated with an increase in the phagocytic cell populations lavaged from the lungs; at 20.0 ppm bactericidal activity against P. mirabilis was impaired. Pulmonary antibacterial defenses against P. pneumotropica were impaired at 10.0 ppm which correlated with a decrease in the retrieved phagocytic lung cell population. Reversing the order of treatment (ie., NO/sub 2/ exposure prior to bacterial challenge) raised the threshold concentration for NO/sub 2/-induced impairment of intrapulmonary bacterial killing. With S. aureus the effect was not observed at 5.0 ppm but at 10.0 ppm and with P. mirabilis not at 20.0 ppm but at 30.0 ppm intrapulmonary killing was enhanced. Exposures up to 20.0 ppm of NO/sub 2/ did not effect the physical translocation mechanisms of the lung as quantitated by declines in pulmonary radiotracer activity following aerogenic challenge with /sup 32/P-labeled staphylococci.

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

    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.

  9. Early growth rates and their relationships to mortalities of five breeds of chickens following exposure to acute gamma radiation stress

    Growth and mortality responses were recorded for 541 chicks, representing five different breeds of chickens, following acute exposures to gamma radiation stress at two days of age. Although there were no statistically significant differences in the LD50/30 of the five breeds studied, Cobb broilers showed the highest (1580R) and White Leghorn bantams the lowest (980R) levels, respectively. Other breeds studied included the standard White Leghorn, Athens Randombreds and a strain of feral bantam. Growth rates of body weights were proportionately more depressed by radiation stress than were body sizes, as measured by the lengths of the culmen, tarsus, middle toe and longest primary wing feather of all 32 day-old survivors. Among these structures, the length of the culmen seemed to be the least affected by radiation stress in all of the breeds studied. Feral bantams were able to tolerate the greatest depression in weight gain before exhibiting mortality at exposures below their LD50/30' while Cobb broilers tolerated the greatest depression of weight gain at higher exposure levels. There was a suggestion that those characteristics which were strongly selected for in the course of a particular breed's development were those which experienced the greatest proportional depressions following exposure to gamma radiation stress

  10. Acute effect of copper exposure on serum biochemical characteristics of common carp (Cyprinus carpio L.

    Melika Ghelichpour

    2014-07-01

    Full Text Available Effects of ambient copper was investigated on serum stress markers, sodium and enzyme levels in Common carp (Cyprinus carpio L. over a 14-d exposure period. Fish were exposed to 0, 25 and 100 μg L-1 copper (as copper sulfate and blood was sampled at 0, 3, 7 and 14 d after exposure. Serum profile was significantly affected by copper concentration, sampling time and their interaction. Increase in serum levels of cortisol, glucose, alanine aminotransferase and aspartate aminotransferase and decrease in serum sodium levels were observed in both copper-exposed groups, 3 d after copper exposure, which lasted until the end of the experiment. It is concluded that copper exposure causes stress response and sodium loss in common carp. Likewise alanine aminotransferase and aspartate aminotransferase increase after exposure which might be as results of either tissue damage or stress.

  11. The effects of acute stress exposure on neural correlates of Pavlovian conditioning with monetary gains and losses

    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.

  12. Phenobarbital plasma level/dose ratio in monotherapy. Influence of age, sex and dose.

    Durán, J A; Sánchez, A; Serrano, M I; Serrano, J S

    1988-05-01

    Phenobarbital plasma level/dose ratio (L/D) has been studied in 536 outpatients distributed in groups according to age, sex and drug dosage. Samples were obtained prior to the first morning dose. Plasma levels that correspond to the steady-state phase were determined by homogeneous enzymatic immunoassay (EMITR). From the results it must be pointed out: 1) An increase of L/D as the age increases within each group; 2) A decrease of L/D as the dose of phenobarbital increases in the overall sample; 3) Sex does not affect L/D in any of the subgroups studied; 4) For a given dose higher blood levels are reached in children 7 to 15 years old in our sample than in other comparable studies in Spain. PMID:3398650

  13. Purification and immunochemical detections of ?-naphthoflavone- and phenobarbital-induced avian cytochrome P450 enzymes

    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.

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

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

    2008-01-01

    INTRODUCTION: Delirium tremens (DT) is the most severe manifestation of alcohol withdrawal which--if untreated--has a high rate of mortality. Barbiturates are the most effective drug but respiratory depression may occur. In the present study we investigated the frequency of respiratory problems......-DT and full blown DT were included in the study. RESULTS: While we did not detect any respiratory problems among patients with pre-DT, we found 9 cases among 73 patients with full blown DT, 5 of which were considered serious. In two of these the frequency of respiration (FR) was decreased (5-6 per min). Both...... 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...

  15. Acute and chronic effects of pulse exposure of Daphnia magna to dimethoate and pirimicarb.

    Andersen, Tobias Henrik; Tjørnhøj, Rikke; Wollenberger, Leah; Slothuus, Tina; Baun, Anders

    2006-05-01

    Short-term (Daphnia magna exposed to pulses of 0.5 to 8 h in duration. During a 21-d postexposure observation period, the following parameters were monitored: Mortality, mobility, day for first offspring, animal size, weight of offspring and adults, and number of offspring produced. In general, animals exposed to a single pulse of dimethoate or pirimicarb regained mobility after 24 to 48 h in clean media. Animals exposed to repeated pulses of dimethoate did not recover mobility during a 48-h postexposure observation period, and mortality was significantly increased. Animals exposed to two pulses of pirimicarb showed less recovery of mobility compared with those exposed to one pulse. Exposure of D. magna to 30 mg/L of dimethoate or 100 microg/L of pirimicarb for 2 to 6 h resulted in a significant reduction in the number of offspring and in the average weight of offspring. The average body length was reduced after pulse exposure to 30 mg/L of dimethoate for 3 h or 70 microg/L of pirimicarb for 4 h, and these exposure concentrations caused a delay in the day for first offspring at exposure durations of 2 to 6 h. The most important new findings in the present study are that short-term (<4 h) pulse exposure of neonates to acetylcholinesterase-inhibiting pesticides caused reproductive damage in D. magna and that repeated-pulse exposure significantly increased mortality in animals that apparently had recovered after a single-pulse exposure. PMID:16704047

  16. Side effects of phenobarbital and carbamazepine in childhood epilepsy: randomised controlled trial

    Banu, S. H.; Jahan, M.; Koli, U. K.; Ferdousi, S.; Khan, N. Z.; Neville, B.

    2007-01-01

    Objective: To compare the behavioural side effects associated with two commonly used antiepilepsy drugs--phenobarbital and carbamazepine--in children in Bangladesh. Design: Prospective randomised controlled single centre trial. Setting: Specialist children's hospital in Dhaka, Bangladesh. Participants: 108 children aged 2-15 with generalised tonic-clonic (n=51) or partial and secondary generalised seizures (n=57). Main outcome measures: Seizure control and behavioural side effects. Results: 9...

  17. Phenytoin induced chorea in a pediatric patient: An interaction between phenytoin, phenobarbital and clobazam

    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.

  18. COMPARISON BETWEEN DIAZEPAM AND PHENOBARBITAL IN PREVENTION OF FEBRILE SEIZURE: CLINICAL TRIAL

    N. Beyraghi

    2008-06-01

    Full Text Available ObjectiveFebrile convulsions (FC are the most common convulsive events in childhood, occurring in 2-5% of children. About one third of these children will have a recurrence during a subsequent febrile infection. This sudden neurologic problem is extremely frightening and emotionally traumatic for parents so some physicians try to prevent recurrence of FC by prescribing different drugs.Materials and MethodsThis is a randomized clinical trial in 85 healthy children, aged 6 months to 5 years, who were not treated before. These children received randomly either oral diazepam (0.33 mg/kg/TDS for two days during febrile illness or continuous oral Phenobarbital (3-5mg/kg /24 h.ResultsUltimately 64 patients completed the study and were followed up for an average of 13 months (12-18 months. The rate of recurrence of febrile seizure was 18.2% in diazepam group and 32.3% in Phenobarbital group; the difference is not statistically significant (p=0.16.ConclusionThere was no significant difference between intermittent oral diazepam and continuous oral Phenobarbital for FC prevention.

  19. Dynamics of DNA-protein complex formation in rat liver during induction by phenobarbital and triphenyldioxane.

    Pustylnyak, V O; Zacharova, L Yu; Gulyaeva, L F; Lyakhovich, V V; Slynko, N M

    2004-10-01

    CYP2B gene expression in liver of rats treated with phenobarbital and triphenyldioxane at early stage of induction (40 min-18 h) was studied using electrophoretic mobility shift assay (EMSA) and RT-PCR. During first 6 h after induction, differences in the dynamics of formation of DNA-protein complexes were shown for each inducer. Later (18 h after induction), the intensity pattern of these complexes became the same for both phenobarbital and triphenyldioxane treated animals. This suggests the existence of specific signaling for each inducer only in early stages of CYP2B activation. Increase in nuclear protein (possible transcription factor) binding to Barbie-box regulatory sequence of CYP2B genes was accompanied by their increased expression. Thus, we have demonstrated for the first time that early stages of induction (40 min and 3 h after administration of phenobarbital and triphenyldioxane, respectively) are accompanied by activation of nuclear proteins that can bind to Barbie-box element of CYP2B. Although various chemical inducers cause distinct activation of such binding, this process involves activation of gene transcription. PMID:15527410

  20. Phenobarbital-induced hepatocellular proliferation: anti-bromodeoxyuridine and anti-proliferating cell nuclear antigen immunocytochemistry.

    Jones, H B; Clarke, N A; Barrass, N C

    1993-01-01

    We report modifications to immunocytochemical detection procedures for proliferating cell nuclear antigen (PCNA) which permit its identification in liver samples previously fixed for BrdU immunocytochemistry. Both methods have been used for the assessment of phenobarbital-induced cell proliferation in rat liver. The difficulties associated with the hitherto unsuccessful application of PCNA immunocytochemical methods to tissues fixed in formalin for BrdU visualization were overcome by epitope unmasking with acid hydrolysis, extension of primary antiserum (PC10) incubation, and employment of streptavidin-ABC-HRP. BrdU delivery via osmotic minipumps for 48 hr before euthanasia, followed by fixation in cold formalin for 14 days, yielded reliable and reproducible hepatocellular labeling and a peak of cell proliferation in all lobes on Day 3 (i.e., labeling during Days 1-3) of dosing with 80 mg/kg/day phenobarbital. Labeling indices (LI) of both control and phenobarbital-treated liver were lower in the left and right median lobes as compared with the lateral lobes. In sections of the left lateral lobe from the same liver, PCNA immunocytochemistry revealed a peak of proliferative activity (about one third of the maximum LI generated by BrdU incorporation) on Day 1. These findings, together with the advantages and disadvantages of both techniques, are discussed in the context of their applications to different investigative requirements. PMID:8093255

  1. Phenobarbital induced Stevens-Johnson syndrome: a case report

    Hari Babu Ramineni; Pravallika Eluri; Kumudini Vipparla; Vidyadhara Suryadevara

    2015-01-01

    Stevens-Johnson Syndrome (SJS) is a life-threatening acute hypersensitive reaction affecting the skin and mucous membranes. We report a case with SJS likely induced by phenobarbitone during the switch of sodium valproate and phenobarbitone regimen. The patient reported fever with fluid-filled lesions all over the body and redness and burning sensation of both the eyes. Peeling of the skin due to rupture of the fluid-filled lesions and pigmentation on the skin for 10 days. Based on a physical ...

  2. Acute Phase Response, Inflammation and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure

    Background: Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. Objective: We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help ...

  3. Acute Phase Response and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure

    Identification of biomarkers assists in the disease diagnosis and environmental health risk assessment. Exposure to Libby amphibole (LA) has been associated with increased cardiovascular mortality. We hypothesized that rats exposed to LA would present a unique serum proteomic pro...

  4. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    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...

  5. Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

    Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A.; Kash, Thomas L.

    2014-01-01

    Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased a...

  6. Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat.

    Kotyzová, Dana; Hodková, Anna; Bludovská, Monika; Eybl, Vladislav

    2015-11-01

    Occupational exposure to hexavalent chromium (Cr(VI)) compounds is of concern in many Cr-related industries and their surrounding environment. Cr(VI) is a proven toxin and carcinogen. The Cr(VI) compounds are easily absorbed, can diffuse across cell membranes, and have strong oxidative potential. Despite intensive studies of Cr(VI) pro-oxidative effects, limited data exist on the influence of Cr(VI) on selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx)-important components of antioxidant defense system. This study investigates the effect of Cr(VI) exposure on antioxidant defense status, with focus on these selenoenzymes, and on trace element homeostasis in an acute experiment in rat. Male Wistar rats (130-140g) were assigned to two groups of 8 animals: I. control; and II. Cr(VI) treated. The animals in Cr(VI) group were administered a single dose of K2Cr2O7 (20 mg /kg, intraperitoneally (ip)). The control group received saline solution. After 24 h, the animals were sacrificed and the liver and kidneys were examined for lipid peroxidation (LP; thiobarbituric acid reactive substances (TBARS) concentration), the level of reduced glutathione (GSH) and the activities of GPx-1, TrxR-1, and glutathione reductase (GR). Samples of tissues were also used to estimate Cr accumulation and alterations in zinc, copper, and iron levels. The acute Cr(VI) exposure caused an increase in both hepatic and renal LP (by 70%, p effect of Cr(VI) was found on TrxR-1 activity in both the liver and the kidneys. The ability of Cr(VI) to cause TrxR inhibition could contribute to its cytotoxic effects. Further investigation of oxidative responses in different in vivo models may enable the development of strategies to protect against Cr(VI) oxidative damage. PMID:23625905

  7. Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task.

    Shawn K Acheson

    Full Text Available Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0 g/kg 30 min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0 g/kg for 16 days (PND30 To PND46 prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.

  8. Mimicking exposures to acute and lifetime concentrations of inhaled silver nanoparticles by two different in vitro approaches

    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. The acute and sub-chronic exposures of goldfish to naphthenic acids induce different host defense responses.

    Hagen, Mariel O; Garcia-Garcia, Erick; Oladiran, Ayoola; Karpman, Matthew; Mitchell, Scott; El-Din, Mohamed Gamal; Martin, Jonathan W; Belosevic, Miodrag

    2012-03-01

    Naphthenic acids (NAs) are believed to be the major toxic component in oil sands process-affected water (OSPW) produced by the oil sands mining industry in Northern Alberta, Canada. We recently reported that oral exposure to NAs alters mammalian immune responses, but the effect of OSPW or NAs on the immune mechanisms of aquatic organisms has not been fully elucidated. We analyzed the effects of acute and sub-chronic NAs exposures on goldfish immune responses by measuring the expression of three pro-inflammatory cytokine genes, antimicrobial functions of macrophages, and host defense after challenge with a protozoan pathogen (Trypanosoma carassii). One week after NAs exposure, fish exhibited increased expression of pro-inflammatory cytokines (IFNγ, IL-1β1, TNF-α2) in the gills, kidney and spleen. Primary macrophages from fish exposed to NAs for one week, exhibited increased production of nitric oxide and reactive oxygen intermediates. Goldfish exposed for one week to 20 mg/L NAs were more resistant to infection by T. carassii. In contrast, sub-chronic exposure of goldfish (12 weeks) to NAs resulted in decreased expression of pro-inflammatory cytokines in the gills, kidney and spleen. The sub-chronic exposure to NAs reduced the ability of goldfish to control the T. carassii infection, exemplified by a drastic increase in fish mortality and increased blood parasite loads. This is the first report analyzing the effects of OSPW contaminants on the immune system of aquatic vertebrates. We believe that the bioassays depicted in this work will be valuable tools for analyzing the efficacy of OSPW remediation techniques and assessment of diverse environmental pollutants. PMID:22227375

  10. Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera).

    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. PMID:26802564

  11. Histopathological and biochemical changes in rat thyroid following acute exposure to hexavalent chromium

    Mahmood, Tariq; Zia Quresh, Irfan; Javed Iqbal, Muhammad

    2010-01-01

    Chromium in hexavalent form is highly toxic and a known carcinogen, although its effects on thyroid structure and function are relatively unexplored. Workers in an industrial environment can be, at times, exposed to this form of chromium. The present study was, therefore, designed using laboratory rats as a model system to investigate the effect on thyroid structure and function following two acute intraperitoneal doses of 30 mg/kg b.w. potassium dichromate administere...

  12. Acute and chronic exposure in mussel (aulacomya ater) and clam (semelle solida) with Cs137

    Two of the most common Peruvian benthonic molluscs, have been shown to be effective concentrators of Cesium-137 and have also proven useful as indicators of that radionuclide in their natural environment, according with results in this paper. However the clam is a better indicator, when determining environmental acute release of Cesium-137 due to reactor accidents, nuclear tests, accidents in nuclear ships, submarines and radioactive material transport, and the mussel for a continuous monitoring of environmental radio contaminant levels. (author). 11 refs

  13. Partial recovery of erythrocyte glycogen in diabetic rats treated with phenobarbital

    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

  14. Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

    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

  15. Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse

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

    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

  17. MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor.

    Ryota Shizu

    Full Text Available 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.

  18. MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor.

    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. PMID:22815988

  19. Acute short-term dim light exposure can lower muscle strength endurance

    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.

  20. Effect of acute ozone exposure on the proteinase-antiproteinase balance in the rat lung

    Lung disease may result from a persisting proteinase excess or a depletion of antiproteinase in pulmonary parenchyma. We investigated the in vivo effect of a 48-hr exposure to ozone at 0.5, 1.0, or 1.5 ppm on proteinase and antiproteinase activity of rat lungs. Elastase inhibitory capacities of serum, lung tissue, and airway washings were measured as indicators of antielastase activity. Trypsin inhibitory capacity was measured using an esterolytic procedure. Proteinase was measured as radioactive release from a 14C-globin substrate. The 48-hr exposures to O3 at levels up to 1 ppm produced concentration-dependent decreases of 35-80% of antiproteinase activities in serum and in lung tissue. However, exposure to 1.5 ppm O3 resulted in no decrease in antiproteinase activities. Acid proteinase activities (pH 4.2) were increased 65-120% by exposure to 1 or 1.5 ppm O3, which correlated with inflammatory cells noted histologically. At 1.5 ppm O3, pulmonary edema and hemorrhage were noted in histologic sections. These changes led to a flooding of the alveoli with up to 40 times normal protein levels and a greater than fivefold increase in airway antiproteinase. These data suggest that serum and soluble lung tissue antiproteinase activity decreased upon exposure to low levels of ozone. However, if O3 exposure is high enough to produce pulmonary hemorrhage, antiproteinase may increase following serum exudation. These changes may be important in the development of ozone-induced lung diseases, especially emphysema

  1. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    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

  2. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl Phthalate in Rats

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

    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 albumi...

  4. Electrocardiographic and autonomic effects of acute particulate matter (PM) exposure in a rat model of cardiomyopathy

    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 ...

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

    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...... and cereals. The probabilistic approach was used in the assessments. Residue data obtained from the Danish monitoring programme carried out in the period 2004-2007, which included 6704 samples of fruit, vegetables and cereals, were used in the calculations. Food consumption data were obtained from...... 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...

  6. Combined exposure to simulated microgravity and acute or chronic radiation reduces neuronal network integrity and cell survival

    Benotmane, Rafi

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. This study aimed at assessing the effect of these combined conditions on neuronal network density, cell morphology and survival, using well-connected mouse cortical neuron cultures. To this end, neurons were exposed to acute low and high doses of low LET (X-rays) radiation or to chronic low dose-rate of high LET neutron irradiation (Californium-252), under the simulated microgravity generated by the Random Positioning Machine (RPM, Dutch space). High content image analysis of cortical neurons positive for the neuronal marker βIII-tubulin unveiled a reduced neuronal network integrity and connectivity, and an altered cell morphology after exposure to acute/chronic radiation or to simulated microgravity. Additionally, in both conditions, a defect in DNA-repair efficiency was revealed by an increased number of γH2AX-positive foci, as well as an increased number of Annexin V-positive apoptotic neurons. Of interest, when combining both simulated space conditions, we noted a synergistic effect on neuronal network density, neuronal morphology, cell survival and DNA repair. Furthermore, these observations are in agreement with preliminary gene expression data, revealing modulations in cytoskeletal and apoptosis-related genes after exposure to simulated microgravity. In conclusion, the observed in vitro changes in neuronal network integrity and cell survival induced by space simulated conditions provide us with mechanistic understanding to evaluate health risks and the development of countermeasures to prevent neurological disorders in astronauts over long-term space travels. Acknowledgements: This work is supported partly by the EU-FP7 projects CEREBRAD (n° 295552)

  7. Longitudinal tracking of cytokines after acute exposure to tuberculosis: association of distinct cytokine patterns with protection and disease development.

    Hussain, Rabia; Talat, Najeeha; Shahid, Firdaus; Dawood, Ghaffar

    2007-12-01

    Household contacts (HCs) of patients with tuberculosis (TB) are at higher risk of infection as well as the development of active disease. Longitudinal tracking of antigen-specific cytokines after acute exposure may significantly advance our understanding of the dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study with healthy HCs after exposure to TB. The patterns of cytokines (gamma interferon [IFN-gamma] and interleukin 10 [IL-10]) in response to mycobacterial antigens (culture filtrate [CF] proteins) and nonspecific mitogens (phytohemagglutinin [PHA] and lipopolysaccharide [LPS]) were assessed at 0, 6, 12, and 24 months after exposure. Seven of 109 (6.4%) HCs developed active disease. Six of the seven individuals were females, and active disease developed between 12 and 15 months after exposure in 5/20 families. The most significant findings were the exponential increases ( approximately 1,000-fold) in both the CF protein- and the PHA- or LPS-induced IFN-gamma/IL-10 ratio in healthy HCs (n = 26), which peaked at 12 months, compared to the levels in HCs who developed disease (n = 7), in whom relatively flat responses were observed during the 24-month period. Linear trends for 0 to 12 and 0 to 24 months for the CF protein-induced IFN-gamma/IL-10 ratio showed significant differences between the two groups, as determined by the use of the Mantel extension test for chi(2) analysis (odds ratio = 0.45; 95% confidence interval = 0.295 to 0.685; P = 0.0002). Our results strongly suggest that the magnitude of the IFN-gamma/IL-10 ratio at 12 months after exposure may be a critical determinant in the resolution of infection. These studies provide new insights into the cytokine responses associated with disease establishment or the resolution of infection after natural exposure to TB and have implications for TB control programs as well vaccine efficacy studies. PMID:17928427

  8. Induction of genomic instability after an acute whole-body exposure of mice to 56Fe ions

    Rithidech, Kanokporn; Supanpaiboon, Wisa; Whorton, Elbert

    Different types of galactic cosmic rays (GCR) are present in space and have large mass and energy (HZE particles). Among these, stripped 56 Fe ions are of major concern. Although HZE particles are approximately 1% of GCR, their contribution to health risk could be significant because of (1) their high linear energy transfer (LET) resulting in a larger amount of energy being deposited in the hit cells, and (2) the lack of information on the effectiveness of these particles in cancer induction. To better protect astronauts in space environments, it is essential that we improve our understanding of the 56 Fe-ion-induced damage associated with the increased risk of late occurring diseases (such as cancer). It has been well established that acute myeloid leukemia (AML) is one of the major malignancies associated with exposure to ionizing radiation in both human beings and in mice. It is therefore one of the most important cancers related to space flights. For these reasons, it is important to investigate 56 Fe ion-induced damage in in vivo systems, especially in those cells that are known to be at risk for health problems associated with radiation, such as hematopoietic cells, the known target cell for radiation-induced leukemia. Since in vivo studies of humans are not possible, animal studies are critically important. It has been widely suggested that elevation of delayed chromosomal damage (normally known as genomic instability) is associated with cancer risk. We therefore determined dose-response relationships for the frequencies of micronuclei (MN) in mouse blood erythrocytes as a measure of both initial radiation damage and the induction of genomic instability. The frequencies of MN were measured in mature normochromatic-erythrocytes (MN-NCEs) and immature polychromatic-erythrocytes (MN-PCEs). These measurements were made as a function of radiation dose, radiation quality, time after irradiation and the genetic background of exposed mice. Blood samples were

  9. Acute Exposure to Di(2-Ethylhexyl) Phthalate in Adulthood Causes Adverse Reproductive Outcomes Later in Life and Accelerates Reproductive Aging in Female Mice.

    Hannon, Patrick R; Niermann, Sarah; Flaws, Jodi A

    2016-03-01

    Humans are ubiquitously exposed to di(2-ethylhexyl) phthalate (DEHP), which is an environmental toxicant incorporated in consumer products. Studies have shown that DEHP targets the ovary to disrupt essential processes required for reproductive and nonreproductive health. Specifically, 10-day exposure to DEHP accelerates primordial follicle recruitment and disrupts estrous cyclicity in adult mice. However, it is unknown if these effects on folliculogenesis and cyclicity following acute DEHP exposure can have permanent effects on reproductive outcomes. Further, the premature depletion of primordial follicles can cause early reproductive senescence, and it is unknown if acute DEHP exposure accelerates reproductive aging. This study tested the hypothesis that acute DEHP exposure causes infertility, disrupts estrous cyclicity, alters hormone levels, and depletes follicle numbers by inducing atresia later in life, leading to accelerated reproductive aging. Adult CD-1 mice were orally dosed with vehicle or DEHP (20 μg/kg/day-500 mg/kg/day) daily for 10 days, and reproductive outcomes were assessed at 6 and 9 months postdosing. Acute DEHP exposure significantly altered estrous cyclicity compared to controls at 6 and 9 months postdosing by increasing the percentage of days the mice were in estrus and metestrus/diestrus, respectively. DEHP also significantly decreased inhibin B levels compared to controls at 9 months postdosing. Further, DEHP significantly increased the BAX/BCL2 ratio in primordial follicles leading to a significant decrease in primordial and total follicle numbers compared to controls at 9 months postdosing. Collectively, the adverse effects present following acute DEHP exposure persist later in life and are consistent with accelerated reproductive aging. PMID:26678702

  10. Effect of continuous exposure to apomorphine and acute exposure to fluphenazine-N-mustard on dopaminergic behavior and radioligand binding in supersensitive mice

    Winkler, J.D.

    1987-01-01

    Mice with unilateral, 6-hydroxydopamine-induced lesions of the corpus striatum were exposed to continuous infusion of apomorphine via a subcutaneously implanted osmotic pump. The turning response of these mice when challenged with an acute injection of apomorphine was significantly reduced at one day after chronic implantation and was totally absent at two and four days after implantation. This effect of continuous exposure to apomorphine was found to be concentration- and time-dependent as well as reversible when the implant was removed. Mice tolerant to apomorphine were cross-tolerant to the rotational effects of the D{sub 1} dopaminergic agonist SKF 38393 and the D{sub 2} dopaminergic agonist Ly 171555, but not to amphetamine. Continuous exposure to apomorphine resulted in a decrease in the binding of ({sup 3}H)spiroperidol (D{sub 2} sites) by 44%, whereas the binding of ({sup 3}H)SCH 23390 (D{sub 1} sites) was not affected. Fluphenazine-N-mustard (FNM) has been shown to bind irreversibly to dopaminergic sites. Experiments using varying doses of FNM demonstrated that FNM inhibited Ly 171555-induced rotational behavior at doses ten fold lower than those required to block rotations induced by SKF 38393. In vitro, FNM inhibited the specific binding of ({sup 3}H) spiroperidol at concentrations ten fold lower than those required to inhibit the binding of ({sup 3}H)Sch23390. In vivo, FNM inhibited the binding of ({sup 3}H) spiroperidol measured ex vivo, but did not inhibit the binding of ({sup 3}H) Sch 23390, even when given in doses as high as 100 mg/kg. These studies indicate that FNM was approximately ten times more potent at inhibiting D{sub 2} than D{sub 1} mediated behavior and at displacing D{sub 2} versus D{sub 1} ligands, suggesting that FNM may be useful for studying and differentiating D{sub 2} and D{sub 1} mediated events.

  11. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    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)

  12. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

    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. PMID:26493272

  13. Study on the therapeutic effect of cytokine on acute radiation syndrome induced by 60Co γ ray exposure

    Objective: To examine the therapeutic effect of combined administration of rhIL-11 and rhG-CSF on acute radiation syndrome induced by 60Coγ ray exposure in beagles. Methods: Sixteen beagles were randomly divided into the control (n=5), symptomatic treatment group (n=5) and cytokine treatment group (n=6). All the beagles in the three groups were exposed to the whole-body irradiation of 60Co γ ray at a dose of 4.5 Gy. The animals in the second group accepted active symptomatic treatment. The animals in the cytokine treatment group were sub-cutaneously administered rhIL -11 and rhG -CSF besides active symptomatic treatment. Hemogram of peripheral blood, pristine apoptosis and necrosis ratio of nucleated cells, the content of IL-2 and IFN-γ in plasma and formation of bone marrow were used to evaluate the therapeutic effect. Results: In the cytokine treatment group, the animal' survival rate 45 days after exposure was increased and hemogram of peripheral blood was improved significantly. The rate of pristine apoptosis and necrosis of nucleated cell declined obviously. Early, the content of both IL-2 and IFN-γ in plasma was up significantly, then the content of IL-2 rapidly descended, but that of IFN-γ was relatively stable. Conclusion: The combined administration of rhIL-11 and rhG-CSF significantly improved the recovery of hematopoietic and immunological function. (authors)

  14. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

    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...

  15. Intermittent Exposure to Social Defeat and Open-field Test in Rats : Acute and Long-term Effects on ECG, Body Temperature and Physical Activity

    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

  16. Integrated risk analysis for acute and chronic exposure to toxic chemicals

    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.

  17. DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.;

    2015-01-01

    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......We investigated the inflammatory response, acute phase response and genotoxic effect of diesel exhaust particles (DEPs, NIST1650b) following a single intratracheal instillation. C57BL/6J BomTac mice received 18, 54 or 162 µg/mouse and were killed 1, 3 and 28 days post-exposure. Vehicle controls and...... inflammation but long-lasting pulmonary acute phase response as well as genotoxicity in lung tissue 28 days post-exposure. The observed long-term pulmonary genotoxicity by DEP was less than the previously observed genotoxicity for CB using identical experimental set-up....

  18. Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

    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

  19. Induction of glutathione synthesis in human hepatocytes by acute and chronic arsenic exposure: Differential roles of mitogen-activated protein kinases

    Highlights: • Arsenic exposure increased intracellular levels of glutathione. • Mitogen-activated protein kinases were involved in glutathione homeostasis. • ERK contributed to glutathione synthesis during acute arsenic exposure. • Glutathione synthesis was regulated by p38 at least in part independent of NRF2 during chronic arsenic exposure. - Abstract: Glutathione (GSH) is a vital component of antioxidant defense which protects cells from toxic insults. Previously we found intracellular GSH was involved in cell resistance against arsenic-induced cytotoxicity. However, molecular mechanisms of GSH homeostasis during arsenic exposure are largely undefined. Here, we investigated roles of mitogen-activated protein kinases (MAPKs) in GSH synthesis pathway with two arsenic exposure strategies by using Chang human hepatocytes. In one strategy, acute arsenic exposure (20 μM, 24 h) was applied, as MAPK signaling is generally considered to be transient. In the other one, chronic arsenic exposure (500 nM, 20 weeks) was applied, which mimicked the general human exposure to arsenic. We found that acute arsenic exposure activated extracellular signal-regulated 1/2 kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) in parallel with increased transcription and nuclear translocation of factor-erythroid 2-related factor 2 (NRF2) and enhanced expression of γ-glutamyl cysteine ligase catalytic subunit (GCLC), resulting in elevated intracellular GSH levels. Specific ERK inhibitor abolished arsenic-induced NRF2 nuclear translocation and GSH synthesis. During chronic arsenic exposure which induced a malignant cellular phenotype, continuous p38 activation and NRF2 nuclear translocation were observed with enhanced GSH synthesis. Specific p38 inhibitor attenuated arsenic-enhanced GSH synthesis without changing NRF2 nuclear translocation. Taken together, our results indicate MAPK pathways play an important role in cellular GSH homeostasis in response to arsenic. However, the

  20. Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats

    Highlights: • PM2.5 induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM2.5) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM2.5-induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na+K+-ATPase and Ca2+-ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM2.5-induced heart injury, and may have relations with cardiovascular disease

  1. Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine

    Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 μMol paraoxon (∼ LD75) groups 2-6 received in addition: G2 50 μMol tiapride 30 min before paraoxon; G3 50 μMol tiapride 30 min before paraoxon and 50 μMol pralidoxime 1 min after paraoxon; G4 1 μMol pyridostigmine 30 min before paraoxon; G5 1 μMol pyridostigmine 30 min before paraoxon and 50 μMol pralidoxime 1 min after paraoxon; G6 50 μMol pralidoxime 1 min after paraoxon; Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G3) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G5). Tiapride pretreatment only (G2) is inferior to pyridostigmine pretreatment only (G4). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G4 and G6)

  2. Acute respiratory effects in the potato processing industry due to a bioaerosol exposure.

    Hollander, A; Heederik, D.; Kauffman, H.

    1994-01-01

    The relation between bioaerosol exposure in the potato starch industry and work related respiratory symptoms is described. One group of workers was exposed to high dust concentrations (geometric mean up to 56.0 mg/m3) with low endotoxin and antigen concentrations (geometric mean up to 12.6 ng/m3 and 90 relative antigen units (RAU) per m3). A second group was exposed to low dust concentrations (geometric mean up to 3.9 mg/m3), but the endotoxin and antigen concentrations were high (geometric m...

  3. Efficacy of multiple exposure with low level He-Ne laser dose on acute wound healing: a pre-clinical study

    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.

  4. Effect of Phenobarbital on Chloramphonicol-Induced Toxicity in Rat Liver and Small Intestine

    Massumeh Ahmadizadeh; Masood Esmailpoor; Zahra Goodarzi

    2013-01-01

      Objective(s): The aim of the present study is to determine the effect of Chloramphenicol (CAP) on rat liver and small intestine. Effect of phenobarbital (PB) on CAP toxicity was also investigated.   Materials and Methods:   Rats were received CAP at doses of 0, 200, 400 and 600 mg/kg. Another group was pretreated with 80 mg/kg PB 30 min prior to administration of various doses of CAP. The experiment was repeated for seven consecutive days. Blood was collected for det...

  5. Intercomparison of model predictions of tritium concentrations in soil and foods following acute airborne HTO exposure

    This paper describes the results of a model intercomparision exercise for predicting tritium transport through foodchains. Modellers were asked to assume that farmland was exposed for one hour to an average concentration in air of 104 MBq tritium m-3. They were given the initial soil moisture content and 30 days of hourly averaged historical weather and asked to predict HTO and OBT concentrations in foods at selected times up to 30 days later when crops were assumed to be harvested. Two fumigations were postulated, one at 10.00 h (i.e., in day-light), and the other at 24.00 h (i.e., in darkness).Predicted environmental media concentrations after the daytime exposure agreed within an order of magnitude in most cases. Important sources of differences were variations in choices of numerical values for transport parameters. The different depths of soil layers used in the models appeared to make important contributions to differences in predictions for the given scenario. Following the night-time exposure, however, greater differences in predicted concentrations appeared. These arose largely because of different ways key processes were assumed to be affected by darkness. Uptake of HTO by vegetation and the rate it is converted to OBT were prominent amongst these processes. Further research, experimental data and modelling intercomparisons are required to resolve some of these issues. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. Mental- and physical-health effects of acute exposure to media images of the September 11, 2001, attacks and the Iraq War.

    Silver, Roxane Cohen; Holman, E Alison; Andersen, Judith Pizarro; Poulin, Michael; McIntosh, Daniel N; Gil-Rivas, Virginia

    2013-09-01

    Millions of people witnessed early, repeated television coverage of the September 11 (9/11), 2001, terrorist attacks and were subsequently exposed to graphic media images of the Iraq War. In the present study, we examined psychological- and physical-health impacts of exposure to these collective traumas. A U.S. national sample (N = 2,189) completed Web-based surveys 1 to 3 weeks after 9/11; a subsample (n = 1,322) also completed surveys at the initiation of the Iraq War. These surveys measured media exposure and acute stress responses. Posttraumatic stress symptoms related to 9/11 and physician-diagnosed health ailments were assessed annually for 3 years. Early 9/11- and Iraq War-related television exposure and frequency of exposure to war images predicted increased posttraumatic stress symptoms 2 to 3 years after 9/11. Exposure to 4 or more hr daily of early 9/11-related television and cumulative acute stress predicted increased incidence of health ailments 2 to 3 years later. These findings suggest that exposure to graphic media images may result in physical and psychological effects previously assumed to require direct trauma exposure. PMID:23907546

  7. Multiple biomarkers responses in juvenile rainbow trout, Oncorhynchus mykiss, after acute exposure to a fungicide propiconazole.

    Li, Zhi-Hua; Zlabek, Vladimir; Velisek, Josef; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2013-03-01

    In this study, the toxic effects of propiconazole (PCZ), a triazole fungicide present in aquatic environment, were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute toxicity test with the concentration of 5.04 mg/L (96 h LC50). Morphological indices, hematological parameters, liver xenobiotic-metabolizing response, and tissue antioxidant status were evaluated. Compared with the control group, fish exposed to PCZ showed significantly higher Leuko, PCV, MCHC, and hepatic EROD, and significantly lower MCV. CF and HSI were not significantly different among groups. SOD, CAT, GPx, and GR activities increased significantly in liver of experimental groups, but decreased significantly in gill. In general, antioxidant enzyme activity in intestine was less evident than in liver. Oxidative stress indices (levels of LPO and CP) were significantly higher in gill. Additionally, through chemometrics of all parameters measured in this study, two groups with 67.29% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in different tissues of fish indicated that PCZ-induced the stressful environmental conditions. But according to PCZ residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013. PMID:21384499

  8. Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells

    Phenobarbital (PB) induces or represses a wide spectrum of genes in rodent liver. Much less is known about its effects in human liver. We used pangenomic cDNA microarrays to analyze concentration- and time-dependent gene expression profile changes induced by PB in the well-differentiated human HepaRG cell line. Changes in gene expression profiles clustered at specific concentration ranges and treatment times. The number of correctly annotated genes significantly modulated by at least three different PB concentration ranges (spanning 0.5 to 3.2 mM) at 20 h exposure amounted to 77 and 128 genes (p ≤ 0.01) at 2- and 1.8-fold filter changes, respectively. At low concentrations (0.5 and 1 mM), PB-responsive genes included the well-recognized CAR- and PXR-dependent responsive cytochromes P450 (CYP2B6, CYP3A4), sulfotransferase 2A1 and plasma transporters (ABCB1, ABCC2), as well as a number of genes critically involved in various metabolic pathways, including lipid (CYP4A11, CYP4F3), vitamin D (CYP24A1) and bile (CYP7A1 and CYP8B1) metabolism. At concentrations of 3.2 mM or higher after 20 h, and especially 48 h, increased cytotoxic effects were associated with disregulation of numerous genes related to oxidative stress, DNA repair and apoptosis. Primary human hepatocyte cultures were also exposed to 1 and 3.2 mM PB for 20 h and the changes were comparable to those found in HepaRG cells treated under the same conditions. Taken altogether, our data provide further evidence that HepaRG cells closely resemble primary human hepatocytes and provide new information on the effects of PB in human liver. These data also emphasize the importance of investigating dose- and time-dependent effects of chemicals when using toxicogenomic approaches

  9. Early biochemical biomarkers for zinc in silver catfish (Rhamdia quelen) after acute exposure.

    Leitemperger, Jossiele; Menezes, Charlene; Santi, Adriana; Murussi, Camila; Lópes, Thais; Costa, Maiara; Nogueira, Lygia Sega; Loro, Vania Lucia

    2016-06-01

    Contamination of aquatic ecosystems by metals causes various biochemical changes in aquatic organisms, and fish are recognized as indicators of environmental quality. Silver catfish were exposed to six concentrations of zinc (Zn): 1.0, 2.5, 5.0, 7.5, 10.0 and 12.5 mg/L for 96 h to determine the mean lethal concentration (LC50). The value obtained was 8.07 mg/L. In a second experiment, fish were exposed to concentrations of 1.0 or 5.0 mg/L Zn and a control for 96 h. Afterward, the tissues were collected for biochemical analysis. Lipid peroxidation, as indicated by thiobarbituric acid-reactive substance (TBARS), decreased in the liver and brain for all Zn concentrations tested, while in the gills TBARS levels increased at 1.0 mg/L and declined at 5.0 mg/L. Zn increased protein carbonyls in the muscle of silver catfish and decreased it in the other tissues. The enzyme superoxide dismutase increased in both exposed groups. However, catalase did not change. Glutathione S-transferase decreased in the liver and increased in the gills (1.0 mg/L), muscle (5.0 mg/L) and brain (1.0 and 5.0 mg/L). Nonprotein thiols changed only in brain and muscle tissue. Zn exposure inhibited acetylcholinesterase (AChE) activity in the brain at both concentrations tested, but did not change it in muscle. Exposure to Zn inhibited the activity of Na(+)/K(+)-ATPase in the gills and intestine at both concentrations tested. Our results demonstrate that Zn alters biochemical parameters in silver catfish and that some parameters such as AChE and Na(+)/K(+)-ATPase could be considered as early biomarkers of waterborne Zn toxicity. PMID:26744269

  10. Atrazine in sub-acute exposure results in sperm DNA disintegrity and nuclear immaturity in rats

    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.

  11. Transient cell function disruption by low dose acute exposure of ionizing radiation

    Incubation of BMG-1 cells with thallium chloride (201Tl) in the range of diagnostic dose did not show a smooth uptake curve and appeared to have an unsuspected deviation in initial phase. In the present study this unexpected phenomenon was explored, using commonly used radionuclides (viz., 201Tl and 131I). Comparison was made with technetium-99m pertechnetate (99mTcO4) and technetium-99m labeled methoxyisobutylisonitrile (99mTc-MIBI) that are known to show conventional 2 phase graph representing inflow and outflow segments. Serial in vitro, ex-vivo and in vivo gamma scintigraphy as well as NMR spectroscopy experiments were conducted to corroborate the results. BMG-1 cells demonstrated a four-phase uptake pattern with 201Tl as compared to a conventional biphasic pattern with 99mTc-MIBI. Flow cytometry data however did not reveal any 201Tl induced cell injury. Further, mice tissue extracts injected with 201Tl also showed a transient depression in its uptake. Scintigraphy experiments in rabbits administered with diagnostic dose of 201Tl and 131I confirmed the in vitro and ex vivo findings. Further, proton NMR spectroscopy showed decrease in the level of choline at 3 h and 24 h in 201Tl treated animals as compared to control. Phosphoethanolamine peak firstly decreased at 3 h but reached normal level at 24 h time point. No significant change was observed in the level of betaine. This transient reduction in internalization of 201Tl and 131I may represent a hitherto unknown acute effect of low dose radiation, i.e., transient depression in Na+-K+ ATPase pump activity without any apparent evidence of cell damage, representing a transient cell membrane dysfunction. The phenomenon may present a mechanistical explanation of 'thyroid stunning' at cellular level and suggest that it may be more universal in nature than suspected till now. (author)

  12. Acute exposure of mice to high-dose ultrafine carbon black decreases susceptibility to pneumococcal pneumonia

    Gordon Stephen

    2010-10-01

    Full Text Available Abstract Background Epidemiological studies suggest that inhalation of carbonaceous particulate matter from biomass combustion increases susceptibility to bacterial pneumonia. In vitro studies report that phagocytosis of carbon black by alveolar macrophages (AM impairs killing of Streptococcus pneumoniae. We have previously reported high levels of black carbon in AM from biomass smoke-exposed children and adults. We therefore aimed to use a mouse model to test the hypothesis that high levels of carbon loading of AM in vivo increases susceptibility to pneumococcal pneumonia. Methods Female outbred mice were treated with either intranasal phosphate buffered saline (PBS or ultrafine carbon black (UF-CB in PBS; 500 μg on day 1 and day 4, and then infected with S. pneumoniae strain D39 on day 5. Survival was assessed over 72 h. The effect of UF-CB on AM carbon loading, airway inflammation, and a urinary marker of pulmonary oxidative stress was assessed in uninfected animals. Results Instillation of UF-CB in mice resulted a pattern of AM carbon loading similar to that of biomass-smoke exposed humans. In uninfected animals, UF-CB treated animals had increased urinary 8-oxodG (P = 0.055, and an increased airway neutrophil differential count (P . pneumoniae, whereas morbidity and mortality after infection was reduced in UF-CB treated animals (median survival 48 h vs. 30 h, P . pneumoniae colony forming unit counts, and lower airway levels of keratinocyte-derived chemokine/growth-related oncogene (KC/GRO, and interferon gamma. Conclusion Acute high level loading of AM with ultrafine carbon black particles per se does not increase the susceptibility of mice to pneumococcal infection in vivo.

  13. Follow-up of delayed health consequences of acute radiation exposure. Lessons to be learned from their medical management

    While the use of radioactive materials around the world offers a wide range of benefits in medicine, industry and research, safety precautions are essential to limit the exposure of persons to harmful radiation. When the quantity of radioactive material employed is substantial, as when radioactive sources are used for radiotherapy in medicine or for industrial radiography, extreme care is necessary to prevent accidents that may lead to severe health consequences for the individuals involved. Despite the fact that the precautions to be taken are clearly established, accidents with radiation sources continue to occur, albeit infrequently. The IAEA, as part of its 'Safety of Radiation Sources' and 'Emergency Response' subprogrammes, follows up severe accidents of this kind. In so doing, the IAEA attempts to document both the circumstances leading to the accident and the subsequent medical treatment in order to define the lessons to be learned from these events. The overall objective is to provide information that will be of benefit to organizations with responsibilities for radiation protection, the safety of radiation sources and the medical management of radiation accidents. The International Atomic Energy Agency has issued a number of publications on radiation accidents which have occurred in the past 15 years, reporting on the causes, radiation safety aspects and medical management of those affected particularly in the acute phase following an accident. These reports cover the accidents in Chernobyl, Ukraine (the Republic of the former Soviet Union) and Goiania (Brazil), and those in El Salvador, Vietnam, Belarus, Israel, Estonia, Costa Rica, Georgia, Russian Federation, Turkey, Peru and Panama. In 1998 the IAEA published three Safety Reports, co-sponsored by the World Health Organization, aimed at disseminating medical information on the recognition and treatment of radiation injuries, planning the medical response to radiation accidents and occupational health

  14. Studies on dosage of HIDANTOL-F by simultaneous determination of serum phenobarbital and diphenylhydantoin

    Yamada, Hideo; Tanno, Munehiko; Muraki, Toshio; Fuse, Masaaki.

    1987-10-01

    In order to investigate causes of untoward effects frequently observed in elderly patients on HIDANTOL-F which contains 300 mg of phenobarbital(PB), 100 mg of diphenylhydantoin(DPH) and 200 mg of Na benzoate-caffein, blood levels of both PB and DPH were measured by radioimmunoassay. About half of the patients showed blood levels of PB distributed in therapeutic range, some of which were very cross to toxic range. None of the blood samples except one, however, was in therapeutic range in regard to DPH. There was some degree of correlation between blood levels of these two drugs (r = 0.53). Absolute doses of PB and blood levels showed linear relationship, while DPH was curvelinear in shape in regard to doseblood level relation, suggestive of MichaelisMenten pharmacokinetics. Taking account of blood levels of these two drugs in the present study, phenobarbital must be responsible for untoward effects of HIDANTOL-F as well as anticonvulsive effect. Synergistic effect and mutual influences over pharmacokinetics of PB and DPH were discussed. Ratio of several drugs in case of combination therapy should be determined on the basis of study on pharmacokinetics and interaction of drugs.

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

    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.

  16. An Exploratory Study on the Development of an Animal Model of Acute Pancreatitis Following Nicotine Exposure

    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.

  17. Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

    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.

  18. Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

    Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening

  19. Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD

    Corti, Caspar; Fally, Markus; Fabricius-Bjerre, Andreas; Mortensen, Katrine; Jensen, Birgitte Nybo; Andreassen, Helle F; Porsbjerg, Celeste; Knudsen, Jenny Dahl; Jensen, Jens-Ulrik

    2016-01-01

    Background This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD). Methods One-hundred and twenty adult patients admitted with AECOPD were enrolled in this open-label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58). Results The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0–10) days in the PCT-arm vs 8.5 (IQR 1–11) days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for ≥5 days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher’s exact) in the intention-to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P<0.00001, Fisher’s exact). Within 28-day follow-up, one patient died in the PCT-arm and two died in the control arm. A composite harm end point consisting of death, rehospitalization, or intensive care unit admission, all within 28 days, showed no apparent difference. Conclusion Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AECOPD, with no apparent harm. PMID:27382274

  20. Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations.

    Nunes, B; Antunes, S C; Gomes, R; Campos, J C; Braga, M R; Ramos, A S; Correia, A T

    2015-02-01

    A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity. PMID:25475590

  1. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    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 NaAsO2) was less cytolethal over 24 h in WT cells (LC50 = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC50 = 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

  2. Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.

    Calas, André-Guilhem; Perche, Olivier; Richard, Olivier; Perche, Astrid; Pâris, Arnaud; Lauga, Fabien; Herzine, Ameziane; Palomo, Jennifer; Ardourel, Marie-Yvonne; Menuet, Arnaud; Mortaud, Stéphane; Pichon, Jacques; Montécot-Dubourg, Céline

    2016-05-01

    Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection. PMID:27031874

  3. Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats

    Staphylocococcus aureus is a gram-positive bacterium that produces several enterotoxins, which are responsible for most part of pathological conditions associated to staphylococcal infections, including lung inflammation. This study aimed to investigate the underlying inflammatory mechanisms involved in leukocyte recruitment in rats exposed to staphylococcal enterotoxin B (SEB). Rats were anesthetized with pentobarbital sodium and intratracheally injected with either SEB or sterile phosphate-buffered saline (PBS, 0.4 ml). Airways exposition to SEB (7.5-250 ng/trachea) caused a dose- and time-dependent neutrophil accumulation in BAL fluid, the maximal effects of which were observed at 4 h post-SEB exposure (250 ng/trachea). Eosinophils were virtually absent in BAL fluid, whereas mononuclear cell counts increased only at 24 h post-SEB. Significant elevations of granulocytes in bone marrow (mature and immature forms) and peripheral blood have also been detected. In BAL fluid, marked elevations in the levels of lipid mediators (LTB4 and PGE2) and cytokines (TNF-α, IL-6 and IL-10) were observed after SEB instillation. The SEB-induced neutrophil accumulation in BAL fluid was reduced by pretreatment with dexamethasone (0.5 mg/kg), the COX-2 inhibitor celecoxib (3 mg/kg), the selective iNOS inhibitor compound 1400 W (5 mg/kg) and the lipoxygenase inhibitor AA-861 (200 μg/kg). In separate experiments carried out with rat isolated peripheral neutrophils, SEB failed to induce neutrophil adhesion to serum-coated plates and chemotaxis. In conclusion, rat airways exposition to SEB causes a neutrophil-dependent lung inflammation at 4 h as result of the release of proinflammatory (NO, PGE2, LTB4, TNF-α, IL-6) and anti-inflammatory mediators (IL-10)

  4. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    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.

  5. Lack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice.

    Puatanachokchai, Rawiwan; Kakuni, Masakazu; Wanibuchi, Hideki; KINOSHITA, ANNA; Kang, Jin Seok; Salim, Elsayed I.; Morimura, Keiichirou; Tamano, Seiko; Merlino, Glenn T.; FUKUSHIMA, SHOJI

    2009-01-01

    KEYWORDS-CLASSIFICATION: administration & dosage;Animals;Anticonvulsants;Carcinogenicity Tests;Carcinogens;chemically induced;Diethylnitrosamine;Dose-Response Relationship,Drug;genetics;Japan;Liver Neoplasms;mechanisms of carcinogenesis;metabolism;Mice;Mice,Transgenic;pathology;Phenobarbital;Research;toxicity;Transforming Growth Factor alpha;

  6. Effects of Exposure to Carbon Dioxide and Bioeffluents on Perceived Air Quality, Self-assessed Acute Health Symptoms and Cognitive Performance

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei;

    2016-01-01

    quality, increased the intensity of reported headache, fatigue, sleepiness and difficulty in thinking clearly, and reduced speed of addition, the response time in a redirection task and the number of correct links made in the cue-utilisation test. This suggests that moderate concentrations of bioeffluents...... ratings, physiological responses and cognitive performance were measured. No statistically significant effects on perceived air quality, acute health symptoms or cognitive performance were seen during exposures when CO2 was added. Exposures to bioeffluents with CO2 at 3,000 ppm reduced perceived air...

  7. An evaluation of the influence of substrate on the response of juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea) in acute water exposures to ammonia

    Miao, J.; Barnhart, M.C.; Brunson, E.L.; Hardesty, D.K.; Ingersoll, C.G.; Wang, N.

    2010-01-01

    Acute 96-h ammonia toxicity to three-month-old juvenile mussels (Lampsilis siliquoidea) was evaluated in four treatments (water-only, water-only with feeding, water and soil, and water and sand) using an exposure unit designed to maintain consistent pH and ammonia concentrations in overlying water and in pore water surrounding the substrates. Median effect concentrations (EC50s) for total ammonia nitrogen in the four treatments ranged from 5.6 to 7.7mg/L and median lethal concentrations (LC50s) ranged from 7.0 to 11mg/L at a mean pH of 8.4. Similar EC50s or LC50s with overlapping 95% confidence intervals among treatments indicated no influence of substrate on the response of mussels in acute exposures to ammonia. ?? 2010 SETAC.

  8. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    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

  9. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    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 pAKTThr308 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

  10. Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPARα agonist WY14643 in rat hepatocytes

    Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feedback-controlled regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase II enzymes of xenobiotic metabolism. We have recently shown, that PPARα agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPARα agonist could enhance the phenobarbital-dependent acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPARα agonist WY14643 to a larger extent than after induction with either compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UGT1A10. The PPARα-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-induced reduction in energy expenditure by fatty acids as natural PPARα ligands. The synergism of the PPARα agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics.

  11. Effect of Methomyl on the Phenobarbital and Benzo [a] Pyrene Induced Hepatic Microsomal Mixed Function Oxidase System in Rats

    Jyotsna A. Patil1, Arun J. Patil1*, Ajit V. Sontakke1, Satish D. Kalme2 and Sanjay P. Govindwar3

    2011-04-01

    Full Text Available Methomyl (Lannate is a pesticide widely used to control of insects in grape gardens. Methomyl treatment induces significant alteration in mixed function oxidase system. The present work was designed to study the inhibitory effect of methomyl on different forms of cytochrome P450 induced by phenobarbital (CYP 2B1, 2B2 and 3A and benzo[a]pyrene induced (CYP 1A1. Adult male rats were divided into 8 groups of 6 animals each. Microsomes were isolated by calcium precipitation. The levels of electron transport components, CYP 450, cytochrome b5, and cytochrome c-reductase were determined using extinction coefficients. Activities of drug-metabolizing enzymes were assayed. Inducers like phenobarbital, benzo[a]pyrene, showed significant induction of mixed function oxidase in rat. The methomyl treatment (4mg/kg of inducer-(Phenobarbital, benzop [a] pyrene pretreated rat caused a significant decrease in electron transport components and activities of drug-metabolizing enzymes when compared with treatment of inducer alone. Induction of mixed function oxidase enzymes due to phenobarbital was also altered by the pretreatment of methomyl. Benzo[a]pyrene treatment of methomyl pretreated rats showed significant decreased levels of electron transport components and drug metabolizing enzymes as compared to benzo[a]pyrene treatment alone. These results indicate that the susceptibility of phenobarbital and benzo[a]pyrene induced cytochrome P450 isoform (CYP 2B1, 2B2, 3A; and CYP 1A1 to methomyl and also affected in the induction pattern of some of the inducers with respect to CYP 450 isoforms.

  12. Risk factors for high-altitude headache upon acute high-altitude exposure at 3700 m in young Chinese men: a cohort study

    Bian, Shi-Zhu; Zhang, Ji-Hang; Xu-bin GAO; Li, Ming; Yu, Jie; Liu, Xi; Dong, Jun-Qing; Chen, Guo-Zhu; Huang, Lan

    2013-01-01

    Background This prospective and observational study aimed to identify demographic, physiological and psychological risk factors associated with high-altitude headache (HAH) upon acute high-altitude exposure. Methods Eight hundred fifty subjects ascended by plane to 3700 m above Chengdu (500 m) over a period of two hours. Structured Case Report Form (CRF) questionnaires were used to record demographic information, physiological examinations, psychological scale, and symptoms including headache...

  13. Hemodynamic characteristics of high-altitude headache following acute high altitude exposure at 3700 m in young Chinese men

    Bian, Shi-Zhu; JIN, JUN; Li, Qian-Ning; Yu, Jie; Tang, Cai-Fa; Rao, Rong-Sheng; Yu, Shi-Yong; Zhao, Xiao-Hui; Qin, Jun; Huang, Lan

    2015-01-01

    Background This study aimed to identify the systemic and cerebral hemodynamic characteristics and their roles in high-altitude headache (HAH) among young Chinese men following acute exposure. Methods The subjects (n = 385) were recruited in June and July of 2012. They completed case report form questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and transcranial Doppler examinations at 3700 m following a two-hour plane flight. A subgroup of 129 participants was examined...

  14. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

    Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG) lesions in the transgenic polyomavirus middle T (PyMT) breast cancer mouse model. We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs), demonstrating a relationship between hypoxia and macrophages in an experimental model. These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model

  15. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

    Reactive O2 species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O2 species involved in lung O2 metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O2 consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H2O2 and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O2 consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O2 consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H2O2 production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O2 consumption may account for an augmented Nox activity, causing an increased O2·− production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O2 species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O2 consumption. • Exposure to ROFA produces alterations in mitochondrial function. • ΔΨm decrease in state 3 may be responsible

  16. Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

    Catherine Weber

    2012-01-01

    Full Text Available Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG, and total body irradiation (TBI followed by an allogeneic hematopoietic stem cell transplant (HSCT for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  17. Effects of acute psychosocial stress exposure on endocrine and affective reactivity in college students differing in the 5-HTTLPR genotype and trait neuroticism.

    Verschoor, Ellen; Markus, C Rob

    2011-07-01

    Enhanced stress vulnerability has been implicated in the pathogenesis of affective disorders. Although both genetic (5-HTTLPR) and cognitive (neuroticism) factors are known to increase stress vulnerability, no experimental study has investigated the interaction between these two factors on psychobiological reactivity following acute stress exposure. This study used a balanced experimental design to examine the interaction between the 5-HTTLPR genotype and trait neuroticism in neuroendocrine and affective stress responses. From a large group of 771 students, 48 carriers of the short/short (S/S) allele and 48 carriers of the long/long (L/L) allele with the lowest and the highest neuroticism scores (77 females, 19 males; mean age ± SD: 20.6 ± 2 years) were selected and exposed to an acute psychosocial stressor. Mood was assessed before and after the stressor, and salivary cortisol concentrations were measured before and at 20, 30, and 60 min after stressor onset. Acute stress increased salivary cortisol concentration regardless of either 5-HTTLPR genotype or neuroticism, but it caused a less profound negative mood change in L/L compared to S/S-allele carriers with the lowest neuroticism scores. The 5-HTTLPR genotype influences affective reactivity to acute stress conditional upon neuroticism, improving resilience to acute stress in L/L-allele carriers if they do not already possess high cognitive-affective (neuroticism) vulnerability. PMID:21438771

  18. ANTI-HYPOXIA AND ANTI-OXIDATION EFFECTS OF AMINOPHYLLINE ON HUMAN WITH ACUTE HIGH-ALTITUDE EXPOSURE

    Bo Yang; Guang-yi Wang; Bin Chen; Rong-bin Qin; Si Lang Zha Xi; Lian Chen

    2007-01-01

    Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high-altitude exposure.Methods Totally 100 young male army members newly recruited from Sichuan province (400 meters above sea level) were enrolled. They were randomly divided into two groups; 50 in aminophylline group (A group) and 50 in control group (C group). A group and C group orally took aminophylline and placebo respectively for 10 days, 7 days before entering Lhasa (3 658 meters above sea level) by air and 3 days after it Several parameters were measured at three time points: before drug taken, 7 days after drug taken, and 3 days after ascending high altitude. These parameters included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen saturation (SO2) , arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system.Results There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area. Three days after ascending high altitude, the serum levels of SOD, CAT, H2O2, LA, PaCO2 increased in both groups, yet to a much larger degree in C group than A group (P < 0.01); and NO, SO2, PaO2 decreased more markedly in C group (P < 0.05 for NO, P < 0.0001 for SO2 and PaO2).Conclusion Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.

  19. Acute exposure to Catha edulis depresses contractility and induces myocardial infarction in spontaneously contracting, isolated rabbit's heart.

    Al-Hashem, Fahaid H; Dallak, Mohammad A; Nwoye, Luke O; Bin-Jaliah, Ismaeel M; Al-Amri, Hasan S; Rezk, Mahmoud H; Sakr, Hussein F; Shatoor, Abdullah S; Al-Khateeb, Mahmoud

    2012-01-01

    Khat chewing is a recreational habit known to pose major socio-economic and medical problems in countries of Southern Arabia and the Horn of Africa. Among other adverse health effects, khat chewing has been associated with an increased risk of myocardial infarction (MI) in heavy consumers. This study was carried out to examine the direct effects of Catha edulis extract on contractility of spontaneously contracting, isolated rabbit heart and to investigate its mechanism of action. Isolated six rabbit's hearts attached to a Langendorff apparatus were perfused with extract at a constant flow rate and continuously bubbled with a 95% O2/5% CO2 gas mixture. Each heart served as its own control, as responses were recorded before and after administration of C. edulis extract. Varying concentrations of extract (50, 100 and 250 mg/ml) were loaded in the perfusate, their effects recorded and effluent fluid collected for assay of cardiac enzymes. Histological examination of the cardiac tissue was performed at the end of perfusion with 250 mg/ml extract. This study revealed that acute exposure to C. edulis extract exerted negative inotropic and chronotropic effects on isolated hearts. The extract also had a vasoconstrictor effect on coronary vessels, independent of α1 adrenergic receptor stimulation. Histological examination of hearts perfused with 250 mg/ml C. edulis extract revealed the presence of histological changes unique to myocardial infarction, a finding consistent with observed increased levels of cardiac enzymes in perfusates. Thus, we have demonstrated experimentally a direct cardiac depressant- and MI inducing effects of C. edulis extract. These results are consistent with the earlier reported deleterious effects of khat on cardiovascular function among khat chewers. PMID:23961167

  20. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja;

    2015-01-01

    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 mu...... g/mouse of small, entangled (CNTsmall, 0.8 +/- 0.1 pm long) or large, thick MWCNTs (CNTLarge, 4 +/- 0.4 mu m 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...

  1. Production of DNA Double Strand Breaks in Human Cells due to Acute Exposure to Tritiated Water (HTO)

    significant increase in H2AX phosphorylation in primary human fibroblasts. Thus, immunostaining of D3-H2AX may represent a sensitive biomarker of exposure. The scientific literature contains practically no information about the effect of acute exposure from HTO on the integrity of the DNA, and the present work presents some preliminary results on this subject. The investigation on the formation of the Double Strand Breaks was done by the detection of the phosphorylated histone, D3H2AX. For this research we used Human malignant osteoblast MG-63 cells, and normal peripheral blood lymphocytes

  2. EFFECT OF COADMINISTRATION OF PHENOBARBITAL SODIUM ON N-NITROSODIETHYLAMINE-INDUCED GAMMA-GLYTAMYLTRANSFERASE-POSITIVE FOCI AND HEPATOCELLULAR CARCINOMA IN RATS

    The effect of concurrent administration of phenobarbital on the hepatocarcinogenicity of N-nitrosodiethylamine (diethylnitrosamine; DENA) in rats was investigated by determination of the incidence of gamma-glutamyltransferase (gamma-glutamyltranspeptidase) (GGT)-positive foci and...

  3. Association between exposure to radiofrequency electromagnetic fields assessed by dosimetry and acute symptoms in children and adolescents: a population based cross-sectional study

    Radon Katja

    2010-11-01

    Full Text Available Abstract Background The increase in numbers of mobile phone users was accompanied by some concern that exposure to radiofrequency electromagnetic fields (RF EMF might adversely affect acute health especially in children and adolescents. The authors investigated this potential association using personal dosimeters. Methods A 24-hour exposure profile of 1484 children and 1508 adolescents was generated in a population-based cross-sectional study in Germany between 2006 and 2008 (participation 52%. Personal interview data on socio-demographic characteristics, self-reported exposure and potential confounders were collected. Acute symptoms were assessed twice during the study day using a symptom diary. Results Only few of the large number of investigated associations were found to be statistically significant. At noon, adolescents with a measured exposure in the highest quartile during morning hours reported a statistically significant higher intensity of headache (Odd Ratio: 1.50; 95% confidence interval: 1.03, 2.19. At bedtime, adolescents with a measured exposure in the highest quartile during afternoon hours reported a statistically significant higher intensity of irritation in the evening (4th quartile 1.79; 1.23, 2.61, while children reported a statistically significant higher intensity of concentration problems (4th quartile 1.55; 1.02, 2.33. Conclusions We observed few statistically significant results which are not consistent over the two time points. Furthermore, when the 10% of the participants with the highest exposure are taken into consideration the significant results of the main analysis could not be confirmed. Based on the pattern of these results, we assume that the few observed significant associations are not causal but rather occurred by chance.

  4. 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.

    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. PMID:26558894

  5. Near-term and late biological effects of acute and low-dose-rate continuous gamma-ray exposure in dogs and monkeys

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (inury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with gamma rays at 35 r/day until death to determine the amount of radiation-induced injry remaining in conditioned animals as a reduction in mean survival time. Dogs (50%) and monkeys (8%) died from injury incurred during conditioning exposures. Thus, the comparative response (in terms of lethality) of dogs and monkeys to dose protraction by acute dose fractionation was similar to what we would expect from a single acute dose. The mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approx. 1400 h). Thus, the hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35-R/day gamma-ray challenge exposure were greater (significant in dogs but not in monkeys) than for their control counterparts. Thus, long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than 4 times the acute LD5030 in dogs and approximately 2 times that in monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 Rat/day

  6. Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.

    Williams, Joshua D; Bermudez, Yira; Park, Sophia L; Stratton, Steven P; Uchida, Koji; Hurst, Craig A; Wondrak, Georg T

    2014-03-01

    Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than threefold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

  7. Episodic ozone exposure in adult and Senescent Brown Norway rats: Acute and delayed cardiovascular and thermoregulatory responses

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O(3)) is more reflective of potential exposures occurri...

  8. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    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 (CNTSmall, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNTLarge, 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 CNTLarge 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 different, the two

  9. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    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

  10. Effects of acute millimeter wave exposure on the expression of substance P and c-fos in rat spinal cord

    Yan-wen ZHANG

    2013-04-01

    Full Text Available Objective  To observe the expression changes in substance P (SP and c-fos in rat spinal cord after acute millimeter-wave (MMW exposure, and explore the mechanism of thermal hyperalgesia at the spinal level. Methods  The back skin of SD rats was exposed to 35 GHz MMW (40W/cm2 for 0s (control group, 30s, 1min, or 3min. The corresponding segment of the spinal cord was taken at 0min, 5min, 10min, 1h and 3h after MMW irradiation for total RNA and protein extraction. The expressions of SP and c-fos mRNA were measured by real-time RT-PCR, and the expression of c-fos protein was detected by Western blotting. Results  No significant difference was found between the control group and irradiation groups in SP and c-fos mRNA expression in the corresponding segment of spinal cord after MMW irradiation for 30s. After MMW irradiation for 1min, the SP and c-fos mRNA expressions in the corresponding segment of spinal cord increased significantly at 10min time point, and then decreased to the level of control group. After MMW irradiation for 3min, the SP and c-fos mRNA expression in the corresponding segment of spinal cord increased significantly at 5min, 10min and 1h time points, and decreased to the level of control group at 3h. No significant change was found in c-fos protein expression in the corresponding segment of spinal cord after MMW irradiation for 30s and 1min. After MMW irradiation for 3min, the c-fos protein expression in the corresponding segment of spinal cord increased significantly at 5min and 10min time point, and then decreased to the level of control group. Conclusion  The increase of SP expression in rat skin after MMW irradiation may be related to the increase of SP and c-fos expressions in the corresponding segment of the spinal cord induced by thermal pain stimulation.

  11. No Effects of Acute Exposure to Wi-Fi Electromagnetic Fields on Spontaneous EEG Activity and Psychomotor Vigilance in Healthy Human Volunteers.

    Zentai, Norbert; Csathó, Árpád; Trunk, Attila; Fiocchi, Serena; Parazzini, Marta; Ravazzani, Paolo; Thuróczy, György; Hernádi, István

    2015-12-01

    Mobile equipment use of wireless fidelity (Wi-Fi) signal modulation has increased exponentially in the past few decades. However, there is inconclusive scientific evidence concerning the potential risks associated with the energy deposition in the brain from Wi-Fi and whether Wi-Fi electromagnetism interacts with cognitive function. In this study we investigated possible neurocognitive effects caused by Wi-Fi exposure. First, we constructed a Wi-Fi exposure system from commercial parts. Dosimetry was first assessed by free space radiofrequency field measurements. The experimental exposure system was then modeled based on real geometry and physical characteristics. Specific absorption rate (SAR) calculations were performed using a whole-body, realistic human voxel model with values corresponding to conventional everyday Wi-Fi exposure (peak SAR10g level was 99.22 mW/kg with 1 W output power and 100% duty cycle). Then, in two provocation experiments involving healthy human volunteers we tested for two hypotheses: 1. Whether a 60 min long 2.4 GHz Wi-Fi exposure affects the spectral power of spontaneous awake electroencephalographic (sEEG) activity (N = 25); and 2. Whether similar Wi-Fi exposure modulates the sustained attention measured by reaction time in a computerized psychomotor vigilance test (PVT) (N = 19). EEG data were recorded at midline electrode sites while volunteers watched a silent documentary. In the PVT task, button press reaction time was recorded. No measurable effects of acute Wi-Fi exposure were found on spectral power of sEEG or reaction time in the psychomotor vigilance test. These results indicate that a single, 60 min Wi-Fi exposure does not alter human oscillatory brain function or objective measures of sustained attention. PMID:26600173

  12. [The use of enzymatic hydrolysis for isolation of barbituric acid derivatives from blood (as exemplified by phenobarbital and barbamyl)].

    Chuvina, N A; Kolupaeva, A S; Strelova, O Iu; Zabolotskaia, I V; Gorbacheva, T V

    2010-01-01

    Modern isolation techniques by direct extraction with organic solvents or after protein precipitation by various sedimenting or salting-out agents are characterized by low efficiency and do not permit to liberate derivatives of barbituric acid from their complexes with blood proteins. The use of enzymatic hydrolysis makes it possible to break bonds between barbiturates and protein and thereby improve the efficiency of isolation. We performed enzymatic hydrolysis of the model phenobarbital-blood and barbamyl-blood complexes with the use of trypsin, pepsin, chymotrypsin, and papain. The degree of phenobarbital extraction with trypsin and barbamyl was estimated at 62.1 +/- 1.2% and 75.1 +/- 1.6% respectively; in other words, it was 32.7 +/- 1.0% and 51.1 +/- 1.0% higher than that achieved by traditional methods. Certain validation characteristics of the new method are presented. PMID:21265178

  13. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

    Kuang-Lin Lin

    Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  14. Reduced Hippocampal Dendritic Spine Density and BDNF Expression following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Male Long Evans Rats

    Smith, Catherine A.; Holahan, Matthew R.

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats. PMID:25295592

  15. Biodistribution study of the anesthetic sodium phenobarbital labelled with technetium-99 in swiss mice infected with Schistosoma mansoni Sambon, 1907

    Technetium-99 m (99m Tc) is a radionuclide that has negligible environmental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT) with 99m Tc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with 99m Tc, as sodium pertechnetate. The radioactivity labelling(%) was determined by paper ascending chromatography performed with acetone (solvent). The99m Tc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after different periods of time (0,1,2,3,4 hr) when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. THe radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital. (author)

  16. Biodistribution study of the anesthetic sodium phenobarbital labelled with technetium-99 in swiss mice infected with Schistosoma mansoni Sambon, 1907

    Simoes, Susana Balmant Emerique; Machado Silva, Jose Roberto [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas. Dept. de Patologia e Laboratorios; Gutfilen, Bianca; Oliveira, Marcia Betania; Bernardo Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Presgrave, Otavio Augusto Franca [Fundacao Inst. Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Inst. Nacional de de Controle de Qaulidade em Saude. Dept. de Farmacologia e Toxicologia

    1997-09-01

    Technetium-99 m ({sup 99m} Tc) is a radionuclide that has negligible environmental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT) with {sup 99m} Tc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with {sup 99m} Tc, as sodium pertechnetate. The radioactivity labelling(%) was determined by paper ascending chromatography performed with acetone (solvent). The{sup 99m} Tc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after different periods of time (0,1,2,3,4 hr) when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. THe radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital. (author) 24 refs., 3 tabs.

  17. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

    Lunt Sarah

    2008-05-01

    Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

  18. Novel 14S,21-dihydroxy-docosahexaenoic acid Rescues Wound Healing and Associated Angiogenesis Impaired by Acute Ethanol Intoxication/Exposure

    Tian, Haibin; Lu, Yan; Shah, Shraddha P.; Hong, Song

    2010-01-01

    Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here we found that AE diminished the formation of novel reparative lipid mediator 14S,21-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21-diHDHA) and its biosynthetic intermediate 14S-hydroxy-DHA (14S-HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21-HDHA. These results indicate that in the b...

  19. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

    Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Tasat, Deborah R. [CESyMA, Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); Alvarez, Silvia [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Evelson, Pablo, E-mail: pevelson@ffyb.uba.ar [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina)

    2013-07-01

    Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA

  20. The genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute exposure to the androgen, 17β-trenbolone

    Dorts, Jennifer; Richter, Catherine A.; Wright-Osment, Maureen K.; Ellersieck, Mark R.; Carter, Barbara J.; Tillitt, Donald E.

    2009-01-01

    We investigated the genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute (4 days) exposure to 0.1 or 1.0 ??g/L of 17??-trenbolone (TB), the active metabolite of an anabolic androgenic steroid used as a growth promoter in cattle and a contaminant of concern in aquatic systems. Our objectives were to investigate the gene expression profile induced by TB, define biomarkers of exposure to TB, and increase our understanding of the mechanisms of adverse effects of TB on fish reproduction. In female gonad tissue, microarray analysis using a 22 K oligonucleotide microarray (EcoArray Inc., Gainesville, FL) showed 99 significantly upregulated genes and 741 significantly downregulated genes in response to 1 ??g TB/L. In particular, hydroxysteroid (17??) dehydrogenase 12a (hsd17b12a), zona pellucida glycoprotein 2.2 (zp2.2), and protein inhibitor of activated STAT, 2 (pias2) were all downregulated in gonad. Q-PCR measurements in a larger sample set were consistent with the microarray results in the direction and magnitude of these changes in gene expression. However, several novel potential biomarkers were verified by Q-PCR in the same samples, but could not be validated in independent samples. In liver, Q-PCR measurements showed a significant decrease in vitellogenin 1 (vtg1) mRNA expression. In brain, cytochrome P450, family 19, subfamily A, polypeptide 1b (cyp19a1b, previously known as aromatase B) transcript levels were significantly reduced following TB exposure. Our study provides a candidate gene involved in mediating the action of TB, hsd17b12a, and two potential biomarkers sensitive to acute TB exposure, hepatic vtg1 and brain cyp19a1b.

  1. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. PMID:27154534

  2. Phenobarbital: disposition into fetal tissue and the influence of protein binding

    Antibodies specific for barbiturates were generated in rabbits by administration of a barbiturate-bovine gamma globulin conjugate. Antibodies with a high degree of specificity for barbiturates were obtained after 2-3 months of immunization. Anti-barbiturate antisera were used to passively immunize pregnant animals on day 15 of gestation. The disposition of 3H-Phenobarbital (PhB) in fetal tissue in these mice were compared to normal rabbit serum(NRS)-treated pregnant mice. Following intravenous injection of 3H-PhB (25 pmoles), there were significantly higher levels of radioactivity in the serum of the immunized mice when compared to controls. Both the distribution half-life and the elimination half-life were reduced in the immunized animals (17.2 vs 88.3 min. and 123.7 vs 308.8 min., respectively) when compared to the NRS-treated mice. In contrast, levels of total radioactivity were significantly reduced in whole fetal homogenates in animals pretreated with whole antisera, Fab, or F(ab')2 fragments as compared to control animals. The data indicate that there was a decrease in the ability of 3H-PhB or its metabolites to diffuse into fetal tissue at various time points and that antisera or antisera fragments were instrumental in preventing this diffusion

  3. Promoting and anticarcinogenic effects of phenobarbital and DDT in the rat hepatocarcinogenesis.

    Kitagawa, T

    1986-01-01

    The possible discrepancy between the dose level required for promoting action (when given after the initiation process, and that needed to exert an anticarcinogenic effect when given simultaneously with a carcinogen) of hepatic promoters were investigated in an attempt to obtain a "practical" threshold dose of promoters. Phenobarbital (PB) and dichlorophenyltrichlorethane (DDT) were used as promoters and 3'-methyl-4-(dimethylamino)-azobenzene (3'-Me-DAB) was used as the carcinogen. Male weanling rats were treated with either 600 ppm 3'-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5-500 ppm), or the animals were treated with a low dose (100 ppm) of 3'-Me-DAB plus a promoter at various dose levels (20-500 ppm). The effects of promoters were measured by scoring size and number of enzyme-altered islands (EAIs) at 12 and 24 weeks of age. The promoting effect of PB and DDT was demonstrated in dose-dependent fashion, in the dose range of 10-500 ppm and 20-500 ppm, respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced carcinogenesis at all the dose levels tested, in contrast with the inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens. PMID:3787112

  4. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Ana Cristina Nunes

    2015-12-01

    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  5. Whey protein concentrate promotes the production of glutathione (GSH) by GSH reductase in the PC12 cell line after acute ethanol exposure.

    Tseng, Yang-Ming; Lin, Shu-Kai; Hsiao, Jen-Kuei; Chen, Ing-Jun; Lee, Jang-Hwa; Wu, Szu-Hsien; Tsai, Li-Yu

    2006-04-01

    Excessive ethanol consumption may increase the production of reactive oxygen species (ROS), which results in the damage of tissues, especially the neurons and glial cells in the central nervous system (CNS). The purpose of this study is to evaluate the effects of whey protein concentrate (WPC) on the glutathione (GSH) status after acute ethanol exposure in the pheochromocytoma (PC12) cell line. In this study, we assayed the cell viability, the percentage of lactate dehydrogenase released (% LDH released), the level of GSH, and the activity of GSH reductase (GRx). The results showed that with the supplement of WPC, the cell viability displayed no significant difference after acute exposure of ethanol in groups with or without ethanol treatment. The ethanol-induced cytotoxicity showed a slight decrease ,and the level of GSH showed a significant increase. The activity of GRx significantly increased when 0.1, 10mg/ml of WPC was supplied. In conclusion, these results suggest that WPC in a moderate concentration should be a precursor agent to promote the production of GSH and will enhance the antioxidant capacity in the PC12 cell line. PMID:16360258

  6. Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.

    Panneerselvam, Lakshmikanthan; Govindarajan, Vimal; Ameeramja, Jaishabanu; Nair, Harikumaran Raveendran; Perumal, Ekambaram

    2015-12-01

    Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers. PMID:26455266

  7. EFFECT OF FLUCTUATING EXPOSURES ON THE ACUTE TOXICITY OF AMMONIA TO RAINBOW TROUT (SALMO GAIRDNERI) AND CUTTHROAT TROUT (S. CLARKI)

    Acute toxicity bioassays in which fish were exposed to short-term cyclic fluctuations of ammonia were conducted on rainbow trout (Salmo gairdneri) and on cutthroat trout (S. clarki). Companion tests were also conducted in which test fish were subjected to ammonia at constant conc...

  8. Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function

    Toluene is a volatile organic compound (VOC) and a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several modes of action in the CNS have been proposed. Therefore, we sought to identify potential pathways ...

  9. Time course of maximum expiratory flow volume (MEPV) curves in the Wistar rat after acute ozone exposure

    Boere AJF; Marra M; Rombout PJA; TOX

    1995-01-01

    Acute blootstelling van menselijke vrijwilligers aan een concentratie ozon welke overeenkomt met concentraties welke gedurende smogepisodes in de buitenlucht gemeten worden, resulteert in een afname van de longfunctie en een ontstekingsproces in de longen. Het tijdsverloop van dit ontstekingsproces komt voor mensen en proefdieren overeen. In deze studie wordt het tijdsverloop van longfunctieveranderingen in proefdieren bestudeerd. De effecten op longfunctieparameters blijken maximaal direct n...

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

    Ingersoll, Christopher G.; Contributions by Wang, Ning; Calfee, Robin D.; Beahan, Erinn; Brumbaugh, William G.; Dorman, Rebecca A.; Hardesty, Doug K.; Kunz, James L.; Little, Edward E.; Mebane, Christopher A.; Puglis, Holly J.

    2014-01-01

    White sturgeon (Acipenser transmontanus) are experiencing poor recruitment in the trans boundary reach of the upper Columbia River in eastern Washington State. Limited toxicity data indicated that early life stages of white sturgeon are sensitive to metals. In acute 4-day (d) exposures with larval white sturgeon, previous studies have reported that the 4-day median lethal concentrations (LC50) based on biotic ligand model (BLM) normalization for copper were below the U.S. Environmental Protection Agency national recommended acute water-quality criterion. In previously published chronic 66-d exposures starting with newly fertilized eggs of white sturgeon, 20-percent lethal effect concentrations (LC20s) for copper, cadmium, or zinc generally were within a factor of two of the chronic values of the most sensitive fish species in the databases of the U.S. Environmental Protection Agency water-quality criteria (WQC) for the three metals. However, there were some uncertainties in the chronic exposures previously performed with white sturgeon, including (1) low control survival (37 percent), (2) more control fish tested in each replicate compared to other treatments, (3) limited replication of treatments (n=2), (4) lack of reported growth data (such as dry weight), and (5) wide dilution factors for exposure concentrations (6- to 8-fold dilutions). The U.S. Environmental Protection Agency concluded that additional studies are needed to generate more toxicity data to better define lethal and sublethal toxicity thresholds for metals for white sturgeon. The objective of the study was to further evaluate the acute and chronic toxicity of cadmium, copper, lead, or zinc to early life stages of white sturgeon in water-only exposures. Toxicity tests also were performed with commonly tested rainbow trout (Oncorhynchus mykiss) under similar test conditions to determine the relative sensitivity between white sturgeon and rainbow trout to these metals. Toxicity data generated from

  11. Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells

    Hui WANG; Min HUANG; Ren-xiu PENG; Jiang LE

    2006-01-01

    Aim: To explore the influence and possible mechanism of xenobiotics on adrenal steroidogenesis during fetal development. Methods: Primary human fetal adrenal cortical cells were prepared, cultured and treated with 3-methylcholanthrene, phenobarbital and dexamethasone. The activities of 7-ethoxyresorufin 0-dealkylase, benzphetamine, aminopyrine and erythromycin N-demethylases were measured by enzyme assays. At the same time, quantitative analysis of steroid hormones cortisol, aldosterone, testosterone and progesterone were carried out in cultural medium by radioimmunoassays. Results: The activities of benzphetamine and aminopyrine Ar-demethylase were increased in the cultural fetal adrenal cells treated with phenobarbital (0.25-1 mmol/L) for 24 h. Dexamethasone (25-100 μmol/L) also increased the activity of erythromycin W-demethylase. The activity of 7-ethoxyresorufin 0-dealkylase was undetected in the cells treated without and with 3-methylcholanthrene (0.5-2 μmol/L). Meanwhile, the contents of medium cortisol, aldosterone and progesterone were decreased after treatment with 3-methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the productions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3-methylcholanthrene, phenobarbital or dexamethasone treatment. Conclusion: 3-Methylcholanthrene, phenobarbital or dexamethasone could interfere with the synthesis of cortisol, aldosterone and progesterone in primary human fetal adrenal cortical cells, which likely act through xenobiotic metabolizing-related cytochrome P450 isoform activation.

  12. Simultaneous extraction and quantification of lamotrigine, phenobarbital, and phenytoin in human plasma and urine samples using solidified floating organic drop microextraction and high-performance liquid chromatography.

    Asadi, Mohammad; Dadfarnia, Shayessteh; Haji Shabani, Ali Mohammad; Abbasi, Bijan

    2015-07-01

    A novel and simple method based on solidified floating organic drop microextraction followed by high-performance liquid chromatography with ultraviolet detection has been developed for simultaneous preconcentration and determination of phenobarbital, lamotrigine, and phenytoin in human plasma and urine samples. Factors affecting microextraction efficiency such as the type and volume of the extraction solvent, sample pH, extraction time, stirring rate, extraction temperature, ionic strength, and sample volume were optimized. Under the optimum conditions (i.e. extraction solvent, 1-undecanol (40 μL); sample pH, 8.0; temperature, 25°C; stirring rate, 500 rpm; sample volume, 7 mL; potassium chloride concentration, 5% and extraction time, 50 min), the limits of detection for phenobarbital, lamotrigine, and phenytoin were 1.0, 0.1, and 0.3 μg/L, respectively. Also, the calibration curves for phenobarbital, lamotrigine, and phenytoin were linear in the concentration range of 2.0-300.0, 0.3-200.0, and 1.0-200.0 μg/L, respectively. The relative standard deviations for six replicate extractions and determinations of phenobarbital, lamotrigine, and phenytoin at 50 μg/L level were less than 4.6%. The method was successfully applied to determine phenobarbital, lamotrigine, and phenytoin in plasma and urine samples. PMID:25953277

  13. Phenobarbital but not diazepam reduces AMPA/Kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus

    Romain Nardou

    2011-07-01

    Full Text Available Diazepam (DZP and phenobarbital (PB are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We have now compared the effects of DZP and PB on ictal-like events (ILEs in an in vitro model of mirror focus (MF. Using the three-compartment chamber with the two immature hippocampi and their commissural fibers placed in 3 different compartments, kainate was applied to one hippocampus and PB or DZP to the contralateral one, either after one ILE or after many recurrent ILEs that produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated propagating ILEs from the start and did not prevent the formation of MF. PB reduced and DZP increased the network driven Giant Depolarising Potentials suggesting that PB may exert additional actions that are not mediated by GABA signalling. In keeping with this, PB but not DZP reduced field potentials recorded in the presence of GABA and NMDA receptor antagonists. These effects are mediated by a direct action on AMPA/Kainate receptors since PB: i reduced AMPA/Kainate receptor mediated currents induced by focal applications of glutamate ; ii reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated miniature EPSCs; iii augmented the number of AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly by reducing AMPA/Kainate receptors mediated EPSCs in addition to the pro-GABA effects. We suggest that PB may have advantage over DZP in the treatment of initial neonatal seizures since the additional reduction of glutamate receptors mediated signals may reduce the severity of neonatal seizures.

  14. Behavioral and neuronal recording of the nucleus accumbens in adolescent rats following acute and repetitive exposure to methylphenidate

    Frolov, Alexander; Reyes-Vasquez, Cruz; Dafny, Nachum

    2014-01-01

    The nucleus accumbens (NAc) has been shown to play a key role in the brain's response to methylphenidate (MPD). The present study focuses on neuronal recording from this structure. The study postulates that repetitive exposure to the same dose of MPD will elicit in some rats behavioral sensitization and in others tolerance. Furthermore, the study postulates that NAc neuronal activity recorded from animals expressing behavioral tolerance after repetitive MPD exposure will be significantly diff...

  15. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m3 of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure

  16. Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter.

    Marchini, Timoteo; D'Annunzio, Verónica; Paz, Mariela L; Cáceres, Lourdes; Garcés, Mariana; Perez, Virginia; Tasat, Deborah; Vanasco, Virginia; Magnani, Natalia; Gonzalez Maglio, Daniel; Gelpi, Ricardo J; Alvarez, Silvia; Evelson, Pablo

    2015-11-15

    Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality. PMID:26386109

  17. C-reactive protein and serum amyloid A as early-phase and prognostic indicators of acute radiation exposure in nonhuman primate total-body irradiation model

    Terrorist radiological attacks or nuclear accidents could expose large numbers of people to ionizing radiation. In mass-casualty radiological incidents early medical-management requires triage tools for first-responders to quantitatively identify individuals exposed to life-threatening radiation doses and for early initiation (i.e., within one day after radiation exposure) of cytokine therapy for treatment of bone marrow acute radiation syndrome. Herein, we present results from 30 rhesus macaques total-body irradiated (TBI) to a broad dose range of 1-8.5 Gy with 60Co γ-rays (0.55 Gy min-1) and demonstrate dose- and time-dependent changes in blood of C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) measured by enzyme linked immunosorbent assay (ELISA). CRP and SAA dose-response results are consistent with ∼1 Gy and ∼0.2 Gy thresholds for photon-exposure at 24 h after TBI, respectively. Highly significant elevations of CRP and SAA (p = 0.00017 and p = 0.0024, respectively) were found in animal plasma at 6 h after all TBI doses suggesting their potential use as early-phase biodosimeters. Results also show that the dynamics and content of CRP and SAA levels reflect the course and severity of the acute radiation sickness (ARS) and may function as prognostic indicators of ARS outcome. These results demonstrate proof-of-concept that these radiation-responsive proteins show promise as a complementary approach to conventional biodosimetry for early assessment of radiation exposures and may also contribute as diagnostic indices in the medical management of radiation accidents.

  18. C-reactive protein and serum amyloid A as early-phase and prognostic indicators of acute radiation exposure in nonhuman primate total-body irradiation model

    Ossetrova, N.I., E-mail: ossetrova@afrri.usuhs.mil [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States); Sandgren, D.J.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States)

    2011-09-15

    Terrorist radiological attacks or nuclear accidents could expose large numbers of people to ionizing radiation. In mass-casualty radiological incidents early medical-management requires triage tools for first-responders to quantitatively identify individuals exposed to life-threatening radiation doses and for early initiation (i.e., within one day after radiation exposure) of cytokine therapy for treatment of bone marrow acute radiation syndrome. Herein, we present results from 30 rhesus macaques total-body irradiated (TBI) to a broad dose range of 1-8.5 Gy with {sup 60}Co {gamma}-rays (0.55 Gy min{sup -1}) and demonstrate dose- and time-dependent changes in blood of C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) measured by enzyme linked immunosorbent assay (ELISA). CRP and SAA dose-response results are consistent with {approx}1 Gy and {approx}0.2 Gy thresholds for photon-exposure at 24 h after TBI, respectively. Highly significant elevations of CRP and SAA (p = 0.00017 and p = 0.0024, respectively) were found in animal plasma at 6 h after all TBI doses suggesting their potential use as early-phase biodosimeters. Results also show that the dynamics and content of CRP and SAA levels reflect the course and severity of the acute radiation sickness (ARS) and may function as prognostic indicators of ARS outcome. These results demonstrate proof-of-concept that these radiation-responsive proteins show promise as a complementary approach to conventional biodosimetry for early assessment of radiation exposures and may also contribute as diagnostic indices in the medical management of radiation accidents.

  19. Quantification of acute vocal fold epithelial surface damage with increasing time and magnitude doses of vibration exposure.

    Tsuyoshi Kojima

    Full Text Available Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes and magnitude-doses (control, modal intensity phonation, or raised intensity phonation of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure.

  20. Cumulative exposure to air pollution and long term outcomes after first acute myocardial infarction: A population-based cohort study. Objectives and methodology

    Steinberg David M

    2010-06-01

    Full Text Available Abstract Background Cardiovascular disease is a leading cause of morbidity and mortality worldwide and epidemiological studies have consistently shown an increased risk for cardiovascular events in relation to exposure to air pollution. The Israel Study of First Acute Myocardial Infarction was designed to longitudinally assess clinical outcomes, psychosocial adjustment and quality of life in patients hospitalized with myocardial infarction. The current study, by introducing retrospective air pollution data, will examine the association between exposure to air pollution and outcome in myocardial infarction survivors. This report will describe the methods implemented and measures employed. The study specifically aims to examine the relationship between residential exposure to air pollution and long-term risk of recurrent coronary event, heart failure, stroke, cardiac and all-cause death in a geographically defined cohort of patients with myocardial infarction. Methods/Design All 1521 patients aged ≤65 years, admitted with first myocardial infarction between February 1992 and February 1993 to the 8 hospitals serving the population of central Israel, were followed for a median of 13 years. Data were collected on sociodemographic, clinical and environmental factors. Data from air quality monitoring stations will be incorporated retrospectively. Daily measures of air pollution will be summarised, allowing detailed maps to be developed in order to reflect chronic exposure for each participant. Discussion This study addresses some of the gaps in understanding of the prognostic importance of air pollution exposure after myocardial infarction, by allowing a sufficient follow-up period, using a well-defined community cohort, adequately controlling for multiple and multilevel confounding factors and providing extensive data on various outcomes.

  1. Effects of Neonatal Antiepileptic Drug Exposure on Cognitive, Emotional, and Motor Function in Adult Rats

    Patrick A Forcelli; Kozlowski, Ryan; Snyder, Charles; Kondratyev, Alexei; Gale, Karen

    2012-01-01

    Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13...

  2. A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

    Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T4) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T4 and free T4 occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observed in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T4-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [125I]T4-glucuronide after an intravenous injection of [125I]T4 to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [125I]T4 from the serum, led to a significant increase in the steady-state distribution volumes of [125I]T4, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [125I]T4. The present findings indicate that the PB-mediated decreases in the serum T4 level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T4 in the liver.

  3. In vivo metabolism of CCl/sub 4/ by rats pretreated with chlordecone, mirex, or phenobarbital

    Mehendale, H.M.; Klingensmith, J.S.

    1988-04-01

    The propensity of chlordecone (CD) to potentiate hepatotoxic and lethal effects of CCl4 is well established. Mirex (M), a close structural analogue of CD, or phenobarbital (PB), powerful inducers of hepatic microsomal drug metabolizing enzymes, are much weaker potentiators of CCl4 toxicity. The purpose of this study was to test the possibility that CD potentiates the toxicity of CCl4 by increasing the metabolism of CCl4 to a greater degree than either PB or M. We compared the in vivo metabolism of CCl4 in rats pretreated with CD, M, or PB, by measuring the hepatic content of 14CCl4, the expiration of 14CCl4, expiration of 14CCl4-derived 14CO2, and lipid peroxidation. Male Sprague-Dawley rats (250-270 g) were pretreated with a single oral dose of CD (10 mg/kg), M (10 mg/kg), or corn oil vehicle (1 ml/kg). PB pretreatment consisted of an ip injection of sodium PB (80 mg/kg) in saline (0.9%) for 2 successive days. Twenty-four hours later, 14CCl4 (0.1 ml/kg; sp act: 0.04 mCi/mmol) was administered ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. Excretion of the parent compound as represented by the 14C label in the toluene trap was unchanged by any of the pretreatments. Expiration of 14CO2 measured during the 6 hr after CCl4 administration was increased in animals pretreated with PB or CD. In vivo lipid peroxidation measured as diene conjugation in lipids extracted from the livers was increased to a similar extent in animals pretreated with PB and CD, whereas the serum transaminases (ALT, AST) were significantly elevated only in animals pretreated with CD.M did not affect 14CO2 production and was without a significant effect on the lipid peroxidation.

  4. Increased hepatic nicotine elimination after phenobarbital induction in the conscious rat

    Elimination parameters of [14C]nicotine in conscious rats receiving nicotine (0.3 mg/kg) either intravenously or orally were studied. The oral availability of unchanged nicotine, derived by comparison of the respective areas under the concentration vs time curves (AUC), was 89%, indicating low hepatic extraction ratios of about 10%. Pretreatment of rats with phenobarbital (PB) markedly increased hepatic first-pass extraction of nicotine. The oral availability of unchanged nicotine in plasma dropped to 1.4% of the corresponding values obtained from PB-treated rats receiving nicotine iv. After PB pretreatment, the clearance of iv nicotine was increased approximately twofold over controls, much less than the observed more than ninefold increase of hepatic first-pass extraction. It is assumed that extrahepatic metabolism contributed significantly to the rapid removal of nicotine from the plasma. The elimination of cotinine, originating from nicotine administered either po or iv, was significantly increased by PB pretreatment, as determined by the ratio of corresponding AUCs. The pattern of nicotine metabolites in urine also indicated an increase in the rate of cotinine metabolic turnover. The amount of norcotinine in the organic extract of urine paralleled PB microsomal enzyme induction. The ratio between urinary concentrations of the normetabolite and cotinine correlated strongly with the PB-induced state of rat liver. This may be a suitable indicator of PB-inducible hepatic cytochrome P450 isoenzyme(s). Since smoking habits in man are feedback-regulated by nicotine plasma concentrations, a similar increase of nicotine elimination by microsomal enzyme induction in man may be of relevance for tobacco consumption

  5. Tumor promotion and inhibition by phenobarbital in livers of conditional Apc-deficient mice.

    Braeuning, Albert; Gavrilov, Alina; Geissler, Miriam; Wenz, Christine; Colnot, Sabine; Templin, Markus F; Metzger, Ute; Römer, Michael; Zell, Andreas; Schwarz, Michael

    2016-06-01

    Activation of Wnt/β-catenin signaling is important for human and rodent hepatocarcinogenesis. In mice, the tumor promoter phenobarbital (PB) selects for hepatocellular tumors with activating β-catenin mutations via constitutive androstane receptor activation. PB-dependent tumor promotion was studied in mice with genetic inactivation of Apc, a negative regulator of β-catenin, to circumvent the problem of randomly induced mutations by chemical initiators and to allow monitoring of PB- and Wnt/β-catenin-dependent tumorigenesis in the absence of unknown genomic alterations. Moreover, the study was designed to investigate PB-induced proliferation of liver cells with activated β-catenin. PB treatment provided Apc-deficient hepatocytes with only a minor proliferative advantage, and additional connexin 32 deficiency did not affect the proliferative response. PB significantly promoted the outgrowth of Apc-deficient hepatocellular adenoma (HCA), but simultaneously inhibited the formation of Apc-deficient hepatocellular carcinoma (HCC). The probability of tumor promotion by PB was calculated to be much lower for hepatocytes with loss of Apc, as compared to mutational β-catenin activation. Comprehensive transcriptomic and phosphoproteomic characterization of HCA and HCC revealed molecular details of the two tumor types. HCC were characterized by a loss of differentiated hepatocellular gene expression, enhanced proliferative signaling, and massive over-activation of Wnt/β-catenin signaling. In conclusion, PB exerts a dual role in liver tumor formation by promoting the growth of HCA but inhibiting the growth of HCC. Data demonstrate that one and the same compound can produce opposite effects on hepatocarcinogenesis, depending on context, highlighting the necessity to develop a more differentiated view on the tumorigenicity of this model compound. PMID:26838046

  6. In vivo metabolism of CCl4 by rats pretreated with chlordecone, mirex, or phenobarbital

    The propensity of chlordecone (CD) to potentiate hepatotoxic and lethal effects of CCl4 is well established. Mirex (M), a close structural analogue of CD, or phenobarbital (PB), powerful inducers of hepatic microsomal drug metabolizing enzymes, are much weaker potentiators of CCl4 toxicity. The purpose of this study was to test the possibility that CD potentiates the toxicity of CCl4 by increasing the metabolism of CCl4 to a greater degree than either PB or M. We compared the in vivo metabolism of CCl4 in rats pretreated with CD, M, or PB, by measuring the hepatic content of 14CCl4, the expiration of 14CCl4, expiration of 14CCl4-derived 14CO2, and lipid peroxidation. Male Sprague-Dawley rats (250-270 g) were pretreated with a single oral dose of CD (10 mg/kg), M (10 mg/kg), or corn oil vehicle (1 ml/kg). PB pretreatment consisted of an ip injection of sodium PB (80 mg/kg) in saline (0.9%) for 2 successive days. Twenty-four hours later, 14CCl4 (0.1 ml/kg; sp act: 0.04 mCi/mmol) was administered ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. Excretion of the parent compound as represented by the 14C label in the toluene trap was unchanged by any of the pretreatments. Expiration of 14CO2 measured during the 6 hr after CCl4 administration was increased in animals pretreated with PB or CD. In vivo lipid peroxidation measured as diene conjugation in lipids extracted from the livers was increased to a similar extent in animals pretreated with PB and CD, whereas the serum transaminases (ALT, AST) were significantly elevated only in animals pretreated with CD.M did not affect 14CO2 production and was without a significant effect on the lipid peroxidation

  7. Acclimation-dependent expression of heat shock protein 70 in Pacific abalone (Haliotis discus hannai Ino) and its acute response to thermal exposure

    LI Jiaqi; HE Qingguo; SUN Hui; LIU Xiao

    2012-01-01

    Heat shock protein 70 (Hsp70) is one important member of heat shock protein (Hsp) family that is responsible for various stresses,especially thermal stress.Here we examined the response of Hsp70gene to both chronic and acute thermal exposure in Pacific abalone (Haliotis discus hannai Ino).For the chronic exposure,abalones were maintained at 8,12,20,and 30℃ for four months and their mRNA levels were measured.The highest mRNA level of Hsp70 gene relative to actin gene was detected in the 30℃-acclimated group,followed by the 8℃-acclimated group and then the 12℃- and 20℃-acclimated groups.After the long-term acclimation,gills from each of the above acclimation groups were dissected and exposed to different temperatures between 8℃ and 38℃ for 30 min.Hsp70 expression in gills acclimated to different temperatures responded differentially to the same temperature exposure.The incubation temperature that induced maximum Hsp70 mRNA expression was higher in the higher temperature acclimation groups than lower temperature groups.Pacific abalones could alter the expression pattern of Hsp70 gene according to environmental thermal conditions,through which they deal with the stress of thermal variations.

  8. Discharge behaviors of trapezius motor units during exposure to low and high levels of acute psychosocial stress

    Stephenson, Jennifer L.; Maluf, Katrina S

    2010-01-01

    This study investigated the effects of acute psychosocial stress on trapezius single motor unit discharge behaviors. Twenty-one healthy women performed feedback-controlled isometric contractions under conditions of low and high psychosocial stress in the same experimental session. Psychosocial stress was manipulated using a verbal math task combined with social evaluative threat which significantly increased perceived anxiety, heart rate, and blood pressure (P0.121, N=103) and derecruitment (...

  9. Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog.

    Iwabe, Simone; Ying, Gui-Shuang; Aguirre, Gustavo D; Beltran, William A

    2016-05-01

    The effect of acute exposure to various intensities of white light on visual behavior and retinal structure was evaluated in the T4R RHO dog, a naturally-occurring model of autosomal dominant retinitis pigmentosa due to a mutation in the Rhodopsin gene. A total of 14 dogs (ages: 4-5.5 months) were used in this study: 3 homozygous mutant RHO(T4R/T4R), 8 heterozygous mutant RHO(T4R/+), and 3 normal wild-type (WT) dogs. Following overnight dark adaptation, the left eyes were acutely exposed to bright white light with a monocular Ganzfeld dome, while the contralateral right eye was shielded. Each of the 3 homozygous (RHO(T4R/T4R)) mutant dogs had a single unilateral light exposure (LE) to a different (low, moderate, and high) dose of white light (corneal irradiance/illuminance: 0.1 mW/cm(2), 170 lux; 0.5 mW/cm(2), 820 lux; or 1 mW/cm(2), 1590 lux) for 1 min. All 8 heterozygous (RHO(T4R/+)) mutant dogs were exposed once to the same moderate dose of light. The 3 WT dogs had their left eyes exposed 1, 2, or 3 times to the same highest dose of light. Visual function prior to LE and at 2 weeks and 33 weeks after exposure was objectively assessed in the RHO(T4R/T4R) and WT dogs by using an obstacle-avoidance course. Transit time through the obstacle course was measured under different scotopic to photopic ambient illuminations. Morphological retinal changes were evaluated by non-invasive in vivo cSLO/sdOCT imaging and histology before and at several time-points (2-36 weeks) after light exposure. The analysis of the transit time through the obstacle course showed that no differences were observed in any of mutant or WT dogs at 2 weeks and 33 weeks post LE. The RHO(T4R/T4R) retina exposed to the lowest dose of white light showed no obvious changes in ONL thickness at 2 weeks, but mild decrease was noted 36 weeks after LE. The RHO(T4R/T4R) retina that received a moderate dose (showed an obvious decrease in ONL thickness along the superior and temporal meridians at 2

  10. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome

    Shingade, Pravin U; Wankhede, Vaishali; Kataria, Pritam S; Sonone, Nitin

    2014-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a rare drug induced cutaneous hypersensitivity reaction characterized by sudden onset of fever with sterile pustules overlying an erythematous skin occurring all over the body. The offending drugs are usually B-lactams and macrolides. Among anticonvulsants carbamazepine and Phenobarbital are commonly associated with AGEP. Only one case of phenytoin induced AGEP has been reported in literature. We present a rare case of AGEP with cerebellar syndrome occurring after receiving loading dose of phenytoin. PMID:24700960

  11. Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages.

    Marchini, Timoteo; Wolf, Dennis; Michel, Nathaly Anto; Mauler, Maximilian; Dufner, Bianca; Hoppe, Natalie; Beckert, Jessica; Jäckel, Markus; Magnani, Natalia; Duerschmied, Daniel; Tasat, Deborah; Alvarez, Silvia; Reinöhl, Jochen; von Zur Muhlen, Constantin; Idzko, Marco; Bode, Christoph; Hilgendorf, Ingo; Evelson, Pablo; Zirlik, Andreas

    2016-07-01

    Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed to describe mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were challenged with a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation before MI was induced by permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium 7 days after MI demonstrated an increase in infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Mechanistically, ROFA exposure increased the levels of the circulating pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, activated myeloid and endothelial cells, and enhanced leukocyte recruitment to the peritoneal cavity and the vascular endothelium. Notably, these effects on endothelial cells and circulating leukocytes could be reversed by neutralizing anti-TNF-α treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasal clodronate attenuated inflammation and cell recruitment to infarcted tissue of ROFA-exposed mice. Taken together, our data demonstrate that exposure to environmental PM induces the release of inflammatory cytokines from alveolar macrophages which directly worsens the course of MI in mice. These findings uncover a novel link between air pollution PM exposure and inflammatory pathways, highlighting the importance of environmental factors in cardiovascular disease. PMID:27240856

  12. Evaluation of a new immunoassay for determination of phenytoin and phenobarbital: results of a European collaborative control study.

    Schmidt, D; Goldberg, V; Guelen, P J; Johannessen, S; Kleijn, E; Meijer, J W; Meinardi, H; Richens, A; Schneider, H; Stein-Lavie, Y; Symann-Louette, N

    1977-09-01

    The performance of a new enzyme multiplied immunoassay technique (EMIT) was compared with other current methods, namely gas-liquid chromatography and thin-layer chromatography, for the determination of phenytoin and phenobarbital in serum. Forty-three serum samples were sent as unknowns to the participating laboratories for determination. The precision of repeated determinations was very similar for EMIT and chromatography. There was good agreement among gas chromatography, thin-layer chromatography, and EMIT results. Interlaboratory variability was lower for EMIT determinations of both antiepileptic drugs. The rapid analysis of small samples, made possible by the EMIT system, could have beneficial effects on the treatment of epilepsies. PMID:891490

  13. Effect of Methomyl on the Phenobarbital and Benzo [a] Pyrene Induced Hepatic Microsomal Mixed Function Oxidase System in Rats

    Jyotsna A. Patil1, Arun J. Patil1*, Ajit V. Sontakke1, Satish D. Kalme2 and Sanjay P. Govindwar3

    2011-01-01

    Methomyl (Lannate) is a pesticide widely used to control of insects in grape gardens. Methomyl treatment induces significant alteration in mixed function oxidase system. The present work was designed to study the inhibitory effect of methomyl on different forms of cytochrome P450 induced by phenobarbital (CYP 2B1, 2B2 and 3A) and benzo[a]pyrene induced (CYP 1A1). Adult male rats were divided into 8 groups of 6 animals each. Microsomes were isolated by calcium precipitation. The levels of elec...

  14. Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 2. Irritation and inflammation.

    Ernstgård, Lena; Iregren, Anders; Juran, Stephanie; Sjögren, Bengt; van Thriel, Christoph; Johanson, Gunnar

    2009-04-01

    Low aromatic and dearomatized white spirits (deWS) are often considered less hazardous to health than 'standard' or aromatic white sprit (stdWS, 15-20% aromatics). However, data on health effects of deWS in humans are sparse and controlled exposure studies are lacking. The aim of this study was to compare deWS and stdWS with respect to irritation and inflammation. Six female and six male healthy volunteers were exposed on five occasions in balanced order to 100 or 300 mg m(-3) deWS (0.002% aromatics) or stdWS (19% aromatics), or to clean air, for 4 h at rest. Discomfort in the eyes, nose and throat and breathing difficulty were assessed by ratings on visual analogue scales. The only significant increases in ratings (compared to clean air) were seen for eye irritation at the high stdWS exposure and for solvent smell at all but the low deWS exposure. Excluding smell, all average ratings were at the lower end of the 0-100 mm scale, and did not exceed the verbal expression 'somewhat'. Ratings during stdWS exposure tended to be higher than during deWS exposure. No exposure-related effects on pulmonary function, nasal swelling, nasal airway resistance, breathing frequency, blinking frequency, plasma inflammatory markers (C-reactive protein, interleukin-6) or biochemical variables (sodium, potassium, amylase, creatine kinase, urate) were seen. In conclusion, stdWS appears to be slightly more irritating than deWS. This could, however, not be confirmed by objective measurements. PMID:19086013

  15. Acute and long-lasting cardiac changes following a single whole-body exposure to sarin vapor in rats.

    Allon, N; Rabinovitz, I; Manistersky, E; Weissman, B A; Grauer, E

    2005-10-01

    Epinephrine-induced arrhythmias (EPIA) are known to be associated with local cardiac cholinergic activation. The present study examined the development of QT prolongation and the effect on EPIA of whole-body exposure of animals to a potent acetylcholine esterase inhibitor. Freely moving rats were exposed to sarin vapor (34.2 +/- 0.8 microg/liter) for 10 min. The electrocardiograms (ECG) of exposed and control animals were monitored every 2 weeks for 6 months. One and six months post exposure, rats were challenged with epinephrine under anesthesia, and the threshold for arrhythmias was determined. Approximately 35% of the intoxicated rats died within 24 h of sarin exposure. Additional occasional deaths were recorded for up to 6 months (final mortality rate of 48%). Surviving rats showed, agitation, aggression, and weight loss compared to non-exposed rats, and about 20% of them experienced sporadic convulsions. Sarin-challenged rats with severe symptoms demonstrated QT segment prolongation during the first 2-3 weeks after exposure. The EPIA that appeared at a significantly lower blood pressure in the treated group in the first month after intoxication lasted for up to 6 months. This decrease in EPIA threshold was blocked by atropine and methyl-atropine. Three months post exposure no significant changes were detected in either k(D) or B(max) values of (3)H-N-methyl scopolamine binding to heart homogenates, or in the affinity of carbamylcholine to cardiac muscarinic receptors. The increase in the vulnerability to develop arrhythmias long after accidental or terror-related organophosphate (OP) intoxication, especially under challenging conditions such as stress or intensive physical exercise, may explain the delayed mortality observed following OP exposure. PMID:16033992

  16. Association of short-term exposure to fine particulate matter and nitrogen dioxide with acute cardiovascular effects.

    Wu, Chang-Fu; Shen, Fu-Hui; Li, Ya-Ru; Tsao, Tsung-Ming; Tsai, Ming-Jer; Chen, Chu-Chih; Hwang, Jing-Shiang; Hsu, Sandy Huey-Jen; Chao, Hsing; Chuang, Kai-Jen; Chou, Charles C K; Wang, Ya-Nan; Ho, Chi-Chang; Su, Ta-Chen

    2016-11-01

    This study evaluated whether exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) is associated with cardiovascular effects by examining a panel of 89 healthy subjects in Taipei, Taiwan. The subjects received two health examinations approximately 8months apart in 2013. Brachial-ankle pulse wave velocity (baPWV), a physiological indicator of arterial stiffness, and high-sensitivity C-reactive protein (hsCRP), a biomarker of vascular inflammations, were measured during each examination. Two exposure assessment methods were used for estimating the subjects' exposure to PM2.5 and NO2. The first method involved constructing daily land use regression (LUR) models according to measurements collected at ambient air quality monitoring stations. The second method required combining the LUR estimates with indoor monitoring data at the workplace of the subjects. Linear mixed models were used to examine the association between the exposure estimates and health outcomes. The results showed that a 10-μg/m(3) increase in PM2.5 concentration at a 1-day lag was associated with 2.1% (95% confidence interval: 0.7%-3.6%) and 2.4% (0.8%-4.0%) increases in baPWV based on the two exposure assessment methods, whereas no significant association was observed for NO2. The significant effects of PM2.5 remained in the two-pollutant models. By contrast, NO2, but not PM2.5, was significantly associated with increased hsCRP levels (16.0%-37.3% in single-pollutant models and 26.4%-44.6% in two-pollutant models, per 10-ppb increase in NO2). In conclusion, arterial stiffness might be more sensitive to short-term PM2.5 exposure than is inflammation. PMID:27344119

  17. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio)

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-01-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

  18. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio).

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-04-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

  19. Acute developmental exposure to polybrominated diphenyl ether 47 (PBDE 47) alters dopamine concentration within the brains of male mice.

    Polybrominated diphenyl ethers (PBDEs) are commonly used as commercial flame retardants in a variety of products including plastics and textiles. Previous studies in our laboratory and in the literature have shown that exposure to a specific PBDE congener, PBDE 47, during a criti...

  20. Acute Ozone (O3) Exposure Enhances Aortic Contraction in Healthy Rats while Exacerbating Pulmonary Injury in Diabetics

    Air pollution exposure affects health adversely in individuals with type 2 diabetes (T2D) and diet induced obesity (DIO). We hypothesized that T2D and DIO would exacerbate O3 induced pulmonary responses and alter arterial reactivity. Male Wistar and Goto Kakizaki (GK) rats, a l...

  1. EFFECTS OF ACUTE AND WEEKLY EPISODIC EXPOSURES TO ANATOXIN-A ON THE MOTOR ACTIVITY OF RATS: COMPARISON WITH NICOTINE.

    Anatoxin-a is a potent nicotinic cholinergic agonist, that is produced by many genera of cyanobacteria, and has caused several poisoning episodes of wildlife, livestock, and domestic animals. Cyanobacterial blooms and toxin exposures are likely to occur episodically as environmen...

  2. Acute Effects of Exposure to a Traditional Rural Environment on Urban Dwellers: A Crossover Field Study in Terraced Farmland

    Juyoung Lee

    2015-02-01

    Full Text Available Despite an increasing attention and public preference for rural amenities, little evidence is available on the health benefits of a rural environment. In this study, we identified physiological and psychological benefits of exposure to a rural environment using multiparametric methods. Twelve young male adults participated in a 3-day field experiment (mean ± standard deviation age, 22.3 ± 1.3 years. Sleeping environment, diet program, physical activities, and other factors possibly affecting physiological responses were controlled during experiment period. For all participants, salivary cortisol concentration, heart rate variability, and blood pressure were measured at rural and urban field sites. Self-evaluation questionnaires were administered to analyze the psychological states in two different environments. Volatile compounds in the air were also analyzed to investigate air quality. The data were compared between rural and urban environments. The data showed that exposure to a rural environment reduced stress hormone secretion and sympathetic nervous activity and increased parasympathetic nervous activity. Short-term exposure to a rural environment also improved mood states. Our findings indicate that exposure to a rural environment effectively reduced physiological stress and enhanced psychological well-being.

  3. Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol.

    Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

    2016-03-01

    Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

  4. Acute exposure to Buenos Aires air particles (UAP-BA) induces local and systemic inflammatory response in middle-aged mice: A time course study.

    Orona, Nadia S; Ferraro, Sebastián A; Astort, Francisco; Morales, Celina; Brites, Fernando; Boero, Laura; Tiscornia, Gisela; Maglione, Guillermo A; Saldiva, Paulo H N; Yakisich, Sebastian; Tasat, Deborah R

    2016-01-01

    Exposure to air particulate matter (PM) is associated with increased cardiovascular morbimortality. However, PM doesn't affect equally to all people, being the old cohort the most susceptible and studied. We hypothesized that another specific life phase, the middle-aged subpopulation, may be negatively affected. Therefore, the aim of this study was to analyze in vivo the acute biological impact of two environmental particles, Urban Air Particles from Buenos Aires and Residual Oil Fly Ash, on the cardiorespiratory system of middle-aged mice, evaluating oxidative metabolism and inflammation. Both PM provoked a local and systemic inflammatory response, leading to a reduced alveolar area in the lung, an epicard inflammation in the heart, an increment of IL-6, and a reduction on PON 1 activity in serum of middle-aged animals. The positive correlation of local parameters with systemic markers of oxidative stress and inflammation could be responsible for associations of cardiovascular morbimortality in this subpopulation. PMID:26255684

  5. Intermittent exposure to social defeat and open-field test in rats: acute and long-term effects on ECG, body temperature and physical activity.

    Sgoifo, Andrea; Pozzato, Chiara; Meerlo, Peter; Costoli, Tania; Manghi, Massimo; Stilli, Donatella; Olivetti, Giorgio; Musso, Ezio

    2002-02-01

    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. After implantation of a transmitter for the radiotelemetric recording of electrocardiogram (ECG), body temperature and physical activity, adult male rats (Rattus norvegicus, Wild Type Groningen strain) were repeatedly exposed (10 consecutive times, on alternate days) to either a social stressor (defeat by a con-specific, n = 15) or an open-field, control challenge (transfer to a new cage; n = 8). ECGs, body temperature and physical activity were continuously recorded in baseline, test and recovery periods (each lasting 15 min), at the 1st and 10th episodes of both defeat and open-field challenge. The circadian rhythms of heart rate, body temperature and physical activity were monitored before (5 days), during (16 days) and after (21 days) the intermittent stress protocol. This study indicates that there is no clear habituation of either acute cardiac autonomic responsivity (as estimated by means of time-domain indexes of heart rate variability) or arrhythmia occurrence to a brief, intermittent, homotypic challenge, regardless of the nature of the stressor (social or non-social). On the other hand, rats exposed to social challenge also failed to show adaptation of acute temperature and activity stress responsiveness, whereas rats facing open-field challenge developed habituation of activity and sensitization of temperature responses. Repeated social challenge produced remarkable reductions of the heart rate circadian rhythm amplitude (this effect being significantly greater than that produced by intermittent open-field), but only minor changes in the daily rhythms of body temperature and physical activity. PMID:12171764

  6. Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US.

    Mudarri, David H

    2016-01-01

    Two foundational methods for estimating the total economic burden of disease are cost of illness (COI) and willingness to pay (WTP). WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$) of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3-4.7) billion for allergic rhinitis, $1.9 (1.1-2.3) billion for acute bronchitis, $15.1 (9.4-20.6) billion for asthma morbidity, and $1.7 (0.4-4.5) billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality. PMID:27313630

  7. Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US

    David H. Mudarri

    2016-01-01

    Full Text Available Two foundational methods for estimating the total economic burden of disease are cost of illness (COI and willingness to pay (WTP. WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$ of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3–4.7 billion for allergic rhinitis, $1.9 (1.1–2.3 billion for acute bronchitis, $15.1 (9.4–20.6 billion for asthma morbidity, and $1.7 (0.4–4.5 billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality.

  8. Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US

    2016-01-01

    Two foundational methods for estimating the total economic burden of disease are cost of illness (COI) and willingness to pay (WTP). WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$) of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3–4.7) billion for allergic rhinitis, $1.9 (1.1–2.3) billion for acute bronchitis, $15.1 (9.4–20.6) billion for asthma morbidity, and $1.7 (0.4–4.5) billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality. PMID:27313630

  9. Recovery study of cholinesterases and neurotoxic signs in the non-target freshwater invertebrate Chilina gibbosa after an acute exposure to an environmental concentration of azinphos-methyl.

    Cossi, Paula Fanny; Beverly, Boburg; Carlos, Luquet; Kristoff, Gisela

    2015-10-01

    lethality (30%) was registered in treated snails. C. gibbosa is a very sensitive organism to azinphos-methyl. These snails play an important role in the structure and function of aquatic food webs in this region. Thus, a decline of this species' population would probably have an impact on aquatic and non-aquatic communities. Our results show that C. gibbosa is a relevant sentinel species for studying exposure and effects of azinphos-methyl using behavioral and biochemical biomarkers. Neurotoxic behavioral signs are very sensitive, non-destructive biomarkers, which can be easily detected for about one week after acute exposure. Cholinesterse activity is a very useful biomarker showing a high sensitivity and a slow recovery capacity increasing the possibility to indirectly detect organophosphates for long periods after a contaminant event. PMID:26364254

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

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

    2015-01-01

    INTRODUCTION Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to ...

  11. Chronic cough and dyspnea in ice hockey players after an acute exposure to combustion products of a faulty ice resurfacer.

    Kahan, Erika S; Martin, Ubaldo J; Spungen, Steve; Ciccolella, David; Criner, Gerard J

    2007-01-01

    The aim of this study was to characterize pulmonary function and radiologic testing in ice hockey players after exposure to combustion products of a faulty ice resurfacer. Our patients were 16 previously healthy hockey players who developed chronic cough and dyspnea after exposure. Symptom questionnaires, pulmonary function tests (PFTs), bronchoprovocation testing, cardiopulmonary exercise testing, high-resolution computed tomography (CT) imaging, and impulse oscillometry (IOS) were all used. A normal group was used for PFTs and IOS controls. Patients had onset of cough within 72 h of exposure. Ninety-two percent complained of dyspnea, 75% chest pain, and 33% hemoptysis. Eight percent were initially hospitalized for their symptoms. Eighty-five percent were treated with systemic steroids and 39% with inhaled bronchodilators. Six months postexposure, 54% complained of cough and 46% complained of dyspnea on exertion. All patients had normal PFTs; 8.3% had a significant bronchodilator response. All had normal exercise tests (mean VO2max = 90 +/- 3% predicted) and chest CTs. With IOS, 80% had a significant bronchodilator response (decreased resistance > 12% and SD score > 1; mean change = 21.1 +/- 9.9%, mean SD score = 3.1 +/- 2.5). No correlation existed between changes in resistance or reactance and spirometric values. Patient symptoms correlated significantly with bronchodilator response on IOS resistance (R=0.61, p=0.03). More than 50% of patients exposed to the combustion products of a faulty ice resurfacer remained symptomatic six months after exposure. Despite persistence of symptoms, conventional pulmonary function tests and radiologic evaluation did not reveal airway abnormalities. IOS showed evidence of increased airway resistance and small-airway disease, which correlated with patient symptoms. PMID:17294334

  12. Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used?

    Šlamberová, R.; Pometlová, M.; Macúchová, E.; Nohejlová, K.; Stuchlík, Aleš; Valeš, Karel

    2015-01-01

    Roč. 292, Oct 1 (2015), s. 361-369. ISSN 0166-4328 Grant ostatní: GA ČR(CZ) GA14-03708S; GA MZd(CZ) NT14484 Institutional support: RVO:67985823 Keywords : drug abuse * prenatal exposure * methamphetamine * anxiety * elevated plus-maze * social interaction text * ultrasound vocalization Subject RIV: FH - Neurology Impact factor: 3.028, year: 2014

  13. Effects of Chronic and Acute Ozone Exposure on Lipid Peroxidation and Antioxidant Capacity in Healthy Young Adults

    Chen, Connie; Arjomandi, Mehrdad; Balmes, John; Tager, Ira; Holland, Nina

    2007-01-01

    Background There is growing evidence for the role of oxidative damage in chronic diseases. Although ozone (O3) is an oxidant pollutant to which many people are exposed, few studies have examined whether O3 induces oxidative stress in humans. Objectives This study was designed to assess the effect of short-and long-term O3 exposures on biomarkers of oxidative stress in healthy individuals. Methods Biomarkers of lipid peroxidation, 8-isoprostane (8-iso-PGF), and antioxidant capacity ferric redu...

  14. Development of the drug for acute treatment of emergent exposure to radiation by nuclear power plant accident

    Described is a flow of authors' studies on the drug development in the title, aiming to save the life after the emergent exposure to peri-lethal dose. Medicals with radioprotective properties have been essentially those to be given before the exposure. Authors have studied the mechanism of bystander effect of non-exposed cells where they, localizing around the directly radiation-exposed cells, acquire the radioresistance; have found that nitrogen oxide (NO) is one of mediators for the effect; and have thought to apply the NO generating agents for the drug already clinically available, such as sodium nitroprusside (SNP), isosorbide nitrate (ISDN), nicolandil (NC), nitroglycerin (NG), and nipradilol (NP). ISDN, NC, NG and NP exhibited no in vitro-toxicity in colony formation of human fibroblast AG1522 cells up to 30 micro-M whereas SNP was toxic at the level >3 micro-M due to the formation of cyanide which could be detoxicated in vivo. Actually, the 5 agents were not toxic in vivo. When male jcl/ICR mice were irradiated with lethal dose of 7.5 Gy X-ray and the 5 agents were given to make their level 30 micro-M immediately, 1, 2 and 7 days after the exposure, 3/5 animals given SNP survived. With the half lethal dose of 6.5 Gy X-ray and 50 animals, SNP was further examined in details: survival was found to be 75-85% in mice given SNP in contrast to 30-40% in the control and the life-saving effect was suggested to be due to suppression of intestinal and marrow death with the improved feature of peripheral platelet and leukocyte. Thus SNP, a drug for angina pectoris, is found radioprotective even post exposure. (T.T.)

  15. Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

    Fish, E W; Holloway, H T; Rumple, A; Baker, L K; Wieczorek, L A; Moy, S S; Paniagua, B; Parnell, S E

    2016-09-15

    Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers. PMID:27185739

  16. Metabolism of benzene and phenol by a reconstituted purified phenobarbital induced rat liver mixed function oxidase system

    Cytochrome P-450 and the electron-donor, NADPH-cytochrome c reductase were isolated from phenobarbital induced rat liver microsomes. Both benzene and its primary metabolite phenol, were substrates for the reconstituted purified phenobarbital induced rat liver mixed function oxidase system. Benzene was metabolized to phenol and the polyhydroxylated metabolites; catechol, hydroquinone and 1,2,4 benzenetriol. Benzene elicited a Type I spectral change upon its interaction with the cytochrome P-450 while phenol's interaction with the cytochrome P-450 produced a reverse Type I spectra. The formation of phenol showed a pH optimum of 7.0 compared with 6.6-6.8 for the production of the polyhyrdoxylated metabolites. Cytochrome P-450 inhibitors, such as metyrapone and SKF 525A, diminished the production of phenol from benzene but not the production of the polyhydroxylated metabolites from phenol. The radical trapping agents, DMSO, KTBA and mannitol, decreased the recovery of polyhydroxylated metabolites, from 14C-labeled benzene and/or phenol. As KTBA and DMSO interacted with OH. There was a concomitant release of ethylene and methane, which was measured. Desferrioxamine, an iron-chelator and catalase also depressed the recovery of polyhydroxylated metabolites. In summary, benzene and phenol were both substrates for this reconstituted purified enzyme system, but they differed in binding to cytochrome P-450, pH optima and mode of hydroxylation

  17. Metabolism of benzene and phenol by a reconstituted purified phenobarbital induced rat liver mixed function oxidase system

    Griffiths, J.C.

    1986-01-01

    Cytochrome P-450 and the electron-donor, NADPH-cytochrome c reductase were isolated from phenobarbital induced rat liver microsomes. Both benzene and its primary metabolite phenol, were substrates for the reconstituted purified phenobarbital induced rat liver mixed function oxidase system. Benzene was metabolized to phenol and the polyhydroxylated metabolites; catechol, hydroquinone and 1,2,4 benzenetriol. Benzene elicited a Type I spectral change upon its interaction with the cytochrome P-450 while phenol's interaction with the cytochrome P-450 produced a reverse Type I spectra. The formation of phenol showed a pH optimum of 7.0 compared with 6.6-6.8 for the production of the polyhyrdoxylated metabolites. Cytochrome P-450 inhibitors, such as metyrapone and SKF 525A, diminished the production of phenol from benzene but not the production of the polyhydroxylated metabolites from phenol. The radical trapping agents, DMSO, KTBA and mannitol, decreased the recovery of polyhydroxylated metabolites, from /sup 14/C-labeled benzene and/or phenol. As KTBA and DMSO interacted with OH. There was a concomitant release of ethylene and methane, which was measured. Desferrioxamine, an iron-chelator and catalase also depressed the recovery of polyhydroxylated metabolites. In summary, benzene and phenol were both substrates for this reconstituted purified enzyme system, but they differed in binding to cytochrome P-450, pH optima and mode of hydroxylation.

  18. Possibilities for exposure reduction in computed tomography examination of acute chest pain; Moeglichkeiten der Dosisreduktion bei CT-Untersuchungen des akuten Thoraxschmerzes

    Becker, H.C. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2012-10-15

    Electrocardiogram-gated (ECG) computed tomography (CT) investigations can be accompanied by high amounts of radiation exposure. This is particularly true for the investigation of patients with unclear and acute chest pain. The common approach in patients with acute chest pain is standard spiral CT of the chest. The chest pain or triple-rule-out CT protocol is a relatively new ECG-gated protocol of the entire chest. This article reviews and discusses different techniques for the CT investigation of patients with acute chest pain. By applying the appropriate scan technique, the radiation exposure for an ECG-gated protocol must not necessarily be higher than a standard chest CT scan Aortic pathologies are far better depicted by ECG-gated scan protocols and depending on the heart rate coronary artery disease can also be detected at the same time. The use of ECG-triggered scans will not support the diagnostics of the pulmonary arteries. However, in unspecific chest pain an ECG-triggered scan protocol can provide information on the differential diagnosis. (orig.) [German] EKG-getriggerte CT-Untersuchungen koennen mit einer relativ hohen Strahlenexposition einhergehen. Dies gilt im besonderen Masse fuer die Untersuchung des gesamten Thorax bei Patienten mit unklarem akutem Thoraxschmerz. Bisher wurden Untersuchungen bei Patienten mit akutem Thoraxschmerz in Spiraltechnik ohne EKG-Triggerung durchgefuehrt. Das ''Chest-pain-'' oder ''Triple-rule-out''-Protokoll ist ein neues EKG-getriggertes Untersuchungsprotokoll des gesamten Thorax. Im vorliegenden Artikel werden verschiedene Techniken zur CT-Untersuchung von Patienten mit akutem Thoraxschmerz vorgestellt und besprochen. Mit der richtigen Untersuchungstechnik muss die Strahlenexposition fuer ein EKG-getriggertes Untersuchungsprotokoll nicht hoeher sein als eine Standarduntersuchung ohne EKG. Mit einem EKG-getriggerten Untersuchungsprotokoll laesst sich die Aorta in Hinblick auf

  19. In vivo metabolism of CCl4 by gerbils pretreated with chlordecone, phenobarbital, or mirex

    Gerbils are known to be much more sensitive to CCl4 lethality than rats as indicated by 48 hours LD50 (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl4 toxicity. To investigate the possible mechanism underlying gerbil's high sensitivity to CCl4 lethality, the authors studied in vivo metabolism of CCl4 in gerbils pretreated with dietary CD (10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm). The hepatic content of CCl4, the expiration of 14CCl4 and 14CCl4-derived Co2, and lipid peroxidation were measured and the results were compared with our previous data for rats. After 15-day dietary pretreatment, male gerbils (60-80 g) received 14CCl4 (80 ml/kg; sp act: 0.04 mCi/mmol) ip in corn oil and the expired air was collected for 6 hours. More than 80% of the dose administered was expired as parent compound in 6 hours regardless of pretreatments. Expiration of 14CCl4 derived 14CO2 in control gerbils was 3.5-fold more than in control rats and was increased significantly in pretreated gerbils (M>PB>CD). PB and M pretreatments resulted in significant increase of 14C label bound to non-lipid fraction of hepatic content as compared with CD or control gerbils. The radiolabel present in hepatic content of control gerbils was 5-fold higher than that of control rats. In vivo liquid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and there were no significant differences among control and pretreated gerbils. These data indicate that the more extensive metabolism of CCl4 in gerbils may partially explain their high sensitivity to CCl4 toxicity. However, the significantly enhanced metabolism of CCl4 found in CD, PB, or M pretreated gerbils did not lead to amplification of CCl4 hepatotoxic and lethal effects

  20. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats. The 2nd report

    We examined the effects of acute exposure of heavy ion on the properties of motoneurons and their innervating muscle fibers. A 40 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in five 8-week-old male rats. Five male rats served as controls. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were analyzed. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no changes in the number of motoneurons between the control and heavy-ion-exposed rats. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in motoneurons of the heavy-ion-exposed rats. There were no changes in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the muscles between the control and heavy-ion-exposed rats. It is concluded that a 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there were no influences on the properties of muscle fibers which they innervate. (author)

  1. Acute exposure to UV-B sensitizes cucumber, tomato, and Arabidopsis plants to photooxidative stress by inhibiting thermal energy dissipation and antioxidant defense

    The purpose of this study was to characterize a change in Non-photochemical quenching (NPQ) upon exposure to ultraviolet-B (UV-B), the xanthophyll cycle-dependent and -independent NPQs were compared in Cucumis sativus, Lycopersicum esculentum, and Arabidopsis thaliana leaves. The xanthophyll cycle-dependent NPQ was dramatically but reversibly suppressed by UV-B radiation. This suppression was correlated more strongly with a marked decrease in photosynthetic electron transport rather than changes in xanthophyll cycle enzymes such as violaxanthin de-epoxidase and zeaxanthin epoxidase. Accordingly, the UV-B-induced suppression of NPQ cannot be attributed to changes in expressions of violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP). However, suppression of the xanthophyll cycle-dependent NPQ could only account for the 77 K fluorescence emission spectra of thylakoid membranes and the increased level of 1O2 production, but not for the decreased levels of hydroxyl radical O2- production and H2O2 scavenging. These results suggest that a gradual reduction of H2O2 scavenging activity as well as a transient and reversible suppression of thermal energy dissipation may contribute differentially to increased photooxidative damages in cucumber, tomato, and Arabidopsis plants after acute exposure to UV-B radiation. (author)

  2. Effect of sub-acute exposure to TiO2 nanoparticles on oxidative stress and histopathological changes in Juvenile Carp (Cyprinus carpio)

    HAO Linhua; WANG Zhenyu; XING Baoshan

    2009-01-01

    Increasing application of nanotechnology highlights the need to clarify and understand nanotoxicity. Mammalian and in vitro studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2 NPs), but there are limited data on ecotoxicity to aquatic organisms. In this work, the objective was to assess the sub-acute toxicity of TiO2 NPs to carp (Cyprinus carpio). Superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities and lipid peroxidation (LPO) levels in liver, gill and brain tissues of carps varied with concentration of TiO2 NPs suspensions and exposure time (up to 8 d). As a result, 100 and 200 mg/L TiO2 NPs caused statistically significant decrease in SOD, CAT and POD activities and significant increase in LPO levels in tissues (P < 0.05), suggesting that the fish exposed to these two concentrations of TiO2 NPs suffered from the oxidative stress. The extent of depletion of antioxidant enzymes activities and the elevation of LPO in the liver was the greatest, indicating that the liver might be the most susceptible organ to TiO2 NPs exposure. In addition, carps had gill pathologies including edema and thickening of gill lamellae as well as gill filaments, and liver pathologies including necrotic and apoptosis hepatocytes after exposed to 100 and 200 mg/L TiO2 NPs for 20 d. These results indicate a potential risk from TiO2 NPs released into the aqueous environment.

  3. Does highly symptomatic class membership in the acute phase predict highly symptomatic classification in victims 6 months after traumatic exposure?

    Hansen, Maj; Hyland, Philip; Armour, Cherie

    2016-05-01

    Recently studies have indicated the existence of both posttraumatic stress disorder (PTSD) and acute stress disorder (ASD) subtypes but no studies have investigated their mutual association. Although ASD may not be a precursor of PTSD per se, there are potential benefits associated with early identification of victims at risk of developing PTSD subtypes. The present study investigates ASD and PTSD subtypes using latent class analysis (LCA) following bank robbery (N=371). Moreover, we assessed if highly symptomatic ASD and selected risk factors increased the probability of highly symptomatic PTSD. The results of LCA revealed a three class solution for ASD and a two class solution for PTSD. Negative cognitions about self (OR=1.08), neuroticism (OR=1.09) and membership of the 'High symptomatic ASD' class (OR=20.41) significantly increased the probability of 'symptomatic PTSD' class membership. Future studies are needed to investigate the existence of ASD and PTSD subtypes and their mutual relationship. PMID:27101400

  4. Mitochondrial damage: An important mechanism of ambient PM{sub 2.5} exposure-induced acute heart injury in rats

    Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China); Cai, Zongwei, E-mail: zwcai@hkbu.edu.hk [State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR (China); Dong, Chuan, E-mail: dc@sxu.edu.cn [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China)

    2015-04-28

    Highlights: • PM{sub 2.5} induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM{sub 2.5}) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM{sub 2.5}-induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM{sub 2.5} with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM{sub 2.5} exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM{sub 2.5} exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na{sup +}K{sup +}-ATPase and Ca{sup 2+}-ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM{sub 2.5}-induced heart injury, and may have relations with cardiovascular disease.

  5. Histological changes and antioxidant enzyme activity in signal crayfish (Pacifastacus leniusculus) associated with sub-acute peracetic acid exposure.

    Chupani, Latifeh; Zuskova, Eliska; Stara, Alzbeta; Velisek, Josef; Kouba, Antonin

    2016-01-01

    Peracetic acid (PAA) is a powerful disinfectant recently adopted as a therapeutic agent in aquaculture. A concentration of 10 mg L(-1) PAA effectively suppresses zoospores of Aphanomyces astaci, the agent of crayfish plague. To aid in establishing safe therapeutic guideline, the effects of PAA on treated crayfish were investigated through assessment of histological changes and oxidative damage. Adult female signal crayfish Pacifastacus leniusculus (n = 135) were exposed to 2 mg L(-1) and 10 mg L(-1) of PAA for 7 days followed by a 7 day recovery period in clean water. Superoxide dismutase activity was significantly lower in gill and hepatopancreas after three days exposure to 10 mg L(1) PAA than in the group treated with 2 mg L(-1) PAA and a control in only clean water. Catalase activity in gill and hepatopancreas remained unaffected by both exposures. Glutathione reductase was significantly decreased in gill of 10 mg L(-1) PAA treated crayfish and increased in group exposed to 2 mg L(-1) compared to control after 7 days exposure. Antioxidant enzyme activity in exposed groups returned to control values after recovery period. Gill, hepatopancreas, and antennal gland showed slight damage in crayfish treated with 2 mg L(-1) of PAA compared to the control group. The extent and frequency of histological alterations were more pronounced in animals exposed to 10 mg L(-1). The gill was the most affected organ, infiltrated by granular hemocytes and displaying malformations of lamella tips and disorganization of epithelial cells. After a 7 day recovery period, the infiltrating cells in affected tissues of the exposed crayfish began to return to normal levels. Results suggested that the given concentrations could be applied to signal crayfish against crayfish plague agent in aquaculture; however, further studies are required for safe use. PMID:26611721

  6. Acute embryotoxic effects but no long-term reproductive effects of in ovo methylmercury exposure in zebra finches (Taeniopygia guttata).

    Yu, Maria S; Eng, Margaret L; Williams, Tony D; Basu, Niladri; Elliott, John E

    2016-06-01

    Mercury bioaccumulates in terrestrial ecosystems as methylmercury (MeHg), yet little is known about its effects on terrestrial organisms, including songbirds. The authors used a model songbird species, the zebra finch (Taeniopygia guttata), to assess short-term embryotoxic effects of in ovo MeHg exposure on hatching success and posthatching growth and nestling survival, as well as longer-term effects on mating behavior and reproduction. Egg treatment groups included a low-MeHg dose of 0.2 μg Hg g(-1) egg (n = 36), a high-MeHg dose of 3.2 μg Hg g(-1) egg (n = 49), and a control (n = 34). Doses were dissolved in nanopure filtered water and injected into the albumen on the day eggs showed signs of viability (3 d incubation). In ovo exposure to MeHg significantly reduced hatching success (53% in the high-MeHg dose group vs 94% in vehicle controls). Among hatched chicks, however, no effects of MeHg on growth, hematological variables, or nestling survival were detected. While the in ovo injection method resulted in a dose-dependent pattern of MeHg concentrations in blood of surviving chicks at 15 d and 30 d posthatching, there was evidence of rapid excretion of MeHg with nestling age during that growth period. At reproductive maturity (90 d of age), no long-term effects of in ovo exposure to MeHg on female mating behavior, reproductive effort (egg or clutch size), or growth and survivorship of offspring were observed. Environ Toxicol Chem 2016;35:1534-1540. © 2015 SETAC. PMID:26573953

  7. Acute exposure to mobile phone and assessment of internal cerebral circulation in young healthy subjects : a transcranial Doppler study

    Ghosn, Rania; Thuroczy, Gyorgy; Loos, Nathalie; Brenet-Dufour, Valérie; Liabeuf, Sophie; De Seze, René; Selmaoui, Brahim

    2012-01-01

    The rapid worldwide increase in the use of mobile phones raises questions about the possible adverse effects of RF fields emitted by these devices. The temporal lobe of brain is closest to the mobile phone. This may lead to relatively high energy deposition in these parts of human head during the use of mobile phone. The cerebral circulation may be potentially affected due to the exposure to RF emitted by mobile phone. Therefore the studies on cerebral blood flow are essential in order to eva...

  8. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats

    We investigate effects of localized exposure of heavy ion to the lumbar 4th to 6th segments of the rat spinal cord on the properties of motoneurons and the innervated muscle fibers without surgical treatments. Twenty 7-week-old male Wistar rats were exposed to 5 mm spread-out Bragg peak (SOBP) carbon beam (290 MeV, linear energy transfer (LET)=130 keV/μm): Two doses (15 Gy or 20 Gy) were applied to each group of rats (n=5) in two different depths; one group was exposed only for ventral horn of the spinal cord while other for whole spinal cord. Five rats served as controls. The rats were exposed to carbon irons on October 26, 2002. We will sacrifice the rats soon after they show an abnormal behavior including posture and walking. Cell body size and oxidative enzyme activity of spinal motoneurons of the control and heavy-ion-exposed rats will be analyzed. In addition, cell size, oxidative enzyme activity, and expressions of myosin heavy chain isoforms of the gastrocnemius, soleus, plantaris, extensor digitorum longus, and tibialis anterior muscle fibers will be also determined. This study is performed to test our hypothesis that atrophy and a decrease in cross-sectional area of motoneurons and muscle fibers which they innervate, as well as a decrease in oxidative activity of motoneurons and muscle fibers, will be induced due to exposure to heavy ion. (author)

  9. Acute Onset of Vancomycin Anaphylaxis With Disseminated Intravascular Coagulation in an Orthopedic Patient Despite Prior Repeated Exposure.

    Adams, Brock; Roboubi, Babak; Henshaw, Robert

    2015-12-01

    Vancomycin is a glycopeptide antibiotic that exhibits bactericidal activity against gram-positive cocci. It is commonly recommended for surgical prophylaxis in cases of suspected bacterial resistance or penicillin allergy. There are 2 main types of hypersensitivity reactions associated with vancomycin. Red man syndrome is an anaphylactoid reaction caused by direct release of histamine. The second is an anaphylactic reaction, which is an immunoglobulin E-mediated response. We present the case of a 55-year-old woman with a history of metastatic giant cell tumor of the right proximal tibia. She had undergone multiple surgeries for this and other nonorthopedic conditions. The patient received vancomycin for the majority of these procedures and extended courses of vancomycin on 2 separate occasions. In the present case, the patient was taken to the operating room for a prosthetic infection, and vancomycin was given after cultures were taken. The patient immediately developed signs consistent with anaphylaxis and disseminated intravascular coagulation. This was treated acutely with hemodynamic resuscitation, replacement of blood components, steroids, and repeated boluses of epinephrine. She recovered and was taken back to the operating room during that same admission without incident. The patient has since been treated with systemic daptomycin and a tobramycin cement spacer without further incident. PMID:26665256

  10. Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function

    Ghada Elmhiri

    2014-01-01

    Full Text Available Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG, a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 μmol/l with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine. Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM, MG induced a significant (P<0.05 increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM, MG significantly inhibited insulin secretion (P<0.05. In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (P<0.05, while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (P<0.05. Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells.

  11. Mucin Reactivity after Acute Exposure to Mercury and Zinc Chloride in Neurocytes of Freshwater Snail Bellamya bengalensis: A Histochemical Study

    Sunil Londhe

    2014-01-01

    Full Text Available Central nervous system (CNS of gastropods is extensively studied for its pathology and immunocytology; there is scanty information on histochemical alterations in neuronal cells due to heavy metal. This study was designed to investigate histochemical alterations in cerebral neurons of freshwater snail Bellamya bengalensis after intoxication with mercuric chloride (HgCl2 and zinc chloride (ZnCl2. As per chemical components cerebral ganglia of Bellamya bengalensis showed three different zones, namely, periganglionic connective tissue sheath, interperikaryonal space, and neuropil. After intoxication, increased acidic content in extracellular matrix (ECM of neuronal cells was found. These alterations were directly proportional to time of exposure period. From results, HgCl2 proved its highly toxic nature over chemical composition of cerebral neuronal cells of freshwater snail Bellamya bengalensis compared to ZnCl2 intoxication.

  12. Acute exposure to high-peak-power pulsed microwaves affecting the histamine H3 receptor expression in rat hippocampus

    In the Morris Water test, high-peak-power pulsed microwave (MW)-exposed rats displayed some learning and memory behavior dysfunctions, and their escape time and swimming distance to the submerged platform were longer than those of the sham-exposed rats. to understand the molecular mechanism involved, the reverse transcription-polymerase chain reation (RT-PCR) and the Western-blotting technique were used for investigating the mRNA and protein expression patterns of the histamine H3 receptor (H3R) in rat hippocampus. High-peak-power pulsed microwave-exposure did not remarkably lead to the change in expression of H3R mRNA in rat hippocampi; however, it promoted the up-regulatory expression of the H3R protein, which was possibly triggered through the mitogen-activated protein kinase (MAPK) pathways. Therefore, further investigation of the molecular mechanism of the MW effects on the learning and memory behaviors is required. (authors)

  13. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABAAR) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABAAR positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABAAR antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase inhibitor alters TETS

  14. Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

    Osborne, M; Haltalli, M; Currie, R; Wright, J; Gooderham, N J

    2016-07-01

    Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat. PMID:27427493

  15. Skeletal muscle cells possess a 'memory' of acute early life TNF-α exposure: role of epigenetic adaptation.

    Sharples, Adam P; Polydorou, Ioanna; Hughes, David C; Owens, Daniel J; Hughes, Thomas M; Stewart, Claire E

    2016-06-01

    received an early plus late lifespan dose of TNF-α exhibited reduced morphological (myotube number) and biochemical (creatine kinase activity) differentiation vs. control cells that underwent the same number of proliferative divisions but only a later life encounter with TNF-α. This suggested that muscle cells had a morphological memory of the acute early lifespan TNF-α encounter. Importantly, methylation of myoD CpG islands were increased in the early TNF-α cells, 30 population doublings later, suggesting that even after an acute encounter with TNF-α, the cells have the capability of retaining elevated methylation for at least 30 cellular divisions. Despite these fascinating findings, there were no further increases in myoD methylation or changes in its gene expression when these cells were exposed to a later TNF-α dose suggesting that this was not directly responsible for the decline in differentiation observed. In conclusion, data suggest that elevated myoD methylation is retained throughout muscle cells proliferative lifespan as result of early life TNF-α treatment and has implications for the epigenetic control of muscle loss. PMID:26349924

  16. Acute exposure to high-peak-power pulsed microwaves affecting the histamine H3 receptor expression in rat hippocampus

    2006-01-01

    In the Morris Water Maze test, high-peak-power pulsed microwave (MW)-exposed rats displayed some learning and memory behavior dysfunctions, and their escape time and swimming distance to the submerged platform were longer than those of the sham-exposed rats. To understand the molecular mechanism involved, the reverse transcription-polymerase chain reaction (RT-PCR) and the Western-blotting technique were used for investigating the mRNA and protein expression patterns of the histamine H3 receptor (H3R) in rat hippocampus. High-peak-power pulsed microwave-exposure did not remarkably lead to the change in expression of H3R mRNA in rat hippocampi;however, it promoted the up-regulatory expression of the H3R protein, which was possibly triggered through the mitogen-activated protein kinase (MAPK) pathways. Therefore, further investigation of the molecular mechanism of the MW effects on the learning and memory behaviors is required.

  17. Effect of acute exposure to cadmium on the expression of heat-shock and hormone-nuclear receptor genes in the aquatic midge Chironomus riparius

    Planello, R.; Martinez-Guitarte, J.L. [Grupo de Biologia y Toxicologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, UNED, Senda del Rey 9, 28040 Madrid (Spain); Morcillo, G., E-mail: gmorcillo@ccia.uned.es [Grupo de Biologia y Toxicologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, UNED, Senda del Rey 9, 28040 Madrid (Spain)

    2010-03-01

    Cadmium is a widespread and highly toxic pollutant of particular ecotoxicological relevance for aquatic ecosystems where it accumulates. To identify biomarkers for ecotoxicity monitoring, the effect of cadmium on the expression of different genes related to the stress response as well as to the ecdysone hormone-signalling pathway was studied in the aquatic larvae of Chironomus riparius (Diptera, Chironomidae), a standard test organism in aquatic toxicology testing. Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to evaluate the effects of acute and short-term cadmium exposures (10 mM CdCl{sub 2}, 12 h and 24 h) on the expression of hsp70, hsc70, hsp90 and hsp40 genes, as well as on that of the ecdysone hormonal-receptor genes (EcR and usp). A significant 3-fold increase in the level of hsp70 gene transcripts was induced by the treatment, whereas neither the other stress genes tested (hsp90 and hsp40) nor the constitutive form of hsp70, hsc70, was affected in the larvae exposed to cadmium. These results show that hsp70 is differentially activated to other environmentally regulated heat-shock genes, and constitutes a biomarker of exposure to this toxic metal. In addition, we also found that cadmium is able to alter the expression of the ecdysone receptor gene (EcR), whose mRNA level is significantly increased whereas usp levels remained unaltered. This finding, evidenced for the first time in invertebrates, supports the view that cadmium has the ability to mimic the effect of the hormone by the activation of the ecdysone nuclear receptor, which may partly explain the endocrine disruption capability that has been previously suggested for this toxic metal. Our research adds to the growing evidence implicating heavy metals, and cadmium in particular, as potential endocrine disruptive agents and may have significant implications for ecological risk assessment of endocrine-disrupting compounds in invertebrates.

  18. Effect of acute exposure to cadmium on the expression of heat-shock and hormone-nuclear receptor genes in the aquatic midge Chironomus riparius

    Cadmium is a widespread and highly toxic pollutant of particular ecotoxicological relevance for aquatic ecosystems where it accumulates. To identify biomarkers for ecotoxicity monitoring, the effect of cadmium on the expression of different genes related to the stress response as well as to the ecdysone hormone-signalling pathway was studied in the aquatic larvae of Chironomus riparius (Diptera, Chironomidae), a standard test organism in aquatic toxicology testing. Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to evaluate the effects of acute and short-term cadmium exposures (10 mM CdCl2, 12 h and 24 h) on the expression of hsp70, hsc70, hsp90 and hsp40 genes, as well as on that of the ecdysone hormonal-receptor genes (EcR and usp). A significant 3-fold increase in the level of hsp70 gene transcripts was induced by the treatment, whereas neither the other stress genes tested (hsp90 and hsp40) nor the constitutive form of hsp70, hsc70, was affected in the larvae exposed to cadmium. These results show that hsp70 is differentially activated to other environmentally regulated heat-shock genes, and constitutes a biomarker of exposure to this toxic metal. In addition, we also found that cadmium is able to alter the expression of the ecdysone receptor gene (EcR), whose mRNA level is significantly increased whereas usp levels remained unaltered. This finding, evidenced for the first time in invertebrates, supports the view that cadmium has the ability to mimic the effect of the hormone by the activation of the ecdysone nuclear receptor, which may partly explain the endocrine disruption capability that has been previously suggested for this toxic metal. Our research adds to the growing evidence implicating heavy metals, and cadmium in particular, as potential endocrine disruptive agents and may have significant implications for ecological risk assessment of endocrine-disrupting compounds in invertebrates.

  19. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats (the 3rd report)

    The effects of acute exposure of heavy ion on the properties of spinal motoneurons and their innervating muscle fibers were investigated. A 15, 20, 40, 50, or 70 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in 8-week-old male rats. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of spinal motoneurons innervating the soleus and plantaris muscles were analyzed by a computer-assisted image processing system. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no differences in the number of spinal motoneurons innervating the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in spinal motoneurons of the heavy-ion-exposed rats at the dose levels of 40, 50, and 70 Gy. There were no differences in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. It is concluded that more than 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there are no influences on the properties of muscle fibers which they innervate. (author)

  20. Chemometrics enhanced HPLC-DAD performance for rapid quantification of carbamazepine and phenobarbital in human serum samples.

    Vosough, Maryam; Ghafghazi, Shiva; Sabetkasaei, Masoumeh

    2014-02-01

    This paper describes development and validation of a simple and efficient bioanalytical procedure for simultaneous determination of phenobarbital and carbamazepine in human serum samples using high performance liquid chromatography with photodiode-array detection (HPLC-DAD) regarding a fast elution methodology in less than 5 min. Briefly, this method consisted of a simple deproteinization step of serum samples followed by HPLC analysis on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH=7.5) buffer solution (45:55). Due to the presence of serum endogenous components as non-calibrated components in the sample, second-order calibration based on multivariate curve resolution-alternating least squares (MCR-ALS), has been applied on a set of absorbance matrices collected as a function of retention time and wavelengths. Acceptable resolution and quantification results were achieved in the presence of matrix interferences and the second-order advantage was fully exploited. The average recoveries for carbamazepine and phenobarbital were 89.7% and 86.1% and relative standard deviation values were lower than 9%. Additionally, computed elliptical joint confidence region (EJCR) confirmed the accuracy of the proposed method and indicated the absence of both constant and proportional errors in the predicted concentrations. The developed method enabled the determination of the analytes in different serum samples in the presence of overlapped profiles, while keeping experimental time and extraction steps at minimum. Finally, the serum concentration levels of carbamazepine in three time intervals were reported for morphine-dependents who had received carbamazepine for treating their neuropathic pain. PMID:24401380

  1. The effect of acute stress exposure on ischemia and reperfusion injury in rat heart: role of oxytocin.

    Moghimian, Maryam; Faghihi, Mahdieh; Karimian, Seyed Morteza; Imani, Alireza

    2012-07-01

    Previous studies showed the protective effects of oxytocin (OT) on myocardial injury in ischemic and reperfused rat heart. Moreover, exposure to various stressors not only evokes sudden cardiovascular effects but also triggers the release of OT in the rat. The present study was aimed to evaluate the possible cardioprotective effects of endogenous OT released in response to stress (St), and effects of administration of exogenous OT on the ischemic-reperfused isolated heart of rats previously exposed to St. Wistar rats were divided into six groups: ischemia/reperfusion (IR); St: rats exposed to swim St for 10 min before anesthesia; St+atosiban (ATO): an OT receptor antagonist, was administered (1.5 mg/kg i.p.) prior to St; St+OT: OT was administered (0.03 mg/kg i.p.) prior to St; OT: OT was administrated prior to anesthesia; ATO was given prior to anesthesia. Isolated hearts were perfused with Krebs buffer solution by the Langendorff method and subjected to 30 min of regional ischemia followed by 60 min of reperfusion. The infarct size (IS) and creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in coronary effluent were measured. Hemodynamic parameters were recorded throughout the experiment. The plasma concentrations of OT and corticosterone were significantly increased by St. Unexpectedly St decreased IR injury compared with the IR alone group. OT administration significantly inhibited myocardial injury, and administration of ATO with St abolished recovery of the rate pressure product, and increased IS and levels of CK-MB and LDH. These findings indicate that activation of cardiac OT receptors by OT released in response to St may participate in cardioprotection and inhibition of myocardial IR injury. PMID:22044052

  2. The uptake of ZnO and CuO nanoparticles in the water-flea Daphnia magna under acute exposure scenarios.

    Adam, Nathalie; Leroux, Frédéric; Knapen, Dries; Bals, Sara; Blust, Ronny

    2014-11-01

    In this study the uptake of ZnO and CuO nanoparticles by Daphnia magna was tested. Daphnids were exposed during 48 h to acute concentrations of the nanoparticles and corresponding metal salts. The Daphnia zinc and copper concentration was measured and the nanoparticles were localized using electron microscopy. The aggregation and dissolution in the medium was characterized. A fast dissolution of ZnO in the medium was observed, while most CuO formed large aggregates and only a small fraction dissolved. The Daphnia zinc concentration was comparable for the nanoparticles and salts. Contrarily, a much higher Daphnia copper concentration was observed in the CuO exposure, compared to the copper salt. CuO nanoparticles adsorbed onto the carapace and occurred in the gut but did not internalize in the tissues. The combined dissolution and uptake results indicate that the toxicity of both nanoparticle types was caused by metal ions dissolved from the particles in the medium. PMID:25108488

  3. Effects of Mikania glomerata Spreng. and Mikania laevigata Schultz Bip. ex Baker (Asteraceae) extracts on pulmonary inflammation and oxidative stress caused by acute coal dust exposure

    Freitas, T.P.; Silveira, P.C.; Rocha, L.G.; Rezin, G.T.; Rocha, J.; Citadini-Zanette, V.; Romao, P.T.; Dal-Pizzol, F.; Pinho, R.A.; Andrade, V.M.; Streck, E.L. [University Extremo Catarinense, Criciuma (Brazil)

    2008-12-15

    Several studies have reported biological effects of Mikania glomerata and Mikania laevigata, used in Brazilian folk medicine for respiratory diseases. Pneumoconiosis is characterized by pulmonary inflammation caused by coal dust exposure. In this work, we evaluated the effect of pretreatment with M. glomerata and M. laevigata extracts (MGE and MLE, respectively) (100 mg/kg, s.c.) on inflammatory and oxidative stress parameters in lung of rats subjected to a single coal dust intratracheal instillation. Rats were pretreated for 2 weeks with saline solution, MGE, or MLE. On day 15, the animals were anesthetized, and gross mineral coal dust or saline solutions were administered directly in the lung by intratracheal instillation. Fifteen days after coal dust instillation, the animals were killed. Bronchoalveolar lavage (BAL) was obtained; total cell count and lactate dehydrogenase (LDH) activity were determined. In the lung, myeloperoxidase activity, thiobarbituric acid-reactive substances (TBARS) level, and protein carbonyl and sulfhydryl contents were evaluated. In BAL of treated animals, we verified an increased total cell count and LDH activity. MGE and MLE prevented the increase in cell count, but only MLE prevented the increase in LDH. Myeloperoxidase and TBARS levels were not affected, protein carbonylation was increased, and the protein thiol levels were decreased by acute coal dust intratracheal administration. The findings also suggest that both extracts present an important protective effect on the oxidation of thiol groups. Moreover, pretreatment with MGE and MLE also diminished lung inflammatory infiltration induced by coal dust, as assessed by histopathologic analyses.

  4. 2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

    2014-01-01

    The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

  5. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    Vito, Stephen T., E-mail: stvito@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Austin, Adam T., E-mail: aaustin@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Banks, Christopher N., E-mail: Christopher.Banks@oehha.ca.gov [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Inceoglu, Bora, E-mail: abinceoglu@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Bruun, Donald A., E-mail: dabruun@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Zolkowska, Dorota, E-mail: dzolkowska@gmail.com [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Tancredi, Daniel J., E-mail: djtancredi@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Rogawski, Michael A., E-mail: rogawski@ucdavis.edu [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States)

    2014-12-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase

  6. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both ...

  7. An enriched stable-isotope approach to determine the gill-zinc binding properties of juvenile rainbow trout (Oncorhynchus mykiss) during acute zinc exposures in hard and soft waters

    Todd, A.S.; Brinkman, S.; Wolf, R.E.; Lamothe, P.J.; Smith, K.S.; Ranville, J.F.

    2009-01-01

    The objective of the present study was to employ an enriched stable-isotope approach to characterize Zn uptake in the gills of rainbow trout (Oncorhynchus mykiss) during acute Zn exposures in hard water (???140 mg/L as CaCO 3) and soft water (???30 mg/L as CaCO3). Juvenile rainbow trout were acclimated to the test hardnesses and then exposed for up to 72 h in static exposures to a range of Zn concentrations in hard water (0-1,000 ??g/L) and soft water (0-250 ??g/L). To facilitate detection of new gill Zn from endogenous gill Zn, the exposure media was significantly enriched with 67Zn stable isotope (89.60% vs 4.1% natural abundance). Additionally, acute Zn toxicity thresholds (96-h median lethal concentration [LC50]) were determined experimentally through traditional, flow-through toxicity tests in hard water (580 ??g/L) and soft water (110 ??g/L). Following short-term (???3 h) exposures, significant differences in gill accumulation of Zn between hard and soft water treatments were observed at the three common concentrations (75, 150, and 250 ??g/L), with soft water gills accumulating more Zn than hard water gills. Short-term gill Zn accumulation at hard and soft water LC50s (45-min median lethal accumulation) was similar (0.27 and 0.20 ??g/g wet wt, respectively). Finally, comparison of experimental gill Zn accumulation, with accumulation predicted by the biotic ligand model, demonstrated that model output reflected short-term (trout gills. Our results indicate that measurable differences exist in short-term gill Zn accumulation following acclimation and exposure in different water hardnesses and that short-term Zn accumulation appears to be predictive of Zn acute toxicity thresholds (96-h LC50s). ?? 2009 SETAC.

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

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

    2014-01-01

    The acute toxicity of cadmium, copper, and zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) were determined for 7 developmental life stages in flow-through water-only exposures. Metal toxicity varied by species and by life stage. Rainbow trout were more sensitive to cadmium than white sturgeon across all life stages, with median effect concentrations (hardness-normalized EC50s) ranging from 1.47 µg Cd/L to 2.62 µg Cd/L with sensitivity remaining consistent during later stages of development. Rainbow trout at 46 d posthatch (dph) ranked at the 2nd percentile of a compiled database for Cd species sensitivity distribution with an EC50 of 1.46 µg Cd/L and 72 dph sturgeon ranked at the 19th percentile (EC50 of 3.02 µg Cd/L). White sturgeon were more sensitive to copper than rainbow trout in 5 of the 7 life stages tested with biotic ligand model (BLM)-normalized EC50s ranging from 1.51 µg Cu/L to 21.9 µg Cu/L. In turn, rainbow trout at 74 dph and 95 dph were more sensitive to copper than white sturgeon at 72 dph and 89 dph, indicating sturgeon become more tolerant in older life stages, whereas older trout become more sensitive to copper exposure. White sturgeon at 2 dph, 16 dph, and 30 dph ranked in the lower percentiles of a compiled database for copper species sensitivity distribution, ranking at the 3rd (2 dph), 5th (16 dph), and 10th (30 dph) percentiles. White sturgeon were more sensitive to zinc than rainbow trout for 1 out of 7 life stages tested (2 dph with an biotic ligand model–normalized EC50 of 209 µg Zn/L) and ranked in the 1st percentile of a compiled database for zinc species sensitivity distribution.

  9. Disturbance of Bcl-2, Bax, Caspase-3, Ki-67 and C-myc expression in acute and subchronic exposure to benzo(a)pyrene in cervix.

    Gao, Meili; Li, Yongfei; Ji, Xiaoying; Xue, Xiaochang; Chen, Lan; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Shah, Walayat; Hou, Zhanwu; Kong, Yu

    2016-03-01

    Epidemiological studies have demonstrated that cigarette smoking is an important cofactor or an independent risk factor for the development of cervical cancer. Benzo(a)pyrene (BaP) is one of the most potent tobacco smoke carcinogens in tobacco smoke. BaP induced DNA damage and over expression in p53 cervical tissue of mice as demonstrated in our previous study. Here we present the findings of exposure to BaP on the expression of Bcl-2, C-myc, Ki-67, Caspase-3 and Bax genes in mouse cervix. Acute intraperitoneal administration of BaP (12.5, 25, 50, 100mg/kg body weight) to ICR female mice induced a significant increase in Bcl-2, C-myc, Ki-67 mRNA and protein level till 72h except in Bcl-2 at 24h with 12.5, 25, 50mg/kg as well as at 48h with 12.5mg/kg body weight post treatment. A significant increase was also seen in Caspase-3 and Bax mRNA and protein level with peak level at 24h and gradual decrease till 72h, however, the expression of caspase-3 increased while that of Bax decreased with increasing dose of Bap after 24h. In sub chronic intraperitoneal and oral gavage administration of BaP (2.5, 5, 10mg/kg body weight), similar significant increase was observed for all the examined genes as compared to the control and vehicle groups, however the expression of Bax decreased in a dose dependent manner. The findings of this study will help in further understanding the molecular mechanism of BaP induced carcinogenesis of cervical cancer. PMID:26709117

  10. Phenobarbital and Phototherapy Combination Enhances Decline of Total Serum Bilirubin and May Decrease the Need for Blood Exchange Transfusion in Newborns with Isoimmune Hemolytic Disease

    Mahmoud A.F. Kaabneh; Ghassan S. A. Salama; Ayoub G.A Shakkoury; Ibrahim M. H. Al-abdallah; Afrah Alshamari; Ruba A.A. Halaseh

    2015-01-01

    OBJECTIVE The objective of this study was to evaluate the effect of phenobarbital and phototherapy combination on the total serum bilirubin of the newborn infants with isoimmune hemolytic disease (IHD) and its impact on blood exchange transfusion rates. PATIENTS AND METHOD This single-blinded, prospective, randomized, controlled trial was conducted between March 2013 and December 2014 at the pediatric ward of two Military Hospitals in Jordan. A total of 200 full-term neonates with IHD were di...

  11. 苯巴比妥口服溶液的制备及质量控制%Preparation and Quality Control of Phenobarbital Oral Solution

    刘学红; 张庆莉; 孙晶

    2011-01-01

    OBJECTIVE: To prepare Phenobarbital oral solution and establish quality control method of it. METHODS: Pheno-barbital oral solution was prepared using PEG400, 1,2-propylene glycol and simple syrup. Chemical identification and potentiomet-ric titration were used for qualitative identification and quantitative determination. RESULTS: The prepared Phenobarbital oral solution met the requirements of Chinese Pharmacopeia (2010 edition) on the aspects of character, identification, related substances, determination, and other indicators. CONCLUSION: The preparation technique of Phenobarbital oral solution is reasonable. The established methods of identification and determination are convenient, accurate and reliable.%目的:制备苯巴比妥口服溶液并建立其质量控制方法.方法:以聚乙二醇400、1,2-丙二醇及单糖浆等为辅料制备苯巴比妥口服溶液;采用化学鉴别法和电位滴定法等进行定性鉴别和定量测定.结果:所制备的苯巴比妥口服溶液性状、鉴别、有关物质、含量测定等各项指标均符合2010年版《中国药典》二部附录口服溶液剂的规定.结论:该制剂的制备工艺合理,所建定性、定量方法简便、准确、可靠.

  12. Influence of coadministered antiepileptic drugs on serum phenobarbital concentrations in epileptic patients: quantitative analysis based on a suitable transforming factor.

    Fukuoka, Noriyasu; Tsukamoto, Toyohisa; Uno, Junji; Kimura, Michio; Morita, Shushi

    2004-12-01

    This study investigated most suitable transforming factor related to the daily Phenobarbital dose (D) providing a steady-state serum concentration (Ct) and analyzed the influences of concomitant antiepileptic drugs on Ct quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 326 epileptic patients treated with multiple oral administrations of phenobarbital (PB) as a powder, were used for the analysis. A total of 156 patients were administered PB alone, and 92, 57, and 21 patients were coadministered one, two, and three different antiepileptic drugs, respectively. Valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), zonisamide (ZNS), clonazepam, and ethosuximide were coadministered with PB. For administration of PB alone, four types of transforming factor corresponding to clearance, i.e., total body weight, total body water volume, body surface area and extracellular water volume (VECW) were proposed. With VECW as a transforming factor, the level/dose (L/D) ratio (:Ct/(D/VECW)) was independent of the patient's age and gender. Ct was dependent on only one variable regarding D/VECW and expressed as Ct=0.989 x (D/VECW). The coadministration of one drug caused a difference in the gradient of the regression line of PB alone, and the influence of each drug was detected by dividing each mean L/D ratio of PB plus one other drug by that of PB alone. VPA, CBZ, and PHT significantly increased (pratio to 1.48, 1.35, and 1.23 of the value for PB alone, respectively. With coadministration of multiple drugs, the L/D ratio rose significantly (pratio Ri, representing the influence of each antiepileptic drug on the L/D ratio of PB alone. A model based on the assumption that each coadministered drug competitively inhibited PB-metabolizing enzyme, was adopted. The analysis clarified that VPA, CBZ, and PHT significantly increased (pratio of PB to 1.466, 1.177, and 1.186, respectively. In the case of the addition or discontinuance of concomitant

  13. Delayed myelosuppression with acute exposure to hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and environmental degradation product hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) in rats

    Jaligama, Sridhar; Kale, Vijay M.; Wilbanks, Mitchell S. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209 (United States); Perkins, Edward J. [US Army Engineer Research and Development Center, Vicksburg, MS 39180 (United States); Meyer, Sharon A., E-mail: meyer@ulm.edu [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209 (United States)

    2013-02-01

    Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a widely used munitions compound, and hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), its N-nitroso product of anaerobic microbial nitroreduction, are contaminants of military sites. Previous studies have shown MNX to be the most acutely toxic among the nitroreduced degradation products of RDX and to cause mild anemia at high dose. The present study compares hematotoxicity with acute oral exposure to MNX with parent RDX. Both RDX and MNX caused a modest decrease in blood hemoglobin and ∼ 50% loss of granulocytes (NOAELs = 47 mg/kg) in female Sprague–Dawley rats observed 14 days post-exposure. We explored the possibility that blood cell loss observed after 14 days was delayed in onset because of toxicity to bone marrow (BM) progenitors. RDX and MNX decreased granulocyte/macrophage-colony forming cells (GM-CFCs) at 14, but not 7, days (NOAELs = 24 mg/kg). The earliest observed time at which MNX decreased GM-CFCs was 10 days post-exposure. RDX and MNX likewise decreased BM burst-forming units-erythroid (BFU-Es) at 14, but not 7, days. Granulocyte–erythrocyte–monocyte–megakaryocyte (GEMM)-CFCs were unaffected by RDX and MNX at 7 days suggesting precursor depletion did not account for GM-CFC and BFU-E loss. MNX added to the culture media was without effect on GM-CFC formation indicating no direct inhibition. Flow cytometry showed no differential loss of BM multilineage progenitors (Thy1.1{sup +}) or erythroid (CD71{sup +}) precursors with MNX suggesting myeloid and erythroid lineages were comparably affected. Collectively, these data indicate that acute exposure to both RDX and MNX caused delayed suppression of myelo- and erythropoiesis with subsequent decrease of peripheral granulocytes and erythrocytes. Highlights: ► Acute oral exposure to munitions RDX causes myelosuppression. ► Environmental degradation product MNX is comparable in effect. ► RDX and MNX are cytotoxic to both myeloid and erythroid

  14. Delayed myelosuppression with acute exposure to hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and environmental degradation product hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) in rats

    Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a widely used munitions compound, and hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), its N-nitroso product of anaerobic microbial nitroreduction, are contaminants of military sites. Previous studies have shown MNX to be the most acutely toxic among the nitroreduced degradation products of RDX and to cause mild anemia at high dose. The present study compares hematotoxicity with acute oral exposure to MNX with parent RDX. Both RDX and MNX caused a modest decrease in blood hemoglobin and ∼ 50% loss of granulocytes (NOAELs = 47 mg/kg) in female Sprague–Dawley rats observed 14 days post-exposure. We explored the possibility that blood cell loss observed after 14 days was delayed in onset because of toxicity to bone marrow (BM) progenitors. RDX and MNX decreased granulocyte/macrophage-colony forming cells (GM-CFCs) at 14, but not 7, days (NOAELs = 24 mg/kg). The earliest observed time at which MNX decreased GM-CFCs was 10 days post-exposure. RDX and MNX likewise decreased BM burst-forming units-erythroid (BFU-Es) at 14, but not 7, days. Granulocyte–erythrocyte–monocyte–megakaryocyte (GEMM)-CFCs were unaffected by RDX and MNX at 7 days suggesting precursor depletion did not account for GM-CFC and BFU-E loss. MNX added to the culture media was without effect on GM-CFC formation indicating no direct inhibition. Flow cytometry showed no differential loss of BM multilineage progenitors (Thy1.1+) or erythroid (CD71+) precursors with MNX suggesting myeloid and erythroid lineages were comparably affected. Collectively, these data indicate that acute exposure to both RDX and MNX caused delayed suppression of myelo- and erythropoiesis with subsequent decrease of peripheral granulocytes and erythrocytes. Highlights: ► Acute oral exposure to munitions RDX causes myelosuppression. ► Environmental degradation product MNX is comparable in effect. ► RDX and MNX are cytotoxic to both myeloid and erythroid progenitor

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

    Stephen Thomas Ahlers

    2012-03-01

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

  16. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver

    Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in variou...

  17. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital.

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both agents were stopped and corticosteroids were initiated. Five months later the patient had fully recovered. Although in the literature the hepatotoxicity of noni juice remains speculative, sporadic but emerging cases of noni juice-associated liver injury address the need to clarify and investigate potential harmful effects associated with this supplement. PMID:23467452

  18. Dose-response studies on promoting and anticarcinogenic effects of phenobarbital and DDT in the rat hepatocarcinogenesis.

    Kitagawa, T; Hino, O; Nomura, K; Sugano, H

    1984-12-01

    Possible discrepancy between the dose level required for promoting action, when given after initiation process, and that needed to exert an anticarcinogenic effect when given simultaneously with a carcinogen, of hepatic promoters were investigated in an attempt to obtain a 'practical' threshold dose of promoters. Phenobarbital (PB) and dichlorophenyltrichloroethane (DDT) were used as promoters and 3'-methyl-4-(dimethylamino)-azobenzene (3'-Me-DAB) was used as the carcinogen. Male weanling rats were treated with 600 p.p.m. 3'-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5-500 p.p.m.), or the animals were treated with a low dose (100 p.p.m.) of 3'-Me-DAB plus a promoter at various dose levels (20-500 p.p.m.). The effects of promoters were measured by scoring size and number of enzyme-altered islands at weeks 12 and 24 of rat age. The promoting effect of PB and DDT was demonstrated in dose-dependent fashion, in the dose range of 10-500 p.p.m. and 20-500 p.p.m., respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced the carcinogenesis at all the dose levels tested, quite in contrast with their inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens. PMID:6499117

  19. The problem of the recuperative capacity of mammals after acute sublethal whole-body exposure to high-energy radiation, with special regard to the juvenile organism

    After a single acute whole-body irradiation with 200 kV x-rays (1.5 mm Cu, dose rate 45 min-1), radiosensitivitis (LD 50/30d) have been determined in 9 age groups of lactating mice and compared with those of adult mice. In split-dose experiments (Dc = 300 R) recovery rates after 1, 2, 3, 5, 10, and 100 days of recovery have been determined in animals 1, 6, 12, 16, and 80 days old; further examinations have been carried out after 3 days of recovery in 6 day-old animals. The findings are compared with earlier investigations in the same strain of animals and with literature on comparable investigations in mice and other mammals. During infancy, there is a slight, age-dependent increase in radiation resistance after a single exposure, and adult mice are about 10% more radiosensitive than juveniles. The recovery rate of lactating mice increases until 2 hours after irradiation, as in adult animals. In contrast to the values measured in adults, however, the recovery rate of animals 1 and 6 days old then drops to values of -27% resp. -63% of Dc = 300 R after 1 resp. 3 days: Sensitization. In animals 12 and 16 days old, too there is a decrease in recovery after 2 hours, but no marked sensitization. In all animals pre-irradiated in infancy, the recovery rate after 10 days is not higher than 45%, and even after 100 days there is a clear residual damage. In animals 6 days old, which are particularly radiosensitive, the highest sensitization was found 3 days after a pre-irradiation dose of 150 to 200 R, and a saturation of the sensitization mechanism was derived for higher doses. Biological causes of sensitization are still unknown. According to the author's literature studies, other species of mammals, too do not always follow the assumptions on the recuperative capacity of mammal organisms which have been derived from studies in adult mice. (orig.)

  20. A Challenge for Diagnosing Acute Liver Injury with Concomitant/Sequential Exposure to Multiple Drugs: Can Causality Assessment Scales Be Utilized to Identify the Offending Drug?

    Roxanne Lim; Hassan Choudry; Kim Conner; Wikrom Karnsakul

    2014-01-01

    Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver ...

  1. Effects of short-term exposure to air pollution on hospital admissions of young children for acute lower respiratory infections in Ho Chi Minh City, Vietnam.

    Le, Truong Giang; Ngo, Long; Mehta, Sumi; Do, Van Dzung; Thach, T Q; Vu, Xuan Dan; Nguyen, Dinh Tuan; Cohen, Aaron

    2012-06-01

    There is emerging evidence, largely from studies in Europe and North America, that economic deprivation increases the magnitude of morbidity and mortality related to air pollution. Two major reasons why this may be true are that the poor experience higher levels of exposure to air pollution, and they are more vulnerable to its effects--in other words, due to poorer nutrition, less access to medical care, and other factors, they experience more health impact per unit of exposure. The relations among health, air pollution, and poverty are likely to have important implications for public health and social policy, especially in areas such as the developing countries of Asia where air pollution levels are high and many live in poverty. The aims of this study were to estimate the effect of exposure to air pollution on hospital admissions of young children for acute lower respiratory infection (ALRI*) and to explore whether such effects differed between poor children and other children. ALRI, which comprises pneumonia and bronchiolitis, is the largest single cause of mortality among young children worldwide and is responsible for a substantial burden of disease among young children in developing countries. To the best of our knowledge, this is the first study of the health effects of air pollution in Ho Chi Minh City (HCMC), Vietnam. For these reasons, the results of this study have the potential to make an important contribution to the growing literature on the health effects of air pollution in Asia. The study focused on the short-term effects of daily average exposure to air pollutants on hospital admissions of children less than 5 years of age for ALRI, defined as pneumonia or bronchiolitis, in HCMC during 2003, 2004, and 2005. Admissions data were obtained from computerized records of Children's Hospital 1 and Children's Hospital 2 (CH1 and CH2) in HCMC. Nearly all children hospitalized for respiratory illnesses in the city are admitted to one of these two pediatric

  2. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome

    Pravin U Shingade

    2014-01-01

    Full Text Available Acute generalized exanthematous pustulosis (AGEP is a rare drug induced cutaneous hypersensitivity reaction characterized by sudden onset of fever with sterile pustules overlying an erythematous skin occurring all over the body. The offending drugs are usually B-lactams and macrolides.Among anticonvulsants carbamazepine and Phenobarbital are commonly associated with AGEP. Only one case of phenytoin induced AGEP has been reported in literature. We present a rare case of AGEP with cerebellar syndrome occurring after receiving loading dose of phenytoin.

  3. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja;

    2015-01-01

    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...... 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...

  4. A Novel Antihepatitis Drug, Bicyclol, Prevents Liver Carcinogenesis in Diethylnitrosamine-Initiated and Phenobarbital-Promoted Mice Tumor Model

    Hua Sun

    2012-01-01

    Full Text Available Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN- initiated and phenobarbital- (PB- promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT, alkaline phosphatase (ALP, and α-fetal protein (AFP in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

  5. Induction of monooxygenases and incorporation of radioactivity from 2-14C-lysine into hepatic microsomes of phenobarbital-treated rats fed a diet deficient in lysine, methionine, threonine and vitamine A, C and E

    The effect of diet on induction of monooxygenases and distribution of label from 2-14C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital (80 mg/rg, three days) was studied. 2-14C-lysine was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monooxygenase induction, increase of relative liver weight and incorporation of label from 2-14C-lysine into fractions of liver homogenate in phenobarbital-treated rats were more pronounced as compared with the similarly trated rats that were fed a balanced diet. The possibility of mobilization of deficient essential components to liver from other organs and tissues for maintenance of monooxygenase induction is discussed

  6. Induction of monooxygenases and incorporation of radioactivity from 2-14C-lysine into hepatic microsomes of phenobarbital-treated rats fed a diet deficient in lysine, methionine, threonine and vitamines A, C, E

    The effect of diet on induction of monooxygenases and distribution of radioactivity from 2-14C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital was studied. 2-14C-lysin was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monooxygenase induction, increase of relative liver weight and incorporation of radioactivity from 2-14C-lysine into fractions of liver homogenate in phenobarbital-treated rats fed diet deficient in lysine, methionine, threonine and vitamins A, C, E were more pronounced as compared with the similarly treated rats which were fed a balanced diet. The possibility of mobilization of deficient essencial components to liver from other organs and tissues for maintenance of monooxygenase induction iis discussed

  7. Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72 and microRNA (miR-142-5p and miR-203.

    Lida A Beninson

    Full Text Available Exosomes, biologically active nanoparticles (40-100 nm released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA. Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72 and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS activation of alpha-1 adrenergic receptors (ADRs, since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation.

  8. 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

    While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration o...

  9. A Challenge for Diagnosing Acute Liver Injury with Concomitant/Sequential Exposure to Multiple Drugs: Can Causality Assessment Scales Be Utilized to Identify the Offending Drug?

    Roxanne Lim

    2014-01-01

    Full Text Available Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM, Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.

  10. A challenge for diagnosing acute liver injury with concomitant/sequential exposure to multiple drugs: can causality assessment scales be utilized to identify the offending drug?

    Lim, Roxanne; Choudry, Hassan; Conner, Kim; Karnsakul, Wikrom

    2014-01-01

    Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis. PMID:25506455

  11. USE OF CATEGORICAL REGRESSION IN THE DEFINITION OF THE DURATION/CONCENTRATION CURVE IN THE U.S. EPA'S ACUTE REFEFENCE EXPOSURE (ARE) METHODOLOGY

    The U.S. EPA's current draft ARE methodology offers three different approaches for derivation of health effects values for various chemicals and agents under inhalation exposure scenarios of < 24 hrs. These approaches, the NOAEL, benchmark concentration (BMC), and categorical ...

  12. Psychedelic drugs, hippie counterculture, speed and phenobarbital treatment of sedative-hypnotic dependence: a journey to the Haight Ashbury in the Sixties.

    Wesson, Donald R

    2011-01-01

    The 1960s were a time of social upheaval, wars, vibrant creativity and missed opportunity. Mainstream culture and a psychedelic drug-using counterculture shared a belief in "better living through chemistry'," but they disagreed about the particular chemistry. The Vietnam war and the cold war with the Soviet Union, racial discrimination, and gender roles fueled political activism. "Yes we can" was not a slogan of the time but political activists clearly believed they could change the beliefs, attitudes and behavior of mainstream culture; and they did. Hippie counterculture on the other hand was largely alienated and strove primarily to develop a separate culture with its own mores, beliefs and lifestyles. Although there was some overlap between hippies and activists, hippies didn't generally have the same sense of political empowerment. Hippie enclaves developed in New York; Boston; Seattle; Austin, Texas and elsewhere; but the epicenter was arguably the Haight-Asbury District of San Francisco. Psychedelic drugs, marijuana and the Vietnam war were among many wedge issues. This paper conjures up a personal history related to the evolution of the hippie counterculture, changing drug use patterns in the Haight-Ashbury, and the origins of a technique of withdrawing patients from barbiturates and other sedative-hypnotics using phenobarbital variously known as the "Phenobarbital Withdrawal Protocol, or the "Smith and Wesson Protocol." PMID:21858961

  13. Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic γ-ray-irradiation in the rat liver

    Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. γ-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by γ-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given PB than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver. (author)

  14. Prophylaxis with diphenylhydantoin and phenobarbital in alumina-gel monkey model. II. Fourth-month follow-up period: seizure, EEG, blood and behavioral data.

    Lockard, J S; DuCharme, L L; Congdon, W C; Franklin, S C

    1976-03-01

    This study, a 4-month follow-up period of a 12-month treatment study by the present authors, was concerned with the permanent effects of treatment with diphenylhydantoin and phenobarbital in the alumina-gel monkey model. Whereas the 8 drug animals during withdrawal increased their seizure frequency, duration, and severity, those 4 animals having received 120 mg/kg/day DPH in weeks 6-12 had one-half the number of seizures of the 4 placebo monkeys in the follow-up period. The other 4 drug animals who had continued to receive 60 mg/kg/day DPH during those weeks had two to four times the number of seizures of the placebo group during posttreatment. (All drug monkeys received 80 mg/kg/day of DPH from weeks 13-52 and 6 mg/kg/day of phenobarbital throughout the 12-month treatment period). The results reaffirm the problems of drug withdrawal and the importance of altering seizure mechanisms with sufficiently high doses of efficacious anticonvulsants rather than merely treating epileptic manifestations at lower doses. PMID:817892

  15. Simultaneous analysis method for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin in urine, using C18 poroshell column.

    Anilanmert, Beril; Çavuş, Fatma; Narin, Ibrahim; Cengiz, Salih; Sertler, Şefika; Özdemir, Ali Acar; Açikkol, Münevver

    2016-06-01

    Date-rape drugs have the potential to be used in drug-facilitated sexual assault, organ theft and property theft. Since they are colorless, tasteless and odorless, victims can drink without noticing, when added to the beverages. These drugs must be detected in time, before they are cleared up from the biofluids. A simultaneous extraction and determination method in urine for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin (an anticonvulsant and antiepileptic drug) with LC-MS/MS was developed for the first time with analytically acceptable recoveries and validated. A 4 steps liquid-liquid extraction was applied, using only 1.000mL urine. A new age commercial C18 poroshell column with high column efficiency was used for LC-MS/MS analysis with a fast isocratic elution as 5.5min. A new MS transition were introduced for barbital. 222.7>179.8 with the effect of acetonitrile. Recoveries (%) were between 80.98-99.27 for all analytes, except for GHB which was 71.46. LOD and LOQ values were found in the ranges of 0.59-49.50 and 9.20-80.80ngmL(-1) for all the analytes (except for GHB:3.44 and 6.00μgmL(-1)). HorRat values calculated (between 0.25-1.21), revealed that the inter-day and interanalist precisions (RSD%≤14.54%) acceptable. The simultaneous extraction and determination of these 8 analytes in urine is challenging because of the difficulty arising from the different chemical properties of some. Since the procedure can extract drugs from a wide range of polarity and pKa, it increases the window of detection. Group representatives from barbiturates, z-drugs, ketamine, phenytoin and polar acidic drugs (GHB) have been successfully analyzed in this study with low detection limits. The method is important from the point of determining the combined or single use of these drugs in crimes and finding out the reasons of deaths related to these drugs. PMID:27107852

  16. Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis.

    Yadav, Amit Singh; Bhatnagar, D

    2007-09-20

    The generation of free radicals is a cause of many pathological conditions like diabetes mellitus, cancer, stroke, etc. Free radicals cause damage to cellular DNA and initiate carcinogenesis. Free radicals also bring about proliferation of cells via cell signaling. An inverse relationship between the consumption of vegetable diets and the risk of cancer has been established. In the present study, Star anise (Illicium verum), which is a commonly used condiment in Indian cuisine, was assessed for its anti-carcinogenic potential in N-nitrosodiethylamine (NDEA) initiated and phenobarbital (PB) promoted hepato-carcinogenesis. Rats were randomly selected for eight experimental groups. The carcinogenesis was induced by injecting the rats, with a single dose of NDEA (200mg/kg body weight) intraperitoneally as initiator, followed by promotion with PB (0.05%) in drinking water for 14 consecutive weeks. The treatment with NDEA increased liver weight, while Star anise (Star) treatment reduced the liver weight of rats. The treatment with Star throughout for 20 weeks or during the promotion stage (6-20 weeks) significantly reduced the nodule incidence and nodule multiplicity in the rats, while the treatment with Star at the initiation phase (first 4 weeks) only could not reduce these parameters. The treatment with Star for 20 consecutive weeks significantly reduced the nodule size and nodule volume. The treatment with Star throughout as well as at the promotion stage lowered the lipid peroxidation (LPO) in liver and erythrocytes, while the LPO was not lowered, when Star was administered during initiation stage only. The treatment with Star restored the liver and erythrocyte super-oxide dismutase (SOD) activities to normal in the carcinogenesis-induced rats. The liver catalase (CAT) activity increased in all the treated groups. The erythrocyte CAT activity increased in the rats treated with Star during initiation and promotion stage only. The liver glutathione (GSH) level

  17. Effects of Prebiotics on the Expression of the Integral Membrane Protein Occludin and Cytokines in Rats after Acute High Altitude Exposure

    Fang-Xin Zhang; Zhi-Yun Deng; Ju-Zi Dong; Yun Duan; Shang-Xin Deng; Jia-Yu Chen; Qiang Ma; Ti-Dong Shan

    2013-01-01

    This study is aimed to investigate the effects of prebiotics on the expression of occludin and cytokines in the intestinal mucosal barrier of stressed rats in a high altitude environment. Forty-eight rats were acutely stressed in a high altitude hypoxia environment (3848 m). Rats in the hypoxia control group (n = 24) and prebiotics group (n = 24) were stressed for 2, 4 and 6 days before harvesting the intestinal mucosa. The expression of the occludin protei...

  18. Acute Bronchitis

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  19. Influence of long-term cadmium and selenite exposure on resistance to Listeria monocytogenes during acute and chronic infection in mice

    Šimonytė, Sandrita; Plančiūnienė, Rita; Cherkashin, Gennadij; žekonis, Gediminas

    2006-01-01

    The aim of the present study was to evaluate the effect of long-term exposure to cadmium and selenite ions on the BALB/c mice resistance to experimental Listeria monocytogenes infection. A low-dose six-week exposure to cadmium ions (10 mg/ l in drinking water) decreased the clearance of listeria from mice liver and spleen at 24 h in the early phase of infection. Long-term treatment of mouse with selenite ions (0.15 mg/l) did not activate the elimination of bacteria from the organs. Eight week...

  20. Biochemical Tolerance During Low Dose Propylene Glycol Exposure in Neonates: A Formulation-Controlled Evaluation

    Aida Kulo

    2012-07-01

    Full Text Available Background and purpose of the study: Propylene glycol (PG is a frequently co-administered solvent in formulations administered to neonates, but reports on its (intolerance are limited. We aimed to report on renal, metabolic and hepatic tolerance before, during and following intravenous (iv PG-paracetamol exposure and compared these data with similar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG.Methods: Renal (diuresis, creatinemia, sodium, metabolic (Base Excess, Anion Gap, lactate, bicarbonate and hepatic (liver enzymes, bilirubinemia indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates study (intra-individual trends, ANOVA were collected and analysed.Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test were made. Results: PG exposure (median 34.1 mg/kg/24 h did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital- PG or 172 cases exposed to paracetamol-mannitol.Major conclusion: Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.

  1. Estimation of a contribution of internal exposure to early effects of acute radiation syndrome in victims of the accident at the Chernobyl Nuclear Power Plant

    Materials on internal irradiation of people with accute radiation syndrome, caused by the ChNPP accident are presented. It is shown, that internal exposure is more than important as related to clynical direct accute effects under investigation. Thyroid, lungs and whole body radiation doses are presented. Severity of broncholung and hypophysical-thyroidal system damage was evaluated

  2. SENSITIVITY OF AN INFAUNAL AMPHIPOD, EOHAUSTORIUS ESTUARIUS, TO ACUTE WATER-BORN EXPOSURES OF 4-NONYLPHENOL (NP): EVIDENCE OF A TOXIC HANGOVER

    Three independent trials were conducted using mortality and burial as endpoints. Mean LC50 was 227 ug/l. One hour burial as a sub-lethal endpoint increased the sensitivity of the toxicity test by 40%; however most amphipods that survived exposure were able to recover within 24-48...

  3. Acute and chronic effects of exposure to a 1-mT magnetic field on the cytoskeleton, stress proteins, and proliferation of astroglial cells in culture

    This paper reports the effects of exposure to static, sinusoidal (50 Hz), and combined static/sinusoidal magnetic fields on cultured astroglial cells. Confluent primary cultures of astroglial cells were exposed to a 1-mT sinusoidal, static, or combined magnetic field for 1 h. In another experiment, cells were exposed to the combined magnetic field for 1, 2, and 4 h. The hsp25, hsp60, hsp70, actin, and glial fibrillary acidic protein contents of the astroglial cells were determined by immunoblotting 24 h after exposure. No significant differences were seen between control and exposed cells with respect to their contents of these proteins, neither were any changes in cell morphology observed. In a third experiment to determine the effect of a chronic (11-day) exposure to a combined 1-mT static/sinusoidal magnetic field on the proliferation of cultured astroglial cells, no significant differences were seen between control, sham-exposed, or exposed cells. These results suggest that exposure to 1-mT sinusoidal, static, or combined magnetic fields has no significant effects on the stress, cytoskeletal protein levels in, or proliferation of cultured astroglial cells

  4. Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish

    Liu, Chunsheng; Su, Guanyong; Giesy, John P.; Letcher, Robert J.; Li, Guangyu; Agrawal, Ira; Li, Jing; Yu, Liqin; Wang, Jianghua; Gong, Zhiyuan

    2016-01-01

    Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in environmental media and has adverse health effect on wildlife and humans. It has been implicated to have hepatotoxicity, but its molecular mechanisms remain unclear. In the present study, adult male zebrafish were exposed to TDCIPP and global hepatic gene expression was examined by RNA-Seq and RT-qPCR in order to understand the molecular mechanisms of TDCIPP-induced hepatotoxicity. Our results indicated that TDCIPP exposure significantly up-regulated the expression of genes involved in endoplasmic reticulum stress and Toll-like receptor (TLR) pathway, implying an inflammatory response, which was supported by up-regulation of inflammation-related biomaker genes. Hepatic inflammation was further confirmed by histological observation of increase of infiltrated neutrophils and direct observation of liver recruitment of neutrophils labeled with Ds-Red fluorescent protein of Tg(lysC:DsRed) zebrafish upon TDCIPP exposure. To further characterize the hepatotoxicity of TDCIPP, the expression of hepatotoxicity biomarker genes, liver histopathology and morphology were examined. The exposure to TDCIPP significantly up-regulated the expression of several biomarker genes for hepatotoxicity (gck, gsr and nqo1) and caused hepatic vacuolization and apoptosis as well as increase of the liver size. Collectively, our results suggest that exposure to TDCIPP induces hepatic inflammation and leads to hepatotoxicity in zebrafish.

  5. Acute posttraumatic stress symptoms but not generalized anxiety symptoms are associated with severity of exposure to war trauma: A study of civilians under fire.

    Helpman, Liat; Besser, Avi; Neria, Yuval

    2015-10-01

    Posttraumatic stress (PTSS) and generalized anxiety symptoms (GAS) may ensue following trauma. While they are now thought to represent different psychopathological entities, it is not clear whether both GAS and PTSS show a dose-response to trauma exposure. The current study aimed to address this gap in knowledge and to investigate the moderating role of subjects' demographics in the exposure-outcome associations. The sample included 249 civilian adults, assessed during the 2014 Israel-Gaza military conflict. The survey probed demographic information, trauma exposure, and symptoms. PTSS but not GAS was associated with exposure severity. Women were at higher risk for both PTSS and GAS than men. In addition, several demographic variables were only associated with PTSS levels. PTSS dose-response effect was moderated by education. These findings are in line with emerging neurobiological and cognitive research, suggesting that although PTSS and GAS have shared risk factors they represent two different psychopathological entities. Clinical and theoretical implications are discussed. PMID:26343559

  6. Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

    Bhattacharyya, M.H.; Stebbings, J.H.; Peterson, D.P.; Johnson, S.A.; Kumar, R.; Goun, B.D.; Janssen, I.; Trier, J.E.

    1993-03-01

    This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease in blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account.

  7. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  8. Ethylene evolution from pine seedlings due to acute UV-B exposure as a possible indicator of long-term radio-frequency electromagnetic radiation under natural conditions

    Acute stress treatment in the form of UV-B radiation was used to evaluate possible damage to pine trees caused by radio frequency electromagnetic radiation (RF EMR). While pine seedlings grow from seed material collected in sample plots with different RF EMR intensities had identical in vivo ethylene production rates, the degree of activation of ethylene biosynthesis by UV-B treatment in seedlings was proportional to the EMR intensity in the respective sample plots where the ancestor pine trees has grown. (author)

  9. Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine

    Jane C. Quinn

    2015-01-01

    Full Text Available The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl-(2-piperidyl-4-quinolinemethanol, have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.

  10. Pesticide exposure in children.

    2012-12-01

    This statement presents the position of the American Academy of Pediatrics on pesticides. Pesticides are a collective term for chemicals intended to kill unwanted insects, plants, molds, and rodents. Children encounter pesticides daily and have unique susceptibilities to their potential toxicity. Acute poisoning risks are clear, and understanding of chronic health implications from both acute and chronic exposure are emerging. Epidemiologic evidence demonstrates associations between early life exposure to pesticides and pediatric cancers, decreased cognitive function, and behavioral problems. Related animal toxicology studies provide supportive biological plausibility for these findings. Recognizing and reducing problematic exposures will require attention to current inadequacies in medical training, public health tracking, and regulatory action on pesticides. Ongoing research describing toxicologic vulnerabilities and exposure factors across the life span are needed to inform regulatory needs and appropriate interventions. Policies that promote integrated pest management, comprehensive pesticide labeling, and marketing practices that incorporate child health considerations will enhance safe use. PMID:23184103

  11. Olmesartan medoxomil-induced acute renal failure in a premature newborn following maternal exposure during pregnancy: a case report and review of the literature

    Georgaki-Angelaki, Eleni; Stergiou, Nicolaos; Naoum, Ekaterini; Papassotiriou, Ioannis; Anagnostakou, Marina

    2009-01-01

    Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (AT II) receptor blockers (ARBs) are widely used antihypertensives with well-recognized renoprotective and cardioprotective effects. Although treatment with these agents generally does not result in adverse metabolic consequences, their use during human pregnancy has been associated with negative reactions. Here we report a premature baby with a history of oligohydramnios and maternal exposure to the ARB olmesartan medoxomil wh...

  12. Acute paraquat exposure determines dose-dependent oxidative injury of multiple organs and metabolic dysfunction in rats: impact on exercise tolerance.

    Novaes, Rômulo D; Gonçalves, Reggiani V; Cupertino, Marli C; Santos, Eliziária C; Bigonha, Solange M; Fernandes, Geraldo J M; Maldonado, Izabel R S C; Natali, Antônio J

    2016-04-01

    This study investigated the pathological morphofunctional adaptations related to the imbalance of exercise tolerance triggered by paraquat (PQ) exposure in rats. The rats were randomized into four groups with eight animals each: (a) SAL (control): 0.5 ml of 0.9% NaCl solution; (b) PQ10: PQ 10 mg/kg; (c) PQ20: PQ 20 mg/kg; and (d) PQ30: PQ 30 mg/kg. Each group received a single injection of PQ. After 72 hours, the animals were subjected to an incremental aerobic running test until fatigue in order to determine exercise tolerance, blood glucose and lactate levels. After the next 24 h, lung, liver and skeletal muscle were collected for biometric, biochemical and morphological analyses. The animals exposed to PQ exhibited a significant anticipation of anaerobic metabolism during the incremental aerobic running test, a reduction in exercise tolerance and blood glucose levels as well as increased blood lactate levels during exercise compared to control animals. PQ exposure increased serum transaminase levels and reduced the glycogen contents in liver tissue and skeletal muscles. In the lung, the liver and the skeletal muscle, PQ exposure also increased the contents of malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase and catalase, as well as a structural remodelling compared to the control group. All these changes were dose-dependent. Reduced exercise tolerance after PQ exposure was potentially influenced by pathological remodelling of multiple organs, in which glycogen depletion in the liver and skeletal muscle and the imbalance of glucose metabolism coexist with the induction of lipid, protein and DNA oxidation, a destructive process not counteracted by the upregulation of endogenous antioxidant enzymes. PMID:27277193

  13. Acute effects of low-level sulphur dioxide and nitrogen dioxide exposures on the respiratory tract of susceptible subjects in cold environments

    Salonen, R.O.; Randell, J.T.; Haelinen, A.I.; Pennanen, A.S. [National Public Health Inst., Kuopio (Finland). Div. of Environmental Health; Kosma, V.M. [Kuopio Univ. (Finland). Dept. of Pathology; Pekkarinen, H. [Kuopio Univ. (Finland). Dept. of Physiology; Ruuskanen, J. [Kuopio Univ. (Finland). Dept. of Environmental Sciences; Tukiainen, H. [Kuopio Univ. (Finland). Dept. of Pulmonary Diseases

    1995-12-31

    Several recent epidemiological studies from Finland have suggested that sulphur dioxide (SO{sub 2}) and nitrogen dioxide (NO{sub 2}) cause adverse health effects in susceptible population groups, such as children and asthmatic patients, at much smaller concentrations than the present guideline values of the World Health Organization. One possible explanation of these findings is that the relatively long winter-time increases the sensitivity of the respiratory tract to irritant pollutants. This hypothesis is supported by experimental human and animal studies, which have shown obstruction and inflammatory changes in the conducting airways after ventilation of cold and dry air. Asthmatic patients are much more sensitive than healthy subjects to the irritating effects of cold and dry air and of air pollutants. The airways of many non-asthmatic a topic subjects are also sensitive to cold air, but these subjects are poorly defined as a potential susceptible population group to air pollutants. The aims of this project are: (1) to construct experimental human and animal facilities and protocols for short-term studies on SO{sub 2} and NO{sub 2} exposures at subfreezing temperatures, (2) to apply advanced lung function methodologies and symptom assessment for characterisation of short-term respiratory responses of asthmatic and a topic subjects to these exposures, (3) to apply well-established pulmonary physiological, cytological and morphological methods for characterisation of short-term responses to and mechanisms of these exposures in the guinea-pig lower airways. (author)

  14. Effects of an acute dose of gamma radiation exposure on stem diameter growth, carbon gain, and biomass partitioning in Helianthus annuus

    Thiede, M.E.

    1988-05-25

    Nineteen-day-old dwarf sunflower plants (Helianthus annuus, variety NK894) received a variable dose (0-40 Gy) from a cobalt-60 gamma source. A very sensitive stem monitoring device, developed at Battelle's Pacific Northwest Laboratories, Richland, Washington was used to measure real-time changes in stem diameter. Exposure of plants caused a significant reduction in stem growth and root biomass. Doses as low as 5 Gy resulted in a significant increase in leaf density, suggesting that nonreversible morphological growth changes could be induced by very low doses of radiation. Carbohydrate analysis of 40-Gy irradiated plants demonstrated significantly more starch content in leaves and significantly less starch content in stems 18 days after exposure than did control plants. In contrast, the carbohydrate content in roots of 40-Gy irradiated plants were not significantly different from unirradiated plants 18 days after exposure. These results indicate that radiation either decreased phloem transport or reduced the availability of sugar reducing enzymes in irradiated plants. 44 refs., 12 figs.

  15. Simultaneous spectrophotometric determination of phenobarbital, phenytoin and methylphenobarbital in pharmaceutical preparations by using partial least-squares and principal component regression multivariate calibration.

    Boeris; Luco, J M; Olsina, R A

    2000-12-15

    Two multivariate calibration methods, partial least squares (PLS-2) and principal component regression (PCR) have been applied to the simultaneous spectrophotometric analysis of ternary mixtures of phenytoin (DPH), phenobarbital (PBT) and methylphenobarbital (MPBT) in the Comital-L pharmaceutical formulation. The PLS-2 and PCR procedures were employed to evaluate the data of a variable number of calibration solutions measured over the wavelength range 400-700 nm. The concentration ranges used to construct the calibration matrix were varied between 5 and 30 microg ml(-1). The proposed methods were validated by applying them to the analysis of the Comital-L pharmaceutical formulation and the average relative errors were less than 6% for each one of the analyzed compounds. The results obtained by both proposed methods have been compared with the results obtained by application of a RPLC reference method. PMID:11130205

  16. Current and emerging challenges in toxicopathology: Carcinogenic threshold of phenobarbital and proof of arsenic carcinogenicity using rat medium-term bioassays for carcinogens

    For the last 25 years, Prof. Nobuyuki Ito and his laboratory have focused on the development of liver medium-term bioassay system for detection of carcinogens in F344 rats utilizing glutathione S-transferase placental form (GST-P)-positive foci as an end point marker. In this presentation, the outline and samples of medium-term bioassay systems were described. Furthermore, our data demonstrated the presence of a threshold for the non-genotoxic carcinogen, phenobarbital (PB), and the lack of linearity in the low-dose area of the dose-response curve, providing evidence for hormesis. In addition, the establishment and applications of multiorgan carcinogenicity bioassay (DMBDD model), used for the examination of the carcinogenicity of genotoxic and non-genotoxic chemicals, are discussed. Dimethylarsinic acid, one of organic arsenics, was found to be carcinogenic in rat bladder using DMBDD model and carcinogenicity test

  17. Quantitation of amobarbital, butalbital, pentobarbital, phenobarbital, and secobarbital in urine, serum, and plasma using gas chromatography-mass spectrometry (GC-MS).

    Johnson, Leonard L; Garg, Uttam

    2010-01-01

    Barbiturates are central nervous system depressants with sedative and hypnotic properties. Some barbiturates, with longer half-lives, are used as anticonvulsants. Their mechanism of action includes activation of gamma-aminobutyric acid (GABA) mediated neuronal transmission inhibition. Clinically used barbiturates include amobarbital, butalbital, pentobarbital, phenobarbital, secobarbital, and thiopental. Besides their therapeutic use, barbiturates are commonly abused. Their analysis is useful for both clinical and forensic proposes. Gas chromatography mass spectrometry is a commonly used method for the analysis of barbiturates. In the method described here, barbiturates from serum, plasma, or urine are extracted using an acidic phosphate buffer and methylene chloride. Barbital is used as an internal standard. The organic extract is dried and reconstituted with mixture of trimethylanilinium hydroxide (TMAH) and ethylacetate. The extract is injected into a gas chromatogram mass spectrometer where it undergoes "flash methylation" in the hot injection port. Selective ion monitoring and relative retention times are used for the identification and quantitation of barbiturates. PMID:20077060

  18. Pathological characteristics of extremely severe acute radiation injury in a patient's legs and hands after a very uneven accidental exposure to an extremely high dose of 192Ir

    The pathological characteristics of an extremely high dose radiation in the legs and hands of a patient is reported. the patient was exposed to 192Ir γ-rays for 9 hours and 20 minutes, the activity of which was 2.76 TBq. The amputations of the right thigh and left forearm had to be performed 8 days after the irradiation and the debridements and skin graftings were performed on the right hand and the inner side of left knee 55 days after the radiation. Microscopically, massive necrosis of cells of the epidermis, cutaneous appendages, hypodermics and skeletal muscles, and hemorrhage in the dermis, hypodermics and skeletal muscles were seen in the local irradiated parts of the right shank. But the arrector pili muscles in the dermis of the right shank remained. On the fingers and the palm of the left hand, vacuolar degeneration and massive necrosis of the cells of epidermis were present with extensive neutrophil infiltration. Cysts of large or small size were formed from the necrotic cells, separating epidermis from dermis. There were degeneration and necrosis of glandular epithelium cells of sweat glands. Hemorrhage was present in dermis and hypodermics. All the hematopoietic tissues in the bone marrow in the upper ends of the tibia and fibula and in the lower ends of the femur, the radius and the ulna disappeared. Acute radiation ulcers were present on the skin of the left knee and on the skin of the thumb, index finger and middle finger of the right hand. The extremely severe acute radiation injury caused by extremely high dose of 192Ir led to the necrosis of the extensive soft tissues deep to skeletal muscles and the disappearance of the hematopoietic tissues in the bone marrow

  19. Hematocrit and plasma osmolality values of young-of-year shortnose sturgeon following acute exposures to combinations of salinity and temperature

    Ziegeweid, J.R.; Black, M.C.

    2010-01-01

    Little is known about the physiological capabilities of young-of-year (YOY) shortnose sturgeon. In this study, plasma osmolality and hematocrit values were measured for YOY shortnose sturgeon following 48-h exposures to 12 different combinations of salinity and temperature. Hematocrit levels varied significantly with temperature and age, and plasma osmolalities varied significantly with salinity and age. Plasma osmolality and hematocrit values were similar to previously published values for other sturgeons of similar age and size in similar treatment conditions. ?? 2010 Springer Science+Business Media B.V.

  20. PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure.

    Thomas, R S; Yang, R S; Morgan, D G; Moorman, M P; Kermani, H R; Sloane, R A; O'Connor, R W; Adkins, B; Gargas, M L; Andersen, M E

    1996-01-01

    During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (Vma...

  1. Acute Pancreatitis and Pregnancy

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  2. Acute exposure to fenthion in juveniles of white cachama (Piaractus brachypomus: toxic effects, changes in cholinesterase activity and potential use in environmental monitoring

    Borbón Javier F.

    2012-03-01

    Full Text Available Fenthion is an organophosphate insecticide used worldwide that may pollute waters after itsapplication causing potential problems in public health and poisoning in domestic and wildlifeanimals. Objective: to evaluate toxic effects, butyrylcholinesterase activity (BChE and use inenvironmental monitoring, 34 juveniles of white cachama (Piaractus brachypomus were distributedin 3 groups (control, 0,13 ppm and 2 ppm fenthion for 96 h. Materials and methods: fishwere exposed in 10-gallon tanks; symptoms, gross lesions post-mortem, viscerosomatic index(VSI and plasma BChE activity were evaluated. Mean comparisons for each variable amongtreatments were performed (ANOVA, α=0,05. Results: severe signs were seen in 3 specimens(3/11 of 2 ppm fenthion between 11 and 34 h of exposure. These signs were frantic swimming,muscle tremors and loss of swimming axis. In 0,13 ppm, mild to moderate signs (tremors andcaudal fin flapping were observed in some of the fish. The VSI (control = 5,3 ± 0,5; 0,13 ppm= 6,9 ± 0,3 and 2 ppm = 7,3 ± 0,6 was significantly different between exposed to fenthion andcontrols. BChE activity (control = 185,0 ± 20,4; 0,13 ppm = 12,5 ± 2,3 and 2 ppm = 9,8 ± 1,8nmoles / ml plasma / min showed significant inhibition in exposed to fenthion as compared tocontrols. Conclusions: the present work confirmed the toxic effects of fenthion in white cachamajuveniles. Results found in BChE activity suggest its use in environmental monitoring as a goodbiomarker of organophosphates waterborne exposure.

  3. Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice

    Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure

  4. Bronchitis - acute

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflammation in the main passages ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  5. Bronchitis - acute

    Acute bronchitis is swelling and inflammation in the main passages that carry air to the lungs. The swelling narrows ... makes it harder to breathe. Another symptom of bronchitis is a cough. Acute means the symptoms have ...

  6. Acute Bronchitis

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  7. Efecto del tiempo de exposición a PM10 en las urgencias por bronquitis aguda Effect of exposure time to PM10 on emergency admissions for acute bronchitis

    Franz Muñoz

    2009-03-01

    Full Text Available Este trabajo analiza el efecto de las horas de exposición a PM10 en las urgencias diarias por bronquitis aguda, controlando por temperatura y humedad. El estudio fue realizado en seis sectores de la ciudad de Santiago, Chile, durante el período de invierno de los años 2002 al 2004, para lactantes ( 65 años. Analizamos el retraso de la respuesta mediante una función polinomial distributiva (pdl, incluida en un modelo lineal generalizado (GLM-pdl, y la estructura del efecto de la exposición, mediante modelos aditivos generalizados (GAM, utilizando regresión spline como técnica de estimación. Los resultados mostraron que al cuarto día de retardo, el efecto de la exposición fue mayor, especialmente en lactantes, y varió en la medida que incrementó la concentración atmosférica de PM10. El efecto de las horas de exposición a PM10 mostró una variación significativa, según el sector geográfico. Al estimar linealmente este efecto en el sector Oeste, notamos que el incremento de consultas diarias en lactantes fue de 3% por cada hora de exposición sobre os 150µg/m³.To study the health effect of air pollution, measured as particulate matter greater than 10mm in diameter (PM10, we analyzed the effect of daily hours of exposure on the number of urgency admissions for acute bronchitis, adjusting for temperature and humidity on the same day. The study was conducted in six regions of Santiago, Chile, during the winter of years 2002 to 2004, for infants and elders. The delay between pollution time series and disease was modeled using a polynomial distributed lag (PDL function included in a generalized linear model. The linearity assumption was evaluated using a smooth-spline model approach. The highest effect for exposure to PM10 was detected with 4 days of delay. For both groups, the effect of temperature was linear, but that of humidity was not. Air pollution effect varied according to level of exposure and geographic region, increasing

  8. ENVIRONMENTAL EQUITY AND PESTICIDE EXPOSURE

    Although people of color and low-income groups bear a disproportionate share of the health risks from exposure to pesticides, research attention has been meager, and data on acute and chronic health effects related to their toxic exposures are generally lacking. ncreased resource...

  9. Effects of very low dose-rate 90Sr/90Y exposure on the acute moist desquamation response of pig skin

    Background and objectives: Previous data, predominantly involving high dose-rate fractionated irradiation with incomplete repair intervals, had indicated that the kinetics of repair of sublethal damage for acute radiation reactions in pig skin could best be defined by a biphasic repair model with half-times for repair of 0.2 and 5.4 h, partition coefficient 0.5. To further test the validity of this finding and obtain a better estimate of the repair rate of the slow component of repair, the acute response of pig skin to very low dose-rates (VLDR), originally estimated to be 0.0067-0.0244 Gy/min, was investigated as part of a 4 fraction irradiation protocol involving an overall treatment time of 90Sr/90Y plaques. Irradiation with a 4 fraction protocol included 3 equal, high dose-rate, fractions with full repair, followed by a fourth VLDR fraction. The total doses administered were originally planned to represent the dose associated with the predicted ED20, ED50 and ED80 (75% of total biological dose given at high dose-rate and 25% at VLDR) calculated on the basis of the repair kinetic parameters obtained from earlier studies. However, during the analysis a revision to the physical dosimetry was identified; this had been overlooked prior to the start of the study. Following completion of irradiation the irradiated sites were examined weekly and the presence or absence of moist desquamation recorded. Results: The incidence of moist desquamation was slightly higher than expected on the basis of the parameters used to calculate iso-effective doses, at least in part as a consequence of the change to the dosimetry. Using likelihood methods and the original dose estimates, the best model based estimate of the dose-rate correction factor for the LDR and VLDR plaques was 1.29. This was comparable with the physical calibration factor, median value 1.23. The VLDR fraction associated with a 50% incidence of moist desquamation, based on experimental observation, was 23.2 ± 0

  10. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    Wang Min

    2010-09-01

    Full Text Available Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs, suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We measured the expression of D2Rs dimers and monomers in patients with schizophrenia using Western blots, and then in striatal tissue from rats exhibiting the amphetamine-induced sensitized state (AISS. We further examined the interaction between D2Rs and the dopamine transporter (DAT by co-immunoprecipitation, and measured the expression of dopamine D2High receptors with ligand binding assays in rat striatum slices with or without acute amphetamine pre-treatment. Results We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6% and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. Conclusions Given the fact that amphetamine induces psychosis and that the AISS rat is a widely accepted animal model of psychosis, our data suggest that D2R dimerization may be important in the pathophysiology of schizophrenia and may be a promising new target for novel antipsychotic drugs.

  11. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline) addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingest...

  12. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline) addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion....

  13. High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in Border Collie dogs.

    Mizukami, Keijiro; Yabuki, Akira; Chang, Hye-Sook; Uddin, Mohammad Mejbah; Rahman, Mohammad Mahbubur; Kushida, Kazuya; Kohyama, Moeko; Yamato, Osamu

    2013-01-01

    A single nucleotide substitution (c.-6-180T>G) associated with resistance to phenobarbital therapy has been found in the canine MDR1/ABCB1 gene in Border Collies with idiopathic epilepsy. In the present study, a PCR-restriction fragment length polymorphism assay was developed for genotyping this mutation, and a genotyping survey was carried out in a population of 472 Border Collies in Japan to determine the current allele frequency. The survey demonstrated the frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the mutant G allele is extremely high (24.9%) in Border Collies. The results suggest that this high mutation frequency of the mutation is likely to cause a high prevalence of phenobarbital-resistant epilepsy in Border Collies. PMID:24302812

  14. High Frequency of a Single Nucleotide Substitution (c.-6-180T>G of the Canine MDR1/ABCB1 Gene Associated with Phenobarbital-Resistant Idiopathic Epilepsy in Border Collie Dogs

    Keijiro Mizukami

    2013-01-01

    Full Text Available A single nucleotide substitution (c.-6-180T>G associated with resistance to phenobarbital therapy has been found in the canine MDR1/ABCB1 gene in Border Collies with idiopathic epilepsy. In the present study, a PCR-restriction fragment length polymorphism assay was developed for genotyping this mutation, and a genotyping survey was carried out in a population of 472 Border Collies in Japan to determine the current allele frequency. The survey demonstrated the frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the mutant G allele is extremely high (24.9% in Border Collies. The results suggest that this high mutation frequency of the mutation is likely to cause a high prevalence of phenobarbital-resistant epilepsy in Border Collies.

  15. Retention, distribution, and excretion of 239PuO2 particles labeled with 169Yb in the Rhesus monkey after a single acute inhalation exposure

    Sixteen Rhesus monkeys were exposed to a high fired 239PuO2 aerosol labeled with 169Yb, and retention, distribution, and excretion patterns were determined. After an early rapid clearance phase, which had a half-life of less than one day, the remaining plutonium was retained in the lungs with a half-life that appeared to be greater than 500 days. By 30 days after exposure, 99 percent of the 239Pu in the body was in the lungs. At this time, 6 to 10 percent of the 169Yb burden was in the carcass and skeleton suggesting that there was dissociation of some 169Yb from the particles. The remaining 169Yb activity was in the lungs. There was little 239Pu in the liver, bone, or lymph nodes. The particulate material was cleared rapidly from the gastrointestinal and upper respiratory tracts and appeared in feces over the first four days. The level of 239Pu in feces returned to background by six days. Urinary excretion of 239Pu reached a peak by 8 to 10 days and then remained at a constant rate throughout the remainder of the experiment. These data are useful in calculating radiation dose to a variety of organs and relating this dose to the appearance of late effects from inhaled alpha-emitting particles. (U.S.)

  16. Induction by phenobarbital of aniline-p-hydroxylase in mouse liver under the influence of X-irradiation and 2,4,6-triethyleneimino-1,3,5-triazine

    The phenobarbital-induced activity of aniline-p-hydroxylase in livers of mice was enhanced additionally when the animals were X-irradiated 4-16 hours before the administration of the inducer. The same effect could be demonstrated after repeated irradiation with low doses. 2,4,6-triethyleneimino-1,3,5-triazine (tretamine) inhibited the induction of aniline-p-hydroxylase only when administered in extremely high doses. Lower doses resulted in 'superinduciton'. (orig.)

  17. Mitochondrial energetic defects in muscle and brain of a Hmbs-/- mouse model of acute intermittent porphyria.

    Homedan, Chadi; Schmitt, Caroline; Laafi, Jihane; Gueguen, Naïg; Desquiret-Dumas, Valérie; Lenglet, Hugo; Karim, Zoubida; Gouya, Laurent; Deybach, Jean-Charles; Simard, Gilles; Puy, Hervé; Malthièry, Yves; Reynier, Pascal

    2015-09-01

    Acute intermittent porphyria (AIP), an autosomal dominant metabolic disease (MIM #176000), is due to a deficiency of hydroxymethylbilane synthase (HMBS), which catalyzes the third step of the heme biosynthetic pathway. The clinical expression of the disease is mainly neurological, involving the autonomous, central and peripheral nervous systems. We explored mitochondrial oxidative phosphorylation (OXPHOS) in the brain and skeletal muscle of the Hmbs(-/-) mouse model first in the basal state (BS), and then after induction of the disease with phenobarbital and treatment with heme arginate (HA). The modification of the respiratory parameters, determined in mice in the BS, reflected a spontaneous metabolic energetic adaptation to HMBS deficiency. Phenobarbital induced a sharp alteration of the oxidative metabolism with a significant decrease of ATP production in skeletal muscle that was restored by treatment with HA. This OXPHOS defect was due to deficiencies in complexes I and II in the skeletal muscle whereas all four respiratory chain complexes were affected in the brain. To date, the pathogenesis of AIP has been mainly attributed to the neurotoxicity of aminolevulinic acid and heme deficiency. Our results show that mitochondrial energetic failure also plays an important role in the expression of the disease. PMID:26071363

  18. Acute pancreatitis

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  19. Acute pancreatitis

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  20. The effects of increased constant incubation temperature and cumulative acute heat shock exposures on morphology and survival of Lake Whitefish (Coregonus clupeaformis) embryos.

    Lee, Abigail H; Eme, John; Mueller, Casey A; Manzon, Richard G; Somers, Christopher M; Boreham, Douglas R; Wilson, Joanna Y

    2016-04-01

    Increasing incubation temperatures, caused by global climate change or thermal effluent from industrial processes, may influence embryonic development of fish. This study investigates the cumulative effects of increased incubation temperature and repeated heat shocks on developing Lake Whitefish (Coregonus clupeaformis) embryos. We studied the effects of three constant incubation temperatures (2°C, 5°C or 8°C water) and weekly, 1-h heat shocks (+3°C) on hatching time, survival and morphology of embryos, as these endpoints may be particularly susceptible to temperature changes. The constant temperatures represent the predicted magnitude of elevated water temperatures from climate change and industrial thermal plumes. Time to the pre-hatch stage decreased as constant incubation temperature increased (148d at 2°C, 92d at 5°C, 50d at 8°C), but weekly heat shocks did not affect time to hatch. Mean survival rates and embryo morphometrics were compared at specific developmental time-points (blastopore, eyed, fin flutter and pre-hatch) across all treatments. Constant incubation temperatures or +3°C heat-shock exposures did not significantly alter cumulative survival percentage (~50% cumulative survival to pre-hatch stage). Constant warm incubation temperatures did result in differences in morphology in pre-hatch stage embryos. 8°C and 5°C embryos were significantly smaller and had larger yolks than 2°C embryos, but heat-shocked embryos did not differ from their respective constant temperature treatment groups. Elevated incubation temperatures may adversely alter Lake Whitefish embryo size at hatch, but weekly 1-h heat shocks did not affect size or survival at hatch. These results suggest that intermittent bouts of warm water effluent (e.g., variable industrial emissions) are less likely to negatively affect Lake Whitefish embryonic development than warmer constant incubation temperatures that may occur due to climate change. PMID:27033035

  1. Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital

    Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR

  2. Evaluation of growth, biochemical and bioaccumulation parameters in Pelophylax perezi tadpoles, following an in-situ acute exposure to three different effluent ponds from a uranium mine

    Mining activities invariably produce metal contaminated effluents. Depending on factors such as pH and metal concentration the toxicity of the effluent may vary. To assess the effects of three characteristically different effluent ponds from a deactivated uranium mine, with toxicologically relevant data, an in situ exposure with Pelophylax perezi tadpoles, was conducted. Tadpoles were exposed to the three effluent ponds, ranked by increasing order of metals concentrations (REF, M1, M2). Survival, growth, metal accumulation, antioxidant enzymes (catalase, glutathione peroxidase and glutathione reductase) and lipid peroxidation (LPO) were determined in tadpoles. As well, physical and chemical variables of the effluents were measured. Death percentage in the effluents was 3.17 (REF), 9.84 (M1) and 42.86% (M2) and was not coincident with metal accumulation which was highest in tadpoles exposed to M1, while metal contents in M2 tadpoles were quite similar to those recorded in REF tadpoles. However, high mortality in M2 was attributed to the extremely low pH (≈ 3.77). From the three effluents M2 tadpoles had the lowest growth and the antioxidant enzymatic activity was only affected in the case glutathione peroxidase (GPx) with significantly higher activity in M1, being in accordance with the highest accumulation of metals. LPO, usually associated with metal accumulation, had the following pattern M1 > REF > M2. Overall, effluent toxicity in tadpoles exposed to M2 effluent seems to be primarily an effect of pH while in M1 toxicity is mainly owed to high metal concentrations. The effluent acidity seems to reduce metal accumulation probably due to damage in the integument, affecting ion uptake. The results obtained bring a better understanding of the toxicological processes that local P. perezi population is subjected to, mainly in the early life stages. Furthermore this study highlights the influence of pH in the toxicity of metal rich effluents. - Highlights:

  3. Evaluation of growth, biochemical and bioaccumulation parameters in Pelophylax perezi tadpoles, following an in-situ acute exposure to three different effluent ponds from a uranium mine

    Marques, Sérgio M., E-mail: s.reis.marques@gmail.com [Departamento de Biologia da Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Chaves, Sandra [Universidade de Lisboa, Faculdade de Ciências, Centro de Biodiversidade, Genómica Integrativa e Funcional (BioFIG), Edifício ICAT, Campus da FCUL Campo Grande, Lisboa (Portugal); Gonçalves, Fernando [Departamento de Biologia da Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Pereira, Ruth [CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Departamento de Biologia da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto (Portugal)

    2013-02-15

    Mining activities invariably produce metal contaminated effluents. Depending on factors such as pH and metal concentration the toxicity of the effluent may vary. To assess the effects of three characteristically different effluent ponds from a deactivated uranium mine, with toxicologically relevant data, an in situ exposure with Pelophylax perezi tadpoles, was conducted. Tadpoles were exposed to the three effluent ponds, ranked by increasing order of metals concentrations (REF, M1, M2). Survival, growth, metal accumulation, antioxidant enzymes (catalase, glutathione peroxidase and glutathione reductase) and lipid peroxidation (LPO) were determined in tadpoles. As well, physical and chemical variables of the effluents were measured. Death percentage in the effluents was 3.17 (REF), 9.84 (M1) and 42.86% (M2) and was not coincident with metal accumulation which was highest in tadpoles exposed to M1, while metal contents in M2 tadpoles were quite similar to those recorded in REF tadpoles. However, high mortality in M2 was attributed to the extremely low pH (≈ 3.77). From the three effluents M2 tadpoles had the lowest growth and the antioxidant enzymatic activity was only affected in the case glutathione peroxidase (GPx) with significantly higher activity in M1, being in accordance with the highest accumulation of metals. LPO, usually associated with metal accumulation, had the following pattern M1 > REF > M2. Overall, effluent toxicity in tadpoles exposed to M2 effluent seems to be primarily an effect of pH while in M1 toxicity is mainly owed to high metal concentrations. The effluent acidity seems to reduce metal accumulation probably due to damage in the integument, affecting ion uptake. The results obtained bring a better understanding of the toxicological processes that local P. perezi population is subjected to, mainly in the early life stages. Furthermore this study highlights the influence of pH in the toxicity of metal rich effluents. - Highlights:

  4. Effects of brussels sprouts, indole 3-carbinol and phenobarbital on xenobiotic metabolism and in vivo DNA binding of aflatoxin B/sub 1/ in the rat

    Salbe, A.D.; Bjeldanes, L.F.

    1986-03-05

    Cruciferous vegetables have been shown to be potent inducers of xenobiotic-metabolizing enzymes in the rat and this may offer protection against chemical carcinogenesis. Adult, male, SD rats were fed on purified diets supplemented with 25% freeze-dried Brussels sprouts or 250 ppm idole 3-carbinol (I3C) for 2 weeks, or given phenobarbital (PB, 1 mg/ml) in the drinking water for 7 days prior to killing. Brussels sprouts caused a 50% decrease (p < 0.001) in the in vivo binding of (/sup 3/H) aflatoxin B/sub 1/ (AFB/sub 1/) to liver DNA, and increased intestinal and hepatic glutathione S-transferase (GST) activity. Hepatic monooxygenase activity was not altered in this group but greater than 2-fold increases in intestinal aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECD) activities were found. I3C did not decrease AFB/sub 1/ binding, nor did it increase hepatic or intestinal GST activity. I3C did increase both intestinal AHH and ECD activities. PB treatment significantly decreased AFB/sub 1/ binding by 60%, and significantly elevated hepatic but not intestinal GST activity. Hepatic AHH and ECD activities were also elevated in this group, while intestinal AHH and ECD activities were decreased. These results emphasize the importance of GST activity in the detoxification of AFB/sub 1/ and suggest a less important role for intestinal monooxygenase activity in the metabolism of this hepatocarcinogen.

  5. Effects of brussels sprouts, indole 3-carbinol and phenobarbital on xenobiotic metabolism and in vivo DNA binding of aflatoxin B1 in the rat

    Cruciferous vegetables have been shown to be potent inducers of xenobiotic-metabolizing enzymes in the rat and this may offer protection against chemical carcinogenesis. Adult, male, SD rats were fed on purified diets supplemented with 25% freeze-dried Brussels sprouts or 250 ppm idole 3-carbinol (I3C) for 2 weeks, or given phenobarbital (PB, 1 mg/ml) in the drinking water for 7 days prior to killing. Brussels sprouts caused a 50% decrease (p 3H] aflatoxin B1 (AFB1) to liver DNA, and increased intestinal and hepatic glutathione S-transferase (GST) activity. Hepatic monooxygenase activity was not altered in this group but greater than 2-fold increases in intestinal aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECD) activities were found. I3C did not decrease AFB1 binding, nor did it increase hepatic or intestinal GST activity. I3C did increase both intestinal AHH and ECD activities. PB treatment significantly decreased AFB1 binding by 60%, and significantly elevated hepatic but not intestinal GST activity. Hepatic AHH and ECD activities were also elevated in this group, while intestinal AHH and ECD activities were decreased. These results emphasize the importance of GST activity in the detoxification of AFB1 and suggest a less important role for intestinal monooxygenase activity in the metabolism of this hepatocarcinogen

  6. Severe chorea after acute carbon monoxide poisoning.

    Davous, P; Rondot, P; Marion, M H; Gueguen, B

    1986-01-01

    Ten days after an acute exposure to carbon monoxide, a 33-year-old woman exhibited severe chorea. CT scan revealed bilateral lucencies of the pallidum and anterior arm of the internal capsule. Chorea was successfully treated by chlorpromazine and did not relapse after treatment withdrawal. The mechanism of chorea in acute carbon monoxide poisoning is discussed.

  7. Exposure Forecaster

    U.S. Environmental Protection Agency — The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure...

  8. Facilitation of the HPA Axis to a Novel Acute Stress Following Chronic Stress Exposure Modulates Histone Acetylation and the ERK/MAPK Pathway in the Dentate Gyrus of Male Rats

    Ferland, Chantelle L.; Harris, Erin P.; Lam, Mai; Schrader, Laura A.

    2014-01-01

    Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal or enhanced hypothalamic-pituitary-adrenal (HPA) response compared with animals exposed solely to that acute stressor. The molecular mechanisms involved in this effect remain unknown. The extracellular signal-regulated kinase (ERK) is one of the key pathways regulated in the hippocampus in both acute and chronic stress. The aim of this study wa...

  9. SOMATOSENSORY DYSFUNCTION FOLLOWING ACUTE TRIMETHYLTIN EXPOSURE

    A variety of trimethyltin (TMT) -produced sensory and behavioral dysfunctions have been reported. In this study the functional integrity of the somatosensory system was evaluated. Animals were tested using three different measures prior to (day 0) and 1,4, and 16 days following d...

  10. Mercury Exposure and Children’s Health

    Bose-O’Reilly, Stephan; McCarty, Kathleen M; Steckling, Nadine; Lettmeier, Beate

    2010-01-01

    Acute or chronic mercury exposure can cause adverse effects during any period of development. Mercury is a highly toxic element; there is no known safe level of exposure. Ideally, neither children nor adults should have any mercury in their bodies because it provides no physiological benefit. Prenatal and postnatal mercury exposures occur frequently in many different ways. Pediatricians, nurses, and other health care providers should understand the scope of mercury exposures and health proble...

  11. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

  12. Acute pancreatitis

    ... page: //medlineplus.gov/ency/article/000287.htm Acute pancreatitis To use the sharing features on this page, ... fatty foods after the attack has improved. Outlook (Prognosis) Most cases go away in a week. However, ...

  13. Acute Pericarditis

    ... Sugar Control Helps Fight Diabetic Eye Disease Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... cancer, or heart surgery, the fluid is blood. Causes Acute pericarditis usually results from infection or other ...

  14. Acute dyspnea

    Radiodiagnosis is applied to determine the causes of acute dyspnea. Acute dyspnea is shown to aggravate the course of pulmonary diseases (bronchial asthma, obstructive bronchitis, pulmonary edema, throboembolism of pulmonary arteries etc) and cardiovascular diseases (desiseas of myocardium). The main tasks of radiodiagnosis are to determine volume and state of the lungs, localization and type of pulmonary injuries, to verify heart disease and to reveal concomitant complications

  15. Bronchitis (acute)

    Wark, Peter

    2008-01-01

    Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens.The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.A third of people may have longer-term symptoms or recurrence.

  16. Effects of Anti Epileptic Drugs; Phenytoin and Phenobarbital on Ossification Indices of Mouse Femur And Tibia And The Anti Teratogenic Effects of Folic Acid on the Reduction of Their Effects

    E Aliabadi

    2005-10-01

    Full Text Available Introduction: Patients suffering from epilepsy have to take antiepileptic drugs forever. It has been suggested that epilepsy itself and antiepileptic drugs are teratogenic. All aspects of the abnormalities that are induced by these drugs are unclear. Therefore, the objectives of this study were to determine the effects of two routine antiepileptic drugs on ossification. Besides, there was an attempt to decrease their teratogenic effects by using folic acid. Materials and Methods: 81 female mice (BALB/c were selected and divided into six groups. Pregnant mice were fed with phenytoin (45mg/kg, Phenobarbital (30mg/kg, phenytoin and folic acid (15

  17. Feedlot Acute Interstitial Pneumonia.

    Woolums, Amelia R

    2015-11-01

    Acute interstitial pneumonia (AIP) of feedlot cattle is a sporadically occurring respiratory condition that is often fatal. Affected cattle have a sudden onset of labored breathing. There is no confirmed effective treatment of feedlot AIP; however, administration of antibiotics effective against common bacterial respiratory pathogens and nonsteroidal anti-inflammatory drugs, especially aspirin, has been recommended. Protective strategies are not well defined, but efforts to limit dust exposure and heat stress; to ensure consistent formulation, mixing, and delivery of feed; and to identify and treat infectious respiratory disease in a timely manner may decrease rates of feedlot AIP. PMID:26253266

  18. 氯化石蜡急性暴露对斑马鱼胚胎发育的毒性效应%Toxicity effects on zebrafish(Danio rerio) larvae following embryonic acute exposure to chlorinated paraffins

    高永飞; 李佳; 李俊峰; 袁博; 张捷; 王亚韡; 梁勇

    2013-01-01

    比较研究了8种商品化氯化石蜡( CPs)急性暴露对斑马鱼( Danio rerio)胚胎早期发育的影响。实验结果表明,浓度分别为1、5、10和20 mg·L-1的CPs暴露7 d后均不会造成斑马鱼胚胎死亡,对斑马鱼胚胎的孵化率也无明显影响,但部分商品化CPs暴露对斑马鱼幼鱼鱼鳔发育具有明显的致畸效应,且随着暴露浓度的升高,鱼鳔畸形率显著上升,存在着明显的剂量-效应关系;此外,4种未氯化的短链石蜡烃( C10-C13)暴露对斑马鱼胚胎发育没有明显的毒性。上述研究结果表明,CPs急性暴露可造成斑马鱼幼鱼鱼鳔发育畸形,而这种致畸效应与CPs的含氯量不相关,与CPs中未经氯化的短链石蜡烃也无相关性,CPs对鱼类胚胎早期发育的潜在毒性效应需要进一步关注。%This paper compares the effects of eight commercial chlorinated paraffins ( CPs ) on early embryonic development of zebrafish( Danio rerio) following embryonic acute exposure. The results showed that after 7 days exposure, CPs did not lead to embryonic mortality at the concentration of 1, 5, 10, 20 mg·L-1 . Meanwhile, no significant effects were observed on hatching rate among all groups, while gas bladders deformity was observed in zebrafish larvae exposed with some of the chlorinated paraffins. As the concentration of the CPs increased, deformity rate of gas bladders of zebrafish larvae raised, with an obvious dose-response correlation. Besides, four non-chlorinated short chain paraffins(C10-13) had no obvious toxicity on zebrafish embryonic development. These data indicated that CPs could cause deformity on the development of gas bladders of zebrafish larvae. However, the deformity effect on larvae had no relevance with either the chlorine content or the percentage of non-chlorinated short-chain paraffins in CPs. The potential toxicity of CPs on early embryonic development of fish needs further attention.

  19. Acute myelogenous leukemia (AML) - children

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  20. CONSTITUTIVE ANDROSTANE RECEPTOR DEPENDENT AND INDEPENDENT MODULATION OF CYP3A2, CYP1A2 BY PHENOBARBITAL AND FIBRATE IN RATS’ LIVER

    Zein Shaban Ibrahim

    2013-01-01

    Full Text Available Cytochrome P450 enzymes, CYP3A and CYP1A are major drug metabolizing enzymes in the liver. CYP3A enzymes have a major role in the metabolism of 30-40% of all used drugs. CYP1A2 is a key enzyme having an important role in the metabolic clearance of 5% of currently marketed drugs. CYP1A2 participates in the metabolic activation of chemical mutagens in cooked food, therefore its activity is suspected to be one of the possible risk factors determining the carcinogenicity of heterocyclic amines in human beings. In a previous report, we have reported the induction of CYP3A2 and the inhibition of CYP1A2 by Fibrate (CFA and proved CYP1A2 inhibition to be PPARα-dependent. CYP3A2 and CYP1A2 have been reported to be induced in the liver by Phenobarbital (PB while Fibrates was reported to induce CYP3A2. However the exact mechanism of the induction of CYP3A2 by CFA and PB and induction of CYP1A2 by PB has not been clarified yet whether it is through Constitutive Androstane Receptor (CAR or other receptor as PPARα or Pregnane X Receptor (PXR. We treated Wistar female rats (with normal expression of CAR protein and Wistar femal Kyoto rats (with low expression of CAR protein with PB and Clofibric Acid (CFA. PB caused a high CYP3A2 induction in Wistar female rats and a low induction in (WKY indicating that PB induced CYP3A2 in a CAR-dependent manner. Interestingly, PB treatment induced CYP1A2 in Wistar female rats and failed to induce it in (WKY indicating that the induction of CYP1A2 by PB to be CAR-dependent. Moreover CFA induced CYP3A2 protein similarly in both rat strains indicating that CYP3A2 induction by Fibrates is CAR-independent and most probably to be PXR or PPARα-dependent. For the best of our knowledge this is the first report that shows a clear evidence of the CAR-dependent induction of CYP1A2 and CYP3A2 by PB and the CAR-independent induction of CYP3A2 by fibrates.