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Sample records for acute phenobarbital exposure

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

    Science.gov (United States)

    Khoutorsky, A; Bruchim, Y

    2008-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    C.M. Yokoro

    2001-03-01

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

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

    Science.gov (United States)

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

    2001-04-15

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

  5. Belladonna Alkaloid Combinations and Phenobarbital

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    Belladonna alkaloid combinations and phenobarbital are used to relieve cramping pains in conditions such as irritable bowel syndrome and ... Belladonna alkaloid combinations and phenobarbital come as a regular tablet, a slow-acting tablet, capsule, and liquid to take ...

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

    Science.gov (United States)

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

  7. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  8. In Vivo Nanodetoxication for Acute Uranium Exposure

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    Luis Guzmán

    2015-06-01

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

  9. Compound list: phenobarbital [Open TG-GATEs

    Lifescience Database Archive (English)

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

  10. Occupational exposure to solvents and acute myeloid leukemia

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. Health Impacts from Acute Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2003-09-30

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

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

    Science.gov (United States)

    Castellani, John W; Young, Andrew J

    2016-04-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  14. Continuous phenobarbital treatment leads to recurrent plantar fibromatosis.

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

    2008-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-11

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

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

    Directory of Open Access Journals (Sweden)

    Dörr Harald

    2011-11-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

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

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

    2017-01-01

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

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

    Science.gov (United States)

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

    1987-06-01

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

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

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-01-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

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    Jacopo M. Legramante

    2012-01-01

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

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

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    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.

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

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Moshiri

    2017-03-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

    Cesaroni, Giulia; Forastiere, Francesco; Stafoggia, Massimo

    2014-01-01

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

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

    Science.gov (United States)

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

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

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc; Gyongyi Szabo

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

    2014-10-23

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

  17. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Nielsen, M. Gissel

    1978-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  19. Pulmonary CT findings in acute mercury vapour exposure

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kathi A Lefebvre

    Full Text Available 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  2. Phenobarbital use and neurological problems in FMR1 premutation carriers

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    , and afterwards transferred to clean medium and observed for 48 h (post-exposure period) for acute effects and for 21 d for chronic effects. AgNO3 and CuCl2 were used as reference materials for dissolved silver and copper, respectively. For all test materials, a 3 h pulse caused comparable immobility in D. magna...... decreased more with increasing concentrations than for CuCl2 exposures when taking the measured dissolved copper into account. This indicates a nanoparticle-specific effect for CuONPs, possibly related to the CuONPs accumulated in the gut of D. magna during the pulse exposure. Pulse exposure...

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Brooke Riley

    2015-08-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-11-01

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

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

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1991-01-01

    . Normal therapeutic doses of cimetidine or propranolol have no measurable effect on toluene metabolism. Exposure to 100 ppm during 7 h causes irritation in the eyes and airways as well as feeling of intoxication, dizziness, and headache. There are signs of impairment in the performance in test concerning...

  10. Commuters’ air pollution exposure and acute health effects

    NARCIS (Netherlands)

    Zuurbier, M.M.M.

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-01-01

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

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

    Science.gov (United States)

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

    2010-10-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-01

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

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

    Science.gov (United States)

    Riley, Elizabeth; Kopotiyenko, Konstantin; Zhdanova, Irina

    2015-01-01

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

  2. Acute and Chronic Exposure to CO2 in Space Flight

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M Dominik Fischer

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

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

    Science.gov (United States)

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

    2013-11-27

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    龙尧

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Akay Metin

    2010-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2006-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Sun Mi Choi

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2012-02-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

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

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    Seok Kyu eKang

    2015-05-01

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

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

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    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.

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

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    Elke S. Reichwaldt

    2016-08-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-09-10

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-03-01

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

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

    Science.gov (United States)

    Sisodia, Rashmi; Sharma, K; Singh, Smita

    2009-01-01

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

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Michael S Madejczyk

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-06-15

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

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

    Science.gov (United States)

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

    1999-03-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    Stark, John D; Walthall, William K

    2003-12-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Christine E. Baer

    2014-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M Ahmadimanesh

    2014-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Science.gov (United States)

    Khozhaĭ, L I; Otellin, V A

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-05-15

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Reshma Sebastian Cherian

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2011-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dorit Kalo

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

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Pankaj Gupta

    2014-01-01

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

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

    Science.gov (United States)

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

    2000-08-01

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

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

    Science.gov (United States)

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

    2010-12-25

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Argiles Angel

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-08-10

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-02-26

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-08-01

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

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

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    Gorlin A

    2015-03-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anne-Christin Stöwhas

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

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

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

    Science.gov (United States)

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

    2006-05-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

    Khaksary Mahabady, Mahmood; Najafzadeh Varzi, Hossein

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-06-15

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

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

    Directory of Open Access Journals (Sweden)

    Rudolf L Riepl

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-02-26

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

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

    Science.gov (United States)

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

    2016-03-21

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

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

    Directory of Open Access Journals (Sweden)

    Rosiane V da Silva

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈惠金; 吴圣楣; 黄萍; 孙建华; 陈冠仪; 储凇雯

    2000-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

    WANG Dayong; XING Xiaojuan

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

    Mager, Edward M; Grosell, Martin

    2011-06-01

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

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

    OpenAIRE

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

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid recept...

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

    Science.gov (United States)

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

    2015-04-10

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

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

    Directory of Open Access Journals (Sweden)

    Ian L Megson

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

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

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Maria

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Walailuk Kerdsan

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-09-05

    Biospectroscopic investigations have attracted attention of both the clinicians and basic sciences researchers in recent years. Scientists are discovering new areas for FTIR biospectroscopy applications in medicine. The aim of this study was to measure the possibility of FTIR-MSP application for the recognition and detection of fetus abnormalities after exposure of pregnant mouse to phenobarbital (PB) and levamisole (LEV) alone or in combination. PB is one of the most widely used antiepileptic drugs (AEDs), with sedative and hypnotic effects. When used by pregnant women, it is known to be a teratogenic agent. LEV is an antihelminthic drug with some applications in immune-deficiency as well as colon cancer therapy. Four groups of ten pregnant mice were selected for the experiments as follows: one control group received only standard diet, one group was injected with 120mg/kg of BP, one group was injected with 10mg/kg of LEV, and the last group was treated simultaneously with both BP and LEV at the above mentioned doses. Drugs administration was performed on gestation day 9 and fetuses were dissected on pregnancy day 15. Each dissected fetus was fixed, dehydrated and embedded in paraffin. Sections of liver (10μm) were prepared from control and treated groups by microtome and deparaffinized with xylene. The spectra were taken by FTIR-MSP in the region of 4000-400cm(-1). All the spectra were normalized based on amide II band (1545cm(-1)) after baseline correction of the entire spectrum, followed by classification using PCA, ANN and SVM. Both morphological and spectral changes were shown in the treated fetuses as compared to the fetuses in the control group. While cleft palate and C-R elongation were seen in PB injected fetuses, developmental retardation was mostly seen in the LEV injected group. Biospectroscopy revealed that both drugs mainly affected the cellular lipids and proteins, with LEV causing more changes in amide I and lipid regions than PB. Application of

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

    Directory of Open Access Journals (Sweden)

    Masuko Alice Hatsue

    2003-01-01

    Full Text Available Convulsions triggered by fever are the most common type of seizures in childhood, and 20% to 30% of them have recurrence. The prophylactic treatment is still controversial, so we performed a systematic review to find out the effectiveness of continuous phenobarbital and intermittent diazepam compared to placebo for febrile seizure recurrence. METHOD: Only randomized, double-blind, placebo-controlled trials were analyzed. The recurrence of febrile seizure was assessed for each drug. RESULTS: Ten eligible clinical trials were included. Febrile seizure recurrence was smaller in children treated with diazepam or phenobarbital than in placebo group. Prophylaxis with either phenobarbital or diazepam reduces recurrences of febrile seizures. The studies were clinical, methodological, and statistically heterogeneous. CONCLUSION: The effectiveness of phenobarbital and diazepam could not be demonstrated because clinical trials were heterogeneous, and the recommendation for treatment recurrence should rely upon the experience of the assistant physician yet.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

    Science.gov (United States)

    2010-09-01

    induced airway blockage and acute autonomic effects such as mucoid-salivary hypersecretion, reduced airway patency, bradycardia, atrioventricular (AV...acute agent exposure. These included oro- facial movements (indicative of immoderate secretion), mild degree of dystonia/ataxia, and a short period of...intoxicated animals. At 24 hr post-CWA exposure, both the respiratory rate and breathing patterns across Groups 6-10 were comparable to those of

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-08-15

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

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Science.gov (United States)

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

  9. Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats.

    Science.gov (United States)

    Shenoy, A K; Miyahara, J T; Swinyard, E A; Kupferberg, H J

    1982-08-01

    The 1.5-benzodiazepine (clobazam), the 1,4-benzodiazepine (diazepam), and two nonbenzodiazepine antiepileptic drugs (phenobarbital and valproate) were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that clobazam and valproate exhibit a wider range of experimental anticonvulsant activity than either diazepam or phenobarbital. Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine). Clobazam is effective by the MES test in rats only in doses that exceed the median minimal toxic dose. Phenobarbital is effective against all of the above tests, but minimal toxic doses must be employed to prevent strychnine seizures. Diazepam, on the other hand, is effective in nontoxic doses against seizures induced by Metrazol, bicuculline, and picrotoxin, but protects animals from maximal electroshock and strychnine seizures only when given in toxic doses. When compared on the basis of protective indices (PI = TD50/ED50) calculated from intraperitoneal data, the PIs for clobazam were 1.6 to 13 times higher than those for diazepam. Overall, except for the MES test in rats, the PIs for clobazam were from 1.5 to 44 times higher than those for any of the other three substances. With respect to the MES test in rats, the PI for clobazam was 10.8 times higher than that for diazepam; however, the PIs for phenobarbital and valproate were 3.5 and 4.4 times higher, respectively, than that for clobazam. These data suggest that the spectrum of anticonvulsant activity for the 1,5-benzodiazepine (clobazam) is superior to that for the 1,4-benzodiazepine (diazepam). Also, the broad experimental profile of anticonvulsant activity of clobazam agrees well with its reported broad clinical efficacy.

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

    Directory of Open Access Journals (Sweden)

    Manish Barvaliya

    2011-01-01

    Full Text Available A 3-year-old female patient developed chorea possibly due to an interaction between phenytoin, phenobarbital and clobazam used for generalized tonic clonic seizures. Phenytoin withdrawal resulted in recovery within 24 hours. Post reaction computerized tomography (CT-scan of brain was normal. Combined use of anti-seizure drugs and interactions between them may be responsible for the reaction. Therapeutic drug monitoring is important while prescribing two or more anti-seizure drugs.

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

    Science.gov (United States)

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

    2012-03-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Antony P McNamee

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cristina Vázquez

    2016-09-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Sinclair, Brent J; Rajamohan, Arun

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana ePalomino

    2014-03-01

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

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

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

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

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

    Science.gov (United States)

    2015-02-12

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    1985-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gabriel Willmann

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

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

    Science.gov (United States)

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

    2011-01-01

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

  8. DNA breaks induced by micromolar concentrations of dimethylnitrosamine in liver primary cell cultures from untreated and phenobarbital treated rats.

    Science.gov (United States)

    Mendoza-Figueroa, T; López-Revilla, R; Villa-Treviño, S

    1983-05-01

    Direct genotoxic effects of the alkylating agent dimethylnitrosamine (DMN) have been difficult to detect in several short-term tests. We simplified our method to detect DNA breaks induced by DMN in rat liver primary cell cultures, and increased its sensitivity about 150 times by changing the conditions of ultracentrifugation and exposure to DMN. Additionally we increased 4 times the sensitivity of the improved assay by isolating hepatocytes from rats treated with phenobarbital (PB). Treatment for 24 h with 60 microM and 13.5 microM DMN of hepatocytes isolated from untreated and PB-treated rats, respectively, decreased the molecular weight of DNA by 50%. After 24 h exposure to 13.5 microM [14C]DMN, hepatocytes from PB-treated rats incorporated 3 times more radioactivity into trichloroacetic acid precipitable material than hepatocytes from untreated rats. Also PB-treatment increased remarkably cytotoxic effects of DMN while it did not modify the cytotoxicity nor the genotoxicity of the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. These results show that DMN is more genotoxic for hepatocytes from PB-treated rats, and suggest that the enhanced genotoxicity is probably due to an augmented metabolism of DMN by these cultures. Our improved assay of DNA breaks as an indicator of DMN genotoxicity is now as sensitive but faster to perform than hepatocyte-mediated mutagenesis. It could be used to explore genotoxic effects of other alkylating agents and the action of microsomal enzyme modifiers on genotoxicity.

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

    Directory of Open Access Journals (Sweden)

    Nirmalla Barros

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Abhilasha Shourie

    2014-06-01

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

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

    Science.gov (United States)

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

    2016-01-06

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

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

    Directory of Open Access Journals (Sweden)

    Krutika T. Deshpande

    2016-01-01

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

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

    Science.gov (United States)

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

    2009-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

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

    Science.gov (United States)

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

    2005-04-01

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

  16. 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure.

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    E.G.M. Mogoa

    2000-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Carriere, Marie [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: carriere@drecam.cea.fr; Gouget, Barbara [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gallien, Jean-Paul [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Avoscan, Laure [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gobin, Renee [Laboratoire d' imagerie cellulaire et moleculaire, DBJC/SBFM/LTMD, CEA/Saclay, 91191 Gif sur Yvette (France); Verbavatz, Jean-Marc [Laboratoire d' imagerie cellulaire et moleculaire, DBJC/SBFM/LTMD, CEA/Saclay, 91191 Gif sur Yvette (France); Khodja, Hicham [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)

    2005-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrea H Lewis

    2014-05-01

    Full Text Available Pavlovian conditioning involves the association of an inherently neutral stimulus with an appetitive or aversive outcome, such that the neutral stimulus itself acquires reinforcing properties. Across species, this type of learning has been shown to involve subcortical brain regions such as the striatum and the amygdala. It is less clear, however, how the neural circuitry involved in the acquisition of Pavlovian contingencies in humans is affected by acute stress. In the current study, we investigate the effect of acute stress exposure on Pavlovian conditioning using monetary reinforcers. Participants underwent a partial reinforcement conditioning procedure in which neutral stimuli were paired with high and low magnitude monetary gains and losses. A between-subjects design was used, such that half of the participants were exposed to cold stress while the remaining participants were exposed to a no stress control procedure. Cortisol measurements and subjective ratings were used as measures of stress. We observed an interaction between stress, valence and magnitude in the ventral striatum, with the peak in the putamen. More specifically, the stress group exhibited an increased sensitivity to magnitude in the gain domain. This effect was driven by those participants who experienced a larger increase in circulating cortisol levels in response to the stress manipulation. Taken together, these results suggest that acute stress can lead to individual differences in circulating cortisol levels which influence brain regions involved in associative learning such as the ventral striatum.

  20. The effects of acute stress exposure on striatal activity during Pavlovian conditioning with monetary gains and losses.

    Science.gov (United States)

    Lewis, Andrea H; Porcelli, Anthony J; Delgado, Mauricio R

    2014-01-01

    Pavlovian conditioning involves the association of an inherently neutral stimulus with an appetitive or aversive outcome, such that the neutral stimulus itself acquires reinforcing properties. Across species, this type of learning has been shown to involve subcortical brain regions such as the striatum and the amygdala. It is less clear, however, how the neural circuitry involved in the acquisition of Pavlovian contingencies in humans, particularly in the striatum, is affected by acute stress. In the current study, we investigate the effect of acute stress exposure on Pavlovian conditioning using monetary reinforcers. Participants underwent a partial reinforcement conditioning procedure in which neutral stimuli were paired with high and low magnitude monetary gains and losses. A between-subjects design was used, such that half of the participants were exposed to cold stress while the remaining participants were exposed to a no stress control procedure. Cortisol measurements and subjective ratings were used as measures of stress. We observed an interaction between stress, valence, and magnitude in the ventral striatum, with the peak in the putamen. More specifically, the stress group exhibited an increased sensitivity to magnitude in the gain domain. This effect was driven by those participants who experienced a larger increase in circulating cortisol levels in response to the stress manipulation. Taken together, these results suggest that acute stress can lead to individual differences in circulating cortisol levels which influence the striatum during Pavlovian conditioning with monetary reinforcers.

  1. Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea.

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    Yunji Hwang

    Full Text Available This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC.The Thyroid Cancer Longitudinal Study (T-CALOS included 2,258 DTC patients (449 men and 1,809 women and 22,580 healthy participants (4,490 men and 18,090 women who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs and 95% confidence intervals (95%CI were estimated using conditional regression models.While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion was associated with increased risks in men (OR = 2.22, 95%CI = 1.27-3.87 and women (OR = 3.61, 95%CI = 1.52-8.58 compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31-40 years: OR = 1.58, 95%CI = 1.10-2.28; 41+ years: OR = 3.46, 95%CI = 2.06-5.80 and women (31-40 years: OR = 2.18, 95%CI = 1.62-2.92; 41+ years: OR = 2.71, 95%CI = 1.36-5.05 compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage.The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.

  2. Monitorização terapêutica de fenobarbital = Therapeutic control of phenobarbital

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    Marcela Elisa Pastore

    2007-07-01

    Full Text Available Apesar do desenvolvimento de novos fármacos, o fenobarbital ainda temdestaque no tratamento da epilepsia por ser completo, efetivo e apresentar baixo custo. A margem terapêutica relativamente estreita e o risco do desenvolvimento de crises convulsivas, caso a dosagem não esteja adequada, fazem da monitorização terapêutica um procedimento de rotina na conduta do tratamento. O objetivo deste trabalho de caracterizar o perfil dos pacientes que se submeteram à monitorização terapêutica de fenobarbital em um laboratório de ensino em análises clínicas, no Estado do Paraná, nos anos de 2004 e 2005. Foi realizado um levantamento das fichas do laboratório e obtidos dados de 104pessoas que realizaram 119 determinações séricas do fármaco, dentre as quais 116 foram para a monitorização terapêutica. A maioria dos pacientes era adulta e realizou exames por solicitação de um serviço público de saúde. Observou-se que 49,1% dos resultados estavamacima ou abaixo da faixa terapêutica considerada. Foram realizados 49 exames em pacientes que faziam uso do fenobarbital em regime de monoterapia e 67 exames em pacientes que utilizavam este fármaco em associação com outros agentes antiepilépticos. A monitorizaçãode níveis séricos de fenobarbital mostra-se vantajosa frente ao grande número de fatores que evidenciam a necessidade de se correlacionar a concentração do fármaco com o estado clínico do paciente.Despite the development of new drugs, the phenobarbital still has prominence in the treatment of the epilepsy for being complete, effective and to present low cost. The relatively narrow therapeutical range and the risk of the development of convulsive crises in case the dosage is not well adjusted, make the therapeutical control a routine procedure. The aim of this work is to characterize the profile of the patients submitted to the therapeutical control of phenobarbital in a laboratory of clinical analysis in Paraná State

  3. Renal excretion in coho salmon (Oncorhynchus kisutch) after acute exposure to 3-trifluoromethyl-4-nitrophenol

    Science.gov (United States)

    Hunn, J.B.; Allen, J.L.

    1975-01-01

    COHO SALMON (ONCORHYNCHUS KISUTCH) EXPOSED TO AN ACUTE, SUBLETHAL CONCENTRATION OF 3-TRIFLUOROMETHLY 1-4 NITROPHENOL (TFM) EXHIBITED AN INCREASED OUTPUT OF URINE WHEN COMPARED WITH CONTROLS, BUT THE URINARY EXCRETION OF NA, K, CA, MG AND C1 WAS NOT AFFECTED. ABOUT 35 TIMES MORE CONJUGATED TFM THAN FREE TFM WAS EXCRETED DURING THE 24-HOUR STUDY PERIOD.

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

    Science.gov (United States)

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  5. Acute exposure to high environmental ammonia (HEA) triggers the emersion response in the green shore crab.

    Science.gov (United States)

    Zimmer, Alex M; Wood, Chris M

    2017-02-01

    The physiological effects of high environmental ammonia (HEA) exposure have been well documented in many aquatic species. In particular, it has recently been demonstrated that exposure to ammonia in fish leads to a similar hyperventilatory response as observed during exposure to hypoxia. In littoral crabs, such as the green crab (Carcinus maenas), exposure to severe hypoxia triggers an emersion response whereby crabs escape hypoxia to breathe air. We hypothesized that exposure to HEA in green crabs would lead to a similar behavioural response which is specific to ammonia. Using an experimental arena containing a rock bed onto which crabs could emerse, we established that exposure to HEA (4mmol/l NH4HCO3) for 15min triggers emersion in crabs. In experiments utilizing NaHCO3 controls and NH4HCO3 injections, we further determined that emersion was triggered specifically by external ammonia and was independent of secondary acid-base or respiratory disturbances caused by HEA. We then hypothesized that emersion from HEA provides a physiological benefit, similar to emersion from hypoxia. Exposure to 15min of HEA without emersion (no rock bed present) caused significant increases in arterial haemolymph total ammonia (Tamm), pH, and [HCO3(-)]. When emersion was allowed, arterial haemolymph Tamm and [HCO3(-)] increased, but no alkalosis developed. Moreover, emersion decreased haemolymph partial pressure of NH3 relative to crabs which could not emerse. Overall, we demonstrate a novel behavioural response to HEA exposure in crabs which we propose may share similar mechanistic pathways with the emersion response triggered by hypoxia.

  6. Exploring uncoupling proteins and antioxidant mechanisms under acute cold exposure in brains of fish.

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    Yung-Che Tseng

    Full Text Available Exposure to fluctuating temperatures accelerates the mitochondrial respiration and increases the formation of mitochondrial reactive oxygen species (ROS in ectothermic vertebrates including fish. To date, little is known on potential oxidative damage and on protective antioxidative defense mechanisms in the brain of fish under cold shock. In this study, the concentration of cellular protein carbonyls in brain was significantly increased by 38% within 1 h after cold exposure (from 28 °C to 18 °C of zebrafish (Danio rerio. In addition, the specific activity of superoxide dismutase (SOD and the mRNA level of catalase (CAT were increased after cold exposure by about 60% (6 h and by 60%-90% (1 and 24 h, respectively, while the specific glutathione content as well as the ratio of glutathione disulfide to glutathione remained constant and at a very low level. In addition, cold exposure increased the protein level of hypoxia-inducible factor (HIF by about 50% and the mRNA level of the glucose transporter zglut3 in brain by 50%-100%. To test for an involvement of uncoupling proteins (UCPs in the cold adaptation of zebrafish, five UCP members were annotated and identified (zucp1-5. With the exception of zucp1, the mRNA levels of the other four zucps were significantly increased after cold exposure. In addition, the mRNA levels of four of the fish homologs (zppar of the peroxisome proliferator-activated receptor (PPAR were increased after cold exposure. These data suggest that PPARs and UCPs are involved in the alterations observed in zebrafish brain after exposure to 18°C. The observed stimulation of the PPAR-UCP axis may help to prevent oxidative damage and to maintain metabolic balance and cellular homeostasis in the brains of ectothermic zebrafish upon cold exposure.

  7. Transient activation of microglia following acute alcohol exposure in developing mouse neocortex is primarily driven by BAX-dependent neurodegeneration.

    Science.gov (United States)

    Ahlers, Katelin E; Karaçay, Bahri; Fuller, Leah; Bonthius, Daniel J; Dailey, Michael E

    2015-10-01

    Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in the developing brain in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice, we found that alcohol-induced neuroapoptosis in the neocortex is closely correlated in space and time with the appearance of activated microglia near dead cells. The timing and molecular pattern of microglial activation varied with the level of cell death. Although microglia rapidly mobilized to contact and engulf late-stage apoptotic neurons, apoptotic bodies temporarily accumulated in neocortex, suggesting that in severe cases of alcohol toxicity the neurodegeneration rate exceeds the clearance capacity of endogenous microglia. Nevertheless, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, there was a transient increase in expression of pro-inflammatory factors, TNFα and IL-1β, after severe (5 g/kg) but not moderate (3 g/kg) EtOH levels. Alcohol-induced microglial activation and pro-inflammatory factor expression were largely abolished in BAX null mice lacking neuroapoptosis, indicating that microglial activation is primarily triggered by apoptosis rather than the alcohol. Therefore, acute alcohol exposure in the developing neocortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain.

  8. Effect of Acute Noise Exposure on Salivary Cortisol: A Randomized Controlled Trial.

    Science.gov (United States)

    Pouryaghoub, Gholamreza; Mehrdad, Ramin; Valipouri, Alireza

    2016-10-01

    Cardiovascular adverse effects are interesting aspects of occupational noise exposure. One possible mechanism of these effects is an alternation in hypothalamic-pituitary-adrenal axis. Our aim was to measure salivary cortisol response to relatively high-intensity noise exposure in a controlled randomized trial study. We exposed 50 male volunteers to 90 dBA noise for 20 minutes and compared their level of salivary cortisol with 50 non-exposed controls. Salivary samples obtained before and after exposure. Before intervention means (SD) salivary cortisol level were 3.24 (0.47)ng/ml and 3.25 (0.41)ng/ml for exposed and non-exposed groups respectively. Mean salivary cortisol level increased to 4.17 ng/mlafter intervention in exposure group. This increment was statistically significant (P=0.00). Mean salivary cortisol level of the non-exposed group had statistically non-significant decrement after this period (0.2 ng/ml). The difference between salivary cortisol level of non-exposed and exposed groups after the intervention was statistically significant. Noise exposure may affect the hypothalamic-pituitary-adrenal axis activity, and this may be one of the mechanisms of noise exposure cardiovascular effects.

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

    Directory of Open Access Journals (Sweden)

    Fabian Herzog

    2014-08-01

    Full Text Available In the emerging market of nano-sized products, silver nanoparticles (Ag NPs are widely used due to their antimicrobial properties. Human interaction with Ag NPs can occur through the lung, skin, gastrointestinal tract, and bloodstream. However, the inhalation of Ag NP aerosols is a primary concern. To study the possible effects of inhaled Ag NPs, an in vitro triple cell co-culture model of the human alveolar/airway barrier (A549 epithelial cells, human peripheral blood monocyte derived dendritic and macrophage cells together with an air–liquid interface cell exposure (ALICE system was used in order to reflect a real-life exposure scenario. Cells were exposed at the air–liquid interface (ALI to 0.03, 0.3, and 3 µg Ag/cm2 of Ag NPs (diameter 100 nm; coated with polyvinylpyrrolidone: PVP. Ag NPs were found to be highly aggregated within ALI exposed cells with no impairment of cell morphology. Furthermore, a significant increase in release of cytotoxic (LDH, oxidative stress (SOD-1, HMOX-1 or pro-inflammatory markers (TNF-α, IL-8 was absent. As a comparison, cells were exposed to Ag NPs in submerged conditions to 10, 20, and 30 µg Ag/mL. The deposited dose per surface area was estimated by using a dosimetry model (ISDD to directly compare submerged vs ALI exposure concentrations after 4 and 24 h. Unlike ALI exposures, the two highest concentrations under submerged conditions promoted a cytotoxic and pro-inflammatory response after 24 h. Interestingly, when cell cultures were co-incubated with lipopolysaccharide (LPS, no synergistic inflammatory effects were observed. By using two different exposure scenarios it has been shown that the ALI as well as the suspension conditions for the lower concentrations after 4 h, reflecting real-life concentrations of an acute 24 h exposure, did not induce any adverse effects in a complex 3D model mimicking the human alveolar/airway barrier. However, the highest concentrations used in the ALI setup, as well

  10. Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier

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    Enrrico Bloise

    2017-02-01

    Full Text Available Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB. As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C, increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5 were injected (i.p. with PolyI:C (5 mg/kg or 10 mg/kg or vehicle (saline. [3H]digoxin (P-gp substrate was injected (i.v. 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus, and fetal brains were collected. Results: PolyI:C exposure (4h significantly elevated maternal plasma IL-6 (P<0.001 and increased [3H]digoxin accumulation in the fetal brain (P<0.05. In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.

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

    Science.gov (United States)

    Marchini, T; Magnani, N D; Paz, M L; Vanasco, V; Tasat, D; González Maglio, D H; Alvarez, S; Evelson, P A

    2014-01-15

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

  12. Oxidative DNA damage after acute exposure to arsenite and monomethylarsonous acid in biomethylation-deficient human cells.

    Science.gov (United States)

    Orihuela, Ruben; Kojima, Chikara; Tokar, Erik J; Person, Rachel J; Xu, Yuanyuan; Qu, Wei; Waalkes, Michael P

    2013-07-01

    The carcinogen inorganic arsenic (iAs) undergoes biomethylation (BMT) in some cells. The methylated metabolite, monomethylarsonous (MMA(3+)), may cause oxidative DNA damage (ODD). With chronic iAs exposure, BMT-competent cells show ODD while BMT-deficient do not. To further define these events, we studied ODD produced by acute iAs or MMA(3+) in the BMT-deficient human prostate cell line, RWPE-1. ODD, measured by the immuno-spin trapping method, was assessed after exposure to iAs or MMA(3+) alone, with the arsenic BMT inhibitor selenite or after glutathione (GSH) depletion. The expression of oxidative stress-related genes (HO-1, SOD-1, SOD-2, Nrf2 and Keap-1) was also assessed. Exposure to iAs at 24 h (0-20 µM), stimulated ODD only at levels above the LC50 of a 48 h exposure (17 µM). If iAs induced ODD, it also activated oxidative stress-related genes. Selenium did not alter iAs-induced ODD. MMA(3+) at 24 h (0-0.5 µM) caused ODD at levels below the LC50 of a 48 h exposure (1.5 µM), which were greatly increased by GSH depletion but not selenite. MMA(3+) induced ODD at levels not activating oxidant stress response genes. Overall, iAs induced ODD in BMT-deficient cells only at toxic levels. MMA(3+) caused ODD at non-toxic levels, independently of cellular BMT capacity and in a fashion not requiring further BMT.

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

    Science.gov (United States)

    Burden, Christina M; Elmore, Christopher; Hladun, Kristen R; Trumble, John T; Smith, Brian H

    2016-05-01

    A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium-contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony.

  14. Maternal benzene exposure during pregnancy and risk of childhood acute lymphoblastic leukemia: a meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Yanfeng Zhou

    Full Text Available The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.Relevant studies up to September 1st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR with 95% confidence interval (CI for ALL was 1.25 (1.09, 1.45 for solvent, 1.23 (1.02, 1.47 for paint, 1.42 (1.10, 1.84 for petroleum exposure, and 0.99 (0.93, 1.06 for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.

  15. Acute cold- and chronic heat-exposure upregulate hepatic leptin and muscle uncoupling protein (UCP) gene expression in broiler chickens.

    Science.gov (United States)

    Dridi, Sami; Temim, Soraya; Derouet, Michel; Tesseraud, Sophie; Taouis, Mohammed

    2008-08-01

    Emerging evidence showed that variations in environmental temperature affect both leptin and uncoupling protein (UCP) gene expression in mammals, whereas a little is known about such interactions in birds. Thus, we conducted the present study to investigate the influence of acute (2 hours) cold (4 degrees C) and chronic (10 days) heat (32 degrees C) exposure on hepatic leptin and muscle UCP gene expression in 5-wk-old broiler chickens. Both cold- and heat-exposure significantly (P < 0.05 to P < 0.001) upregulated hepatic leptin (by 35 and 46%, respectively) and muscle UCP mRNA levels (by 71 and 71%, respectively) compared to the thermoneutrality (22 degrees C). This result suggests that leptin and UCP may be involved in the thermoregulation response of chickens to extreme climate (cold and hot temperatures). The upregulation of hepatic leptin gene expression was accompanied by an increase in plasma leptin levels, indicating that leptin may be regulated at transcriptional level. The increase of leptin and UCP mRNA abundance, and leptinemia we report here were not related to plasma glucose or insulin levels. In conclusion, the exposure of broiler chickens to extreme ambient temperatures (cold and heat) increases hepatic leptin and muscle UCP gene expression.

  16. Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

    Science.gov (United States)

    Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

    2016-12-01

    Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng‑1 bee), or one of two low doses (0.377 or 0.091 ng‑1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

  17. Associations of acute exposure to fine and coarse particulate matter and mortality among older people in Tokyo, Japan.

    Science.gov (United States)

    Yorifuji, Takashi; Kashima, Saori; Doi, Hiroyuki

    2016-01-15

    Recent studies have reported adverse health effects of short-term exposure to coarse particles independent of particulate matter less than 2.5 μm in diameter (PM2.5), but evidence in Asian countries is limited. We therefore evaluated associations between short-term exposure to particulate matter (PM) and mortality among older people in Tokyo, Japan. We used a time-stratified, case-crossover design. Study participants included 664,509 older people (≥65 years old) in the 23 urbanized wards of the Tokyo Metropolitan Government, who died between January 2002 and December 2013. We obtained PM2.5 and suspended particulate matter (SPM; PMrespiratory diseases; for example, both pollutants were positively associated with increased risk of all-cause mortality even after simultaneous adjustment for each pollutant: OR of 1.006 (95% CI: 1.003, 1.009) for PM2.5 and 1.016 (95% CI: 1.011, 1.022) for PM7-2.5. Even below concentrations stipulated by the Japanese air quality guidelines for PM2.5 and SPM (PM7), we observed adverse health effects. This study provides further evidence that acute exposure to PM2.5 and coarse particles is associated with increased risk of mortality among older people. Rigorous evaluation of air quality guidelines for daily average PM2.5 and larger particles should be continued.

  18. Strain- and context-dependent behavioural responses of acute alarm substance exposure in zebrafish.

    Science.gov (United States)

    Quadros, Vanessa A; Silveira, Ariane; Giuliani, Giulie S; Didonet, Fernanda; Silveira, Alessandra S; Nunes, Mauro E; Silva, Tális O; Loro, Vania L; Rosemberg, Denis B

    2016-01-01

    We investigate the behavioural responses of wild type (WT) and leopard (leo) zebrafish elicited by alarm substances of conspecifics at three contexts: during the exposure period (Experiment 1); after exposure, in habituation to novelty (Experiment 2); or after exposure, in the light-dark preference test (Experiment 3), and analyse their influence on pigment response. During the exposure, leo showed decreased vertical drifts, increased number and duration of erratic movements, while WT had increased erratic movements and latency to enter the top. In the novel tank, we observed that angular velocity decreased in WT exposed to alarm substance, which also presented increased fear responses. Contrastingly, leo increased the number of entries and time in top, indicating differences in habituation profile. Alarm substance increased the number of erratic movements in the light-dark test, but elicited different responses between strains in scototaxis, latency to enter the dark compartment and risk assessment episodes. Moreover, the body colour of zebrafish did not change after alarm substance exposure. Principal component analyses suggest that burst swimming, anxiety-like behaviours, and locomotion/exploration were the components that most accounted for total variances of Experiments 1, 2, and 3, respectively. We conclude that chemical cue from conspecifics triggers strain- and context-dependent responses.

  19. A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy.

    Science.gov (United States)

    Fredsø, N; Sabers, A; Toft, N; Møller, A; Berendt, M

    2016-02-01

    Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control. In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P = 0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy.

  20. Acute respiratory distress syndrome following cutaneous exposure to Lysol: a case report.

    Science.gov (United States)

    Liu, Y Y; Lu, C C; Perng, R P

    1999-12-01

    Lysol (mixed cresols) is a brand of popular detergent commonly used to disinfect toilets and floors in Taiwan. We report a patient with acute respiratory failure immediately following chemical burns caused by skin contact with Lysol solution. On admission, chest radiography showed bilateral diffuse pulmonary infiltrates and an arterial blood gas analysis disclosed hypoxemia refractory to a high concentration of oxygen by inhalation. Under the impression of acute respiratory distress syndrome, our patient was admitted to the intensive care unit for respiratory care. Poor clinical improvement was noted, despite aggressive respiratory therapy. High-dose steroid therapy (hydrocortisone 30 mg/kg/day) was administered from the seventh day after mechanical ventilation began and the ratio of arterial partial pressure of oxygen to fractional concentration of oxygen in inspired gas improved thereafter. The amount of steroid was gradually tapered to the maintenance dose and the patient was successfully weaned from the ventilator after a 93-day course of mechanical ventilation.

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

    Science.gov (United States)

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and

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

    Institute of Scientific and Technical Information of China (English)

    Arnold G. Nelson; Joke Kokkonen; Megan Mickenberg

    2015-01-01

    Background:Since it has been shown that spending 18 h under dim light conditions can result in reduced handgrip endurance, it was questioned whether or not a shorter exposure to dim light (i.e., 1 h) would have similar influence upon muscular endurance. Therefore this study compared the number of weighted knee extension lifts that could be done after spending 1 h in either dim or bright light. Methods:Participants (5 women, 11 men, college students 19-26 years) performed knee extension lifts to exhaustion with a load approximating 40%of their body weight. The lifts to exhaustion were measured immediately following 1 h of exposure to each of the following three con-ditions:dark (DL), room light (RL), and room light plus 5 mg melatonin (RLM). A minimum of 48 h separated each condition, and all par-ticipants started the exposures in a rested fed condition. Results:Average (±SD) number of knee extension lifts for RL (62.0 ± 22.0) was significantly ( p<0.05) greater than DL (51.4 ± 14.7) and RLM (57.8 ± 22.9). The number of RLM knee extension lifts was not significantly different from DL. Exposure to 1 h of dim light immediately prior to activity can result in a reduction in thigh muscle endurance. The decline in performance to short-term dim light exposure was similar to that found following longer-term exposure. Conclusion: It appears that light intensity can influence muscle endurance, however, at this time this effect cannot be directly related to endogenous melatonin production.

  3. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    Science.gov (United States)

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

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

    Science.gov (United States)

    Smith, Catherine A; Farmer, Kyle; Lee, Hyunmin; Holahan, Matthew R; Smith, Jeffrey C

    2015-10-27

    Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl) phthalate (DEHP) disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

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

    Directory of Open Access Journals (Sweden)

    Catherine A. Smith

    2015-10-01

    Full Text Available Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl phthalate (DEHP disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

  6. Increase in phorbol ester binding in liver microsomes after chronic administration of phenobarbital

    Energy Technology Data Exchange (ETDEWEB)

    Menez, J.F.; Deitrich, R.A. (Univ. of Colorado, Denver (United States))

    1991-03-15

    The effect of chronic administration of phenobarbital on the binding of phorbol-12,13-dibutyrate (({sup 3}H)PDBu), an activator of protein kinase C (PKC), was examined in rat liver microsomes. A significant increase in the number of binding sites was observed in microsomes of Fisher 344 rats. However, no change appeared in liver cytosol binding of PDBu. Consequently, a translocation process of PKC is unlikely. The increase in ({sup 3}H)PDBu binding in liver microsomes is significant 24 h. after one injection of phenobarbital and reaches its maximum in 2 days. In other strains of rats (ACI and lean Zucker), significant differences were found in the increase of ({sup 3}H)PDBu binding in microsomes. Fisher 344 were the most sensitive, lean Zucker rats, the least sensitive. Those results parallel the pentoxy-resorufin O demethylase activity in the microsomes of the same animals. EC{sub 50} values for inhibition of ({sup 3}H)PDBu binding by pentobarbital were determined in control microsomes from Fisher and Zucker rats. In Fisher rats, ({sup 3}H)PDBu binding in microsomes was found to be more sensitive to the inhibitory effect of pentobarbital than in lean Zucker rats, which suggests that the more microsomes are inhibited in vitro the greater the increase in PKC in microsomes following chronic barbiturate treatment.

  7. Histopathological Alterations of Hybrid Walking Catfish (Clarias macrocephalus x Clarias gariepinus in Acute and Subacute Cadmium Exposure

    Directory of Open Access Journals (Sweden)

    Nuntiya Pantung

    2008-01-01

    Full Text Available Histopathological alterations occur in the gills, livers and kidneys of 3-month old hybrid walking catsfich (Clarias macrocephalus x Clarias gariepinos after acute and subacute cadmium exposure in water, and after intraperitoneal injection.The 96-h LC50 for cadmium in recirculation open systems was 13.6 mg/l, and the 96-h LD50 1.6 mg/kg of fish. Light microscopic studies were carried out in gills, livers and kidneys. Gill alterations included an increased number of chloride cells, breakdown of the pillar cells and edema of the epithelial cells. In the liver there was blood conjestion in sinusoids and swelling of hepatocytes. The kidneys showed vacuolation and necrosis of proximal tubular cells.

  8. [Retrospective Cytogenetic Dose Evaluation. I. Chromosome Aberration Levels in Remote Periods after Acute External Exposure in Different Situations].

    Science.gov (United States)

    Nugs, V Yu; Khvostunov, I K; Goloub, E V; Kozlova, M G; Nadejina, N M; Galstian, I A

    2015-01-01

    Cytogenetic analysis of peripheral blood lymphocyte cultures of 22 persons was performed in remote terms after acute external γ-, γ-β- or γ-neutron irradiation as a result of various accidents using the classical me- thod. The initial dose estimates were obtained using physical calculations, the method of measuring the EPR signal in tooth enamel, according to haematological and/or cytogenetic parameters. The purpose of this study was to obtain evidence about the state of the lymphocyte chromosome apparatus of people approxi- mately 17-50 years after an accidental radiation exposure. In general, elevated levels of chromosome aberra- tions were detected. An average correlation was observed between the atypical chromosome frequency and absorbed dose. It is proposed to use the obtained results in the future to explore the possibility of retrospective dose evaluation on the basis of a special computer program.

  9. Changes of autonomic nervous system function in healthy young men during initial phase at acute high-altitude exposure

    Institute of Scientific and Technical Information of China (English)

    Qin Jun; Huang Lan; Tian Kaixin; Yu Shiyong; Yu Yang; Long Min

    2008-01-01

    Objective: To investigate the changes of autonomic nervous system (ANS) function during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level male residents were studied in Chengdu plain and then Tibet plateau. Heart rate variability (HRV), cold pressor test (CPT), resting heart rate (HR) and blood pressure (BP) were measured at baseline (560 m altitude) and in 2 to 4 d after arriving at Tibet plateau (3 675 m altitude) to assess the ANS function. Results: Compared with baseline, on day 2 in Tibet the standard deviation of normal to normal intervals (SDNN), high-frequency (HF) power, total power (TP), root mean square of delta RR (rMSSD), percentage of delta RR>50 ms (PNN50), normalized high-frequency (Hfnu) and fractal dimension (FD) decreased significantly (SDNN, HF,TP P<0.01, rMSSD, PNNs0, Hfnu, FD P<0.05), while the normalized low-frequency (Lfnu) and LF/HF increased significantly (P<0.01). During day 3-4 in Tibet, SDNN, rMSSD, HF, TP and Hfnu tended to rebound while Lfnu and LF/HF decreased towards baseline day by day. In addition, in Tibet the increase in systolic pressure (SP) and diastolic pressure (DP) during CPT decreased significantly (P<0.01, 0.05), but resting HR increased compared with baseline (P<0.01). Conclusion: ANS modulation is generally blunted, and the relatively predominant sympathetic control is enhanced originally, then it reverts to the sea level states gradually during the initial days of acute high-altitude exposure.

  10. Effects of Acute and Subacute Oral Methylnitroguanidine (MeNQ) Exposure to Rats (Rattus norvegicus)

    Science.gov (United States)

    2016-04-20

    Assay Testing and sampling procedures for the micronucleus assay followed the methodology outlined in the protocol provided in the MicroFlow Basic...or female rats up to the limit dose of 2000 milligrams/kilogram (mg/kg) body weight in the acute test . There were also no signs clinical signs of...toxicity or morbidity in the subacute 14-day study up to 1250 mg/kg-day, the highest dose tested in both males and females. As no signs of toxicity were

  11. Cellular metabolic, stress, and histological response on exposure to acute toxicity of endosulfan in tilapia (Oreochromis mossambicus).

    Science.gov (United States)

    Kumar, Neeraj; Sharma, Rupam; Tripathi, Gayatri; Kumar, Kundan; Dalvi, Rishikesh S; Krishna, Gopal

    2016-01-01

    Endosulfan is one of the most hazardous organochlorines pesticides responsible for environmental pollution, as it is very persistent and shows bio-magnification. This study evaluated the impact of acute endosulfan toxicity on metabolic enzymes, lysozyme activities, heat shock protein (Hsp) 70 expression, and histopathology in Tilapia (Oreochromis mossambicus). Among the indicators that were induced in dose dependent manner were the enzymes of amino acid metabolism (serum alanine aminotransferase and aspartate aminotransferase), carbohydrate metabolism (serum lactate dehydrogenase), pentose phosphate pathway (Glucose-6-phosphate dehydrogenase) as well as lysozyme and Hsp70 in liver and gill, while liver and gill Isocitrate dehydrogenase (TCA cycle enzyme) and marker of general energetics (Total adenosine triphosphatase) were inhibited. Histopathological alterations in gill were clubbing of secondary gill lamellae, marked hyperplasia, complete loss of secondary lamellae and atrophy of primary gill filaments. Whereas in liver, swollen hepatocyte, and degeneration with loss of cellular boundaries were distinctly noticed. Overall results clearly demonstrated the unbalanced metabolism and damage of the vital organs like liver and gill in Tilapia due to acute endosulfan exposure.

  12. Pulmonary Inflammatory Responses To Acute Meteorite Dust Exposures - Implications For Human Space Exploration

    Science.gov (United States)

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

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive, and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative

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

    Science.gov (United States)

    2015-05-19

    to ROS production [22]. The International Agency for Research on Cancer (IARC) has classified both Cd and Cr as known human carcinogens [23]. Although...metabolism. There were thirteen pathways that were common to both exposures. The majority of the identified inflam - mation pathways were found after Cd...by macrophages and neutrophils. ROS can interact with DNA, leading to ad- duct formation that impairs base-pairing and/or blocks DNA replication and

  14. The Acute Effects of Single Exposures to White Phosphorus Smoke in Rats and Guinea Pigs

    Science.gov (United States)

    1980-09-01

    males and three females per dose, were used. The animals, weighing between 200 and 300 grams, were fasted overnight prior to desing . The liquid used in...min_’u n, nfinc animals died during exposure. The sunivine animal had respirator, problems far i houlr and t!-_- gradually recovered. 3. Hematology and...ATTN: MAJ Borges APO San Francisco 96328) Defense- Technical Information Center ATTN: DTIC-DDA-2 2 Commander Cau;icon Station, Building 5 2d Infantry

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

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures. (ACR)

  16. Estimating the acute health effects of coarse particulate matter accounting for exposure measurement error.

    Science.gov (United States)

    Chang, Howard H; Peng, Roger D; Dominici, Francesca

    2011-10-01

    In air pollution epidemiology, there is a growing interest in estimating the health effects of coarse particulate matter (PM) with aerodynamic diameter between 2.5 and 10 μm. Coarse PM concentrations can exhibit considerable spatial heterogeneity because the particles travel shorter distances and do not remain suspended in the atmosphere for an extended period of time. In this paper, we develop a modeling approach for estimating the short-term effects of air pollution in time series analysis when the ambient concentrations vary spatially within the study region. Specifically, our approach quantifies the error in the exposure variable by characterizing, on any given day, the disagreement in ambient concentrations measured across monitoring stations. This is accomplished by viewing monitor-level measurements as error-prone repeated measurements of the unobserved population average exposure. Inference is carried out in a Bayesian framework to fully account for uncertainty in the estimation of model parameters. Finally, by using different exposure indicators, we investigate the sensitivity of the association between coarse PM and daily hospital admissions based on a recent national multisite time series analysis. Among Medicare enrollees from 59 US counties between the period 1999 and 2005, we find a consistent positive association between coarse PM and same-day admission for cardiovascular diseases.

  17. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

  18. Effect of acute and chronic arsenic exposure on growth, structure and virulence of Aeromonas hydrophila isolated from fish.

    Science.gov (United States)

    Goswami, Ramansu; Ghosh, Debabrata; Saha, Dhira Rani; Padhy, Pratap Kumar; Mazumder, Shibnath

    2011-02-01

    Aeromonas hydrophila being a ubiquitous bacterium is prone to arsenic exposure. The present study was designed to determine the role of arsenic on growth and virulence of A. hydrophila. Exposure to arsenic (1 mg L(-1) and 2 mg L(-1)) had no effect on growth but significantly inhibited the hemolytic and cytotoxic potential of exposed bacteria. Transmission electron microscopy revealed loss of membrane integrity and presence of condensed cytoplasm suggestive of acute stress in bacteria exposed to arsenic. Arsenic-adapted bacteria were developed by repeated sub-culturing in presence of arsenic. Arsenic-adaptation led to significant recovery in hemolytic and cytotoxic potential. The arsenic-adapted bacteria exhibited normal membrane integrity, decreased cytoplasmic condensation and possessed scattered polysome like structures in the cytoplasm. A positive correlation was observed between arsenic tolerance and resistance to several antimicrobials. Arsenic-adaptation failed to confer cross-protection to mercury and cadmium stress. SDS-PAGE analysis revealed the expression of two new proteins of approximately 85 kDa and 79 kDa respectively in arsenic-adapted A. hydrophila. Plasmid-curing and transformation studies clearly indicate plasmid has no role on arsenic resistance trait of the bacteria. Our study, for the first time, reports a structure and function relationship of xenobiotics on bacteria.

  19. Early changes in gene expression induced by acute UV exposure in leaves of Psychotria brachyceras, a bioactive alkaloid accumulating plant.

    Science.gov (United States)

    do Nascimento, Naíla Cannes; Menguer, Paloma Koprovski; Sperotto, Raul Antonio; de Almeida, Márcia Rodrigues; Fett-Neto, Arthur Germano

    2013-05-01

    UV-B radiation can damage biomolecules, such as DNA, RNA, and proteins, halting essential cellular processes; this damage is partly due to ROS generation. Plant secondary metabolites may protect against UV-B. Psychotria brachyceras Müll. Arg. (Rubiaceae), a subtropical shrub, produces brachycerine, a monoterpene indole alkaloid mainly accumulated in leaf tissues, which displays antioxidant and antimutagenic activities. Exposure of P. brachyceras cuttings to UV-B radiation significantly increases leaf brachycerine concentration. It has been suggested that this alkaloid might contribute to protection against UV-B damage both through its quenching activity on ROS and as UV shield. To identify differentially expressed genes of P. brachyceras in response to UV-B and investigate a possible influence of this stimulus on putative brachycerine-related genes, suppressive subtractive hybridization was applied. Complementary DNA from UV-B-treated leaves for 24 h was used as tester, and cDNA from untreated leaves, as driver. After BLASTX alignments, 134 sequences matched plant genes. Using quantitative RT-PCR, selected genes potentially related to brachycerine showed significant increases in transcription after UV-B exposure: tryptophan decarboxylase, ACC oxidase, UDP-glucose glucosyltransferase, lipase, and serine/threonine kinase. Results suggest a possible involvement of brachycerine in acute UV-B responses and show that alkaloid accumulation seems at least partly regulated at transcriptional level.

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

    Science.gov (United States)

    Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

    2016-04-01

    Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs.

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

    Science.gov (United States)

    To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  3. Occupational exposure levels of bioaerosol components are associated with serum levels of the acute phase protein Serum Amyloid A in greenhouse workers

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Thilsing, Trine; Bælum, Jesper;

    2016-01-01

    to elevated levels of bioaerosols. The objective of this study is to assess whether greenhouse workers personal exposure to bioaerosol components was associated with serum levels of the acute phase proteins Serum Amyloid A (SAA) and C-reactive protein (CRP). METHODS: SAA and CRP levels were determined...

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

    NARCIS (Netherlands)

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

    2002-01-01

    This study investigated the effects of exposure to an intermittent homotypic stressor on: (i) habituation of acute autonomic responsivity (i.e. cardiac sympathovagal balance and susceptibility to arrhythmias), and (ii) circadian rhythmicity of heart rate, body temperature, and physical activity. Aft

  5. USE OF THE FUNGICIDE CARBENDAZIM AS A MODEL COMPOUND TO DETERMINE THE IMPACT OF ACUTE CHEMICAL EXPOSURE DURING OOCYTE MATURATION AND FERTILIZATION ON PREGNANCY OUTCOME IN THE HAMSTER

    Science.gov (United States)

    Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected...

  6. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures.

    Science.gov (United States)

    Wang, Ning; Mebane, Christopher A; Kunz, James L; Ingersoll, Christopher G; Brumbaugh, William G; Santore, Robert C; Gorsuch, Joseph W; Arnold, W Ray

    2011-09-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO(3) , pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72 µg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267 µg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61 µg Cu/L for survival; 8.8-38 µg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215 µg Cu/L) for survival or approximately fourfold (12-42 µg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

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

    Directory of Open Access Journals (Sweden)

    Tornero-Velez Rogelio

    2008-11-01

    Full Text Available Abstract Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg or permethrin (1 – 100 mg/kg followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM and isotonic regression (PIR methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1 was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25% in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of

  8. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness.

    Science.gov (United States)

    Hamilton, Trevor James; Kwan, Garfield T; Gallup, Joshua; Tresguerres, Martin

    2016-01-25

    Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab.

  9. Influence of Phenobarbital and Carbon tetrachloride on the Modulation of Tissue Retention Profile of Hexachlorocyclohexane in Rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The study was designed to investigate the role of hepatic metabolic activity on body burden of HCH residue. Male albino rats were orally administered 0, 5, and 10 mg/kg HCH for 90 days, followed by either sodium phenobarbital or carbon tetrachloride treatment for 0, 15 and 30 days after withdrawal of their respective HCH administration. The liver weight was significantly increased at 30 days after the administration of phenobarbital and carbon tetrachloride in both 5 mg and 10 mg/kg HCH withdrawal groups when compared to control. HCH residue was maximun in fat followed by adrenal>thymus>liver>kidney>spleen>testes>brain>plasma. Carbon tetrachloride caused an accumul-ation of HCH residues in the liver 15 and 30 days after administration of both doses of HCH. Phenobarbital did not show significant variation in HCH residues in hepatic tissue. Phenobarbital treatment caused significant induction of hepatic RED, APD, AHH, GST and QR activities. Significant decreases in activities were observed by carbon tetrachloride when compared to animals treated with HCH alone. The overall results clearly suggest the role of P450 protein on the body burden of HCH residues.

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

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

    2014-02-01

    Investigations on the use of Low Level Laser Therapy (LLLT) for wound healing especially with the red laser light have demonstrated its pro-healing potential on a variety of pre-clinical and surgical wounds. However, until now, in LLLT the effect of multiple exposure of low dose laser irradiation on acute wound healing on well-designed pre-clinical model is not much explored. The present study aimed to investigate the effect of multiple exposure of low dose Helium Neon laser on healing progression of full thickness excision wounds in Swiss albino mice. Further, the efficacy of the multiple exposure of low dose laser irradiation was compared with the single exposure of optimum dose. Full thickness excision wounds (circular) of 15 mm diameter were created, and subsequently illuminated with the multiple exposures (1, 2, 3, 4 and 5 exposure/ week until healing) of He-Ne (632.8 nm, 4.02 mWcm-2) laser at 0.5 Jcm-2 along with single exposure of optimum laser dose (2 J/cm-2) and un-illuminated controls. Classical biophysical parameters such as contraction kinetics, area under the curve and the mean healing time were documented as the assessment parameters to examine the efficacy of multiple exposures with low level laser dose. Experimental findings substantiated that either single or multiple exposures of 0.5 J/cm2 failed to produce any detectable alterations on wound contraction, area under the curve and mean healing time compared to single exposure of optimum dose (2 Jcm-2) and un-illuminated controls. Single exposure of optimum, laser dose was found to be ideal for acute wound healing.

  11. Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2004-04-15

    Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.

  12. Oxidative stress in toadfish (Halobactrachus didactylus) cardiac muscle. Acute exposure to vanadate oligomers.

    Science.gov (United States)

    Aureliano, M; Joaquim, N; Sousa, A; Martins, H; Coucelo, J M

    2002-06-07

    Vanadate solutions as "metavanadate" (containing ortho and metavanadate species) and "decavanadate" (containing mainly decameric species) (5 mM; 1 mg/kg) were injected intraperitoneously in Halobatrachus didactylus (toadfish), in order to evaluate the contribution of decameric vanadate species to vanadium (V) intoxication on the cardiac tissue. Following short-term exposure (1 and 7 days), different changes on antioxidant enzyme activities-superoxide dismutase (SOD), catalase (CAT), selenium-glutathione peroxidase (Se-GPx), total glutathione peroxidase (GPx), lipid peroxidation and subcellular vanadium distribution were observed in mitochondrial and cytosolic fractions of heart ventricle toadfish. After 1 day of vanadium intoxication, SOD, CAT and Se-GPx activities were decreased up to 25%, by both vanadate solutions, except mitochondrial CAT activity that increased (+23%) upon decavanadate administration. After 7 days of exposure, decavanadate versus metavanadate solutions promoted different effects mainly on cytosolic CAT activity (-56% versus -5%), mitochondrial CAT activity (-10% versus +10%) and total GPx activity (+1% versus -35%), whereas lipid peroxidation products were significantly increased (+82%) upon 500 microM decavanadate intoxication. Accumulation of vanadium in total (0.137+/-0.011 microg/g) and mitochondrial (0.022+/-0.001 microg/g) fractions was observed upon 7 days of metavanadate exposure, whereas for decavanadate, the concentration of vanadium increased in cytosolic (0.020+/-0.005 microg/g) and mitochondrial (0.021+/-0.009 microg/g) fractions. It is concluded that decameric vanadate species are responsible for a strong increase on lipid peroxidation and a decrease in cytosolic catalase activity thus contributing to oxidative stress responses upon vanadate intoxication, in the toadfish heart.

  13. Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.

    Science.gov (United States)

    Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu; Rousseau, Bernard

    2016-10-01

    Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases.

  14. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    a portion of the proliferative cells in this model using the one-target-one-hit theory of cell damage (Lea, 1955) Another powerful model of small...71.5, pp. 786–792. Sato F et al. (1972). “Radiation effects on cell populations in the intestinal epithelium of mice and its theory ”. Cell and Tissue...DTRA-TR-16-059 DISTRIBUTION A. Approved for public release: distribution is unlimited. Exposure to burn and radiation elicit epithelial cell death in

  15. Risk of cataract in the context of acute and chronic exposure

    Directory of Open Access Journals (Sweden)

    Tukov A.R.

    2016-12-01

    Full Text Available Purpose: estimation of the risk of cataract using doses of different types of radiation. Material and methods. The study is carried out using the information database of the NP, recovery workers of the accident at the Chernobyl NP. Professional exposure and dose received during 30 km zone were used to calculate the risk. Results. The study shows the use of one of their parts of the total radiation dose of man, leads to obtaining of different levels of the risk of disease. Conclusion. Only use of a total radiation dose can lead to obtaining of the correct results of evaluating the risk of the emergence of the radiation- induced diseases.

  16. Acute high-intensity sound exposure alters responses of place cells in hippocampus.

    Science.gov (United States)

    Goble, T J; Møller, A R; Thompson, L T

    2009-07-01

    Overstimulation is known to activate neural plasticity in the auditory nervous system causing changes in function and re-organization. It has been shown earlier that overstimulation using high-intensity noise or tones can induce signs of tinnitus. Here we show in studies in rats that overstimulation causes changes in the way place cells of the hippocampus respond as rats search for rewards in a spatial maze. In familiar environments, a subset of hippocampal pyramidal neurons, known as place cells, respond when the animal moves through specific locations but are relatively silent in others. This place-field activity (i.e. location-specific firing) is stable in a fixed environment. The present study shows that activation of neural plasticity through overstimulation by sound can alter the response of these place cells. Rats implanted with chronic drivable dorsal hippocampal tetrodes (four microelectrodes) were assessed for stable single-unit place-field responses that were extracted from multiunit responses using NeuroExplorer computer spike-sorting software. Rats then underwent either 30 min exposure to a 4 kHz tone at 104 dB SPL or a control period in the same sound chamber. The place-field activity was significantly altered after sound exposure showing that plastic changes induced by overstimulation are not limited to the auditory nervous system but extend to other parts of the CNS, in this case to the hippocampus, a brain region often studied in the context of plasticity.

  17. Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells.

    Science.gov (United States)

    Briffa, Jessica F; Grinfeld, Esther; Mathai, Michael L; Poronnik, Phillip; McAinch, Andrew J; Hryciw, Deanne H

    2015-02-05

    Increased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-β1 (TGF-β1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-β1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-β1 secretion (0.50 µg/ml) and phosphorylated AMPKα (at 0.25, and 0.50 µg/ml), and downregulates megalin expression at all concentrations (0.05-0.50 µg/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-β1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 µg/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-β1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway.

  18. Cholinesterase inhibition and depression of the photic after discharge of flash evoked potentials following acute or repeated exposures to a mixture of carbaryl and propoxur.

    Science.gov (United States)

    Mwanza, Jean-Claude; Lyke, Danielle F; Hertzberg, Richard C; Haber, Lynne; Kohrman-Vincent, Melissa; Li, Ruosha; Pan, Yi; Lyles, Robert H; Simmons, Jane Ellen; Macmillan, Denise K; Zehr, R Dan; Swank, Adam E; Herr, David W

    2012-06-01

    Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had

  19. Telomere dynamics in human mesenchymal stem cells after exposure to acute oxidative stress

    DEFF Research Database (Denmark)

    Harbo, M.; Koelvraa, S.; Serakinci, N.;

    2012-01-01

    A gradual shortening of telomeres due to replication can be measured using the standard telomere restriction fragments (TRF) assay and other methods by measuring the mean length of all the telomeres in a cell. In contrast, stress-induced telomere shortening, which is believed to be just...... as important for causing cellular senescence, cannot be measured properly using these methods. Stress-induced telomere shortening caused by, e.g. oxidative damage happens in a stochastic manner leaving just a few single telomeres critically short. It is now possible to visualize these few ultra-short telomeres...... due to the advantages of the newly developed Universal single telomere length assay (STELA), and we therefore believe that this method should be considered the method of choice when measuring the length of telomeres after exposure to oxidative stress. In order to test our hypothesis, cultured human...

  20. Reinforcer devaluation as a consequence of acute nicotine exposure and withdrawal

    Science.gov (United States)

    Kirshenbaum, Ari; Green, John; Fay, Michael; Parks, Angelique; Phillips, Jesse; Stone, Jason; Roy, Tessa

    2014-01-01

    RATIONALE Nicotine discontinuation produces behaviors in rats that are congruent with anhedonia, and these symptoms may be related to the devaluation of non-nicotine reinforcers. OBJECTIVE Four separate experiments were performed to explore the parameters surrounding nicotine-induced reinforcer devaluation. METHODS In Experiments 1 and 2, nicotine (0.1 or 0.3 mg/kg) or 0.3 mg/kg nicotine plus 1.0 mg/kg mecamylamine was delivered to rats prior to progressive ratio (PR) schedule sessions in which sucrose was used as a reinforcer. In order to (a) evaluate reinforcer enhancement by nicotine, and (b) reinforcer devaluation in the absence of nicotine, all rats experienced two PR schedule sessions per day for 10 days. Experiment 3 involved nicotine (0.3 mg/kg) and a visual stimulus in place of sucrose reinforcement. In Experiment 4, rats received nicotine (0.3 mg/kg) either before or after a single PR-schedule session for 10 days. RESULTS Experiments 1 and 2 demonstrate that reinforcer devaluation is related to the occupation of nicotinic-acetylcholine receptors. Results from Experiment 3 provide some evidence that devaluation occurs with either sucrose or visual-stimulus reinforcement. Experiment 4 demonstrates that a necessary condition for reinforcer devaluation to occur is the concurrent exposure to the reinforcer and nicotine. CONCLUSIONS Reinforcer devaluation in rats emerges rapidly in a progressive, orderly fashion that coincides with accumulated exposure to nicotine. These results suggest that reinforcer devaluation may be a feature of nicotine that contributes to the abuse liability of tobacco products. PMID:25401169

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

    Directory of Open Access Journals (Sweden)

    Rajab-Ali Sadrkhanloo

    2012-03-01

    Full Text Available This study was designed to evaluate the detrimental effect of atrazine (ATR on germinal epitheliums (GE cytoplasmic carbohydrate (CH and unsaturated fatty acids (UFA ratio and to clarify the effect of ATR on serum levels of FSH, LH, testosterone and inhibin-B (INH-B. The impact of ATR exposure on total antioxidant capacity (TAC, sperm DNA packing and integrity were also investigated. Seventy two Wistar rats were used. The rats in control group received vehicle and the animals in test groups received 100, 200 and 300 mg kg-1 BW of ATR orally on daily bases for 12, 24 and 48 days. In ATR-received groups the spermatogenesis cell were presented with dense reactive sites for lipidophilic staining associated with faint cytoplasmic CH accumulation. Dissociated germinal epithelium, negative tubular and repopulation indexes were manifested. The serum levels of testosterone, FSH, LH and INH-B decreased by 85% after 48 days exposure to high dose of ATR. TAC was reduced in a time- and dose-dependent manner. The sperm DNA damage was marked in animals which exposed to high dose of ATR (72.50 ± 2.25% and the percentage of nuclear immature sperm increased up to 83.40 ± 0.89%. In conclusion, ATR not only induced its detrimental effect on the endocrine function of the testes and pituitary gland but also affected the cytoplasmic CH ratio and consequently leads to inadequate energy supplement in spermatogenesis cells. Therefore the imbalanced oxidative stress occurs in testicular tissue, which in turn enhances the sperm DNA disintegrity and nuclear immaturity.

  2. Effects of Air Pollutant Exposure on Acute Myocardial Infarction, According to Gender

    Science.gov (United States)

    Tuan, Tássia Soldi; Venâncio, Taís Siqueira; Nascimento, Luiz Fernando Costa

    2016-01-01

    Background: There is evidence of the effects of air pollution on hospital admissions due to cardiovascular diseases, including myocardial infarction. Objective: To estimate the association between exposure to air pollutants and hospital admissions due to myocardial infarction according to gender, between January 1st 2012 and December 31st 2013, in São Jose dos Campos-SP. Methods: An ecological time series study was carried out with daily data of admissions due to AMI, pollutants CO, O3, PM10, SO2, and NO2, according to gender. We used the Poisson regression generalized linear model to estimate the relative risks of hospital admissions with lags of 0-5 days, adjusted for temperature, humidity, seasonality and days of the week. Results: There were 1837 admissions for ischemic heart diseases, with 636 women and 1201 men. For females, the risks were significant for CO in lag 0 (RR = 1,09), lag1 (RR = 1,08) and lag 5 (RR = 1,10) and SO2 in lag 0 (RR = 1,10) and 3 (RR = 1,09). For men there was significance of the CO in, lag 3 and lag 5 (RR = 1,05). There was significance, regardless of gender, for CO at lag 1 (RR = 1,05) and lag 5 (RR = 1,07) and lag 0 for SO2 (RR = 1,06). Conclusion: The data presented show the important role of CO and SO2 in the genesis of myocardial infarction admissions, and responses to pollutant exposure are different if analyzed by gender and together - hence the importance of a stratified analyses. PMID:27533257

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    cases occurred in the same patient at two different admissions. It was not considered necessary to move the patient to the Intensive Care Unit (ICU). Three patients developed pneumonia and were moved to the ICU, one of whom developed a life-threatening sepsis. One patient with chronic emphysema died due...... in DT patients treated with phenobarbital. MATERIALS AND METHODS: We examined the medical records of patients who were treated as inpatients in 1998-2006 and discharged with the ICD-10 diagnoses F10.4 (alcohol withdrawal delirium) or F10.5 (alcohol induced psychotic disorder). Patients with pre....... An intensive focus on the patient's somatic condition in DT is therefore recommended, and it should always be possible to move the patient to the ICU Udgivelsesdato: 2008/6/2...

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

    Directory of Open Access Journals (Sweden)

    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.

  5. In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model.

    Directory of Open Access Journals (Sweden)

    Barbara Ambruosi

    Full Text Available Phthalates are ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl phthalate (DEHP is the most abundant phthalate and it impairs fertility by acting as an endocrine disruptor. The aim of the present study was to analyze the effects of in vitro acute exposure to DEHP on oocyte maturation, energy and oxidative status in the horse, a large animal model. Cumulus cell (CC apoptosis and oxidative status were also investigated. Cumulus-oocyte complexes from the ovaries of slaughtered mares were cultured in vitro in presence of 0.12, 12 and 1200 µM DEHP. After in vitro maturation (IVM, CCs were removed and evaluated for apoptosis (cytological assessment and TUNEL and intracellular reactive oxygen species (ROS levels. Oocytes were evaluated for nuclear chromatin configuration. Matured (Metaphase II stage; MII oocytes were further evaluated for cytoplasmic energy and oxidative parameters. DEHP significantly inhibited oocyte maturation when added at low doses (0.12 µM; P<0.05. This effect was related to increased CC apoptosis (P<0.001 and reduced ROS levels (P<0.0001. At higher doses (12 and 1200 µM, DEHP induced apoptosis (P<0.0001 and ROS increase (P<0.0001 in CCs without affecting oocyte maturation. In DEHP-exposed MII oocytes, mitochondrial distribution patterns, apparent energy status (MitoTracker fluorescence intensity, intracellular ROS localization and levels, mt/ROS colocalization and total SOD activity did not vary, whereas increased ATP content (P<0.05, possibly of glycolytic origin, was found. Co-treatment with N-Acetyl-Cysteine reversed apoptosis and efficiently scavenged excessive ROS in DEHP-treated CCs without enhancing oocyte maturation. In conclusion, acute in vitro exposure to DEHP inhibits equine oocyte maturation without altering ooplasmic energy and oxidative stress parameters in matured oocytes which retain the potential to be fertilized and develop into

  6. Acute ocular injuries caused by 60-Ghz millimeter-wave exposure.

    Science.gov (United States)

    Kojima, Masami; Hanazawa, Masahiro; Yamashiro, Yoko; Sasaki, Hiroshi; Watanabe, Soichi; Taki, Masao; Suzuki, Yukihisa; Hirata, Akimasa; Kamimura, Yoshitsugu; Sasaki, Kazuyuki

    2009-09-01

    The goal of this study was to examine the clinical course of 60-GHz millimeter-wave induced damages to the rabbit eye and to report experimental conditions that allow reproducible induction of these injuries. The eyes of pigmented rabbits (total number was 40) were irradiated with 60-GHz millimeter-waves using either a horn antenna or one of two lens antennas (6 and 9 mm diameter; phi6, phi9) Morphological changes were assessed by slit-lamp microscopy. Additional assessments included corneal fluorescein staining, iris fluorescein angiography, and lens epithelium light microscopy. Under the standardized eye-antenna positioning, the three antennas caused varying damages to the eyelids or eyeglobes. The most reproducible injuries without concurrent eyelid edema and corneal desiccation were achieved using the phi6 lens antenna: irradiation for 6 min led to an elevation of the corneal surface temperature (reaching 54.2 +/- 0.9 degrees C) plus corneal edema and epithelial cell loss. Furthermore, mitotic cells appeared in the pupillary area of the lens epithelium. Anterior uveitis also occurred resulting in acute miosis (from 6.6 +/- 1.4 to 2.2 +/- 1.4 mm), an increase in flares (from 6.7 +/- 0.9 to 334.3 +/- 130.8 photons per second), and iris vasodilation or vessel leakage. These findings indicate that the three types of millimeter-wave antennas can cause thermal injuries of varying types and levels. The thermal effects induced by millimeter-waves can apparently penetrate below the surface of the eye.

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

    Science.gov (United States)

    Crawford, Charles G.

    2004-01-01

    The Food Quality Protection Act of 1996 requires that human exposure to pesticides through drinking water be considered when establishing pesticide tolerances in food. Several systematic and seasonally weighted systematic sampling strategies for estimating pesticide concentrations in surface water were evaluated through Monte Carlo simulation, using intensive datasets from four sites in northwestern Ohio. The number of samples for the strategies ranged from 4 to 120 per year. Sampling strategies with a minimal sampling frequency outside the growing season can be used for estimating time weighted mean and percentile concentrations of pesticides with little loss of accuracy and precision, compared to strategies with the same sampling frequency year round. Less frequent sampling strategies can be used at large sites. A sampling frequency of 10 times monthly during the pesticide runoff period at a 90 km 2 basin and four times monthly at a 16,400 km2 basin provided estimates of the time weighted mean, 90th, 95th, and 99th percentile concentrations that fell within 50 percent of the true value virtually all of the time. By taking into account basin size and the periodic nature of pesticide runoff, costs of obtaining estimates of time weighted mean and percentile pesticide concentrations can be minimized.

  8. Nose-to-brain transport of aerosolised quantum dots following acute exposure.

    Science.gov (United States)

    Hopkins, Laurie E; Patchin, Esther S; Chiu, Po-Lin; Brandenberger, Christina; Smiley-Jewell, Suzette; Pinkerton, Kent E

    2014-12-01

    Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots (QDs) are semiconductor nanocrystals possessing unique optical and electrical properties. Although QDs are commonly made of cadmium, a metal known to have neurological effects, potential transport of QDs directly to the brain has not been assessed. This study evaluated whether QDs (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of QDs for 1 h via nasal inhalation, and nanoparticles were detected 3 h post-exposure within the olfactory tract and olfactory bulb by a wide range of techniques, including visualisation via fluorescent and transmission electron microscopy. We conclude that, following short-term inhalation of solid QD nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response. To our knowledge, this is the first study to clearly demonstrate that QDs can be rapidly transported from the nose to the brain by olfactory uptake via axonal transport following inhalation.

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

    Directory of Open Access Journals (Sweden)

    Chowdhury P

    2003-09-01

    Full Text Available Abstract Cigarette smoking is known to be a major risk factor for pancreatic cancer and pancreatitis is believed to be a predisposed condition for pancreatic cancer. As of this date, there is no established experimental animal model to conduct detailed studies on these two deadly diseases. Our aim is to establish a rodent model by which we can systematically study the pathogenesis of pancreatitis and pancreatic cancer. Methods Adult Male Sprague Dawley rats were exposed to graded doses of nicotine by various routes for periods of three to 16 weeks. Blood samples were measured for hormonal and metabolic parameters. The pancreas was evaluated for histopathological changes and its function was assessed in isolated pancreatic acini upon stimulation with cholecystokinin (CCK or carbachol (Cch. The pancreatic tissue was evaluated further for oncogene expression. Results Body weight, food and fluid intakes, plasma glucose and insulin levels were significantly reduced in animals with nicotine exposure when compared to control. However, CCK and gastrin levels in the blood were significantly elevated. Pancreatic function was decreased significantly with no alteration in CCK receptor binding. Pancreatic histology revealed vacuolation, swelling, cellular pyknosis and karyorrhexis. Mutant oncogene, H-ras, was overexpressed in nicotine-treated pancreatic tissue. Summary and conclusion The results suggest that alterations in metabolic, hormonal and pathologic parameters following nicotine-treatment appear consistent with diagnostic criteria of human pancreatitis. It is proposed that rats could be considered as a potential animal model to study the pathogenesis of pancreatitis.

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

    Directory of Open Access Journals (Sweden)

    Tiffany-Jane Evans

    Full Text Available Genome wide association studies (GWAS have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL. Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358 and population controls (n = 1192. Furthermore, we utilised family trio (n = 204 genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9, and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9. There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05. There were no interactions of risk genotypes with age or sex (P-values >0.2. Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.

  11. Coronary CT angiography for acute chest pain triage: Techniques for radiation exposure reduction; 128 vs. 64 multidetector CT

    Energy Technology Data Exchange (ETDEWEB)

    Goitein, Orly; Eshet, Yael; Konen, Eli (Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)), email: orly.goitein@sheba.health.gov.il; Matetzky, Shlomi (Heart Inst., Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)); Goitein, David (Surgery C, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)); Hamdan, Ashraf; Di Segni, Elio (Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel); Heart Inst., Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel))

    2011-10-15

    Background. Coronary CT angiography (CCTA) is used daily in acute chest pain triage, although exposing patients to significant radiation dosage. CCTA using prospective ECG gating (PG CCTA) enables significant radiation reduction Purpose. To determine whether the routine use of 128 vs. 64 multidetector CT (MDCT) can increase the proportion of patients scanned using PG CCTA technique, lowering radiation exposure, without decreasing image quality. Material and Methods. The study comprised 232 patients, 116 consecutive patients scanned using 128 MDCT (mean age 49 years, 79 men, BMI 28) and 116 consecutive patients (mean age 50 years, 75 men, BMI 28) which were scanned using 64 MDCT. PG CCTA was performed whenever technically permissible by each type of scanner: 64 MDCT = stable heart rate (HR) <60/min and weight <110 kg; 128 MDCT = stable HR < 70/min and weight <140 kg. All coronary segments were evaluated for image quality using a visual scale of 1-5. An estimated radiation dose was recorded. Results. PC CCTA was performed in 84% and 49% of the 128 and 64 MDCT groups, respectively (P < 0.0001). Average image quality score were 4.6 +- 0.3 and 4.7 +- 0.1 for the 128 and 64 MDCT, respectively (P = 0.08). The mean radiation dose exposure was 6.2 +- 4.8 mSv and 10.4 +- 7.5 mSv for the 128 and 64 MDCT, respectively (P = 0.008). Conclusion. The 128 MDCT scanner enables utilization of PG CCTA technique in a greater proportion of patients, thereby decreasing the related radiation significantly, without hampering image quality

  12. Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion.

    Science.gov (United States)

    Mickley, G Andrew; Remus, Jennifer L; Ramos, Linnet; Wilson, Gina N; Biesan, Orion R; Ketchesin, Kyle D

    2012-01-18

    opportunity to drink saccharin was provided (spontaneous recovery test). Saline-treated control rats that went through the EU-EXT procedure achieved asymptotic extinction more quickly than did the CSO-EXT rats and did not exhibit a spontaneous recovery of the CTA. Chronic DCS treatments did not significantly reduce the time to achieve asymptotic CTA extinction in rats exposed to either CSO or EU extinction methods. Further, animals treated with DCS throughout EU-EXT exhibited a spontaneous recovery of the CTA whereas the saline-treated, EU-EXT rats did not. Thus, chronic DCS treatment did not shorten the time to extinguish a CTA and this treatment eliminated the ability of EU-EXT to block spontaneous recovery of the CTA. Acute DCS treatments were more effective in reducing the time required to extinguish a CTA than were chronic drug treatments. Moreover, the timing of these acute DCS treatments affected spontaneous recovery of the CTA depending on the extinction method employed. Acute DCS administrations later in extinction were more effective in reducing spontaneous recovery than were early administrations if the rats went through the CSO-EXT procedure. However, late-in-extinction administrations of DCS facilitated spontaneous recovery of the CTA in rats that experienced the EU-EXT method. These data agree with other findings suggesting that DCS treatments are more effective when administered a limited number of times. Our data extend these findings to the CTA paradigm and further suggest that, depending on the extinction paradigm employed, acute exposure to DCS can speed up CTA extinction and reduce spontaneous recovery of the aversion. The timing of the acute DCS treatment during extinction is generally less important than its duration in predicting the rate of CTA extinction. However, the timing of acute DCS treatments during extinction and the method of extinction employed can interact to affect spontaneous recovery of a CTA.

  13. Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment

    Directory of Open Access Journals (Sweden)

    Cherry eIgnacio

    2014-09-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of Social Enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or Social Enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by Social Enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for Social Enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression.

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

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

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

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2017-01-01

    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...... 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  17. Phenobarbital influence on neuromuscular block produced by rocuronium in rats Influência do fenobarbital no bloqueio neuromuscular produzido pelo rocurônio em ratos

    OpenAIRE

    Angélica de Fátima de Assunção Braga; Caroline Coutinho de Barcelos; Franklin Sarmento da Silva Braga; Samanta Cristina Antoniassi Fernandes; Yoko Oshima Franco; Mario Mantovani; Léa Rodrigues Simioni

    2008-01-01

    PURPOSE: To evaluate in vitro and in vivo neuromuscular blockade produced by rocuronium in rats treated with Phenobarbital and to determine cytochrome P450 and cytochrome b5 concentrations in hepatic microsomes. METHODS: Thirty rats were included in the study and distributed into 6 groups of 5 animals each. Rats were treated for seven days with phenobarbital (20 mg/kg) and the following parameters were evaluated: 1) the amplitude of muscle response in the preparation of rats exposed to phenob...

  18. Effects of Acute Exposure to Increased Plasma Branched-Chain Amino Acid Concentrations on Insulin-Mediated Plasma Glucose Turnover in Healthy Young Subjects

    OpenAIRE

    Sarah Everman; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

    2015-01-01

    Background Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. Objective To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Methods Ten healthy subjects were randomly assigned to...

  19. Effects of prenatal maternal injections of phenobarbital on brain neurotransmitters and behavior of young C57 mice.

    Science.gov (United States)

    Middaugh, L D; Thomas, T N; Simpson, L W; Zemp, J W

    1981-01-01

    Offspring of C57BL/6J mice injected daily with phenobarbital (20 or 40 mg/kg) for the last 6 or 7 days of pregnancy were compared with offspring of saline control mice on behavioral and neurochemical measures of brain function at 21 days of age. Activity in an open field arena was elevated in male offspring and reactivity to presentation of a tone-light stimulus was increased for female offspring of drug treated dams. Brain concentration of dopamine and norepinephrine was reduced and the uptake of dopamine, norepinephrine serotonin and gamma-aminobutyric acid into synaptosomal preparations of brain tissue was greater for treated offspring. Both the behavioral and neurochemical indices indicate that the brain is altered by maternal prenatal injections of phenobarbital but the relationship between these changes remains speculative.

  20. Determination of phenobarbital in human plasma by a specific liquid chromatography method: application to a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Sérgio Luiz Dalmora

    2010-01-01

    Full Text Available A liquid chromatography method was developed and validated for the determination of phenobarbital in human plasma using phenytoin as internal standard. The drugs were extracted from plasma by liquid-liquid extraction and separated isocratically on a C12 analytical column, maintained at 35 ºC, with water:acetonitrile:methanol (58.8:15.2:26, v/v/v as mobile phase, run at a flow rate of 1.2 mL/min with detection at 205 nm. The method was linear in the range of 0.1-4 μg/mL (r²=0.9999 and demonstrated acceptable results for the precision, accuracy and stability studies. The method was successfully applied for the bioequivalence study of two tablet formulations (test and reference of phenobarbital 100 mg after single oral dose administration to healthy human volunteers.

  1. Metabolism of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent.

    Science.gov (United States)

    Wu, Xianai; Kania-Korwel, Izabela; Chen, Hao; Stamou, Marianna; Dammanahalli, Karigowda J; Duffel, Michael; Lein, Pamela J; Lehmler, Hans-Joachim

    2013-11-01

    1. Chiral polychlorinated biphenyls (PCBs) such as PCB 136 enantioselectively sensitize the ryanodine receptor (RyR). In light of recent evidence that PCBs cause developmental neurotoxicity via RyR-dependent mechanisms, this suggests that enantioselective PCB metabolism may influence the developmental neurotoxicity of chiral PCBs. However, enantioselective disposition of PCBs has not been fully characterized. 2. The effect of sex and cytochrome P450 (P450) enzyme induction on the enantioselective metabolism of PCB 136 was studied using liver tissue slices prepared from naïve control (CTL), phenobarbital (PB; CYP2B inducer) or dexamethasone (DEX; CYP3A inducer) pretreated adult Sprague-Dawley rats. PCB 136 metabolism was also examined in hippocampal slices derived from untreated rat pups. 3. In liver tissue slices, hydroxylated PCB (OH-PCB) profiles depended on sex and inducer pretreatment, and OH-PCB levels followed the rank orders male > female and PB > DEX > CTL. In contrast, the enantiomeric enrichment of PCB 136 and its metabolites was independent of sex and inducer pretreatment. Only small amounts of PCB 136 partitioned into hippocampal tissue slices and no OH-PCB metabolites were detected. 4. Our results suggest that enantioselective metabolism, sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs.

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

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    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.

  3. Acute Kidney Injury, Risk Factors, and Prognosis in Hospitalized HIV-Infected Adults in South Africa, Compared by Tenofovir Exposure

    Science.gov (United States)

    Martinson, Neil; Motlhaoleng, Katlego; Abraham, Pattamukkil; Mancama, Dalu; Naicker, Saraladevi; Variava, Ebrahim

    2017-01-01

    Abstract There are limited data describing acute kidney injury (AKI) in HIV-infected adult patients in resource-limited settings where tenofovir disoproxil fumarate (TDF), which is potentially nephrotoxic, is increasingly prescribed. We describe risk factors for and prognosis of AKI in HIV-infected individuals, stratified by those receiving and those naive to TDF. A prospective case cohort study of hospitalized HIV-infected adults with AKI stratified by TDF exposure. Adults (≥18 years) were recruited: clinical and biochemical data were collected at admission; their renal recovery, discharge, or mortality was ascertained as an in-patient and, subsequently, to a scheduled 3-month follow-up. Among this predominantly female (61%), almost exclusively black African cohort of 175 patients with AKI, 93 (53%) were TDF exposed; median age was 41 years (interquartile range 35–50). Median CD4 count and viral load and creatinine at baseline were 116 cells/mm3 and 110,159 copies/ml, respectively. A greater proportion of the TDF group had severe AKI on admission (61% vs. 43%, p = .014); however, both groups had similar rates of newly diagnosed tuberculosis (TB; 52%) and nonsteroidal anti-inflammatory drug (NSAID; 32%) use. Intravenous fluid was the therapeutic mainstay; only seven were dialyzed. Discharge median serum creatinine (SCr) was higher in the TDF group (p = .032) and fewer in the TDF group recovered renal function after 3 months (p = .043). Three-month mortality was 27% in both groups, but 55% of deaths occurred in hospital. Those that died had a higher SCr and more severe AKI than survivors; TB was diagnosed in 33 (70%) of those who died. AKI was more severe and renal recovery slower in the TDF group; comorbidities, risk factors, and prognosis were similar regardless of TDF exposure. Because TB is linked to higher mortality, TB coinfection in HIV-infected patients with AKI warrants more intensive monitoring. In all those with poor renal recovery, our

  4. Prior exposure to capture heightens the corticosterone and behavioural responses of little penguins (Eudyptula minor) to acute stress.

    Science.gov (United States)

    Carroll, Gemma; Turner, Emma; Dann, Peter; Harcourt, Rob

    2016-01-01

    Studies of physiology can provide important insight into how animals are coping with challenges in their environment and can signal the potential effects of exposure to human activity in both the short and long term. In this study, we measured the physiological and behavioural response of little penguins (Eudyptula minor) that were naïve to human activity over 30 min of capture and handling. We assessed relationships between corticosterone secretion, behaviour, sex and time of day in order to characterize the determinants of the natural stress response. We then compared the response of these naïve penguins with the responses of female little penguins that had been exposed to research activity (bimonthly nest check and weighing) and to both research activity (monthly nest check and weighing) and evening viewing by tourists. We found that corticosterone concentrations increased significantly over 30 min of capture, with naïve penguins demonstrating a more acute stress response during the day than at night. Penguins that had previously been exposed to handling at the research and research/visitor sites showed elevated corticosterone concentrations and consistently more aggressive behaviour after 30 min compared with naïve birds, although there were no significant differences in baseline corticosterone concentrations. Our findings demonstrate that these little penguins have not habituated to routine capture, but rather mount a heightened physiological and behavioural response to handling by humans. Less invasive research monitoring techniques, such as individual identification with PIT tags and automatic recording and weighing, and a reduction in handling during the day should be considered to mitigate some of the potentially negative effects of disturbance. Given the paucity of data on the long-term consequences of heightened stress on animal physiology, our study highlights the need for further investigation of the relationship between the corticosterone

  5. Postradiation-time dependant dose-response of bone-marrow-cell genetic structures in mice given acute gamma-ray exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, B.; Bulanova, M.; Praskova, L.; Filev, G. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1981-01-01

    Adult mice have received acute exposures to cesium-137 gamma rays at four dose lebels ranging from 0.029 to 0.129 K/kg. 20 hours after the exposure bone-marrow-cell metaphase slides were prepared for cytogemetic analysis. The findings indicated quantitative relations to exist between the scores of structural chromosome aberrations and radiation dose. The chromosome and chromatid fragment fitted to an equation of the Y = aDsup(n) type, chromosome and chromatid exchanges exhibited a linear relationship, and aberrant-cell data were described a linear-quadratic equation. The aberrant-cell percentage seen 20 hrs and 30 hrs after exposure to 0.03225 K/kg proved higher than the one observed at 40 hrs and 72 hrs postradiation.(A.B.).

  6. Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure.

    Science.gov (United States)

    Tolu, Pierluigi; Masi, Flavio; Leggio, Benedetta; Scheggi, Simona; Tagliamonte, Alessandro; De Montis, M Graziella; Gambarana, Carla

    2002-09-01

    Acetyl-L-carnitine (ALCAR) is the acetyl ester of carnitine that has been reported to be beneficial in depressive disorders and Alzheimer's disease. A 7-day administration of ALCAR in rats increased dopamine and serotonin output in the nucleus accumbens shell and it prevented the development of escape deficit produced by acute exposure to unavoidable stress. No tolerance developed to this protective effect, which appeared to be mediated by (1) the activation of 5-HT(1A) receptors, as it was antagonized by the administration of WAY100635 30 min before stress exposure; and (2) a process of neuronal plasticity dependent on NMDA receptor activity, as subcutaneous dizocilpine infusion during ALCAR treatment prevented the development of the protective effect on stress. Chronic stress exposure maintains an escape deficit condition that is reverted by a long-term treatment with antidepressants, but the same condition was not modified by long-term ALCAR administration. Thus, ALCAR cannot be defined as an antidepressant.

  7. The quantitative distinction of hyperplasia from hypertrophy in hepatomegaly induced in the rat liver by phenobarbital.

    Science.gov (United States)

    Carthew, P; Edwards, R E; Nolan, B M

    1998-07-01

    A histological method utilizing the optical dissector principle has been developed for determining the absolute numbers of rat hepatocytes in the liver after treatment with phenobarbital (PB). The optical dissector is a technique derived from the "new stereology" used to measure the number of features, in this case hepatocyte nuclear profiles, that are present in a reference volume of tissue. The method has been applied to distinguish between the hepatomegaly that commonly occurs in rodents after treatment with chemicals, due to an increase in the number of cells caused by cell division (hyperplasia), rather than the size of cells (hypertrophy). In the case of PB treatment, the hepatomegaly was found to be partly due to hypertrophy and partly to hyperplasia after 2 weeks of treatment. While the increase in the absolute number of hepatocytes was not significant after 2 weeks, after 12 weeks of treatment with PB the number of hepatocytes was significantly increased, compared to the controls at that time point. PCNA labeling index measurements of liver hepatocytes confirmed that there was a significant increase in the growth fraction of hepatocytes during PB treatment. The induction of hyperplasia can be associated with an increased risk of eventual liver tumor formation, and the distinction of hyperplasia from hypertrophy, using a purely histological method, for the determination of increases in absolute hepatocyte cell numbers, will be useful in assessing whether treatment-related sustained hyperplasia is occurring in the liver, although this methodology could be applied to any organ.

  8. Phenobarbital and Insulin Reciprocate Activation of the Nuclear Receptor Constitutive Androstane Receptor through the Insulin Receptor.

    Science.gov (United States)

    Yasujima, Tomoya; Saito, Kosuke; Moore, Rick; Negishi, Masahiko

    2016-05-01

    Phenobarbital (PB) antagonized insulin to inactivate the insulin receptor and attenuated the insulin receptor downstream protein kinase B (AKT)-forkhead box protein O1 and extracellular signal-regulated kinase 1/2 signals in mouse primary hepatocytes and HepG2 cells. Hepatic AKT began dephosphorylation in an early stage of PB treatment, and blood glucose levels transiently increased in both wild-type and constitutive androstane receptor (CAR) knockout (KO) mice. On the other hand, blood glucose levels increased in wild-type mice, but not KO mice, in later stages of PB treatment. As a result, PB, acting as an insulin receptor antagonist, elicited CAR-independent increases and CAR-dependent decreases of blood glucose levels at these different stages of treatment, respectively. Reciprocally, insulin activation of the insulin receptor repressed CAR activation and induction of its target CYP2B6 gene in HepG2 cells. Thus, PB and insulin cross-talk through the insulin receptor to regulate glucose and drug metabolism reciprocally.

  9. Modifications of benzene myelotoxicity and metabolism by phenobarbital, SKF-252A and 3-methylcholanthrene

    Energy Technology Data Exchange (ETDEWEB)

    Gill, D.P.; Kempen, R.R.; Nash, J.B.; Ellis, S.

    1979-11-05

    It has recently been suggested that the primary myelotoxic species generated from benzene is not produced directly from the parent compound, but from phenol or an even later metabolite. Several compounds that alter the activities of microsomal oxidative and conjugating enzymes were studied for their effects on benzene's myelotoxicity and metabolism. Phenobarbital (PB) protected animals from leucopnia and increased both to total amount of phenol as well as the amount of unconjugated phenol excreted in the urine. SKF-525A had no effect on the leucopenia, whereas it reduced the conversion of benzene to phenol without changing the excretion of unconjugated phenol. 3-Methylcholanthrene also did not prevent the leucopenia, but it did increase the conversion of benzene to phenol and the amount of unconjugated phenol excreted during the first days of the experiment. These data indicate that the early phases of benzene's metabolism may be modulated by the drug pretreatments employed, but myelotoxicity was abated only by PB. We conclude that the marrow effect of benzene is due to a metabolic product other than phenol and, furthermore that the formation of this toxic principle is not strictly dependent on the rate of phenol production.

  10. Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120 exposure.

    Directory of Open Access Journals (Sweden)

    Andrew J Shepherd

    Full Text Available Infection with human immunodeficiency virus-1 (HIV-1 within the brain has long been known to be associated with neurodegeneration and neurocognitive disorder (referred as HAND, a condition characterized in its early stages by declining cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat glycoprotein 120 (gp120 has been suggested to be a critical factor inducing apoptotic cell death in neurons via the activation of p38 mitogen-activated protein kinase (MAPK, upon chronic exposure to the virus. Here we show that acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which provides protection against non-apoptotic cell death, involving the major somatodendritic voltage-gated K⁺ (Kv channel Kv2.1 as the key mediator. The Kv2.1 channel has recently been shown to provide homeostatic control of neuronal excitability under conditions of seizures, ischemia and neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which ultimately leads to changes in specific sub-cellular localization and voltage-dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and subsequent activation of the protein phosphatase calcineurin. This leads to the overall suppression of neuronal excitability and provides neurons with a homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1 channel activity led to significant enhancement of non-apoptotic neuronal death upon acute gp120 treatment. These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections.

  11. Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120 exposure.

    Science.gov (United States)

    Shepherd, Andrew J; Loo, Lipin; Mohapatra, Durga P

    2013-01-01

    Infection with human immunodeficiency virus-1 (HIV-1) within the brain has long been known to be associated with neurodegeneration and neurocognitive disorder (referred as HAND), a condition characterized in its early stages by declining cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat glycoprotein 120 (gp120) has been suggested to be a critical factor inducing apoptotic cell death in neurons via the activation of p38 mitogen-activated protein kinase (MAPK), upon chronic exposure to the virus. Here we show that acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which provides protection against non-apoptotic cell death, involving the major somatodendritic voltage-gated K⁺ (Kv) channel Kv2.1 as the key mediator. The Kv2.1 channel has recently been shown to provide homeostatic control of neuronal excitability under conditions of seizures, ischemia and neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which ultimately leads to changes in specific sub-cellular localization and voltage-dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and subsequent activation of the protein phosphatase calcineurin. This leads to the overall suppression of neuronal excitability and provides neurons with a homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1 channel activity led to significant enhancement of non-apoptotic neuronal death upon acute gp120 treatment. These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections.

  12. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Science.gov (United States)

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  13. Relationship between the crystallization rates of amorphous nifedipine, phenobarbital, and flopropione, and their molecular mobility as measured by their enthalpy relaxation and (1)H NMR relaxation times.

    Science.gov (United States)

    Aso, Y; Yoshioka, S; Kojima, S

    2000-03-01

    Isothermal crystallization of amorphous nifedipine, phenobarbital, and flopropione was studied at temperatures above and below their glass transition temperatures (T(g)). A sharp decrease in the crystallization rate with decreasing temperature was observed for phenobarbital and flopropione, such that no crystallization was observed at temperatures 20-30 degrees C lower than their T(g) within ordinary experimental time periods. In contrast, the crystallization rate of nifedipine decreased moderately with decreasing temperature, and considerable crystallization was observed at 40 degrees C below its T(g) within 4 months. The molecular mobility of these amorphous drugs was assessed by enthalpy relaxation and (1)H-NMR relaxation measurements. The enthalpy relaxation time of nifedipine was smaller than that of phenobarbital or flopropinone at the same T - T(g) values, suggesting higher molecular mobility of nifedipine. The spin-lattice relaxation time in the rotating frame (T(1rho)) decreased markedly at temperature above T(g). The slope of the Arrhenius type plot of the T(1rho) for nifedipine protons changed at about 10 degrees C below the T(g), whereas the slope for phenobarbital protons became discontinuous at about 10 degrees C above the T(g). Even at temperatures below its T(g), the spin-spin relaxation process of nifedipine could be described by the sum of its Gaussian relaxation, which is characteristic of solid protons, and its Lorentzian relaxation, which is characteristic of protons with higher mobility. In contrast, no Lorentzian relaxation was observed for phenobarbital or flopropione at temperatures below their T(g). These results also suggest that nifedipine has higher molecular mobility than phenobarbital and flopropione at temperatures below T(g). The faster crystallization of nifedipine than that of phenobarbital or flopropione observed at temperatures below its T(g) may be partly ascribed to its higher molecular mobility at these temperatures.

  14. The physiological responses of the Caspian kutum (Rutilus frisii kutum) fry to the static magnetic fields with different intensities during acute and subacute exposures.

    Science.gov (United States)

    Loghmannia, Javad; Heidari, Behrooz; Rozati, Seyed Ali; Kazemi, Soodabeh

    2015-01-01

    In recent years, the application of new technologies producing magnetic fields has widely increased in the aquatic environment. In this study, the effects of variable static magnetic fields on metabolic and immune parameters of the Caspian kutum fry were investigated. The Caspian kutum fry (n=220, body weight 1.78±0.11 g) was exposed to static magnetic fields with different intensities (2.5, 5.0, 7.5 mT) induced by electrical power supply during acute (one week) and subacute (3 weeks) periods. The results showed an increment in the quantity of ALT and AST enzymes (metabolic parameters) with increasing magnetic fields intensities in subacute and acute exposures (p<0.05). The lysozyme level, an immune parameter, showed a significant decrease, especially at intensities higher than 2.5 mT during subacute and acute exposures (p<0.05). It seems that low-intensity static magnetic fields can effect on the metabolism and immunity of the Caspian kutum fry as valuable commercial species.

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

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn (Poland); Wu, Dongmei, E-mail: dongmei.wu@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Wallin, Håkan, E-mail: hwa@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Vogel, Ulla, E-mail: ubv@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically

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

    Science.gov (United States)

    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.

  17. Acute and chronic toxicity of imidacloprid to the aquatic invertebrates Chironomus tentans and Hyalella azteca under constant- and pulse-exposure conditions.

    Science.gov (United States)

    Stoughton, Sarah J; Liber, Karsten; Culp, Joseph; Cessna, Allan

    2008-05-01

    The toxicity of imidacloprid, a nicotinic mimic insecticide, to the aquatic invertebrates Chironomus tentans and Hyalella azteca, was first evaluated in static 96-hour tests using both technical material (99.2% pure) and Admire, a commercially available formulated product (240 g a.i. L(-1)). The 96-h lethal concentration (LC)50 values for technical imidacloprid and Admire were 65.43 and 17.44 microg/L, respectively, for H. azteca, and 5.75 and 5.40 microg/L, respectively, for C. tentans. Admire was subsequently used in 28-day chronic tests with both species. Exposure scenarios consisted of a constant- and a pulse-exposure regime. The pulse exposure lasted for four days, after which time the animals were transferred to clean water for the remaining 24 days of the study. Assessments were made on both day 10 and day 28. In the C. tentans under constant exposure, larval growth on day 10 was significantly reduced at 3.57 microg/L imidacloprid, the lowest-observed-effect concentration (LOEC). The no-observed-effect concentration (NOEC) and LOEC for the 28-day exposure duration (adult survival and emergence) were 1.14 and greater than 1.14 mug/L, respectively; the associated LC50 and LC25 were 0.91 and 0.59 microg/L, respectively. The LOEC for the pulse treatment was greater than 3.47 microg/L, but the day 10 LC25 was 3.03 microg/L. In the H. azteca tests, the day 10 and 28 constant exposure, as well as the day 28 pulse exposure, LOEC (survival) values were similar at 11.95, 11.46, and 11.93 microg/L, respectively. The day 10 and 28 constant exposure effective concentration (EC)25s (dry weight) were also similar, at 6.22 and 8.72 microg/L, respectively, but were higher than the pulse-exposure day 10 LOEC and EC25 (dry weight) values of 3.53 and 2.22 microg/L, respectively. Overall, C. tentans was more sensitive to acute and chronic imidacloprid exposure, but less sensitive to a single pulse, than H. azteca. Chronic, low-level exposure to imidacloprid may therefore reduce

  18. Effects of Acute Ozone Exposure and Methyl Jasmonate Treatment on White Pine Monoterpene and Sesquiterpene Emission Rates

    Science.gov (United States)

    Faiola, C. L.; Wagner, D.; Allwine, E.; Harley, P. C.; Vanreken, T. M.

    2010-12-01

    Biogenic volatile organic compounds (BVOCs) are produced by plants and include monoterpenes, sesquiterpenes, and their oxygenated derivatives. These BVOCs are one of the principal factors influencing the oxidative capacity of the atmosphere in forested regions, and impact both ozone concentration and secondary organic aerosol formation. Under unstressed conditions, the release of BVOCs to the atmosphere is primarily controlled by the vapor pressure of the relevant compounds within the plant tissue, which is in turn dependent on temperature as well as complex biochemical production processes. However, various natural and anthropogenic stressors can alter both the quantity and composition of the BVOCs emitted by plants. Many potential stressors are expected to become stronger as climate change effects escalate. The impacts of most stressors on BVOC emissions have not been well characterized, particularly in a field setting where changes in BVOC emissions could have influential feedbacks with climate. This study investigated the effects of two stressors on monoterpene and sesquiterpene emission rates at a field site in northern Michigan: acute ozone exposure and treatment with methyl jasmonate, an herbivory proxy. The study included six repetitions of the same experiment, each time using a new set of sub-canopy eastern white pine specimens. For each experiment, dynamic branch enclosures were simultaneously used on three specimens for sample collection: one ozone treatment tree, one methyl jasmonate treatment tree, and one control tree. Sampling lines were placed in each enclosure and VOCs were collected onto cartridges packed with Tenax GR adsorbent. Samples were collected several times per day for at least two days before treatment and for five days after treatment. Cartridges were analyzed via thermodesorption with an Agilent GC/MS/FID. This analysis allowed the identification and quantification of several monoterpene and sesquiterpene species in the samples

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

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    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.

  20. Modified Lipoproteins by Acrylamide Showed More Atherogenic Properties and Exposure of Acrylamide Induces Acute Hyperlipidemia and Fatty Liver Changes in Zebrafish.

    Science.gov (United States)

    Kim, Seong-Min; Baek, Ji-Mi; Lim, So-Mang; Kim, Jae-Yong; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-10-01

    Acrylamide is a well-known potent carcinogen and neurotoxin that, until now, has not been sufficiently investigated with regard to its effects on lipid metabolism. We investigated physiological effects of acrylamide (AA) on lipoprotein metabolism using human macrophages, dermal cells, and zebrafish models. Functional and structural properties of lipoproteins were modified by AA (final concentration of 5-100 mM) with loss of antioxidant ability and multimerization of apoA-I in vitro. AA exacerbated LDL oxidation, degradation, and LDL uptake into macrophages with increased ROS production. In human cells, treatment of AA (1-100 μM) caused cellular senescence of dermal cells with severe cytotoxicity. Waterborne exposure of zebrafish in cage water containing AA (300 ppm) resulted in acute death within 26 h along with elevation of body weight, blood glucose, triglyceride, and hepatic inflammation. AA exposure caused fat accumulation in liver in a dose-dependent manner. In conclusion, AA affected lipoprotein metabolism to result exacerbation of atherosclerosis. Exposure of zebrafish to AA resulted in acute inflammatory death with hyperlipidemia.

  1. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

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    Catherine A Smith

    Full Text Available 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.

  2. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl) phthalate in male Long Evans rats.

    Science.gov (United States)

    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.

  3. Effects of pathogenic bacterial challenge after acute sublethal ammonia-N exposure on heat shock protein 70 expression in Botia reevesae.

    Science.gov (United States)

    Qin, Chuanjie; Zhao, Daxian; Gong, Quan; Qi, Zemin; Zou, Yuanchao; Yue, Xingjian; Xie, Biwen

    2013-09-01

    The objective of this study was to investigate the effects of pathogenic bacterial challenge after acute sublethal ammonia-N exposure on heat shock protein 70 expression in Botia reevesae. After ammonia-N exposure at a constant concentration of 7.21 ± 0.10 mg L(-1) for 96 h, B. reevesae was challenged with Aeromonas hydrophila. Quantitative PCR analysis showed predominant and significant expression of HSP70 in liver, gill, skin, spleen and kidney (P ammonia-N exposure and A. hydrophila challenge. Furthermore, following A. hydrophila challenge after ammonia-N exposure, HSP70 mRNA expression was significantly upregulated in kidney and gill tissues, although its expression levels were significantly lower than those detected following A. hydrophila challenge or ammonia-N exposure individually. These results indicate that B. reevesae HSP70 is involved in resistance to pathogenic bacteria. It is hypothesized that ammonia-N results in the downregulation of HSP70 mRNA in immune organs after an A. hydrophila challenge, thus lowering their resistance to pathogenic stress.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  5. β-Catenin loss in hepatocytes promotes hepatocellular cancer after diethylnitrosamine and phenobarbital administration to mice.

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    Prince Kwaku Awuah

    Full Text Available Hepatocellular Carcinoma (HCC is the fifth most common cancer worldwide. β-Catenin, the central orchestrator of the canonical Wnt pathway and a known oncogene is paramount in HCC pathogenesis. Administration of phenobarbital (PB containing water (0.05% w/v as tumor promoter following initial injected intraperitoneal (IP diethylnitrosamine (DEN injection (5 µg/gm body weight as a tumor inducer is commonly used model to study HCC in mice. Herein, nine fifteen-day male β-catenin knockout mice (KO and fifteen wild-type littermate controls (WT underwent DEN/PB treatment and were examined for hepatic tumorigenesis at eight months. Paradoxically, a significantly higher tumor burden was observed in KO (p<0.05. Tumors in KO were β-catenin and glutamine synthetase negative and HGF/Met, EGFR & IGFR signaling was unremarkable. A significant increase in PDGFRα and its ligand PDGF-CC leading to increased phosphotyrosine-720-PDGFRα was observed in tumor-bearing KO mice (p<0.05. Simultaneously, these livers displayed increased cell death, stellate cell activation, hepatic fibrosis and cell proliferation. Further, PDGF-CC significantly induced hepatoma cell proliferation especially following β-catenin suppression. Our studies also demonstrate that the utilized DEN/PB protocol in the WT C57BL/6 mice did not select for β-catenin gene mutations during hepatocarcinogenesis. Thus, DEN/PB enhanced HCC in mice lacking β-catenin in the liver may be due to their ineptness at regulating cell survival, leading to enhanced fibrosis and regeneration through PDGFRα activation. β-Catenin downregulation also made hepatoma cells more sensitive to receptor tyrosine kinases and thus may be exploited for therapeutics.

  6. Protective effects of tetrandrine on brain cells in phenobarbital-dependent and -withdrawn rats.

    Science.gov (United States)

    Han, Bin; Fu, Ping; Ye, Yun; Zhang, Hong; Wang, Guojun

    2015-03-01

    The aim of this study was to investigate the effects of tetrandrine (Tet) on the brain cells of phenobarbital‑dependant and ‑withdrawn rats, and to explore the underlying mechanisms. A total of 100 rats were randomly divided into five groups: The control group, the phenobarbital‑dependent model group, and Tet‑treated groups of low‑, mid‑ and high‑dosages. Following drug withdrawl, the morphological changes of the frontal lobe cells were examined by hematoxylin and eosin (H&E) staining. Immunohistochemical staining was applied to detect the expression of apoptosis‑related proteins Bcl‑2 and Bax. Reverse transcription‑polymerase chain reaction (RT‑PCR) and western blotting methods were applied to detect the mRNA and protein expression levels of Bcl‑2 and Bax, respectively, in the frontal lobe. The results indicated that Tet effectively reduced the withdrawal symptoms, particularly the weight loss, in phenobarbital‑dependent and ‑withdrawn rats. H&E staining revealed that Tet significantly restored the histopathological changes in the addicted rats in a dose‑dependent manner. The immunohistochemical, RT‑PCR, and western blot analyses indicated that Tet treatment significantly increased the Bcl‑2+ brain cells and the mRNA and protein expression levels of Bcl‑2, and decreased the Bax+ cells and the mRNA and protein expression levels of Bax, as well as elevated the ratio of Bcl‑2/Bax, in phenobarbital‑dependent and ‑withdrawn rats. Tet may inhibit apoptosis in these addicted rats, in a dose‑dependent manner. Tet alleviates the phenobarbital withdrawal symptoms and protects the brain cells against apoptosis, which may be a result of the regulation of the mRNA and protein expression levels of Bcl‑2 and Bax.

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

    Energy Technology Data Exchange (ETDEWEB)

    Foth, H.; Walther, U.I.; Kahl, G.F. (Univ. of Goettingen (Germany, F.R.))

    1990-09-15

    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.

  8. Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma.

    Science.gov (United States)

    Lu, Meng; Wu, Jiao; He, Feng; Wang, Xi-Long; Li, Can; Chen, Zhi-Nan; Bian, Huijie

    2015-02-01

    Overexpression of CD147/basigin in hepatic cells promotes the progression of hepatocellular carcinoma (HCC). Whether CD147 also expressed in liver non-parenchymal cells and associated with HCC development was unknown. The aim of the study was to explore time-dependent cell expression patterns of CD147 in a widely accepted N-diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC mouse model. Liver samples collected at month 1-12 of post-DEN/PB administration were assessed the localization of CD147 in hepatocytes, endothelial cells, hepatic stellate cells, and macrophages. Immunohistochemistry analysis showed that CD147 was upregulated in liver tumors during month 1-8 of DEN/PB induction. Expression of CD147 was positively correlated with cytokeratin 18, a hepatocyte marker (r = 0.7857, P = 0.0279), CD31 (r = 0.9048, P = 0.0046), an endothelial cell marker, and CD68, a macrophage marker (r = 0.7619, P = 0.0368). A significant correlation was also observed between CD147 and alpha-smooth muscle actin (r = 0.8857, P = 0.0333) at DEN/PB initiation and early stage of tumor formation. Immunofluorescence and fluorescence in situ hybridization showed that CD147 co-expressed with cytokeratin 18, CD31, alpha-smooth muscle actin, and CD68. Moreover, there existed positive correlations between CD147 and microvessel density (r = 0.7857, P = 0.0279), CD147 and Ki-67 (r = 0.9341, P = 0.0022) in the development of DEN/PB-induced HCC. In conclusion, our results demonstrated that CD147 was upregulated in the liver parenchymal and mesenchymal cells and involved in angiogenesis and tumor cell proliferation in the development of DEN/PB-induced HCC.

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

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    Romain eNardou

    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.

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

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    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.

  11. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to Total Body Irradiation.

    Science.gov (United States)

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  12. No influence of acute RF exposure (GSM-900, GSM-1800, and UMTS) on mouse retinal ganglion cell responses under constant temperature conditions.

    Science.gov (United States)

    Ahlers, Malte T; Ammermüller, Josef

    2014-01-01

    Possible non-thermal effects of radio frequency electromagnetic fields (RF-EMF) on retinal ganglion cells were studied in vitro under conditions of constant temperature. Isolated mouse retinae were exposed to GSM-900, GSM-1800, and universal mobile telecommunication system (UMTS) RF-EMF applying specific absorption rates (SAR) of 0 (sham), 0.02, 0.2, 2, and 20 W/kg. Temperature was kept constant within ±0.5 to 1 °C for GSM-900 and ±0.5 °C for GSM-1800 and UMTS. Responses of retinal ganglion cells to light stimuli of three intensities (0.5, 16, and 445 lx) were recorded before, during, and up to 35 min after exposure. Experiments were performed under double-blind conditions. Changes in light responses during and after exposure were determined for each condition (RF-EMF; SAR value; light intensity) with respect to the responses before exposure, respectively. Changes were calculated using the Euclidian distance of the n-dimensional response vectors, respectively. Some changes already occurred during sham (0 W/kg) exposure, reflecting the intrinsic variability in retinal ganglion cell responses. Comparison of the distance values from sham exposure with those from actual exposure yielded no significant differences. In addition, linear regression analysis of the distance values versus SAR values yielded no consistent dependence of light response changes. From these results we conclude that RF-EMF exposure at three mobile phone frequencies (GSM-900, GSM-1800, UMTS) and SARs up to 20 W/kg has no acute effects on retinal ganglion cell responses under constant temperature conditions.

  13. Intrauterine exposure to fine particulate matter as a risk factor for increased susceptibility to acute broncho-pulmonary infections in early childhood.

    Science.gov (United States)

    Jedrychowski, Wiesław A; Perera, Frederica P; Spengler, John D; Mroz, Elzbieta; Stigter, Laura; Flak, Elżbieta; Majewska, Renata; Klimaszewska-Rembiasz, Maria; Jacek, Ryszard

    2013-07-01

    Over the last decades many epidemiologic studies considered the morbidity patterns for respiratory diseases and lung function of children in the context of ambient air pollution usually measured in the postnatal period. The main purpose of this study is to assess the impact of prenatal exposure to fine particulate matter (PM2.5) on the recurrent broncho-pulmonary infections in early childhood. The study included 214 children who had measurements of personal prenatal PM2.5 exposure and regularly collected data on the occurrence of acute bronchitis and pneumonia diagnosed by a physician from birth over the seven-year follow-up. The effect of prenatal exposure to PM2.5 was adjusted in the multivariable logistic models for potential confounders, such as prenatal and postnatal ETS (environmental tobacco smoke), city residence area as a proxy of postnatal urban exposure, children's sensitization to domestic aeroallergens, and asthma. In the subgroup of children with available PM2.5 indoor levels, the effect of prenatal exposure was additionally adjusted for indoor exposure as well. The adjusted odds ratio (OR) for incidence of recurrent broncho-pulmonary infections (five or more spells of bronchitis and/or pneumonia) recorded in the follow-up significantly correlated in a dose-response manner with the prenatal PM2.5 level (OR=2.44, 95%CI: 1.12-5.36). In conclusion, the study suggests that prenatal exposure to PM2.5 increases susceptibility to respiratory infections and may program respiratory morbidity in early childhood. The study also provides evidence that the target value of 20μg/m(3) for the 24-h mean level of PM2.5 protects unborn babies better than earlier established EPA guidelines.

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

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    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. THE EFFECT OF ANTICONVULSANT DRUGS (PHENOBARBITAL AND VALPROIC ACID ON THE SERUM LEVEL OF CHOLESTEROL, TRIGLYCERIDE, LIPOPROTEIN AND LIVER ENZYMES IN CONVULSIVE CHILDREN

    Directory of Open Access Journals (Sweden)

    Mohammad Reza SALEHIOMRAN

    2010-12-01

    Full Text Available ObjectiveStudies on the effect of various antiepileptic drugs on serum lipids show contradictory results. We aimed to find the effect of Phenobarbital and Sodium Valproate monotherapy on serum lipid profile and liver function tests in epileptic children.Materials & MethodsThis cohort study was conducted in Amirkola Children Hospital. One hundred and ten children with epilepsy were included in this study. Children with hepatic or renal disease, those receiving medications which could alter liver function tests or serum lipid profile were excluded from the study. Patients were allocated into two groups. The first group, including 63 patients, received Phenobarbital and the second group, including 47 patients, received Sodium Valproate, both in divided doses. A venous blood sample was collected after overnight fasting to evaluate serum triglyceride, total cholesterol, LDL, HDL, and liver function tests. Data was analyzed with SPSS version 17.ResultsIn children receiving Phenobarbital, total cholesterol, LDL, HDL, ALP, SGOT and SGPT increased significantly after treatment, but TG level showed no significant changes. In children receiving Sodium Valproate, HDL, ALP, SGOT, SGPT significantly increased after treatment but there were no statistically significant changes in total cholesterol, LDL and TG. In our study, the plasma levels of LPa elevated significantly after treatment with Phenobarbital and Sodium Valproate (P Value=0.0001. This increase was more significant in patients receiving Sodium Valproate.ConclusionOur results suggested a need for monitoring serum total cholesterol, HDL, LDL, and TG levels in patients receiving Phenobarbital and Valproic Acid.Keywords: Seizure, Phenobarbital, Sodium Valproate.

  18. Microcystin-LR acute exposure does not alter in vitro and in vivo ATP, ADP and AMP hydrolysis in adult zebrafish (Danio rerio brain membranes

    Directory of Open Access Journals (Sweden)

    Luiza Wilges Kist

    2012-10-01

    Full Text Available Microcystins (MCs are toxins produced by cyanobacteria during the blooms that could accumulate in aquatic animals and be relocated to higher trophic levels. Adenosine triphosphate (ATP acts as an excitatory neurotransmitter and/or a neuromodulator in the extracellular space playing important roles in physiological and pathological conditions. The aim of this study was, therefore, to evaluate the acute effects of different concentrations of MC-LR on nucleoside triphosphate diphosphohydrolases and 5’-nucleotidade in adult zebrafish (Danio rerio brain membranes. The results have shown no significant changes in ATP, adenosine diphosphate (ADP and adenosine monophosphate (AMP hydrolysis in zebrafish brain membranes. MC-LR in vitro also did not alter ATP, ADP and AMP hydrolysis in the concentrations tested. These findings show that acute exposure to MC-LR did not modulate ectonucleotidase activity in the conditions tested. However, additional studies including chronic exposure should be performed in order to achieve a better understanding about MC-LR toxicity mechanisms in the central nervous system.

  19. Biochemical and histological evaluation of kidney damage after sub-acute exposure to 2,4-dichlorophenoxyacetic herbicide in rats: involvement of oxidative stress.

    Science.gov (United States)

    Tayeb, Wafa; Nakbi, Amel; Trabelsi, Mounir; Miled, Abdelhedi; Hammami, Mohamed

    2012-11-01

    The present study evaluated the effects of sub-acute exposure to different doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on rat kidney. Forty animals were divided into four equal groups and treated with different doses of 2,4-D: 0, 15, 75 and 150 mg/kg body weight per day via oral gavage for 28 consecutive days. Renal function, histopathology, tissue malondialdehyde and antioxidant enzyme activities were evaluated. The results showed a significant decrease (p kidney MDA as compared to controls. The histopathological study revealed tubular damages, glomerular alterations, vascular congestion and increased number of pyknotic nuclei in kidneys of all 2,4-D treated groups. The severity of these alterations increase in a dose-dependent manner. Our findings confirm that sub-acute exposure to 2,4-D induced oxidative renal dysfunction in rats. Therefore, at higher doses, 2,4-D may be implicated in the pathogenesis of kidney failure via lipid peroxidation and oxidative stress.

  20. Effects on Pharmacokinetics of Propranolol and Other Factors in Rats After Acute Exposure to High Altitude at 4,010 m.

    Science.gov (United States)

    Wenbin, Li; Rong, Wang; Hua, Xie; Juanhong, Zhang; Xiaoyu, Wu; Zhengping, Jia

    2015-05-01

    A series of pathological, physiological, and biochemical changes, even anatomical histological changes happen while humans arrive at the high plateau region from plain area. There is a certain relationship between the body's compensatory or decompensated adjustments to the environment and the changes of absorption, distribution, metabolism, and excretion of drugs. The objective of the study is to observe the effects of acute exposure to high altitude at 4,010 m on pharmacokinetics of propranolol in rats, and to provide basis and new ideas to adjust drug dosage and administration, so as to promote rational drug use in high altitude. 28 healthy male wistar rats were randomly divided into four groups, group A and B which were in plain area; group C and D which were acutely exposed to high altitude by aviation; group A and C were used for pharmacokinetics determination of propranolol, while group B and D had no drug administration for physiological and pathological changes research at high altitude. The pharmacokinetics of propranolol significantly changed; area under curve, C max (the peak concentration), mean residence time, and t 1/2 (the biological half-life) increased significantly by 481.72, 398.94, 44.87, and 58.77 %, respectively; clearance and V (apparent volume of distribution) decreased by 81.50 and 70.56 %, respectively, after acute exposure to high altitude at 4,010 m; Analytic results show that pH, buffer base, base excess, ctCO2 (content of total carbon dioxide), sO2 (oxygen saturation of arterial blood), pO2 (oxygen tension of arterial blood), and cNa(+) severely decreased by 2.43, 630.00, 311.00, 11.48, 91.38, 76.22, and 2.82 %, respectively, while pCO2 (carbon dioxide tension of arterial blood) and cCl(-) significantly increased by 47.40 and 6.76 %. Lactate dehydrogenase and total protein significantly decreased by 58.44 and 26.82 %, while total bilirubin and alkaline phosphatase severely increased by 338 and 24.94 % after acute exposure to high

  1. Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium.

    Science.gov (United States)

    Foote, A P; Penner, G B; Walpole, M E; Klotz, J L; Brown, K R; Bush, L P; Harmon, D L

    2014-07-01

    Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers (n=6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium (P>0.51). Inulin flux (P=0.16) and G t (P>0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is ~0.25 to 0.44 ng/cm2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that

  2. Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione.

    Science.gov (United States)

    Pauluhn, Jürgen; Hai, Chun Xue

    2011-01-01

    Phosgene is an important high-production-volume intermediate with widespread industrial use. Consistent with other lung irritants causing ALI (acute lung injury), mode-of-action-based countermeasures remain rudimentary. This study was conducted to analyze whether extremely short high-level exposure to phosgene gas could be mitigated using three different inhaled nucleophiles administered by inhalation instantly after exposure to phosgene. Groups of young adult male Wistar rats were acutely exposed to carbonyl chloride (phosgene) using a directed-flow nose-only mode of exposure of 600 mg/m³ for 1.5 min (225 ppm × min). Immediately after exposure to phosgene gas the rats were similarly exposed to three strong nucleophiles with and without antioxidant properties for 5 or 15 min. The following nucleophiles were used: hexamethylenetetramine (HMT), l-cysteine (Cys), and l-glutathione (GSH). The concentration of the aerosol (mass median aerodynamic diameter 1.7-2 µm) was targeted to be in the range of 1 mg/L. Cys and GSH have antioxidant properties in addition. The calculated alveolar molar dosage of phosgene was 9 µmol/kg. At 15-min exposure duration, the respective inhaled dose of HMT, Csy, and GSH were 111, 103, and 46 µmol/kg, respectively. The alveolar dose of drugs was ~10-times lower. The efficacy of treatment was judged by protein concentrations in bronchoalveolar lavage fluid (BALF) collected 1 day post-exposure. In spite of using optimized aerosolization techniques, none of the nucleophiles chosen had any mitigating effect on BALF-protein extravasation. This finding appear to suggest that inhaled phosgene gas acylates instantly nucleophilic moieties at the site of initial deposition and that the resultant reaction products can not be reactivated even following instant inhalation treatment with competing nucleophilic agents. In spite of using maximal technically attainable concentrations, it appears to be experimentally challenging to deliver

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

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Z.; Mehendale, H.M. (Univ. of Mississippi, Jackson (United States))

    1990-02-26

    Gerbils are known to be much more sensitive to CCl{sub 4} lethality than rats as indicated by 48 hours LD{sub 50} (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl{sub 4} toxicity. To investigate the possible mechanism underlying gerbil's high sensitivity to CCl{sub 4} lethality, the authors studied in vivo metabolism of CCl{sub 4} in gerbils pretreated with dietary CD (10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm). The hepatic content of CCl{sub 4}, the expiration of {sup 14}CCl{sub 4} and {sup 14}CCl{sub 4}-derived Co{sub 2}, 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 {sup 14}CCl{sub 4} (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 {sup 14}CCl{sub 4} derived {sup 14}CO{sub 2} 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 {sup 14}C 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 CCl{sub 4} in gerbils may partially explain their high sensitivity to CCl{sub 4} toxicity. However, the significantly enhanced metabolism of CCl{sub 4} found in CD, PB, or M pretreated gerbils did not lead to amplification of CCl{sub 4} hepatotoxic and lethal effects.

  4. Kinetic studies on toluene metabolism in ethanol- and phenobarbital-induced rat liver microsomes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wang Ruisheng; Nakajima, Tamie (Shinshu Univ., Matsumoto (Japan). Dept. of Hygiene)

    1991-01-01

    In vitro metabolism of toluene was investigated at substrate concentrations of 0.03-6.25 mM in liver microsomes from control and ethanol- and phenobarbital (PB)-treated rats. Three metabolites, benzylalcohol (BA), o-and p-cresol, were measured by high-performance liquid chromatograph. BA was the main metabolite of toluene, whereas o- and p-creasol contributed only 1.1-1.5% and 1.7-2.8% of total metabolites, respectively, in microsomes from control rats. Ethanol treatment showed little effect on the percentages of three metabolites, but PB increased the percentages of o- and p-cresol to as high as 5.5% and 8.0%, respectively, following the increase in toluene concentration. There were two different isozymes with different K{sub m} involved in the side-chain hydroxylation of toluene in microsomes from control and ethanol-treated rats. One had a low K{sub m} value (0.13-0.17 mM) and could be greatly induced with ethanol treatment. The other was a high K{sub m} isozyme (0.60-0.87 mM). PB-induced isozyme showed a similar K{sub m} value to that of the high K{sub m} isozyme existing in microsomes from control and ethanol-treated rats. Two isozymes were involved in the formation of p-cresol in microsomes of control rats; the low-K{sub m} type had a similar value (0.15 mM) to the low isozyme of BA formation, but the high K{sub m} isozyme had a larger value (2.04 mM) than the high isozyme of BA. Only one enzyme responsible for o-cresol formation was detected in microsomes of control rats, and had a similar K{sub m} (2.11 mM) to that of the high K{sub m} isozyme of p-cresol. The high K{sub m} and low V{sub max} values of isozymes of aromatic hydroxylation account for the minor proportion of cresols. Ethanol and PB treatments enhanced the metabolism of toluene, but they differ in that the ethanol-inducible isozyme metabolized toluene at a faster rate at low substrate concentrations, whereas PB did so at high toluene concentrations. (orig./MG).

  5. Impaired acquired resistance of mice to Klebsiella pneumoniae infection induced by acute NO/sub 2/ exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bouley, G.; Azoulay-Dupuis, E.; Gaudebout, C.

    1985-12-01

    The natural resistance of nonimmunized C57B1/6 mice to an intraperitoneal Klebsiella pneumoniae challenge was not significantly affected by prior continuous exposure to 20 ppm NO/sub 2/ for 4 days. In contrast, the acquired resistance of mice immunized just before and infected just after NO/sub 2/ exposure was seriously impaired. This could not be explained by the loss of appetite (about 30%) observed in NO/sub 2/ treated mice, for neither the natural nor acquired resistance of control air exposure mice given approximately 70% ad libitum food and water were significantly modified.

  6. Induction of hepatic cytochrome P-450 activity in wild cotton rats (Sigmodon hispidus) by phenobarbital and 3-methylcholanthrene

    Energy Technology Data Exchange (ETDEWEB)

    Elangbam, C.S.; Qualls, C.W.,Jr.; Bauduy, M. (Oklahoma State Univ., Stillwater (USA))

    1989-05-01

    Wild cotton rats (Sigmodon hispidus) are ubiquitous throughout the Southeast quadrant of the United States, easy to capture, have a generation interval of less than one year and a limited range of movement (less than one hectare). This species may prove to be an excellent model for monitoring environmental contamination. Traditionally, cytochrome P-450 inducing agents are grouped into two classes. One, represented by phenobarbital, induces P-450b and P-450e; the other, represented by 3-methylcholanthrene, induces P-450c and P-450d isoenzymes. The types and amounts of cytochrome P-450 vary among species, organs, health status, sex, and stress of the animal. If the levels of cytochrome P-450 of wild cotton rats are to be used in monitoring environmental pollution, it is necessary to characterize the inducibility and concentration of cytochrome P-450 in this species. This study was designed to determine the concentration and inducibility of cytochrome P-450 in the livers of cotton rats after intraperitoneal (ip) administration of phenobarbital and 3-methylcholanthrene.

  7. A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy

    DEFF Research Database (Denmark)

    Fredsø, N.; Sabers, A.; Toft, Nils;

    2016-01-01

    Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to inves......Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study...... was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided...... levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control.In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital...

  8. 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

    Science.gov (United States)

    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

  9. Acute toxicity test for terrestrial hazard assessment with exposure of Folsomia candida to pesticides in an aqueous medium

    NARCIS (Netherlands)

    Houx, N.W.H.; Dekker, A.; Kammen-Polman, van A.M.M.; Ronday, R.

    1996-01-01

    An acute-toxicty test is described in which the springtail Folsomia candida was exposed to pesticides in water for four days. The test method has been designed for the direct and economical chemical analyses of all the concentrations during the execution of the test. The 96-hour EC50 values determin

  10. Acute sensory irritation from exposure to isopropanol(2-propanol) at TLV in workers and controls : objective versus subjective effects

    NARCIS (Netherlands)

    Smeets, M.A.M.; Maute, C.; Dalton, P.H.

    2002-01-01

    Objectives. Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and naïve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using

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

    Science.gov (United States)

    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 ...

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

    Science.gov (United States)

    Nambiar, Madhusoodana P; Gordon, Richard K; Rezk, Peter E; Katos, Alexander M; Wajda, Nikolai A; Moran, Theodore S; Steele, Keith E; Doctor, Bhupendra P; Sciuto, Alfred M

    2007-03-01

    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/m(3) 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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 1H NMR spectroscopic analysis detects metabolic disturbances in rat urine on acute exposure to heavy metal tungsten alloy based metals salt.

    Science.gov (United States)

    Tyagi, Ritu; Rana, Poonam; Gupta, Mamta; Bhatnagar, Deepak; Srivastava, Shatakshi; Roy, Raja; Khushu, Subash

    2014-03-25

    Heavy metal tungsten alloys (HMTAs) have been found to be safer alternatives for making military munitions. Recently, some studies demonstrating the toxic potential of HMTAs have raised concern over the safety issues, and further propose that HMTAs exposure may lead to physiological disturbances as well. To look for the systemic effect of acute toxicity of HMTA based metals salt, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic profiling of rat urine was carried out. Male Sprague Dawley rats were administered (intraperitoneal) low and high dose of mixture of HMTA based metals salt and NMR spectroscopy was carried out in urine samples collected at 8, 24, 72 and 120 h post dosing (p.d.). Serum biochemical parameters and liver histopathology were also conducted. The (1)H NMR spectra were analysed using multivariate analysis techniques to show the time- and dose-dependent biochemical variations in post HMTA based metals salt exposure. Urine metabolomic analysis showed changes associated with energy metabolism, amino acids, N-methyl nicotinamide, membrane and gut flora metabolites. Multivariate analysis showed maximum variation with best classification of control and treated groups at 24h p.d. At the end of the study, for the low dose group most of the changes at metabolite level reverted to control except for the energy metabolites; whereas, in the high dose group some of the changes still persisted. The observations were well correlated with histopathological and serum biochemical parameters. Further, metabolic pathway analysis clarified that amongst all the metabolic pathways analysed, tricarboxylic acid cycle was most affected at all the time points indicating a switchover in energy metabolism from aerobic to anaerobic. These results suggest that exposure of rats to acute doses of HMTA based metals salt disrupts physiological metabolism with moderate injury to the liver, which might indirectly result from heavy metals induced oxidative stress.

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

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    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.

  17. Role of Electromagnetic Field Exposure in Childhood Acute Lymphoblastic Leukemia and No Impact of Urinary Alpha- Amylase--a Case Control Study in Tehran, Iran.

    Science.gov (United States)

    Tabrizi, Maral Mazloomi; Hosseini, Seyed Ahmad

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies which accounts for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring. This study aimed to evaluate the influence of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL. It also examines the role of various factors such as environmental factors and alpha-amylase as a marker in the development of leukemia. This cross-sectional case control study was carried out on 22 cases and 100 controls who born and lived in low socioeconomic families in Tehran and were hospitalized for therapeutic purposes in different hospitals of rom 2013-2014. With regard to the underlying risk factors; familial history and parental factors were detected as risk factors of ALL but in this age, socioeconomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factor (p=0.006, OR=3.651, CI 95% 1.692-7.878). As the population study was from low socioeconomic state, use of mobiles, computers and microwaves was negligible. Moreover prenatal and postnatal exposure to all indoor electrically charged objects were not detected as significant environmental factors in the present study. This work defined the risk of environmental especially continuous pre and postnatal exposure to high voltage power lines and living in pollutant regions through the parents or children as well as the previously described risk factors of ALL for the first time in low socioeconomic status Iranian population.

  18. Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs.

    Science.gov (United States)

    Rezk, Peter E; Graham, Jacob R; Moran, Theodore S; Gordon, Richard K; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2007-03-01

    Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.

  19. Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.

    Science.gov (United States)

    Zmyślony, Marek; Politanski, Piotr; Rajkowska, Elzbieta; Szymczak, Wieslaw; Jajte, Jolanta

    2004-07-01

    The aim of this study was to test the hypothesis that the 930 MHz continuous wave (CW) electromagnetic field, which is the carrier of signals emitted by cellular phones, affects the reactive oxygen species (ROS) level in living cells. Rat lymphocytes were used in the experiments. A portion of the lymphocytes was treated with iron ions to induce oxidative processes. Exposures to electromagnetic radiation (power density 5 W/m2, theoretical calculated SAR = 1.5 W/kg) were performed within a GTEM cell. Intracellular ROS were measured by the fluorescent probe dichlorofluorescin diacetate (DCF-DA). The results show that acute (5 and 15 min) exposure does not affect the number of produced ROS. If, however, FeCl2 with final concentration 10 microg/ml was added to the lymphocyte suspensions to stimulate ROS production, after both durations of exposure, the magnitude of fluorescence (ROS level during the experiment) was significantly greater in the exposed lymphocytes. The character of the changes in the number of free radicals observed in our experiments was qualitatively compatible with the theoretical prediction from the model of electromagnetic radiation effect on radical pairs.

  20. Effect of zinc on acute pulmonary edema and changes of essential metal contents produced by nitrogen dioxide exposure to mice

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Y.; Mimura, S.; Sakai, K.; Yamane, Y. (Chiba Univ., Chiba (Japan). Faculty of Pharmaceutical Sciences); Ito, M. (Chiba Prefectural Government, Chiba (Japan))

    1992-01-10

    This is a report on the protective effect of zinc (Zn) pretreatment of mice against lung edema caused by high-level, short-term NO{sub 2} exposure. There were significant increases of Fe content at 15ppm NO{sub 2}, Ca at 25ppm NO{sub 2}, Ca and Cu at 35ppm NO{sub 2}, and Ca and Zn at 40 and 50ppm NO{sub 2}. Zn pretreatment inhibited significantly the augmentation of Fe at 15ppm NO{sub 2}, that of Cu at 35ppm NO{sub 2}, and that of Ca at 25 to 50ppm NO{sub 2} exposure. The Ca content in serum at 25 to 50ppm NO{sub 2} exposure showed a significant decrease, and the decrease was significantly suppressed by Zn pretreatment. The ratio of Ca content in serum to that in lung was also decreased significantly at 25 to 50ppm NO{sub 2} exposure, and the decrease of the ratio was significantly suppressed by Zn pretreatment. Zn seems to depress the influx of serum Ca to lung caused by NO{sub 2} exposure. 26 refs., 4 tabs.

  1. Effect of acute exposure to nonylphenol on biochemical, hormonal, and hematological parameters and muscle tissues residues of Nile tilapia; Oreochromis niloticus

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    Hager Tarek H. Ismail

    2016-06-01

    Full Text Available Aim: This study is aimed to evaluate some biochemical, hormonal, hematological, and histopathological changes in Nile tilapia, Oreochromis niloticus, after acute exposure to nonylphenol (NP. In addition to detection of NP residues in the fish, muscle tissues for human health concern. Materials and Methods: A total of 90 apparently healthy Nile tilapia, O. niloticus, were randomly divided into three equal groups; each containing 30 fish (three replicates. Groups 1 and 2 kept as a control and solvent control (acetone, respectively, and Group 3 exposed to NP at a dose level of 500 μg/L water for 7 successive days. Blood and tissue samples were collected 2 times randomly from each group after 7 days from fish exposure to NP and 10 days from exposure stopping. Results: Fish exposed to NP Group 3 showed anorexia, sluggish movement, erythema of the skin, areas of scales loss, and hemorrhagic ulcers in some areas of body region leading to exposing the viscera. Biochemical results revealed a significant increase in serum total proteins and globulins levels, a highly significant increase in serum alanine aminotransferase and aspartate aminotransferase activities, triglycerides, cholesterol, and creatinine levels, insignificant increase in serum uric acid level, and a highly significant decrease in serum testosterone and estradiol-β17 levels in Group 3 in compare with the control group. Histopathological finding confirms these results. While hematological results of the same group revealed a significant increase in red blood cells count and packed cell volume value, insignificant increase in hemoglobin concentration, leukopenia, lymphopenia, and monocytopenia in compared with the control group. All of these changes appeared after 7 days from fish exposure to NP. Most of these alterations returned toward the normal level after 10 days from stopping exposure to NP. NP residues detected in fish muscle tissues of Group 3 during exposure and after stopping

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

    Science.gov (United States)

    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

  3. Effect in vitro of the Phenobarbital on the Activity of the Enzyme Adenosine Triphosphatase (ATPase of Sodium and Potassium Dependent in Human Placenta.

    Directory of Open Access Journals (Sweden)

    María De Jesús Sánchez Bouza

    2007-12-01

    Full Text Available Background: Most of the drugs can pass to the fetus through the placenta, conditioning alterations of the development and fetal growth. Objective: To evaluate the effect in vitro of Phenobarbital on the activity of adenosine triphosphatase of sodium and potassium dependent in human placenta. Method: A study in vitro was carried out, in total homogenizes of placentas coming from 30 mothers that were assisted in the Gynecological and Obstetric Educational Provincial Hospital ¨Mariana Grajales¨, in Santa Clara, during the period March-July 1993. Phenobarbital was administered in concentrations of 0,1 mg/ml, 0,15 mg/ml and 0,2 mg/ml, keeping in mind the therapeutic dose to which was prescribed. The analyzed variables were: enzymatic activity and inhibition type. Results: The enzymatic activity of the adenosine triphosphatase of sodium and potassium dependent, diminished in a significant way, proportionally with the diminishment of the administered concentration of Phenobarbital. The inhibitory effect of the drug also turned out to be dependent of the concentration, presenting a major inhibition as the dose was increased. Conclusion: Phenobarbital produced highly significant decrease in the activity of adenosine triphosphatase of sodium and dependent potassium. This inhibition is of competitive type.

  4. Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

    Science.gov (United States)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

    2011-06-14

    A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were

  5. Opposite effects of acute ethanol exposure on GAP-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats.

    Science.gov (United States)

    Kulkarny, V V; Wiest, N E; Marquez, C P; Nixon, S C; Valenzuela, C F; Perrone-Bizzozero, N I

    2011-08-01

    The adolescent brain is particularly vulnerable to the effects of alcohol, with intoxications at this developmental age often producing long-lasting effects. The present study addresses the effects of a single acute ethanol exposure on growth-associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) gene expression in neurons in the cerebellum and hippocampus of adolescent rats. Male postnatal day 23 (P23) Sprague-Dawley rats were exposed to ethanol vapors for 2h and after a recovery period of 2h, the cerebellum and hippocampus were harvested and samples were taken for blood alcohol concentration (BAC) determinations. We found that this exposure resulted in a mean BAC of 174 mg/dL, which resembles levels in human adolescents after binge drinking. Analyses of total RNA and protein by quantitative reverse transcription PCR and western blotting, respectively, revealed that this single ethanol exposure significantly decreased the levels of GAP-43 mRNA and protein in the cerebellum but increased the levels of mRNA and protein in the hippocampus. BDNF mRNA and protein levels were also increased in the hippocampus but not in the cerebellum of these animals. In situ hybridizations revealed that GAP-43 and BDNF mRNA levels were primarily increased by alcohol exposure in hippocampal dentate granule cells and CA3 neurons. Overall, the reported alterations in the expression of the plasticity-associated genes GAP-43 and BDNF in juvenile rats are consistent with the known deleterious effects of binge drinking on motor coordination and cognitive function.

  6. Evaluation of semi-generic PBTK modeling for emergency risk assessment after acute inhalation exposure to volatile hazardous chemicals

    NARCIS (Netherlands)

    Olie, J. Daniël N; Bessems, Jos G.; Clewell, Harvey J.; Meulenbelt, Jan; Hunault, Claudine C.

    2015-01-01

    BACKGROUND: Physiologically Based Toxicokinetic Models (PBTK) may facilitate emergency risk assessment after chemical incidents with inhalation exposure, but they are rarely used due to their relative complexity and skill requirements. We aimed to tackle this problem by evaluating a semi-generic PBT

  7. Electrocardiographic, hemodynamic, and biochemical responses to acute particulate matter (PM) exposure in aged heart failure-prone rats

    Science.gov (United States)

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiac disease-especially heart failure (HF). The mechanisms explaining PM-induced exacerbation ofHF are unclear. Some o...

  8. Acute Exposure to Particulate Matter (PM) Alters Physiologic and Toxicologic Endpoints in a Rat Model of Heart Failure

    Science.gov (United States)

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). We previously examined the effects of PM on HF by exposing Sponta...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Assessment of early life stage mahi-mahi windows of sensitivity during acute exposures to Deepwater Horizon crude oil.

    Science.gov (United States)

    Mager, Edward M; Pasparakis, Christina; Schlenker, Lela S; Yao, Zongli; Bodinier, Charlotte; Stieglitz, John D; Hoenig, Ronald; Morris, Jeffrey M; Benetti, Daniel D; Grosell, Martin

    2017-01-27

    Windows of exposure to a weathered Deepwater Horizon oil sample (slick A) were examined for early life stage mahi-mahi (Coryphaena hippurus) to determine whether there are developmental periods of enhanced sensitivity during the course of a standard 96-h bioassay. Survival was assessed at 96 h following oil exposures ranging from 2 h to 96 h and targeting 3 general periods of development, namely the prehatch phase, the period surrounding hatch, and the posthatch phase. In addition, 3 different oil preparations were used: high- and low-energy water accommodated fractions of oil and very thin surface slicks of oil (∼1 μm). The latter 2 were used to distinguish between effects due to direct contact with the slick itself and the water underlying the slick. Considering the data from all 3 exposure regimes, it was determined that the period near or including hatch was likely the most sensitive. Furthermore, toxicity was not enhanced by direct contact with slick oil. These findings are environmentally relevant given that the concentrations of polycyclic aromatic hydrocarbons eliciting mortality from exposures during the sensitive periods of development were below or near concentrations measured during the active spill phase. Environ Toxicol Chem 2016;9999:1-9. © 2016 SETAC.

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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.

  13. Effect of Xiao-tan-jie-yu Prescription on sleep quality of soldiers acute exposure to high altitude

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    Yu-xing YANG

    2016-10-01

    Full Text Available Objective  To observe the efficacy of Xiao-tan-jie-yu prescription (XTJYF on sleep quality of the soldiers who acutely exposed to western area of high altitude. Methods  In this prospective, completely randomized, parallel, placebo-controlled study, 550 soldiers acutely exposed to western area of high altitude were investigated by the Pittsburgh Sleep Quality Index (PSQI, 100 soldiers with sleep disorder were selected and divided into two groups (50 each: treatment group received TCM XTJYF therapy and control group was treated with placebo. After 2 weeks' treatment, PSQI total score and respective factor scores before and after treatment were assessed, and clinical therapeutic efficacy and adverse reactions were observed. Results  The PSQI total score and respective factor scores of these soldiers were significantly higher than those of normal adults, but significantly lower than those of insomnia patients, while their sleep disorder factor score was significantly higher compared with insomnia patients. XTJYF reduced the total score and some factor scores (subjective sleep quality, time for initiating sleep, total sleep time, and sleep efficiency for PSQI in the soldiers with sleep disorder, and the overall response rate was 91.49% which is higher than those in the placebo control group (P<0.05 or 0.01, without toxic side effects. Conclusions  The sleep quality of soldiers who acutely exposed to western area of high altitude in China is not high, and XTJYF may safely and effectively improve the sleep quality. DOI: 10.11855/j.issn.0577-7402.2016.10.15

  14. Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation.

    Science.gov (United States)

    Tian, Jian; Zhao, WeiLing; Tian, Sisi; Slater, James M; Deng, Zhiyong; Gridley, Daila S

    2011-11-01

    The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.

  15. Parental exposure to medications and hydrocarbons and ras mutations in children with acute lymphoblastic leukemia: A report from the Children's Oncology Group

    Energy Technology Data Exchange (ETDEWEB)

    Shu, X.O.; Perentesis, J.P.; Wen, W.Q.; Buckley, J.D.; Boyle, E.; Ross, J.A.; Robison, L.L. [Childrens Oncology Group, Arcadia, CA (United States)

    2004-07-01

    Using data from a large case-control study of childhood acute lymphoblastic leukemia (ALL; age < 15 years), we used a case-case comparison approach to examine whether reported parental exposure to hydrocarbons at work or use of specific medications are related to ras gene mutations in the leukemia cells of children with ALL. We examined mutations in K-ras and N-ras genes atcodons 12, 13, and 61 by PCR and allele-specific oligonucleotide hybridization and confirmed them by DNA sequencing. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression to examine the association of parental exposures with ras mutations. A total of 127 (15.2%) cases had ras mutations (K-ras 4.7% and N-ras 10.68%). Both maternal (OR 3.2,95% CI 1.7-6.1) and paternal (OR 2.0, 95% CI 1.1-3.7) reported use of mind-altering drugs were associated with N-ras mutations. Paternal use of amphetamines or diet pills was associated with N-ras mutations (OR 4.1, 95% CI 1.1-15.0). Maternal exposure to solvents (OR 3.1, 95% CI 1.0-9.7) and plastic materials (OR 6.9, 95% CI 1.2-39.7) during pregnancy and plastic materials after pregnancy (OR 8.3, 95% CI 1.4-48.8) were related to K-ras mutation. Maternal over exposure to oil and coal products before case diagnosis (OR 2.3, 95% CI 1.1-4.8) and during the postnatal period (OR 2.2, 95% CI 1.0-5.5) and paternal exposure to plastic materials before index pregnancy (OR 2.4, 95% CI 1.1-5.1) and other hydrocarbons during the postnatal period (OR 1.8, 95% CI 1.0-1.3) were associated with N-ras mutations. This study suggests that parental exposure to specific chemicals may be associated with distinct ras mutations in children who develop ALL.

  16. Biochemical, oxidative and histological changes caused by sub-acute oral exposure of some synthetic cyanogens in rats: ameliorative effect of α-ketoglutarate.

    Science.gov (United States)

    Bhattacharya, Rahul; Rao, Pooja; Singh, Poonam; Yadav, Shiv Kumar; Upadhyay, Preeti; Malla, Sandhya; Gujar, Niranjan Laxman; Lomash, Vinay; Pant, Satish Chandra

    2014-05-01

    Time-dependent cyanide generation and acute toxicity of six different cyanogens were reported earlier, out of which malononitrile (MCN), propionitrile (PCN), and sodium nitroprusside (SNP) were found to be very toxic. We report here 14 d sub-acute toxicity of MCN, PCN, and SNP (oral; 1/10 LD50 daily) in female rats, and its amelioration by α-ketoglutarate (α-KG; oral; 5.26 mmol/kg; +5 min), a potential cyanide antidote. Significant decrease in white blood cells (PCN, SNP), platelets count (PCN), and blood glucose levels (MCN, PCN, SNP) was accompanied by elevated levels of alanine aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), and aspartate aminotransferase (PCN, SNP). Oxidative damage was evidenced by diminished total antioxidant status in plasma and enhanced malondialdehyde levels in liver and kidney. This was accompanied by diminished levels of reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the brain, liver and kidney. We also observed increased levels of blood cyanide and thiocyanate, together with inhibition of cytochrome c oxidase and thiosulfate-sulfur transferase activities in total brain and liver homogenate, respectively. Cyanogens also produced several histological changes in all the organs studied. Post-treatment with α-KG significantly abrogated the toxicity of cyanogens, indicating its utility as an antidote for long-term cyanogen exposure.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Enhanced elimination of theophylline, phenobarbital and strychnine from the bodies of rats and mice by squalane treatment.

    Science.gov (United States)

    Kamimura, H; Koga, N; Oguri, K; Yoshimura, H

    1992-05-01

    Our previous study suggested that squalane would be a good candidate for an antidote to reduce the toxicity of drug ingested accidentally at a high dose by enhancing the drug elimination from the body. In the present study, we investigated whether squalane given orally could enhance the elimination of theophylline, phenobarbital and strychnine which were administered parenterally to rats or mice. Squalane increased the fecal excretion of theophylline and reduced the serum level of the drug in rats. Squalane accelerated the fecal excretion of strychnine in mice. These results suggest that squalane may stimulate more the elimination of neutral (theophylline) or basic (strychnine) drugs which should be present in unionized form in intestinal lumen, than that of acidic drugs.

  19. Acute hypoxic exposure affects gamete quality and subsequent fertilization success and embryonic development in a serpulid polychaete.

    Science.gov (United States)

    Shin, P K S; Leung, J Y S; Qiu, J W; Ang, P O; Chiu, J M Y; Thiyagarajan, V; Cheung, S G

    2014-08-30

    Hypoxia likely compromises the reproductive success of those marine organisms carrying out external fertilization because their gametes and embryos are inevitably exposed to the external environment. Hydroides elegans, a dominant serpulid polychaete in Hong Kong waters, can spawn throughout the year but the number of recruits drops during summer when hypoxia commonly occurs. This study attempted to explain such observation by investigating the gamete quality, including sperm motility, egg size, complexity and viability, after 1-h hypoxic exposure (1 mg O2 l(-1)). In addition, how gamete quality affects fertilization success and embryonic development was examined. After 1-h hypoxic exposure, sperm motility was significantly reduced, compromising fertilization success. Although the eggs remained viable, more malformed embryos and retarded embryonic development were observed. We interpreted that the harmful effect of hypoxia on embryonic development was attributed to the teratogenicity and induced oxidative stress, ultimately causing the reduction in recruitment during summer.

  20. Effects of Acute Exposure to Endosulfan (Organochlorine Pesticides) on Hematology of African Mud Catfish, Clarias gariepinus (Burchell, 1822).

    Science.gov (United States)

    Ndimele, P E; Jenyo-Oni, A; Kumolu-Johnson, C A; Chukwuka, K S; Onuoha, S

    2015-08-01

    Changes in the blood parameters of fingerlings of Clarias gariepinus were investigated after 24 and 96-h of exposures to endosulfan. 180 fingerlings of C. gariepinus [mean weight (10.5±1.3 g); total length (11.2±1.2 cm)] were exposed to five different concentrations (1.00, 2.20, 4.80, 11.00, 23.00 µg/L) of endosulfan and a control for 96 h after being acclimatized for 21 days. After 24 h of exposure, microcytic hypochromic anemia was observed and all erythrocyte profiles tested showed significant variation (pgariepinus fingerlings. Therefore, awareness on the hazards associated with the use of endosulfan should be intensified and sound sustainable alternatives to endosulfan should be developed.

  1. Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions.

    Science.gov (United States)

    Maikawa, Caitlin L; Zimmerman, Naomi; Rais, Khaled; Shah, Mittal; Hawley, Brie; Pant, Pallavi; Jeong, Cheol-Heon; Delgado-Saborit, Juana Maria; Volckens, John; Evans, Greg; Wallace, James S; Godri Pollitt, Krystal J

    2016-10-15

    Gasoline direct injection (GDI) engines are increasingly prevalent in the global vehicle fleet. Particulate matter emissions from GDI engines are elevated compared to conventional gasoline engines. The pulmonary effects of these higher particulate emissions are unclear. This study investigated the pulmonary responses induced by GDI engine exhaust using an ex vivo model. The physiochemical properties of GDI engine exhaust were assessed. Precision cut lung slices were prepared using Balb/c mice to evaluate the pulmonary response induced by one-hour exposure to engine-out exhaust from a laboratory GDI engine operated at conditions equivalent to vehicle highway cruise conditions. Lung slices were exposed at an air-liquid interface using an electrostatic aerosol in vitro exposure system. Particulate and gaseous exhaust was fractionated to contrast mRNA production related to polycyclic aromatic hydrocarbon (PAH) metabolism and oxidative stress. Exposure to GDI engine exhaust upregulated genes involved in PAH metabolism, including Cyp1a1 (2.71, SE=0.22), and Cyp1b1 (3.24, SE=0.12) compared to HEPA filtered air (pengine exhaust further increased Cyp1b1 expression compared to filtered GDI engine exhaust (i.e., gas fraction only), suggesting this response was associated with the particulate fraction. Exhaust particulate was dominated by high molecular weight PAHs. Hmox1, an oxidative stress marker, exhibited increased expression after exposure to GDI (1.63, SE=0.03) and filtered GDI (1.55, SE=0.04) engine exhaust compared to HEPA filtered air (pengine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress.

  2. Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone.

    Science.gov (United States)

    Lorke, Dietrich E; Nurulain, Syed M; Hasan, Mohamed Y; Kuča, Kamil; Petroianu, Georg A

    2014-10-01

    Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p ≤ 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option.

  3. Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: a Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Lauren Z. Gashlin

    2015-03-01

    Full Text Available Background: For treatment of severe alcohol withdrawal syndrome, high dose benzodiazepines (BZDs may cause delirium and over-sedation. Phenobarbital (PBT is a long-acting barbiturate effective for the treatment of alcohol withdrawal. Given the potential benefits of PBT, we sought to investigate the effectiveness of PBT as adjunctive treatment for alcohol withdrawal. Methods: This was a retrospective cohort study on patients with a diagnosis of alcohol withdrawal who had a CIWA-Ar score > 10 treated with either BZDs alone (BZD alone group or BZDs with adjunctive PBT (PBT-adjunct group. The patients received at least one dose of PBT in addition to BZDs (variable doses in the PBT-adjunct group, and three doses of 20 mg diazepam equivalents within 6 hours in the BZD alone group. The primary endpoint was the proportion of patients with a CIWA-Ar score < 10 at 24 hours after initial treatment. Duration of withdrawal and cumulative dose of BZDs were also assessed. Results: Seven subjects in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. Two patients (28.6% in the PBT-adjunct group and 5 patients (23.8% in the BZD only group achieved the primary endpoint, though the difference between the two groups was not statistically significant (P = 0.588. The median (IQR duration of withdrawal symptoms was 44 (12-62 hours in the PBT-adjunct group compared to 53 (37-87 hours in the BZD only group, with no significant difference between the groups (P = 0.249. The median (IQR cumulative BZD dose requirement (diazepam equivalent in the PBT-adjunct group was significantly lower than BZD alone group (25 (20-226 vs. 326 (160-550 mg, P = 0.02. Conclusion: PBT appears to be a safe and effective alternative to BZDs for the treatment of alcohol withdrawal in non-critically ill patients and may be BZD sparing.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  5. Liver histopathology of the fish brachydanio rerio hamilton-buchman after acute exposure to sublethal levels of the organophosphate dimethoate 500

    Directory of Open Access Journals (Sweden)

    Edson de Lara Rodrigues

    1998-01-01

    Full Text Available Among the new substances that were synthesised by the chemical industiy during the last decades, with the aim to improve human prosperity, some cause negative effects on non target organisms like fish. Among the pesticides, the organophosphates (OP are widely used in cattle management, agriculture and aquaculture activities. Brachydanio rerio Hamilton-Buchman, 1822 is used world-wide in fish-tests for the establishment of the lethal levels of pesticides. Nevertheless, these fish show morphological changes in their hepatocytes when exposed experimentally for 24 hours to the sublethal dose of 0.025 µl/l of the OP Dimethoate 500, in acute tests. Right hours after exposure, a high density of cells with cytoplasmic granulation is seen as well as focal necrosis. The main changes that occurred in the first 24 hours of exposure were the loss of the typical polygonal cell shape and of detectable cell limits, lateral migration of nuclei, nuclear size and shape, condensation of chromatin and pycnosis, increased cytoplasmic granulation followed by vacuolisation. After 48 hours in clean water, 72 hours from contamination, besides significant morphological changes and necrosis, focal regeneration of the hepatocytes, canaliculi, ducts and sinusoids were seen. Even having been exposed to the half of the dose considered as safe according to the general pesticide allowance rules, significant changes of the liver tissue were observed.

  6. Impact of acute Cd²⁺ exposure on the antioxidant defence systems in the skin and red blood cells of common carp (Cyprinus carpio).

    Science.gov (United States)

    Ferencz, Ágnes; Hermesz, Edit

    2015-05-01

    Cd(2+)-induced oxidative stress and its effects on the expression of stress biomarkers and on macromolecule damage in the skin and blood of common carp were studied. Both tissues play important roles in the defence mechanisms against external hazards, serving as an anatomical barrier and as connecting tissue between the organs. In the skin, the production of peroxynitrite anion and hydrogen peroxide was almost doubled after exposure to 10 mg/L Cd(2+). The accumulation of these oxidant molecules suggests an intensive production of superoxide anion and nitrogen monoxide and the development of oxidative and/or nitrosative stress. Although the metallothioneins and the components of the glutathione redox system were activated in the skin, the accumulation of reactive intermediates led to the enhanced damage of lipid molecules after 24 h of metal exposure. In the blood, the basal levels of metallothionein messenger RNAs (mRNAs) were 2-2.5-fold of that measured in the skin. This high level of metallothionein expression could be the reason that the blood was less affected by an acute Cd(2+) challenge and the metallothionein and glutathione systems were not activated.

  7. Sublethal and Reproductive Effects of Acute and Chronic Exposure to Flowback and Produced Water from Hydraulic Fracturing on the Water Flea Daphnia magna.

    Science.gov (United States)

    Blewett, Tamzin A; Delompré, Perrine L M; He, Yuhe; Folkerts, Erik J; Flynn, Shannon L; Alessi, Daniel S; Goss, Greg G

    2017-02-13

    Hydraulic fracturing is an industrial process allowing for the extraction of gas or oil. To fracture the rocks, a proprietary mix of chemicals is injected under high pressure, which later returns to the surface as flowback and produced water (FPW). FPW is a complex chemical mixture consisting of trace metals, organic compounds, and often, high levels of salts. FPW toxicity to the model freshwater crustacean Daphnia magna was characterized utilizing acute (48 h median lethal concentrations; LC50) and chronic (21 day) exposures. A decrease in reproduction was observed, with a mean value of 18.5 neonates produced per replicate over a 21 day chronic exposure to 0.04% FPW, which was a significant decrease from the average of 64 neonates produced in the controls. The time to first brood was delayed in the highest FPW (0.04%) treatment. Neonates exhibited an LC50 of 0.19% of full-strength FPW, making them more sensitive than adults, which displayed an LC50 value of 0.75%. Quantitative PCR highlighted significant changes in expression of genes encoding xenobiotic metabolism (cyp4) and moulting (cut). This study is the first to characterize chronic FPW toxicity and will help with the development of environmental monitoring and risk assessment of FPW spills.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Pinon-Lataillade, G.; Maas, J. (CEA Centre d' Etudes de Bruyeres-le-Chatel, 91 (FR)); Viguier-Martinez, M.C. (Tours Univ., 37 (FR) Institut National de Recherches Agronomiques, 37 - Nouzilly (FR)); Touzalin, A.M.; Jegou, B. (Rennes-1 Univ., 35 (FR))

    1991-01-01

    Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of {gamma} rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in caput epididymis and plasma follicle stimulating hormone, FSH) and Leydig cell parameters (plasma luteinizing hormone, LH, testosterone and prostate and seminal vesicle weights) were determined together with the number of germ cells and Sertoli cells. Irradiation did not affect body weight but significantly reduced testicular and epididymal weights from day 7 and day 15 post-irradiation respectively. The cells killed by irradiation were mainly spermatogonia and preleptotene spermatocytes engaged in replicating their DNA at the time of exposure, but all spermatocytes seemed damaged as they gave abnormal descendent cells. By day 34, only elongated spermatids remained in a few tubules and thereafter very little regeneration of the seminiferous epithelium occurred, except for one rat which showed a better regeneration. Levels of ABP decreased by day 15 when the germ cell depletion had reached the pachytene spermatocytes, whereas FSH and LH levels rose when the number of elongated spermatids decreased. Levels of testosterone and the weight of the seminal vesicles did not change; occasionally, the prostate weight was slightly reduced. These results support our hypothesis that pachytene spermatocytes and elongated spermatids are involved in influencing some aspects of Sertoli cell function in the adult rat.

  10. Phenobarbital influence on neuromuscular block produced by rocuronium in rats Influência do fenobarbital no bloqueio neuromuscular produzido pelo rocurônio em ratos

    Directory of Open Access Journals (Sweden)

    Angélica de Fátima de Assunção Braga

    2008-08-01

    Full Text Available PURPOSE: To evaluate in vitro and in vivo neuromuscular blockade produced by rocuronium in rats treated with Phenobarbital and to determine cytochrome P450 and cytochrome b5 concentrations in hepatic microsomes. METHODS: Thirty rats were included in the study and distributed into 6 groups of 5 animals each. Rats were treated for seven days with phenobarbital (20 mg/kg and the following parameters were evaluated: 1 the amplitude of muscle response in the preparation of rats exposed to phenobarbital; 2 rocuronium effect on rat preparation exposed or not to phenobarbital; 3 concentrations of cytochrome P450 and cytochrome b5 in hepatic microsomes isolated from rats exposed or not to phenobarbital. The concentration and dose of rocuronium used in vitro and in vivo experiments were 4 µg/mL and 0,6 mg/kg, respectively. RESULTS: Phenobarbital in vitro and in vivo did not alter the amplitude of muscle response. The neuromuscular blockade in vitro produced by rocuronium was significantly different (p=0.019 between exposed (20% and not exposed (60% rats; the blockade in vivo was significantly greater (p=0.0081 in treated rats (93.4%. The enzymatic concentrations were significantly greater in rats exposed to phenobarbital. CONCLUSIONS: Phenobarbital alone did not compromise neuromuscular transmission. It produced enzymatic induction, and neuromuscular blockade in vivo produced by rocuronium was potentiated by phenobarbital.OBJETIVO: Avaliar in vitro e in vivo o bloqueio neuromuscular produzido pelo rocurônio em ratos tratados com fenobarbital e determinar as concentrações de citocromo P450 e b5 em microssomos hepáticos. MÉTODOS: Trinta ratos foram incluídos no estudo e distribuídos em seis grupos de cinco animais cada. Ratos foram tratados por sete dias com fenobarbital (20 mg/kg e avaliou-se: 1 amplitude das respostas musculares em preparação de ratos expostos ao fenobarbital; 2 o efeito do rocurônio em preparações de ratos expostos ou n

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  13. Acute exposure to synthetic pyrethroids causes bioconcentration and disruption of the hypothalamus–pituitary–thyroid axis in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Wenqing [Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029 (China); Institute of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Xu, Chao, E-mail: chaoxu@zjut.edu.cn [Institute of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Lu, Bin; Lin, Chunmian [Institute of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Wu, Yongming [Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029 (China); Liu, Weiping [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-01-15

    Synthetic pyrethroids (SPs) have the potential to disrupt the thyroid endocrine system in mammals; however, little is known of the effects of SPs and underlying mechanisms in fish. In the current study, embryonic zebrafish were exposed to various concentrations (1, 3 and 10 μg/L) of bifenthrin (BF) or λ-cyhalothrin (λ-CH) until 72 h post fertilization, and body condition, bioaccumulation, thyroid hormone levels and transcription of related genes along the hypothalamus–pituitary–thyroid (HPT) axis examined. Body weight was significantly decreased in the λ-CH exposure groups, but not the BF exposure groups. BF and λ-CH markedly accumulated in the larvae, with concentrations ranging from 90.7 to 596.8 ng/g. In both exposure groups, alterations were observed in thyroxine (T{sub 4}) and triiodothyronine (T{sub 3}) levels. In addition, the majority of the HPT axis-related genes examined, including CRH, TSHβ, TTR, UGT1ab, Pax8, Dio2 and TRα, were significantly upregulated in the presence of BF. Compared to BF, λ-CH induced different transcriptional regulation patterns of the tested genes, in particular, significant stimulation of TTR, Pax8, Dio2 and TRα levels along with concomitant downregulation of Dio1. Molecular docking analyses revealed that at the atomic level, BF binds to thyroid hormone receptor (TRα) protein more potently than λ-CH, consequently affecting HPT axis signal transduction. In vitro and in silico experiments disclosed that during the early stages of zebrafish development, BF and λ-CH have the potential to disrupt thyroid endocrine system. - Highlights: • Following respective exposure of embryos to BF and λ-CH, thyroid endocrine disruption was investigated in zebrafish embryos. • Thyroid hormones (T3 and T4 levels) were significantly altered after being exposed to BF and λ-CH. • Gene transcription modulation in the HPT axis was examined. • BF and λ-CH bioconcentration in zebrafish larvae were evident. • BF binds to thyroid

  14. Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue.

    Science.gov (United States)

    Polak, Jan; Moro, Cédric; Bessière, David; Hejnova, Jindra; Marquès, Marie A; Bajzova, Magda; Lafontan, Max; Crampes, Francois; Berlan, Michel; Stich, Vladimir

    2007-10-01

    The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  17. Acute cytotoxicity and apoptotic effects after l-Pam exposure in different cocultures of the proximal and distal respiratory system.

    Science.gov (United States)

    Pohl, Christine; Hofmann, Helene; Moisch, Michaela; Papritz, Mirko; Iris Hermanns, M; Dei-Anang, Jasmin; Mayer, Eckhard; Kehe, Kai; Kirkpatrick, Charles James

    2010-07-01

    Sulphur and nitrogen mustard are strong alkylating agents which can cause after inhalation acute lung injury in the larynx, trachea and large bronchi and can lead to alveolar edema. In our study we tested the N-Lost l-Phenylalanine Mustard (l-Pam). Therefore we seeded the alveolar type II cell line NCI H441 on the upper membrane of a Transwell filter plate and the endothelial cell line ISO-Has-1 on the lower side of the membrane for the alveolar model and combined the human bronchial explant-outgrowth cells and fibroblasts in the bronchial model and exposed both models with various concentrations of l-Pam. Treatment with l-Pam led to a concentration-dependent decrease of the transepithelial electrical resistance and therefore impairment of barrier function in both models. Changes in morphology could be observed. In the bronchial model damaged cell organelles whereas in the alveolar model a widening of intercellular spaces could be seen. Loss of cell-matrix adhesion as well as apoptotic and necrotic cell death could be demonstrated. In conclusion, treatment with the nitrogen mustard in the coculture models showed comparable results to sulphur mustard treatment and thus this model could be useful to explore similarities and differences in signal transduction pathways after treatment with both sulphur and nitrogen mustard.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Acute toxicity, respiratory reaction, and sensitivity of three cyprinid fish species caused by exposure to four heavy metals.

    Directory of Open Access Journals (Sweden)

    Hongjun Wang

    Full Text Available Using 3 cyprinid fish species zebra fish, rare minnow, and juvenile grass carp, we conducted assays of lethal reaction and ventilatory response to analyze sensitivity of the fish to 4 heavy metals. Our results showed that the 96 h LC50 of Hg(2+ to zebra fish, juvenile grass carp, and rare minnow were 0.14 mg L(-1, 0.23 mg L(-1, and 0.10 mg L(-1, respectively; of Cu(2+0.17 mg L(-1, 0.09 mg L(-1, and 0.12 mg L(-1 respectively; of Cd(2+6.5 mg L(-1, 18.47 mg L(-1, 5.36 mg L(-1, respectively; and of Zn(2+44.48 mg L(-1, 31.37 mg L(-1, and 12.74 mg L(-1, respectively. Under a 1-h exposure, the ventilatory response to the different heavy metals varied. Ventilatory frequency (Vf and amplitude (Va increased in zebra fish, juvenile grass carp, and rare minnows exposed to Hg(2+ and Cu(2+ (P<0.05, and the Vf and Va of the 3 species rose initially and then declined when exposed to Cd(2+. Zn(2+ had markedly different toxic effects than the other heavy metals, whose Vf and Va gradually decreased with increasing exposure concentration (P<0.05. The rare minnow was the most highly susceptible of the 3 fish species to the heavy metals, with threshold effect concentrations (TEC of 0.019 mg L(-1, 0.046 mg L(-1, 2.142 mg L(-1, and 0.633 mg L(-1 for Hg(2+, Cu(2+, Cd(2+, and Zn(2+, respectively. Therefore, it is feasible to use ventilatory parameters as a biomarker for evaluating the pollution toxicity of metals and to recognize early warning signs by using rare minnows as a sensor.

  20. Differential influence of the 5-HTTLPR genotype, neuroticism and real-life acute stress exposure on appetite and energy intake.

    Science.gov (United States)

    Capello, Aimée E M; Markus, C Rob

    2014-06-01

    Stress or negative mood often promotes energy intake and overeating. Since the serotonin transporter-linked polymorphic region (5-HTTLPR) is found to mediate stress vulnerability as well as to influence energy intake, this gene may also influence the negative effects of stress exposure on overeating. Moreover, since stress proneness also reflects cognitive stress vulnerability - as often defined by trait neuroticism - this may additionally predispose for stress-induced overeating. In the present study it was investigated whether the 5-HTTLPR genotype interacted with neuroticism on changes in mood, appetite and energy intake following exposure to a real-life academic examination stressor. In a balanced-experimental design, homozygous S-allele and L-allele carriers (N = 94) with the lowest and highest neuroticism scores were selected from a large database of 5-HTTLPR genotyped students. Mood, appetite and energy intake were measured before and after a 2-hour academic examination and compared with a control day. Examination influenced appetite for particular sweet snacks differently depending on 5-HTTLPR genotype and neuroticism. S/S compared with L/L subjects reported greater examination stress, and this was accompanied by a more profound post-stress increase in appetite for sweet snacks. Data also revealed a 5-HTTLPR genotype by trait neuroticism interaction on energy intake, regardless of examination. These results consolidate previous assumptions of 5-HTTLPR involvement in stress vulnerability and suggest 5-HTTLPR and neuroticism may influence stress-induced overeating depending on the type of food available. These findings furthermore link previous findings of increased risk for weight gain in S/S-allele carriers, particularly with high scores on trait neuroticism, to increased energy intake.

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

    Science.gov (United States)

    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.

  2. Response of AMP-activated protein kinase and energy metabolism to acute nitrite exposure in the Nile tilapia Oreochromis niloticus.

    Science.gov (United States)

    Xu, Zhixin; Li, Erchao; Xu, Chang; Gan, Lei; Qin, Jian G; Chen, Liqiao

    2016-08-01

    Adenosine monophosphate-activated protein kinase (AMPK) is a prevalent mammalian energy metabolism sensor, but little is known about its role as an energy sensor in fish experiencing stress. We aimed to study AMPK in Oreochromis niloticus on both the molecular and the physical level. We found that the cDNAs encoding the AMPKα1 and AMPKα2 variants of the O. niloticus catalytic α subunit were 1753bp and 2563 bp long and encoded 571 and 557 amino acids, respectively. Both the AMPKα1 and the AMPKα2 isoform possess structural features similar to mammalian AMPKα, including a phosphorylation site at Thr172 in the N-terminus, and exhibit high homology with other fish and vertebrate AMPKα sequences (81.3%-98.1%). mRNA encoding the AMPKα isoforms was widely expressed in various tissues with distinctive patterns. AMPKα1 and AMPKα2 were primarily expressed in the intestines and brain, respectively. Under acute nitrite challenge, the mRNA encoding the AMPKα isoforms, as well as AMPK activity, changed over time. Its recovery period in freshwater, combined with the fact that it is highly conserved, suggests that fish AMPK, like its mammalian orthologues, acts as an energy metabolism sensor. Furthermore, subsequent decreases in AMPK mRNA levels and activity suggested that its action was transient but efficient. Physically, glucose, lactic acid and TGs in plasma, as well as energy materials in the hepatopancreas and muscle, were significantly altered over time, indicating changes in energy metabolism during the experimental period. These data have enabled us to characterize energy utilization in O. niloticus and further illustrate the role of fish AMPK as an energy sensor. This study provides new insight into energy metabolism and sensing by AMPK in teleost and necessitates further study of the multiple physiologic roles of AMPK in fish.

  3. Choline acetyltransferase expression in rat prefrontal cortex and hippocampus after acute and chronic exposure to amisulpride, haloperidol, and risperidone.

    Science.gov (United States)

    Huang, Guang-Biao; Zhao, Tong; Li, Chun-Rong; Sui, Zhi-Yan; Kang, Nam-In; Han, Eui-Hyeog; Chung, Young-Chul

    2012-10-24

    Recently, there has been an increasing concern that atypical antipsychotics as well as typical ones may cause detrimental effects on cognitive function. Supporting evidence comes from many preclinical studies demonstrating that long-term administration of haloperidol, risperidone, and ziprasidone reduced choline acetyltransferase (ChAT) expression in rat hippocampus (HIP). However, to the best of our knowledge, no studies have examined the effects of amisulpride on ChAT expression in rats. Therefore, the aim of this study was to investigate the effects of acute and chronic administration of amisulpride, haloperidol, and risperidone on ChAT expression in the rat prefrontal cortex (PFC) and HIP. Animals received daily intraperitoneal (i.p.) injections of amisulpride (5 or 100mg/kg), haloperidol (1 or 2mg/kg), risperidone (1 or 2mg/kg) or vehicle for 7 or 45 days. One day after the last injection, rats were sacrificed. ChAT immunoreactivity was assessed with immunofluorescence staining. Target areas of brain were PFC and HIP (CA1, CA3 and DG). The short-term administration of haloperidol and risperidone produced significant decrease of ChAT immunoreactivity in the PFC and HIP compared to vehicle whereas amisulpride had no effects on ChAT immunoreactivity in the PFC and HIP. In long-term study, haloperidol and risperidone decreased ChAT-positive cells and/or fiber pixel density in the PFC and HIP whereas amisulpride decreased ChAT-positive cells in the PFC and had no effects on fiber pixel density of ChAT in the HIP. The results suggest that both short-term and long-term administration of haloperidol and risperidone, and long-term administration of amisulpride may produce detrimental effects on cognitive function by reducing ChAT expression in the PFC and/or HIP.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Variation in quantity and composition of cuticular hydrocarbons in the scorpion Buthus occitanus (Buthidae) in response to acute exposure to desiccation stress.

    Science.gov (United States)

    Gefen, E; Talal, S; Brendzel, O; Dror, A; Fishman, A

    2015-04-01

    Scorpions exhibit some of the lowest recorded water loss rates among terrestrial arthropods. Evaporative water loss to the surrounding environment occurs mainly through the integument, and thus its resistance to water loss has paramount significance for the ability of scorpions to tolerate extremely dry habitats. Cuticular hydrocarbons (HCs) deposited on the outer epicuticle play an important role in determining cuticular waterproofing, and seasonal variation in both cuticular HC quantity and composition has been shown to correlate with water loss rates. Precursor incorporation rates into cuticle HCs have been observed to be extremely low in scorpions compared with insects. We therefore used adult male Buthus occitanus (Buthidae) in order to test HC profile plasticity during acute exposure to 14 d and 28 d of experimental desiccation. Cuticular HC profile of hydrated scorpions was similar to that reported for several other scorpion species, consisting of similar fractions of n-alkanes and branched alkanes, with no evidence for unsaturation. Most abundant of the n-alkanes were n-heptacosane (C27; 19±2% of total HCs), n-nonacosane (C29; 16±1%) and n-hentriacontane (C31; 11±1%). Exposure to desiccation stress resulted in a significant increase in the total amount of extracted HCs, and in the relative abundance of branched alkanes at the expense of n-alkanes. Together with an increase in HC chain lengths, these changes mimic previously-reported seasonal variation among freshly-collected specimens. This indicates that scorpions respond to water shortage by regulating the properties of their passive integumental barrier to water loss.

  7. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Directory of Open Access Journals (Sweden)

    Sarah Everman

    Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  8. 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

    Science.gov (United States)

    Kaabneh, Mahmoud AF; Salama, Ghassan SA; Shakkoury, Ayoub GA; Al-abdallah, Ibrahim MH; Alshamari, Afrah; Halaseh, Ruba AA

    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 divided randomly into two groups: (1) the phenobarbital plus phototherapy group (n = 103), and (2) the phototherapy-only group (n = 97). Infants in group 1 received an oral dose of 2.5 mg/kg phenobarbital every 12 hours for 3 days in addition to phototherapy. The total serum bilirubin was observed. RESULTS Of the total 200 included newborn infants, 186 infants completed the study: 97 infants were included in group 1 and 89 infants in group 2. The difference between the mean total serum bilirubin levels at 24, 48, and 72 hours after starting the trial was clinically and statistically significant at P < 0.05. The differences between the two groups were also statistically significant at P < 0.05. Of the total 186 who completed the study, only 22 underwent blood exchange transfusion [7 from group 1, and 15 from group 2 (P = 0.0478)]. CONCLUSION In a limited-resources setting, phenobarbital in combination with phototherapy may be helpful to newborn infants with IHD, as it results in a faster decline in total serum bilirubin, thus decreasing the need for blood exchange transfusion than phototherapy alone. PMID:26309423

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

    Directory of Open Access Journals (Sweden)

    Alberto Teodorico Correia

    2015-12-01

    Full Text Available Data about the toxicological effects of cerium dioxide nanoparticles (CeO2 NP in fish are scarce. This work aimed to assess the CeO2 NP possible deleterious effects on the gills of Oncorhynchus mykiss. A semi-continuous acute test was conducted to expose the rainbow trout to a freshwater control, 0.25, 2.50 and 25.00 mg/L CeO2 NPs for up to 96 hours. Gills pathological index showed a dose-effect relationship for the individuals exposed to CeO2. Gills showed aneurisms, epithelial lifting and hyperplasia. Furthermore exposure to CeO2 NPs caused statistical differences in some biomarkers determinations, namely a significant increase in the catalase activity and genotoxicity the higher concentrations. No significant changes were however observed in thiobarbituric acid reactive substances content, Na+-K+ ATPase and glutathione s-transferase activities. This study suggests that CeO2 nanoparticles are toxic compounds that can lead to histological, biochemical and genotoxic alterations.

  10. Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity

    Science.gov (United States)

    Yang, Daqian; Tan, Xiao; Lv, Zhanjun; Liu, Biying; Baiyun, Ruiqi; Lu, Jingjing; Zhang, Zhigang

    2016-01-01

    Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo. Furthermore, luteolin reversed the changes in levels of inflammation- and apoptosis-related proteins involving NF-κB, TNF-α, Sirt1, mTOR, Bax, p53, and Bcl-2, and inhibited p38 MAPK activation. Luteolin enhanced antioxidant defense system based on Keap1, Nrf2, HO-1, NQO1, and KLF9. Moreover, luteolin did not affect miRNA-146a expression. Collectively, our findings, for the first time, elucidate a precise mechanism for attenuation of HgCl2-induced liver dysfunction by dietary luteolin via regulating Sirt1/Nrf2/TNF-α signaling pathway, and provide a foundation for further study of luteolin as a novel therapeutic agent against inorganic mercury poisoning. PMID:27853236

  11. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    King, L.M. [ARS USDA, Germplasm and Gamete Physiology Lab., Beltsville, MD (United States); Anderson, M.B. [Dept. of Anatomy, Tulane Univ. School of Medicine, New Orleans, LA (United States); Sikka, S.C. [Dept. of Urology, Tulane Univ. School of Medicine, New Orleans, LA (United States); George, W.J. [Dept. of Pharmacology, Tulane Univ. School of Medicine, New Orleans, LA (United States)

    1998-10-01

    The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 {mu}mol/kg CdCl{sub 2}). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 {mu}mol/kg ZnAc), given 24 h prior to 20 {mu}mol/kg CdCl{sub 2} administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible

  13. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital.

    Science.gov (United States)

    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.

  14. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia Juice and Phenobarbital

    Directory of Open Access Journals (Sweden)

    Anna Mrzljak

    2013-01-01

    Full Text Available 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.

  15. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

    Science.gov (United States)

    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

  16. Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

    Directory of Open Access Journals (Sweden)

    Cylene Zambrozi Garcia

    2012-09-01

    Full Text Available Microcystins are secondary metabolites produced by different species of cyanobacteria, such as Microcystis aeruginosa (MA. In this study, the biochemical and genetic effects of lyophilized MA were evaluated in the neotropical fish Prochilodus lineatus exposed to 1 or 2 mg L-1 lyophilized MA (treated group or only water (control group in static toxicity tests for 24 and 96 h. The gills and liver were used in the analysis of biotransformation enzymes and antioxidant defenses, blood and gill cells in genetic analysis and in brain and muscle it was determined the activity of acetylcholinesterase (AChE. The results showed the biotransformation pathway activation due to the increase in hepatic CYP1A and in branchial and hepatic glutathione S-transferase (GST. The antioxidant defense proved to be greatly affected by MA exposure leading to changes, both in gills and liver, in the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione reductase (GR and in the content of tripeptide glutathione (GSH. Lipid peroxidation was not detected, but damage to DNA molecule was observed in blood cells. In conclusion, it can be state the lyophilized MA is able to promote changes in the biochemical and genetic parameters of P. lineatus.As microcistinas são metabólitos secundários produzidos por diferentes espécies de cianobactérias, como a Microcystis aeruginosa (MA. Neste estudo, os efeitos bioquímicos e genéticos de liofilizado de MA foram avaliados para juvenis da espécie de peixe Neotropical Prochilodus lineatus expostos a 1 ou 2 mg L-1 de liofilizado de MA (grupo tratado ou apenas à água (grupo controle, em testes de toxicidade estáticos, durante 24 e 96 h. As brânquias e o fígado foram usados para as análises das enzimas de biotransformação e defesas antioxidantes, células do sangue e das brânquias para análises genéticas e no cérebro e músculo foi determinada a atividade da acetilcolinesterase (ACh

  17. 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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  19. Effect of baicalin capsules on acute mountain sickness in healthy young males at acute high altitude exposure%黄芩苷与红景天胶囊对急性高原病预防作用比较

    Institute of Scientific and Technical Information of China (English)

    段炜; 孙书红; 惠增骞; 高钊; 胡建库; 金峰; 陈虹

    2015-01-01

    ), systolic blood pressure(SBP), diastolic blood pressure ( DBP) , pulmonary artery systolic pressure ( PASP) and mean pulmonary arterial pressure ( MPAP) were assessed both at 397 m and 3658 m.Results After high-altitude exposure, significantly fewer participants in the baicalin capsules group (n=8, 25.0%) and rhodiola capsules group(n=7, 29.2%) developed acute mountain sickness compared with participants receiving placebo (n=14, 58.3%) (P<0.05) .HR, SBP, DBP, PASP and MPAP increased with altitude exposure (P<0.05), and SpO2 decreased with alti-tude exposure (P<0.05).AMS, HR, SBP and DBP with baicalin capsules was lower than those with placebo (P<0.05); AMS, PASP, MPAP with rhodiola capsules were lower than those with placebo (P<0.05) and SpO2 was higher than that with placebo (P<0.05).Conclusions Baicalin capsules for AMS prevention also reduce HR , SBP and DBP with rapid airlift ascent to high altitude and rhodiola capsules for AMS prevention also reduce PASP , MPAP, increase SpO2 with rapid airlift ascent to high altitude .

  20. 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

    Science.gov (United States)

    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 (predicted observed differences in accumulation between hard and soft water rainbow 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.

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

    Science.gov (United States)

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

    2014-10-01

    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.

  2. Development of contrast-induced acute kidney injury after elective contrast media exposure in patients with type 2 diabetes mellitus: effect of albuminuria.

    Directory of Open Access Journals (Sweden)

    Jun-qing Yang

    Full Text Available The influence of albuminuria and urinary pH on the development of contrast-induced acute kidney disease (CI-AKI in patients with type 2 diabetes mellitus (T2DM after elective coronary angiography (CAG or percutaneous coronary intervention (PCI is unknown.CI-AKI was defined as an increase in serum creatinine >26.4 µmol/L or ≥50% of baseline value within 48 hours after contrast media exposure. Demographics, traditional risk factors, clinical outcomes and CI-AKI incidence were compared between groups. Univariate analysis and multivariate logistic regression were performed to assess risk factors of CI-AKI.We observed 597 patients with T2DM after CAG or PCI. Patients were divided into 3 groups based on early morning urinary albumin: negative group (urine dipstick negative, n = 483, trace group (urine dipstick trace, n = 60, and positive group (urine dipstick ≥1+, n = 54. CI-AKI occurred in 33 (5.5% patients, including 19 (3.9% in the negativealbuminuria group, 4 (6.7% in the trace group, and 10 (18.5% in the positive group (p< 0.001, respectively. After adjusting for potential confounding risk factors, positive albuminuria (OR = 3.8, 95% CI: 1.5 to 9.2, p = 0.004 and urinary pH<6 (OR = 2.4, 95% CI: 1.1 to 5.1, p = 0.020 remained significantly associated with CI-AKI.Preprocedural albuminuria and urinary pH <6 are independent risk factors of CI-AKI in patients with T2DM undergoing elective cardiac catheterization, and may be used to identify patients at high risk of post-procedural CI-AKI.

  3. Disturbance of Bcl-2, Bax, Caspase-3, Ki-67 and C-myc expression in acute and subchronic exposure to benzo(a)pyrene in cervix.

    Science.gov (United States)

    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.

  4. Dual acute proinflammatory and antifibrotic pulmonary effects of short palate, lung, and nasal epithelium clone-1 after exposure to carbon nanotubes.

    Science.gov (United States)

    Di, Y Peter; Tkach, Alexey V; Yanamala, Naveena; Stanley, Shyla; Gao, Shengli; Shurin, Michael R; Kisin, Elena R; Kagan, Valerian E; Shvedova, Anna

    2013-11-01

    Carbon nanotubes (CNTs; allotropes of carbon with a cylindrical nanostructure) have emerged as one of the most commonly used types of nanomaterials, with numerous applications in industry and biomedicine. However, the inhalation of CNTs has been shown to elicit pulmonary toxicity, accompanied by a robust inflammatory response with an early-onset fibrotic phase. Epithelial host-defense proteins represent an important component of the pulmonary innate immune response to foreign inhalants such as particles and bacteria. The short palate, lung, and nasal epithelium clone-1 (SPLUNC1) protein, a member of the bactericidal/permeability-increasing-fold (BPIF)-containing protein family, is a 25-kD secretory protein that is expressed in nasal, oropharyngeal, and lung epithelia, and has been shown to have multiple functions, including antimicrobial and chemotactic activities, as well as surfactant properties. This study sought to assess the importance of SPLUNC1-mediated pulmonary responses in airway epithelial secretions, and to explore the biological relevance of SPLUNC1 to inhaled particles in a single-walled carbon nanotube (SWCNT) model. Using Scgb1a1-hSPLUNC1 transgenic mice, we observed that SPLUNC1 significantly modified host inflammatory responses by increasing leukocyte recruitment and enhancing phagocytic activity. Furthermore, we found that transgenic mice were more susceptible to SWCNT exposure at the acute phase, but showed resistance against lung fibrogenesis through pathological changes in the long term. The binding of SPLUNC1 also attenuated SWCNT-induced TNF-α secretion by RAW 264.7 macrophages. Taken together, our data indicate that SPLUNC1 is an important component of mucosal innate immune defense against pulmonary inhaled particles.

  5. Effects of Short-Term Exposure to Lithium on Antiapoptotic Bcl-xL Protein Expression in Cortex and Hippocampus of Rats after Acute Stress.

    Science.gov (United States)

    Dygalo, N N; Bannova, A V; Sukhareva, E V; Shishkina, G T; Ayriyants, K A; Kalinina, T S

    2017-03-01

    The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.

  6. Exposições tóxicas agudas em crianças: um panorama Acute toxic exposure in children: an overview

    Directory of Open Access Journals (Sweden)

    Fábio Bucaretchi

    2005-11-01

    Full Text Available OBJETIVO: Revisar a literatura das exposições tóxicas em pediatria, excluindo os acidentes por animais peçonhentos. FONTES DE DADOS: Revisão narrativa dos principais trabalhos indexados no MEDLINE, especialmente da última década, incluindo as revisões de consenso baseadas em evidências sobre as medidas de descontaminação gastrintestinal e de aumento da eliminação de agentes tóxicos, estabelecidas em conjunto pela Academia Americana de Toxicologia Clínica e Associação Européia dos Centros de Intoxicação e dos Toxicologistas Clínicos. SÍNTESE DOS DADOS: A exposição tóxica em pediatria é um evento comum, principalmente em crianças abaixo de 6 anos. A letalidade é baixa. Embora amplamente empregadas, não há evidências de que as medidas de descontaminação gastrintestinal e de aumento de eliminação de agentes tóxicos melhore o prognóstico dos pacientes intoxicados. São poucos os antídotos disponíveis e eficazes, sendo alguns de alto custo, e vários não disponíveis no Brasil; seu uso é limitado para indicações precisas. CONCLUSÕES: Não há evidências que apóiem a recomendação do uso do xarope de ipeca e de catárticos, seja no atendimento pré-hospitalar ou nas salas de emergência. O uso de carvão ativado em dose única e da lavagem gástrica, afastadas as contra-indicações, somente deve ser considerado se o procedimento puder ser realizado até 60 minutos da ingestão de doses potencialmente tóxicas ou potencialmente letais. A irrigação intestinal, a administração de carvão ativado em doses múltiplas e a alcalinização urinária podem ser consideradas em situações isoladas. Fomepizol e octreotida são antídotos seguros e eficazes no tratamento das intoxicações graves por álcoois (metanol e etilenoglicol e sulfoniluréias, respectivamente.OBJECTIVE: To review the literature on acute toxic exposure in children, excluding envenomations. SOURCES OF DATA: MEDLINE review (emphasis on the

  7. [BIS values were useful on the evaluation of consciousness recovery in acute Vegetamin-A poisoning: report of a case].

    Science.gov (United States)

    Matsumoto, Hironori; Umakoshi, Kensuke; Kikuchi, Satoshi; Takeba, Jun; Aibiki, Mayuki

    2014-12-01

    A 37-year-old man was admitted to our hospital with acute phenobarbital poisoning. On arrival, he was in deep coma with respiro-circulatory depressions. The serum concentration of the agent was elevated to 149.04 μg/mL which was consistent with a lethal concentration level. He underwent a gastric lavage, administration of activated charcoal, urinary alkalinazation and bowel irrigation. Respiro-circulatory status was recovered rapidly, while the serum concentration of phenobarbital did not decrease smoothly. Although the concentration of the agent decreased to 77.07 μg/mL that should be a comatose level, BIS values were gradually elevated, and then eventually the patient regained his consciousness. Because he was a chronic user of Vegetamin-A containing phenobarbital, the serum level might not have been correlated with symptoms. BIS values were highly reflective of the consciousness level, so it could be a useful indicator for predicting the consciousness levels of patients in deep coma with acute poisoning from hypnotic agents.

  8. A Novel Antihepatitis Drug, Bicyclol, Prevents Liver Carcinogenesis in Diethylnitrosamine-Initiated and Phenobarbital-Promoted Mice Tumor Model

    Directory of Open Access Journals (Sweden)

    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.

  9. Kinetics of carbon monoxide binding to phenobarbital-induced cytochrome P-450 from rat liver microsomes: a simple bimolecular process.

    Science.gov (United States)

    Oertle, M; Richter, C; Winterhalter, K H; Di Iorio, E E

    1985-01-01

    The kinetics of carbon monoxide binding to phenobarbital-induced cytochrome P-450 (P-450PB) and to its enzymatically inactive form P-420PB have been investigated by both stopped-flow and flash-photolysis spectrophotometry. When the simultaneous presence of both forms of the enzyme is taken into account, the binding of CO to these two proteins can be described in terms of two bimolecular processes with rate constants of 4.5 X 10(6) M-1.S-1 and 4.7 X 10(5) M-1.S-1 for P-450PB and 1.7 X 10(7) M-1.S-1 and 1.5 X 10(6) M-1.S-1 for P-420PB. From kinetic studies of the binding of CO to P-450PB under different experimental conditions, investigations of the homogeneity of our P-450PB preparations, and comparative kinetic investigations of P-450s from different sources, we conclude that CO binding to reduced P-450PB is a simple bimolecular process and that the observed biphasic traces are due to heterogeneity of the proteins. This conclusion is in contrast with previous reports of complex reaction mechanisms for the binding of CO to P-450PB. Optical spectroscopy studies indicate the existence of an equilibrium between P-450PB and P-420PB, at least for the reduced carbonyl derivatives of the enzymes. The interconversion is strongly influenced by the aggregation state of the protein. Large differences between the CO binding properties of P-450PB and those of P-420PB are found. These are discussed in terms of possible effects of the proximal ligation state of the iron on heme reactivity. PMID:3860832

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Directory of Open Access Journals (Sweden)

    Stephen Thomas Ahlers

    2012-03-01

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

  12. Effect of treatment with phenobarbital and stiripentol on carbamazepine-induced teratogenicity and reactive metabolite formation.

    Science.gov (United States)

    Finnell, R H; Bennett, G D; Slattery, J T; Amore, B M; Bajpai, M; Levy, R H

    1995-12-01

    A model using SWV mice was developed to investigate the mechanistic basis of carbamazepine (CBZ)-related fetotoxicity. Drug administration was initiated prior to conception and continued until day 18 of gestation. The incidence of malformation was 33% following CBZ exposure (1,500 mg/kg/day), compared with a 5% incidence in pair-fed control animals (P stiripentol (STP; a cytochrome P-450 inhibitor) (300 mg/kg/day) decreased the incidence of malformations produced by CBZ (1,500 mg/kg/day) from 33% to 16.7% (P < 0.05). The effect of PB administration on the binding of 14C in maternal and fetal tissue was assessed in dams that received CBZ (1,000 mg/kg/day) with or without PB (45 mg/kg/day) or STP (300 mg/kg/day) chronically and a single i.p. dose of 14C-CBZ on day 12 of gestation. In all instances, binding was greatest in maternal liver, then in the placenta, fetal head and body, and maternal thigh muscle. In all tissues, PB caused a two-to threefold increase in binding, compared with binding in mice exposed to CBZ alone. STP administration decreased protein adduct formation only in maternal liver. The binding of 14C was also assessed in hepatic microsomes prepared from female mice exposed to CBZ and PB or STP as in the in vivo study of 14C binding. The extent of irreversible binding was 67% greater in microsomes prepared from mice pretreated with PB and CBZ than with CBZ alone, while STP resulted in only 21% inhibition of 14C adduct formation (P < 0.05). The results are consistent with the formation of a chemically reactive teratogenic metabolite of CBZ in mice by cytochrome(s) P-450.

  13. Human health screening level risk assessments of tertiary-butyl acetate (TBAC): calculated acute and chronic reference concentration (RfC) and Hazard Quotient (HQ) values based on toxicity and exposure scenario evaluations.

    Science.gov (United States)

    Bus, James S; Banton, Marcy I; Faber, Willem D; Kirman, Christopher R; McGregor, Douglas B; Pourreau, Daniel B

    2015-02-01

    A screening level risk assessment has been performed for tertiary-butyl acetate (TBAC) examining its primary uses as a solvent in industrial and consumer products. Hazard quotients (HQ) were developed by merging TBAC animal toxicity and dose-response data with population-level, occupational and consumer exposure scenarios. TBAC has a low order of toxicity following subchronic inhalation exposure, and neurobehavioral changes (hyperactivity) in mice observed immediately after termination of exposure were used as conservative endpoints for derivation of acute and chronic reference concentration (RfC) values. TBAC is not genotoxic but has not been tested for carcinogenicity. However, TBAC is unlikely to be a human carcinogen in that its non-genotoxic metabolic surrogates tertiary-butanol (TBA) and methyl tertiary butyl ether (MTBE) produce only male rat α-2u-globulin-mediated kidney cancer and high-dose specific mouse thyroid tumors, both of which have little qualitative or quantitative relevance to humans. Benchmark dose (BMD)-modeling of the neurobehavioral responses yielded acute and chronic RfC values of 1.5 ppm and 0.3 ppm, respectively. After conservative modeling of general population and near-source occupational and consumer product exposure scenarios, almost all HQs were substantially less than 1. HQs exceeding 1 were limited to consumer use of automotive products and paints in a poorly ventilated garage-sized room (HQ = 313) and occupational exposures in small and large brake shops using no personal protective equipment or ventilation controls (HQs = 3.4-126.6). The screening level risk assessments confirm low human health concerns with most uses of TBAC and indicate that further data-informed refinements can address problematic health/exposure scenarios. The assessments also illustrate how tier-based risk assessments using read-across toxicity information to metabolic surrogates reduce the need for comprehensive animal testing.

  14. Monitorização terapêutica de fenobarbital - DOI: 10.4025/actascihealthsci.1082 Therapeutic control of phenobarbital - DOI: 10.4025/actascihealthsci.1082

    Directory of Open Access Journals (Sweden)

    Paula Nishiyama

    2008-03-01

    Full Text Available Apesar do desenvolvimento de novos fármacos, o fenobarbital ainda tem destaque no tratamento da epilepsia por ser completo, efetivo e apresentar baixo custo. A margem terapêutica relativamente estreita e o risco do desenvolvimento de crises convulsivas, caso a dosagem não esteja adequada, fazem da monitorização terapêutica um procedimento de rotina na conduta do tratamento. O objetivo deste trabalho de caracterizar o perfil dos pacientes que se submeteram à monitorização terapêutica de fenobarbital em um laboratório de ensino em análises clínicas, no Estado do Paraná, nos anos de 2004 e 2005. Foi realizado um levantamento das fichas do laboratório e obtidos dados de 104 pessoas que realizaram 119 determinações séricas do fármaco, dentre as quais 116 foram para a monitorização terapêutica. A maioria dos pacientes era adulta e realizou exames por solicitação de um serviço público de saúde. Observou-se que 49,1% dos resultados estavam acima ou abaixo da faixa terapêutica considerada. Foram realizados 49 exames em pacientes que faziam uso do fenobarbital em regime de monoterapia e 67 exames em pacientes que utilizavam este fármaco em associação com outros agentes antiepilépticos. A monitorização de níveis séricos de fenobarbital mostra-se vantajosa frente ao grande número de fatores que evidenciam a necessidade de se correlacionar a concentração do fármaco com o estado clínico do pacienteDespite the development of new drugs, the phenobarbital still has prominence in the treatment of the epilepsy for being complete, effective and to present low cost. The relatively narrow therapeutical range and the risk of the development of convulsive crises in case the dosage is not well adjusted, make the therapeutical control a routine procedure. The aim of this work is to characterize the profile of the patients submitted to the therapeutical control of phenobarbital in a laboratory of clinical analysis in Paraná State

  15. UGT1A9 -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients.

    Science.gov (United States)

    van Schaik, R H N; van Agteren, M; de Fijter, J W; Hartmann, A; Schmidt, J; Budde, K; Kuypers, D; Le Meur, Y; van der Werf, M; Mamelok, R; van Gelder, T

    2009-09-01

    Mycophenolate mofetil (MMF) is an immunosuppressive drug commonly used in the context of kidney transplantation. Exposure to the active metabolite mycophenolic acid (MPA) is associated with risk of allograft rejection. MPA pharmacokinetics varies between individuals, the potential cause being the presence of genetic polymorphisms in key enzymes. We genotyped 338 kidney transplant patients for UGT1A8, UGT1A9, UGT2B7, and MRP2 polymorphisms and recorded MPA exposure and biopsy-proven acute rejections (BPARs) during a 1-year follow-up. Tacrolimus-treated patients who were UGT1A9 -275T>A and/or -2152C>T carriers displayed a 20% lower MPA area under the concentration-time curve from 0 to 12 h (AUC(0-12)) (P = 0.012). UGT1A9*3 carriers displayed a 49% higher MPA AUC(0-12) when treated with tacrolimus and a 54% higher MPA AUC(0-12) when treated with cyclosporine (P A and/or -2152C>T polymorphism significantly predicted acute rejection in fixed-dose (FD) MMF-treated patients receiving tacrolimus (odds ratio 13.3, 95% confidence interval 1.1-162.3; P A and/or -2152C>T genotyping may identify patients at risk of MPA underexposure and acute rejection when receiving treatment with MMF and tacrolimus.

  16. Simultaneous analysis method for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin in urine, using C18 poroshell column.

    Science.gov (United States)

    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.

  17. Adaptation of microvolume EMIT assays for theophylline, phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, and gentamicin to a CentrifiChem chemistry analyzer.

    Science.gov (United States)

    Studts, D; Haven, G T; Kiser, E J

    1983-01-01

    We have developed microvolume EMIT procedures for theophylline, phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, and gentamicin using a centrifugal analyzer (CentrifiChem and Pipettor 1000) to reduce the manufacturer's recommended manual reagent consumption by one-sixth. In addition to developing the EMIT procedure, the performance of the analyzer and pipettor were verified. The analyzer and pipettor are capable of producing within-run precision at a 3-microliters sample volume and 210-microliters analyzer cuvette volume equal to or less than 1.5%. The performance of the EMIT procedures on the analyzer yielded spike drug recoveries of 90.8 to 106.1% for drug concentrations throughout the calibration concentration range of each assay. The percent error on standard reference material of the National Bureau of Standards ranged from a +12.0% to a -0.6% for ethosuximide, phenobarbital, phenytoin, and primidone. Patient comparison data yielded slopes from 0.930 to 1.110 for all assays. The other important feature of the adapted EMIT assay is its simplicity for use on a routine basis.

  18. Acute massive splenic infarction with splenic vein thrombosis following altitude exposure of a Sri Lankan male with undetected sickle cell trait.

    Science.gov (United States)

    Abeysekera, Walimuni Yohan Mendis; de Silva, Warusha Dhammika Dulantha; Pinnaduwa, Sharika Shashindrani; Banagala, Anura Sarath Kumara

    2012-12-01

    Even though sickle cell disease is not common in Sri Lanka, we report an acute splenic infarction at high altitude of a Sri Lankan male with previously undetected sickle cell trait (SCT). This is the first time such a case is reported from the South Asian region. Early recognition of this hematological condition would simplify the management of acute splenic infarction in these patients, avoiding irreversible surgery.

  19. 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.

    Science.gov (United States)

    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

  20. Pressure Physiology: Studies of Acute and Chronic Exposures to Increased Pressures of Oxygen and Inert Gases in Diving, Decompression and Therapy of Decompression and Isobaric Gas Lesion Diseases

    Science.gov (United States)

    1985-12-31

    Oxygen Exposures. Completion of Design for Human Studies of CNS, Pulmon - ary, and Cardiac Oxygen Tolerance Extension at 2.5 and 3.0 ATA. (Based on prior...intoxication at that pressure. Of all pulmon - ary function-indices that are known to be affected by oxygen to date, repeated post-exposure measurements of

  1. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute ... bleeding and forming blood clots. Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk ...

  2. Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-alpha-like effector A, in rat interscapular brown adipose tissue by sympathetically activated beta3-adrenoreceptors.

    Science.gov (United States)

    Shimizu, Takahiro; Yokotani, Kunihiko

    2009-09-18

    The thermogenic activity of brown adipose tissue (BAT) largely depends on the mitochondrial uncoupling protein 1 (UCP1), which is up-regulated by environmental alterations such as cold. Recently, CIDEA (cell death-inducing DNA fragmentation factor-alpha-like effector A) has also been shown to be expressed at high levels in the mitochondria of BAT. Here we examined the effect of cold on the mRNA and protein levels of CIDEA in interscapular BAT of conscious rats with regard to the sympathetic nervous system. Cold exposure (4 degrees C for 3h) elevated the plasma norepinephrine level and increased norepinephrine turnover in BAT. Cold exposure resulted in down-regulation of the mRNA and protein levels of CIDEA in BAT, accompanied by up-regulation of mRNA and protein levels of UCP1. The cold exposure-induced changes of CIDEA and UCP1 were attenuated by intraperitoneal pretreatment with propranolol (a non-selective beta-adrenoreceptor antagonist) (2mg/animal) or SR59230A (a selective beta(3)-adrenoreceptor antagonist) (2mg/animal), respectively. These results suggest that acute cold exposure resulted in down-regulation of CIDEA in interscapular BAT by sympathetically activated beta(3)-adrenoreceptor-mediated mechanisms in rats.

  3. Acute anxiolytic effects of quetiapine during virtual reality exposure--a double-blind placebo-controlled trial in patients with specific phobia.

    Science.gov (United States)

    Diemer, Julia; Domschke, Katharina; Mühlberger, Andreas; Winter, Bernward; Zavorotnyy, Maxim; Notzon, Swantje; Silling, Karen; Arolt, Volker; Zwanzger, Peter

    2013-11-01

    Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms.

  4. Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72 and microRNA (miR-142-5p and miR-203.

    Directory of Open Access Journals (Sweden)

    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.

  5. Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

    Science.gov (United States)

    Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of...

  6. Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur

    Science.gov (United States)

    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...

  7. 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?

    Directory of Open Access Journals (Sweden)

    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.

  8. USE OF CATEGORICAL REGRESSION IN THE DEFINITION OF THE DURATION/CONCENTRATION CURVE IN THE U.S. EPA'S ACUTE REFEFENCE EXPOSURE (ARE) METHODOLOGY

    Science.gov (United States)

    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 ...

  9. Age-dependent acute interference with stem and progenitor cell proliferation in the hippocampus after exposure to 1800 MHz electromagnetic radiation.

    Science.gov (United States)

    Xu, Falin; Bai, Qiongdan; Zhou, Kai; Ma, Li; Duan, Jiajia; Zhuang, Fangli; Xie, Cuicui; Li, Wenli; Zou, Peng; Zhu, Changlian

    2017-01-01

    To investigate the effects of exposure to an 1800 MHz electromagnetic field on cell death and cell proliferation in the developing brain, postnatal day 7 (P7) and P21 healthy Kunming mice were randomly assigned into the experimental and control groups. The experimental groups were exposed to an 1800 MHz electromagnetic field for 8 h daily for three consecutive days. The thymidine analog 5-bromo-2-deoxyuridine (BrdU) was injected intraperitoneally 1 h before each exposure session, and all animals were sacrificed 24 h after the last exposure. Cell death and proliferation markers were detected by immunohistochemistry in the dentate gyrus of the hippocampus. Electromagnetic exposure has no influence on cell death in the dentate gyrus of the hippocampus in P7 and P21 mice as indicated by active caspase-3 immunostaining and Fluoro-Jade labeling. The basal cell proliferation in the hippocampus was higher in P7 than in P21 mice as indicated by the number of cells labeled with BrdU and by immunohistochemical staining for phosphor-histone H3 (PHH3) and brain lipid-binding protein (BLBP). Electromagnetic exposure stimulated DNA synthesis in P7 neural stem and progenitor cells, but reduced cell division and the total number of stem cells in the hippocampus as indicated by increased BrdU labeling and reduced PHH3 and BLBP labeling compared to P7 control mice. There were no significant changes in cell proliferation in P21 mice after exposure to the electromagnetic field. These results indicate that interference with stem cell proliferation upon short-term exposure to an 1800 MHz electromagnetic field depends on the developmental stage of the brain.

  10. Detection of acute diazepam exposure in bone and marrow: influence of tissue type and the dose-death interval on sensitivity of detection by ELISA with liquid chromatography tandem mass spectrometry confirmation.

    Science.gov (United States)

    Watterson, James H; Botman, Jolina E

    2009-05-01

    Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography tandem mass spectrometry (LC/MS/MS) were used to detect diazepam exposure in skeletal tissues of rats (n = 15) given diazepam acutely (20 mg/kg, i.p.), and killed at various times postdose. Marrow, epiphyseal, and diaphyseal bone were isolated from extracted femora. Bone was cleaned, ground, and incubated in methanol. Marrow underwent ultrasonic homogenization. Extracts and homogenates were diluted in phosphate buffer, and then underwent solid-phase extraction and ELISA. Relative sensitivity of detection was examined in terms of relative decrease in absorbance (ELISA) and binary classification sensitivity (ELISA and LC/MS/MS). Overall, the data showed differences in relative sensitivity of detection of diazepam exposure in different tissue types (marrow > epiphyseal bone > diaphyseal bone), which is suggestive of heterogenous distribution in these tissues, and a decreasing sensitivity with increasing dose-death interval. Thus, the tissue type sampled and dose-death interval may contribute to the probability of detection of diazepam exposure in skeletal tissues.

  11. Biochemical Tolerance During Low Dose Propylene Glycol Exposure in Neonates: A Formulation-Controlled Evaluation

    Directory of Open Access Journals (Sweden)

    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.

  12. Patterns of secretion of transforming growth factor-alpha (TGF-alpha) in experimental silicosis. Acute and subacute effects of cristobalite exposure in the rat.

    Science.gov (United States)

    Absher, M; Sjöstrand, M; Baldor, L C; Hemenway, D R; Kelley, J

    1993-01-01

    Transforming growth factor-alpha (TGF-alpha) a cytokine having potent mitogenic activity for epithelial and mesenchymal cells, may play a role in the lung remodeling of silicosis. Lung macrophages are among the major cells producing TGF-alpha in a lung tissue. A pivotal event in the cascade of pathologic events leading to pulmonary silicosis is the interaction between inhaled silica and macrophages. TGF-alpha may be critical in directing the proliferation of type II pneumocytes that characterize silicosis. An inhalation model of brief exposure of pathogen-restricted male rats to 25 mg/M3 cristobalite, a highly reactive form of silicon dioxide was used to study experimental silicosis. This model is characterized by a rapid, intense, and sustained increase in macrophages, neutrophils, and lymphocytes in both alveolar and interstitial compartments of the lung. TGF-alpha was measured in an A431 cell proliferation assay made specific with the use of anti-TGF-alpha neutralizing antiserum in epithelial lining fluid (ELF) and conditioned media harvested from cultured alveolar and interstitial macrophages. Soluble TGF-alpha levels found in ELF were slightly elevated above control values during the exposure period, then increased 5-fold during the 20 weeks after the 8-day exposure period. Secretion of TGF-alpha by macrophages was elevated during exposure to cristobalite but then fell during the early post exposure period. Marked elevations in TGF-alpha secretion from both interstitial and alveolar macrophages (10- and 12-fold, respectively) occurred 8-16 weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer; Taylor, Ronald C.; Stenoien, David L.

    2016-11-01

    Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. A total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.

  14. Effect of acutely and chronically administered venlafaxine on the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock model.

    Science.gov (United States)

    Borowicz, Kinga K; Gołyska, Dorota; Luszczki, Jarogniew J; Czuczwar, Stanislaw J

    2011-11-16

    The influence of acute and chronic treatments with intraperitoneal venlafaxine, a selective serotonin/norepinephrine reuptake inhibitor, on the anticonvulsant activity of selected antiepileptic drugs was studied in the maximal electroshock test in mice. Venlafaxine (12.5 and 25mg/kg), given either acutely or chronically, significantly increased the electroconvulsive threshold. Moreover, both acute and chronic venlafaxine, applied at the highest subprotective dose of 6.25mg/kg, enhanced the anticonvulsant effect of valproate, without affecting the protective action of carbamazepine, phenobarbital and phenytoin. The antidepressant did not affect brain concentration of valproate, indicating that the interaction between the two drugs seems pharmacodynamic in nature. Despite the lack of effect on the antielectroshock action of the remaining antiepileptics, acute venlafaxine increased the brain concentration of phenobarbital, while chronic venlafaxine reduced the brain level of phenytoin. In terms of adverse effects, acute/chronic venlafaxine and antiepileptic drugs alone, as well as their combinations, did not produce significant motor or long-term memory deficits in mice. Summing up, it seems that venlafaxine may be considered as a safe drug for the clinical use in patients with epilepsy and depressive disorders.

  15. Ambient Particulate Matter (PM2.5/PM10) Exposure and Emergency Department Visits for Acute Myocardial Infarction in Chaoyang District, Beijing, China During 2014: A Case-Crossover Study

    Science.gov (United States)

    Zhang, Qian; Qi, Weipeng; Yao, Wei; Wang, Mei; Chen, Yiyong; Zhou, Yujie

    2016-01-01

    Background Epidemiology studies have shown a consistently increased risk of acute myocardial infarction (AMI) correlated with particulate matter (PM) exposure. However, little is known about the association with specific AMI subtypes. In this work, we investigated the association between short-term PM exposure and emergency department visits (EDVs) for AMI, ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). Methods We based this case-crossover study on 2749 patients from Chaoyang District hospitalized with AMI in Anzhen Hospital during 2014. Meteorological and air pollution data were collected during this period. We used a time-stratified case-crossover design with lag model, adjusted for meteorological conditions and/or other gaseous pollutants, to estimate risk of EDVs for AMI, STEMI, and NSTEMI. We conducted stratified analyses by gender, age, season, and comorbid conditions to examine potential effect modification. Results We found that each 10 µg/m3 increment of PM2.5 concentration (1-day lagged) was associated with an increased risk of EDVs for STEMI (OR 1.05; 95% CI, 1.00–1.11). We found no association of PM2.5 concentration with overall AMI or NSTEMI. No effect modification was found when stratified by gender, season, or comorbid conditions, even though the effect size was larger in patients who were male, smokers, and comorbid with hypertension. Patients aged ≥65 years showed a significantly increased risk of STEMI associated with PM2.5 in the previous day than those aged <65 years. Conclusions Our study indicated a transient effect of short-term PM2.5 exposure on EDVs for STEMI. Patients aged ≥65 years appeared to be particularly susceptible. Our findings suggest that studies of the association between PM exposure and AMI should consider AMI subtypes, lag times, and individual characteristics. PMID:27064131

  16. Occupational exposure levels of bioaerosol components are associated with serum levels of the acute phase protein Serum Amyloid A in greenhouse workers

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Thilsing, Trine; Bælum, Jesper

    2016-01-01

    -glucan. RESULTS: Serum levels of SAA and CRP were not significantly different in greenhouse workers and a reference group, or on the two work days. In a mixed model, SAA levels were positively associated with endotoxin exposure levels (p = 0.0007). Results for fungi were not clear. CRP levels were positively...

  17. Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish

    Science.gov (United States)

    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.

  18. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    Science.gov (United States)

    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...

  19. Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 用地西泮联合苯巴比妥治疗小儿热性惊厥的效果探讨%Curative Effect Discussion on Combination of Diazepam and Phenobarbital in the Treatment of Children Febrile Convulsion

    Institute of Scientific and Technical Information of China (English)

    唐中贤; 许正香; 周泉良

    2016-01-01

    Objective To Discuss the Curative effect of combination of diazepam and phenobarbital in the treatment of children febrile convulsion.Methods Randomly divided 98 children with febrile convulsion from October 2013 to October 2015 into diazepam group,phenobarbital group and combined treatment group, respective intravenous with diazepam,phenobarbital and combination of diazepam and Phenobarbital.Compare the anticonvulsant effect and recurrence of convulsion rate.Results Combined treatment group anticonvulsant effect is better than that of phenobarbit al group and the recurrence rate is lower than that of diazepam group, the differences shows statis tically significant(P<0.05). Conclusion Combination of diazepam and phenobarbital has a better anticonvulsant effect and low recurrence rate in treatment of children febrile convulsion,and is worth clinical application.%目的:探讨用地西泮联合苯巴比妥治疗小儿热性惊厥的临床效果。方法:将我院于2013年10月~2015年10月期间收治的98例热性惊厥患儿随机分为地西泮组、苯巴比妥组和联合用药组,为这三组患儿分别使用地西泮、苯巴比妥、地西泮和苯巴比妥进行治疗。比较三组患儿所用药物的镇惊效果及其病情的复发率。结果:经治疗,联合用药组患儿镇惊的效果、惊厥的复发率均好于苯巴比妥组和地西泮组患儿,差异有统计学意义(P <0.05)。结论:用地西泮联合苯巴比妥治疗小儿热性惊厥的效果理想,而且能有效地降低此病患儿惊厥的复发率。

  1. Insuficiência respiratória aguda após exposição a conservantes de alimentos Acute respiratory failure after occupational exposure to food preservatives

    Directory of Open Access Journals (Sweden)

    Maria Auxiliadora Carmo Moreira

    2005-10-01

    Full Text Available Este é um relato de caso de exposição ocupacional a conservantes de alimentos que resultou em insuficiência respiratória aguda em três trabalhadores. A análise toxicológica demonstrou que a mistura dos conservantes, por eles realizada, produziu NO2 que inalado causou quadro compatível com edema pulmonar e insuficiência respiratória aguda. Na evolução, o dano pulmonar regrediu de forma completa nos três indivíduos. Faz-se uma breve revisão sobre dano pulmonar agudo relacionado a exposição ocupacional. Enfatiza-se a importância do treinamento dos trabalhadores que manipulam substâncias químicas bem com da utilização de equipamentos de proteção adequados.Herein, we report an instance of occupational exposure to food preservatives and resultant acute respiratory failure in three workers. The toxicological analysis revealed that mixing the particular food preservatives involved, a procedure that was performed by the three workers involved, produced NO2, the inhalation of which caused the pulmonary edema and respiratory failure. With time, the pulmonary damage was completely reversed in all three individuals. Accompanying this case report is a brief review of the literature regarding acute pulmonary injury resulting from occupational exposure to chemicals. We emphasize the importance of training, as well as of the use of protective gear, for workers who handle chemical substances.

  2. Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine

    Directory of Open Access Journals (Sweden)

    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.

  3. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  4. Cystitis - acute

    Science.gov (United States)

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  5. Acute exposure to 17α-ethinylestradiol disrupts audience effects on male-male interactions in Siamese fighting fish, Betta splendens.

    Science.gov (United States)

    Dzieweczynski, Teresa L; Buckman, Christina M

    2013-03-01

    Endocrine disrupting chemicals can have profound effects on the behavior of aquatic organisms residing in polluted waters. Males are especially sensitive to the effects of estrogen mimics and both courtship and aggression may be dramatically reduced by chemical exposure. Population-level impacts may occur if these chemicals decrease the ability of males to obtain mates or defend territories. Exposure might also have far-reaching impacts by interfering with information transfer within a network of individuals. For example, males exposed to an endocrine disruptor may be less sensitive to the presence of an audience. Male Siamese fighting fish were used to examine how short-term exposure to 17α-ethinylestradiol (EE2) alters audience effects on male-male interactions. Males either received a nominal dose of EE2 or remained unexposed and then interacted with an opponent in one of three treatments (female, male, or no audience). EE2 altered audience effects in this study. Opponent-directed gill flaring was lower when a female audience was present compared to when there was a male or no audience in both EE2 and control males. The number of opponent-directed tail beats did not differ as a function of audience type in EE2 males. In contrast, unexposed males increased opponent-directed tail beats when a female audience is present. Therefore, EE2 reduces the ability of males to communicate with multiple individuals simultaneously. If this is the case, endocrine disruptor exposure may alter population structure as selection should favor individuals that are able to readily adjust their signaling behavior as a function of social context.

  6. Effects of an acute dose of gamma radiation exposure on stem diameter growth, carbon gain, and biomass partitioning in Helianthus annuus

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Acute effects of low-level sulphur dioxide and nitrogen dioxide exposures on the respiratory tract of susceptible subjects in cold environments

    Energy Technology Data Exchange (ETDEWEB)

    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)

  8. Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available The abuse of psychostimulants, such as methamphetamine (METH, is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigr